TY  - CONF
AU  - Lakić, Iva
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pavlović, Slađan
AU  - Borković-Mitić, Slavica
AU  - Grigorov, Ilijana
AU  - Stanković, Sanja
AU  - Pejić, Snežana
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5933
AB  - Сепса је стање опасно по живот узроковано нерегулисаним и прекомерним
одговором на инфекцију, које праћено инфламацијом и поремећеним
метаболизмом липида доводи до постепеног отказивања органа.1,2 Мелдонијум је
антиинфламаторни лек који се користи за лечење исхемије миокарда.3 Он делује
тако што преусмерава производњу енергије са оксидације масних киселина на
гликолизу, као пут који троши мање кисеоника. На овај начин мелдонијум
негативно утиче на метаболизам липида. Истраживали смо ефекте
четворонедељног претретмана мелдонијумом на ток фекалне сепсе (ФИП) и сепсе
изазиване липополисахаридом (ЛПС), код мужјака пацова. Изненађујуће, у
условима фекалне сепсе, мелдонијум је повећао стопу морталитета животиња у
поређењу са групом која није третирана мелдонијумом. Анализе оксидативног и
инфламаторног статуса ткива (срце, јетра, бубрези) потврдиле су
антиинфламаторне, антиапоптотске и антинекротичке ефекте мелдонијума, код оба
модела сепсе. Када је реч о производњи енергије, упркос неким сличностима,
утврђене су разлике у ова два модела. Једна од очигледних разлика је у одговору
симпатоадреналног система, који је изостао код ФИП модела, док је код ЛПС
модела довео до двоструког повећања концентрације катехоламина у серуму. Ова
студија показује важност ненарушене производње енергије скрећући пажњу на
потребу ревизије постојећих смерница у клиничком лечењу сепсе, али и отвара пут
за откривање нових терапијских приступа.
AB  - Sepsa je stanje opasno po život uzrokovano neregulisanim i prekomernim odgovorom na infekciju, koje praćeno inflamacijom i poremećenim metabolizmom lipida dovodi do postepenog otkazivanja organa.1,2 Meldonijum je antiinflamatorni lek koji se koristi za lečenje ishemije miokarda.3 On deluje tako što preusmerava proizvodnju energije sa oksidacije masnih kiselina na glikolizu, kao put koji troši manje kiseonika. Na ovaj način meldonijum negativno utiče na metabolizam lipida. Istraživali smo efekte četvoronedeljnog pretretmana meldonijumom na tok fekalne sepse (FIP) i sepse izazivane lipopolisaharidom (LPS), kod mužjaka pacova. Iznenađujuće, u uslovima fekalne sepse, meldonijum je povećao stopu mortaliteta životinja u poređenju sa grupom koja nije tretirana meldonijumom. Analize oksidativnog i inflamatornog statusa tkiva (srce, jetra, bubrezi) potvrdile su antiinflamatorne, antiapoptotske i antinekrotičke efekte meldonijuma, kod oba modela sepse. Kada je reč o proizvodnji energije, uprkos nekim sličnostima, utvrđene su razlike u ova dva modela. Jedna od očiglednih razlika je u odgovoru simpatoadrenalnog sistema, koji je izostao kod FIP modela, dok je kod LPS modela doveo do dvostrukog povećanja koncentracije kateholamina u serumu. Ova studija pokazuje važnost nenarušene proizvodnje energije skrećući pažnju na potrebu revizije postojećih smernica u kliničkom lečenju sepse, ali i otvara put za otkrivanje novih terapijskih pristupa.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Efekti pretretmana meldonijumom na tokove različitih modela sepsi kod pacova
T1  - Ефекти претретмана мелдонијумом на токове различитих модела сепси код пацова
SP  - 340
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5933
ER  - 

@conference{
author = "Lakić, Iva and Đurašević, Siniša and Ružičić, Aleksandra and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pavlović, Slađan and Borković-Mitić, Slavica and Grigorov, Ilijana and Stanković, Sanja and Pejić, Snežana and Todorović, Ana and Drakulić, Dunja and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2022",
abstract = "Сепса је стање опасно по живот узроковано нерегулисаним и прекомерним
одговором на инфекцију, које праћено инфламацијом и поремећеним
метаболизмом липида доводи до постепеног отказивања органа.1,2 Мелдонијум је
антиинфламаторни лек који се користи за лечење исхемије миокарда.3 Он делује
тако што преусмерава производњу енергије са оксидације масних киселина на
гликолизу, као пут који троши мање кисеоника. На овај начин мелдонијум
негативно утиче на метаболизам липида. Истраживали смо ефекте
четворонедељног претретмана мелдонијумом на ток фекалне сепсе (ФИП) и сепсе
изазиване липополисахаридом (ЛПС), код мужјака пацова. Изненађујуће, у
условима фекалне сепсе, мелдонијум је повећао стопу морталитета животиња у
поређењу са групом која није третирана мелдонијумом. Анализе оксидативног и
инфламаторног статуса ткива (срце, јетра, бубрези) потврдиле су
антиинфламаторне, антиапоптотске и антинекротичке ефекте мелдонијума, код оба
модела сепсе. Када је реч о производњи енергије, упркос неким сличностима,
утврђене су разлике у ова два модела. Једна од очигледних разлика је у одговору
симпатоадреналног система, који је изостао код ФИП модела, док је код ЛПС
модела довео до двоструког повећања концентрације катехоламина у серуму. Ова
студија показује важност ненарушене производње енергије скрећући пажњу на
потребу ревизије постојећих смерница у клиничком лечењу сепсе, али и отвара пут
за откривање нових терапијских приступа., Sepsa je stanje opasno po život uzrokovano neregulisanim i prekomernim odgovorom na infekciju, koje praćeno inflamacijom i poremećenim metabolizmom lipida dovodi do postepenog otkazivanja organa.1,2 Meldonijum je antiinflamatorni lek koji se koristi za lečenje ishemije miokarda.3 On deluje tako što preusmerava proizvodnju energije sa oksidacije masnih kiselina na glikolizu, kao put koji troši manje kiseonika. Na ovaj način meldonijum negativno utiče na metabolizam lipida. Istraživali smo efekte četvoronedeljnog pretretmana meldonijumom na tok fekalne sepse (FIP) i sepse izazivane lipopolisaharidom (LPS), kod mužjaka pacova. Iznenađujuće, u uslovima fekalne sepse, meldonijum je povećao stopu mortaliteta životinja u poređenju sa grupom koja nije tretirana meldonijumom. Analize oksidativnog i inflamatornog statusa tkiva (srce, jetra, bubrezi) potvrdile su antiinflamatorne, antiapoptotske i antinekrotičke efekte meldonijuma, kod oba modela sepse. Kada je reč o proizvodnji energije, uprkos nekim sličnostima, utvrđene su razlike u ova dva modela. Jedna od očiglednih razlika je u odgovoru simpatoadrenalnog sistema, koji je izostao kod FIP modela, dok je kod LPS modela doveo do dvostrukog povećanja koncentracije kateholamina u serumu. Ova studija pokazuje važnost nenarušene proizvodnje energije skrećući pažnju na potrebu revizije postojećih smernica u kliničkom lečenju sepse, ali i otvara put za otkrivanje novih terapijskih pristupa.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Efekti pretretmana meldonijumom na tokove različitih modela sepsi kod pacova, Ефекти претретмана мелдонијумом на токове различитих модела сепси код пацова",
pages = "340",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5933"
}

Lakić, I., Đurašević, S., Ružičić, A., Tosti, T., Đurović, S., Glumac, S., Pavlović, S., Borković-Mitić, S., Grigorov, I., Stanković, S., Pejić, S., Todorović, A., Drakulić, D., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2022). Efekti pretretmana meldonijumom na tokove različitih modela sepsi kod pacova. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 340.
https://hdl.handle.net/21.15107/rcub_ibiss_5933

Lakić I, Đurašević S, Ružičić A, Tosti T, Đurović S, Glumac S, Pavlović S, Borković-Mitić S, Grigorov I, Stanković S, Pejić S, Todorović A, Drakulić D, Jasnić N, Đorđević J, Todorović Z. Efekti pretretmana meldonijumom na tokove različitih modela sepsi kod pacova. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:340.
https://hdl.handle.net/21.15107/rcub_ibiss_5933 .

Lakić, Iva, Đurašević, Siniša, Ružičić, Aleksandra, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pavlović, Slađan, Borković-Mitić, Slavica, Grigorov, Ilijana, Stanković, Sanja, Pejić, Snežana, Todorović, Ana, Drakulić, Dunja, Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "Efekti pretretmana meldonijumom na tokove različitih modela sepsi kod pacova" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):340,
https://hdl.handle.net/21.15107/rcub_ibiss_5933 .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Sopta, Jelena
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Ivanović, Anđelija
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4090
AB  - Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium
is an anti‑ischemic agent that shifts energy production from fatty acid oxidation to less oxygen‑
consuming glycolysis. Thus, we investigated the effects of a 4‑week meldonium pre‑treatment
(300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that
meldonium ameliorates I/R‑induced liver inflammation and injury, as confirmed by liver histology,
and by attenuation of serum alanine‑ and aspartate aminotransferase activity, serum and liver
high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and
the phosphorylated nuclear factor kappa‑light‑chain‑enhancer of activated B cells. Through the
increased hepatic activation of the nuclear factor erythroid 2‑related factor 2, meldonium improves
the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum
and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione
and free thiol groups content, and hepatic copper‑zinc superoxide dismutase, manganese superoxide
dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results,
it can be concluded that meldonium represent a protective agent against I/R‑induced liver injury, with
a clinical significance in surgical procedures.
PB  - Nature Publishing Group
T2  - Scientific Reports
T1  - The effects of meldonium on the acute ischemia/reperfusion liver injury in rats
IS  - 1
VL  - 11
DO  - 10.1038/s41598-020-80011-y
SP  - 1305
ER  - 

@article{
author = "Đurašević, Siniša and Stojković, Maja and Sopta, Jelena and Pavlović, Slađan and Borković Mitić, Slavica and Ivanović, Anđelija and Jasnić, Nebojša and Tosti, Tomislav and Đurović, Saša and Đorđević, Jelena and Todorović, Zoran",
year = "2021",
abstract = "Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium
is an anti‑ischemic agent that shifts energy production from fatty acid oxidation to less oxygen‑
consuming glycolysis. Thus, we investigated the effects of a 4‑week meldonium pre‑treatment
(300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that
meldonium ameliorates I/R‑induced liver inflammation and injury, as confirmed by liver histology,
and by attenuation of serum alanine‑ and aspartate aminotransferase activity, serum and liver
high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and
the phosphorylated nuclear factor kappa‑light‑chain‑enhancer of activated B cells. Through the
increased hepatic activation of the nuclear factor erythroid 2‑related factor 2, meldonium improves
the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum
and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione
and free thiol groups content, and hepatic copper‑zinc superoxide dismutase, manganese superoxide
dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results,
it can be concluded that meldonium represent a protective agent against I/R‑induced liver injury, with
a clinical significance in surgical procedures.",
publisher = "Nature Publishing Group",
journal = "Scientific Reports",
title = "The effects of meldonium on the acute ischemia/reperfusion liver injury in rats",
number = "1",
volume = "11",
doi = "10.1038/s41598-020-80011-y",
pages = "1305"
}

Đurašević, S., Stojković, M., Sopta, J., Pavlović, S., Borković Mitić, S., Ivanović, A., Jasnić, N., Tosti, T., Đurović, S., Đorđević, J.,& Todorović, Z.. (2021). The effects of meldonium on the acute ischemia/reperfusion liver injury in rats. in Scientific Reports
Nature Publishing Group., 11(1), 1305.
https://doi.org/10.1038/s41598-020-80011-y

Đurašević S, Stojković M, Sopta J, Pavlović S, Borković Mitić S, Ivanović A, Jasnić N, Tosti T, Đurović S, Đorđević J, Todorović Z. The effects of meldonium on the acute ischemia/reperfusion liver injury in rats. in Scientific Reports. 2021;11(1):1305.
doi:10.1038/s41598-020-80011-y .

Đurašević, Siniša, Stojković, Maja, Sopta, Jelena, Pavlović, Slađan, Borković Mitić, Slavica, Ivanović, Anđelija, Jasnić, Nebojša, Tosti, Tomislav, Đurović, Saša, Đorđević, Jelena, Todorović, Zoran, "The effects of meldonium on the acute ischemia/reperfusion liver injury in rats" in Scientific Reports, 11, no. 1 (2021):1305,
https://doi.org/10.1038/s41598-020-80011-y . .

TY  - JOUR
AU  - Todorović, Zoran
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Grigorov, Ilijana
AU  - Pavlović, Slađan
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Bjekić Macut, Jelica
AU  - Thiemermann, Christoph
AU  - Đorđević, Jelena
PY  - 2021
UR  - https://www.mdpi.com/1422-0067/22/6/2798
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4162
AB  - Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.
PB  - Multidisciplinary Digital Publishing Institute
T2  - International Journal of Molecular Sciences
T1  - Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury
IS  - 6
VL  - 22
DO  - 10.3390/ijms22062798
SP  - 2798
ER  - 

@article{
author = "Todorović, Zoran and Đurašević, Siniša and Stojković, Maja and Grigorov, Ilijana and Pavlović, Slađan and Jasnić, Nebojša and Tosti, Tomislav and Bjekić Macut, Jelica and Thiemermann, Christoph and Đorđević, Jelena",
year = "2021",
abstract = "Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.",
publisher = "Multidisciplinary Digital Publishing Institute",
journal = "International Journal of Molecular Sciences",
title = "Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury",
number = "6",
volume = "22",
doi = "10.3390/ijms22062798",
pages = "2798"
}

Todorović, Z., Đurašević, S., Stojković, M., Grigorov, I., Pavlović, S., Jasnić, N., Tosti, T., Bjekić Macut, J., Thiemermann, C.,& Đorđević, J.. (2021). Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury. in International Journal of Molecular Sciences
Multidisciplinary Digital Publishing Institute., 22(6), 2798.
https://doi.org/10.3390/ijms22062798

Todorović Z, Đurašević S, Stojković M, Grigorov I, Pavlović S, Jasnić N, Tosti T, Bjekić Macut J, Thiemermann C, Đorđević J. Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury. in International Journal of Molecular Sciences. 2021;22(6):2798.
doi:10.3390/ijms22062798 .

Todorović, Zoran, Đurašević, Siniša, Stojković, Maja, Grigorov, Ilijana, Pavlović, Slađan, Jasnić, Nebojša, Tosti, Tomislav, Bjekić Macut, Jelica, Thiemermann, Christoph, Đorđević, Jelena, "Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury" in International Journal of Molecular Sciences, 22, no. 6 (2021):2798,
https://doi.org/10.3390/ijms22062798 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Pejić, Snežana
AU  - Grigorov, Ilijana
AU  - Nikolić, Gorana
AU  - Mitić-Ćulafić, Dragana
AU  - Dragićević, Milan
AU  - Đorđević, Jelena
AU  - Todorović Vukotić, Nevena
AU  - Đorđević, Neda
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Veljković, Filip
AU  - Pajović, Snežana B.
AU  - Todorović, Zoran
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4289
AB  - Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.
PB  - MDPI
T2  - Antioxidants
T1  - Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes
IS  - 6
VL  - 10
DO  - 10.3390/antiox10060911
SP  - 911
ER  - 

@article{
author = "Đurašević, Siniša and Pejić, Snežana and Grigorov, Ilijana and Nikolić, Gorana and Mitić-Ćulafić, Dragana and Dragićević, Milan and Đorđević, Jelena and Todorović Vukotić, Nevena and Đorđević, Neda and Todorović, Ana and Drakulić, Dunja and Veljković, Filip and Pajović, Snežana B. and Todorović, Zoran",
year = "2021",
abstract = "Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes",
number = "6",
volume = "10",
doi = "10.3390/antiox10060911",
pages = "911"
}

Đurašević, S., Pejić, S., Grigorov, I., Nikolić, G., Mitić-Ćulafić, D., Dragićević, M., Đorđević, J., Todorović Vukotić, N., Đorđević, N., Todorović, A., Drakulić, D., Veljković, F., Pajović, S. B.,& Todorović, Z.. (2021). Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants
MDPI., 10(6), 911.
https://doi.org/10.3390/antiox10060911

Đurašević S, Pejić S, Grigorov I, Nikolić G, Mitić-Ćulafić D, Dragićević M, Đorđević J, Todorović Vukotić N, Đorđević N, Todorović A, Drakulić D, Veljković F, Pajović SB, Todorović Z. Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants. 2021;10(6):911.
doi:10.3390/antiox10060911 .

Đurašević, Siniša, Pejić, Snežana, Grigorov, Ilijana, Nikolić, Gorana, Mitić-Ćulafić, Dragana, Dragićević, Milan, Đorđević, Jelena, Todorović Vukotić, Nevena, Đorđević, Neda, Todorović, Ana, Drakulić, Dunja, Veljković, Filip, Pajović, Snežana B., Todorović, Zoran, "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes" in Antioxidants, 10, no. 6 (2021):911,
https://doi.org/10.3390/antiox10060911 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Lakić, Iva
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Grigorov, Ilijana
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4413
AB  - Sepsis is a life-threatening condition caused by the dysregulated and overwhelming
response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism
disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory
agent which negatively interferes with lipid metabolism by shifting energy production from fatty
acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects
of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats.
Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with
the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide
support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory
status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After
performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium
harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines
the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible
harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to
the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving
the way for discovering new therapeutic approaches.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats
IS  - 18
VL  - 22
DO  - 10.3390/ijms22189698
SP  - 9698
ER  - 

@article{
author = "Đurašević, Siniša and Ružičić, Aleksandra and Lakić, Iva and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pavlović, Slađan and Borković Mitić, Slavica and Grigorov, Ilijana and Stanković, Sanja and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2021",
abstract = "Sepsis is a life-threatening condition caused by the dysregulated and overwhelming
response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism
disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory
agent which negatively interferes with lipid metabolism by shifting energy production from fatty
acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects
of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats.
Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with
the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide
support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory
status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After
performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium
harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines
the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible
harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to
the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving
the way for discovering new therapeutic approaches.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats",
number = "18",
volume = "22",
doi = "10.3390/ijms22189698",
pages = "9698"
}

Đurašević, S., Ružičić, A., Lakić, I., Tosti, T., Đurović, S., Glumac, S., Pavlović, S., Borković Mitić, S., Grigorov, I., Stanković, S., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2021). The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats. in International Journal of Molecular Sciences
Basel: MDPI., 22(18), 9698.
https://doi.org/10.3390/ijms22189698

Đurašević S, Ružičić A, Lakić I, Tosti T, Đurović S, Glumac S, Pavlović S, Borković Mitić S, Grigorov I, Stanković S, Jasnić N, Đorđević J, Todorović Z. The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats. in International Journal of Molecular Sciences. 2021;22(18):9698.
doi:10.3390/ijms22189698 .

Đurašević, Siniša, Ružičić, Aleksandra, Lakić, Iva, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pavlović, Slađan, Borković Mitić, Slavica, Grigorov, Ilijana, Stanković, Sanja, Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "The effects of a meldonium pre-treatment on the course of the faecal-induced sepsis in rats" in International Journal of Molecular Sciences, 22, no. 18 (2021):9698,
https://doi.org/10.3390/ijms22189698 . .

TY  - CONF
AU  - Lakić, Iva
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Grigorov, Ilijana
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Todorović, Zoran
AU  - Đorđević, Jelena
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4896
AB  - Background: Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure.1, 2 Meldonium is an anti-ischemic and anti-inflammatory agent, clinically used to treat myocardial ischemia.3 By shifting energy production from fatty acid oxidation to glycolysis, as an oxygen less consuming pathway, meldonium interferes negatively with lipid metabolism. 
Methods: Thus, we investigated the effects of a 4-week meldonium pre-treatment in 300 mg/kg b.m./day dosage on the course of the sepsis induced by a single intraperitoneal injection of faeces (0.5 g faeces/1 mL saline/100 g b.m.)in Sprague-Dawley male rats. The degree of the heart injury was evaluated by measuring tissue pro-apoptotic Bax and anti-apoptotic Bcl-2 ratio, tissue level of the necrotic marker - high mobility group box 1 protein level (HMGB1), together with the heart histology analysis. Sepsis-associated heart inflammation
was assessed by measuring level of an activated form of NF-kB p65 (phospho-NF-κB p65).
Results: In the heart whole homogenates of the septic group of animals (S) HMGB1 level increased 1.7-fold, in comparison to control rats, while meldonium reduced sepsis-induced increase by 18 % (M+S). The underlying mechanism of the proinflammatory action of HMGB1 includes activation of NF-κB signalling
pathways tissue, so the increased HMGB1 level was followed by a 1.4-fold increase of p-NF-κB p65 in the heart of the S group of rats and a 19 % decreased in the heart of M+S group. The apoptotic marker Bax/Bcl-2 ratio changed in the same manner: 1.4-fold increase in the heart of animals from the S group and a 32 % decrease in the heart of the M+S group. On the other hand, heart histology analysis shows that meldonium worsened the heart histological score, causing the severe and diffuse interstitial mononuclear infiltration along with a greater loss of myocytes and myofibrillar contraction band necrosis. The heart lipidomic analysis suggests that meldonium exhibits potentially harmful effects under septic condition due to the lipid-mobilization impairment.
Conclusion: Meldonium exerted anti-inflammatory, anti-apoptotic, and anti- necrotic effects, while it worsened the septic rat heart histology.
PB  - Banja Luka: Association of Medical Doctors
PB  - Banja Luka: Faculty of Medicine, University of Banja Luka
C3  - 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
T1  - The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury
SP  - 57
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4896
ER  - 

@conference{
author = "Lakić, Iva and Đurašević, Siniša and Ružičić, Aleksandra and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pavlović, Slađan and Borković Mitić, Slavica and Grigorov, Ilijana and Stanković, Sanja and Jasnić, Nebojša and Todorović, Zoran and Đorđević, Jelena",
year = "2021",
abstract = "Background: Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure.1, 2 Meldonium is an anti-ischemic and anti-inflammatory agent, clinically used to treat myocardial ischemia.3 By shifting energy production from fatty acid oxidation to glycolysis, as an oxygen less consuming pathway, meldonium interferes negatively with lipid metabolism. 
Methods: Thus, we investigated the effects of a 4-week meldonium pre-treatment in 300 mg/kg b.m./day dosage on the course of the sepsis induced by a single intraperitoneal injection of faeces (0.5 g faeces/1 mL saline/100 g b.m.)in Sprague-Dawley male rats. The degree of the heart injury was evaluated by measuring tissue pro-apoptotic Bax and anti-apoptotic Bcl-2 ratio, tissue level of the necrotic marker - high mobility group box 1 protein level (HMGB1), together with the heart histology analysis. Sepsis-associated heart inflammation
was assessed by measuring level of an activated form of NF-kB p65 (phospho-NF-κB p65).
Results: In the heart whole homogenates of the septic group of animals (S) HMGB1 level increased 1.7-fold, in comparison to control rats, while meldonium reduced sepsis-induced increase by 18 % (M+S). The underlying mechanism of the proinflammatory action of HMGB1 includes activation of NF-κB signalling
pathways tissue, so the increased HMGB1 level was followed by a 1.4-fold increase of p-NF-κB p65 in the heart of the S group of rats and a 19 % decreased in the heart of M+S group. The apoptotic marker Bax/Bcl-2 ratio changed in the same manner: 1.4-fold increase in the heart of animals from the S group and a 32 % decrease in the heart of the M+S group. On the other hand, heart histology analysis shows that meldonium worsened the heart histological score, causing the severe and diffuse interstitial mononuclear infiltration along with a greater loss of myocytes and myofibrillar contraction band necrosis. The heart lipidomic analysis suggests that meldonium exhibits potentially harmful effects under septic condition due to the lipid-mobilization impairment.
Conclusion: Meldonium exerted anti-inflammatory, anti-apoptotic, and anti- necrotic effects, while it worsened the septic rat heart histology.",
publisher = "Banja Luka: Association of Medical Doctors, Banja Luka: Faculty of Medicine, University of Banja Luka",
journal = "7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina",
title = "The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury",
pages = "57",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4896"
}

Lakić, I., Đurašević, S., Ružičić, A., Tosti, T., Đurović, S., Glumac, S., Pavlović, S., Borković Mitić, S., Grigorov, I., Stanković, S., Jasnić, N., Todorović, Z.,& Đorđević, J.. (2021). The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
Banja Luka: Association of Medical Doctors., 57.
https://hdl.handle.net/21.15107/rcub_ibiss_4896

Lakić I, Đurašević S, Ružičić A, Tosti T, Đurović S, Glumac S, Pavlović S, Borković Mitić S, Grigorov I, Stanković S, Jasnić N, Todorović Z, Đorđević J. The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina. 2021;:57.
https://hdl.handle.net/21.15107/rcub_ibiss_4896 .

Lakić, Iva, Đurašević, Siniša, Ružičić, Aleksandra, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pavlović, Slađan, Borković Mitić, Slavica, Grigorov, Ilijana, Stanković, Sanja, Jasnić, Nebojša, Todorović, Zoran, Đorđević, Jelena, "The Effects of a Meldonium Pre-Treatment on the Sepsis-Induced Rat Heart Injury" in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina (2021):57,
https://hdl.handle.net/21.15107/rcub_ibiss_4896 .

TY  - CONF
AU  - Todorović, Zoran
AU  - Đurašević, Siniša
AU  - Tosti, Tomislav
AU  - Lakić, Iva
AU  - Grigorov, Ilijana
AU  - Đorđević, Jelena
AU  - Đukanović, Nina
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4895
AB  - Lipidomics deals with small molecules metabolomes with a mass lower than 1500. In recent years, the crucial role of lipidomes in the pathogenesis and therapy of cardiovascular events has become increasingly apparent.1-3 For example, ischemia-reperfusion (IR) injury can initiate oxidative stress that leads to harmful changes in membrane lipids, with an unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of IR disorders and reveals new targets for drug action. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes. Regarding platelet functions, polyunsaturated fatty acids play a role in increasing platelet reactivity, and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies clopidogrel discontinuation in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed “on-demand” in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.
PB  - Banja Luka: Association of Medical Doctors
PB  - Banja Luka: Faculty of Medicine, University of Banja Luka
C3  - 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
T1  - Lipidomics as a Novel Tool in Cardiovascular Research
SP  - 87
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4895
ER  - 

@conference{
author = "Todorović, Zoran and Đurašević, Siniša and Tosti, Tomislav and Lakić, Iva and Grigorov, Ilijana and Đorđević, Jelena and Đukanović, Nina",
year = "2021",
abstract = "Lipidomics deals with small molecules metabolomes with a mass lower than 1500. In recent years, the crucial role of lipidomes in the pathogenesis and therapy of cardiovascular events has become increasingly apparent.1-3 For example, ischemia-reperfusion (IR) injury can initiate oxidative stress that leads to harmful changes in membrane lipids, with an unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of IR disorders and reveals new targets for drug action. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes. Regarding platelet functions, polyunsaturated fatty acids play a role in increasing platelet reactivity, and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies clopidogrel discontinuation in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed “on-demand” in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.",
publisher = "Banja Luka: Association of Medical Doctors, Banja Luka: Faculty of Medicine, University of Banja Luka",
journal = "7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina",
title = "Lipidomics as a Novel Tool in Cardiovascular Research",
pages = "87",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4895"
}

Todorović, Z., Đurašević, S., Tosti, T., Lakić, I., Grigorov, I., Đorđević, J.,& Đukanović, N.. (2021). Lipidomics as a Novel Tool in Cardiovascular Research. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
Banja Luka: Association of Medical Doctors., 87.
https://hdl.handle.net/21.15107/rcub_ibiss_4895

Todorović Z, Đurašević S, Tosti T, Lakić I, Grigorov I, Đorđević J, Đukanović N. Lipidomics as a Novel Tool in Cardiovascular Research. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina. 2021;:87.
https://hdl.handle.net/21.15107/rcub_ibiss_4895 .

Todorović, Zoran, Đurašević, Siniša, Tosti, Tomislav, Lakić, Iva, Grigorov, Ilijana, Đorđević, Jelena, Đukanović, Nina, "Lipidomics as a Novel Tool in Cardiovascular Research" in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina (2021):87,
https://hdl.handle.net/21.15107/rcub_ibiss_4895 .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Nikolić, Gorana
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Pejić, Snežana
AU  - Martinović, Vesna
AU  - Mitić-Ćulafić, Dragana
AU  - Milić, Dragana
AU  - Kop, Tatjana J.
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3645
AB  - The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.
T2  - Food and Chemical Toxicology
T1  - Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats
VL  - 140
DO  - 10.1016/j.fct.2020.111302
SP  - 111302
ER  - 

@article{
author = "Đurašević, Siniša and Nikolić, Gorana and Todorović, Ana and Drakulić, Dunja and Pejić, Snežana and Martinović, Vesna and Mitić-Ćulafić, Dragana and Milić, Dragana and Kop, Tatjana J. and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2020",
abstract = "The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.",
journal = "Food and Chemical Toxicology",
title = "Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats",
volume = "140",
doi = "10.1016/j.fct.2020.111302",
pages = "111302"
}

Đurašević, S., Nikolić, G., Todorović, A., Drakulić, D., Pejić, S., Martinović, V., Mitić-Ćulafić, D., Milić, D., Kop, T. J., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2020). Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats. in Food and Chemical Toxicology, 140, 111302.
https://doi.org/10.1016/j.fct.2020.111302

Đurašević S, Nikolić G, Todorović A, Drakulić D, Pejić S, Martinović V, Mitić-Ćulafić D, Milić D, Kop TJ, Jasnić N, Đorđević J, Todorović Z. Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats. in Food and Chemical Toxicology. 2020;140:111302.
doi:10.1016/j.fct.2020.111302 .

Đurašević, Siniša, Nikolić, Gorana, Todorović, Ana, Drakulić, Dunja, Pejić, Snežana, Martinović, Vesna, Mitić-Ćulafić, Dragana, Milić, Dragana, Kop, Tatjana J., Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats" in Food and Chemical Toxicology, 140 (2020):111302,
https://doi.org/10.1016/j.fct.2020.111302 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Nikolić, Gorana
AU  - Zaletel, Ivan
AU  - Grigorov, Ilijana
AU  - Memon, Lidija
AU  - Mitić-Ćulafić, Dragana
AU  - Vujović, Predrag
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2020
UR  - https://www.sciencedirect.com/science/article/pii/S1756464619305250?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3512
UR  - https://s100.copyright.com/AppDispatchServlet?publisherName=ELS&contentID=S1756464619305250&orderBeanReset=true
AB  - Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgin coconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to control glycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementation with coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity of steatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on heart histology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither in non-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementation with coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development of severe insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contraindicated in diabetic condition.
T2  - Journal of Functional Foods
T1  - Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats
VL  - 64
DO  - 10.1016/J.JFF.2019.103601
SP  - 103601
ER  - 

@article{
author = "Đurašević, Siniša and Nikolić, Gorana and Zaletel, Ivan and Grigorov, Ilijana and Memon, Lidija and Mitić-Ćulafić, Dragana and Vujović, Predrag and Đorđević, Jelena and Todorović, Zoran",
year = "2020",
abstract = "Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgin coconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to control glycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementation with coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity of steatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on heart histology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither in non-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementation with coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development of severe insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contraindicated in diabetic condition.",
journal = "Journal of Functional Foods",
title = "Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats",
volume = "64",
doi = "10.1016/J.JFF.2019.103601",
pages = "103601"
}

Đurašević, S., Nikolić, G., Zaletel, I., Grigorov, I., Memon, L., Mitić-Ćulafić, D., Vujović, P., Đorđević, J.,& Todorović, Z.. (2020). Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats. in Journal of Functional Foods, 64, 103601.
https://doi.org/10.1016/J.JFF.2019.103601

Đurašević S, Nikolić G, Zaletel I, Grigorov I, Memon L, Mitić-Ćulafić D, Vujović P, Đorđević J, Todorović Z. Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats. in Journal of Functional Foods. 2020;64:103601.
doi:10.1016/J.JFF.2019.103601 .

Đurašević, Siniša, Nikolić, Gorana, Zaletel, Ivan, Grigorov, Ilijana, Memon, Lidija, Mitić-Ćulafić, Dragana, Vujović, Predrag, Đorđević, Jelena, Todorović, Zoran, "Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats" in Journal of Functional Foods, 64 (2020):103601,
https://doi.org/10.1016/J.JFF.2019.103601 . .

TY  - CONF
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Bogdanović, Ljiljana
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Jasnić, Nebojša
AU  - Vujović, Predrag
AU  - Dakić, Tamara
AU  - Todorović, Zoran
AU  - Đorđević, Jelena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6333
AB  - Acute renal ischemia/reperfusion (I/R) is a temporary restriction of kidney blood supply, followed by blood flow restoration and re-oxygenation. During I/R, decreased oxygen supply disturbs ion transport, intracellular ATP, calcium and pH levels, and numerous signalling pathways. Upon reperfusion, a restoration of oxygen level rises a reactive oxygen species generation, cytokines and chemokines release from activated tissue-resident macrophages, and infiltration of pro-inflammatory neutrophils into ischemic tissues. All these changes result in cell swelling and rupturing, and consequent necrotic or apoptotic cell death. Meldonium is an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, which acts by shifting energy production from fatty acid oxidation to glycolysis. We investigated the effects of a 4-week meldonium pre-treatment with 300 mg/kg b.m./day of rats subjected to a well-established experimental model of renal I/R, with ischemia lasting for 45 minutes, followed by 4 hours of reperfusion. The degree of apoptosis and necrosis was evaluated by measuring renal pro-apoptotic Bax and anti-apoptotic Bcl-2 ratio, serum and kidney levels of necrotic marker - high mobility group box 1 protein (HMGB1), together with the kidney histology analysis. Our results showed that apoptotic and necrotic cell death occur simultaneously under I/R conditions, judging by the renal Bax/Bcl2 ratio rise (2.7-fold), increase in serum (22%) and renal (30%) levels of HMGB1, as well as severe tubular necrosis with dilatation of the tubular structure, cast formation, tubular lumina dilatation, brush border reduction, and loss in some renal areas cells. Meldonium pretreatment reduced the elevated Bax/Bcl2 ratio by 35%, as well as the serum and renal HMGB1 levels by 20% and notably diminished histological evidence of renal I/R necrotic injury, especially regarding tubular structures. These findings proved that meldonium protects renal cells against I/R-induced necrosis and apoptosis.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches
T1  - Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats
SP  - 86
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6333
ER  - 

@conference{
author = "Đurašević, Siniša and Stojković, Maja and Bogdanović, Ljiljana and Grigorov, Ilijana and Bogojević, Desanka and Jasnić, Nebojša and Vujović, Predrag and Dakić, Tamara and Todorović, Zoran and Đorđević, Jelena",
year = "2019",
abstract = "Acute renal ischemia/reperfusion (I/R) is a temporary restriction of kidney blood supply, followed by blood flow restoration and re-oxygenation. During I/R, decreased oxygen supply disturbs ion transport, intracellular ATP, calcium and pH levels, and numerous signalling pathways. Upon reperfusion, a restoration of oxygen level rises a reactive oxygen species generation, cytokines and chemokines release from activated tissue-resident macrophages, and infiltration of pro-inflammatory neutrophils into ischemic tissues. All these changes result in cell swelling and rupturing, and consequent necrotic or apoptotic cell death. Meldonium is an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, which acts by shifting energy production from fatty acid oxidation to glycolysis. We investigated the effects of a 4-week meldonium pre-treatment with 300 mg/kg b.m./day of rats subjected to a well-established experimental model of renal I/R, with ischemia lasting for 45 minutes, followed by 4 hours of reperfusion. The degree of apoptosis and necrosis was evaluated by measuring renal pro-apoptotic Bax and anti-apoptotic Bcl-2 ratio, serum and kidney levels of necrotic marker - high mobility group box 1 protein (HMGB1), together with the kidney histology analysis. Our results showed that apoptotic and necrotic cell death occur simultaneously under I/R conditions, judging by the renal Bax/Bcl2 ratio rise (2.7-fold), increase in serum (22%) and renal (30%) levels of HMGB1, as well as severe tubular necrosis with dilatation of the tubular structure, cast formation, tubular lumina dilatation, brush border reduction, and loss in some renal areas cells. Meldonium pretreatment reduced the elevated Bax/Bcl2 ratio by 35%, as well as the serum and renal HMGB1 levels by 20% and notably diminished histological evidence of renal I/R necrotic injury, especially regarding tubular structures. These findings proved that meldonium protects renal cells against I/R-induced necrosis and apoptosis.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches",
title = "Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats",
pages = "86",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6333"
}

Đurašević, S., Stojković, M., Bogdanović, L., Grigorov, I., Bogojević, D., Jasnić, N., Vujović, P., Dakić, T., Todorović, Z.,& Đorđević, J.. (2019). Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats. in Immunology at the Confluence of Multidisciplinary Approaches
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 86.
https://hdl.handle.net/21.15107/rcub_ibiss_6333

Đurašević S, Stojković M, Bogdanović L, Grigorov I, Bogojević D, Jasnić N, Vujović P, Dakić T, Todorović Z, Đorđević J. Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats. in Immunology at the Confluence of Multidisciplinary Approaches. 2019;:86.
https://hdl.handle.net/21.15107/rcub_ibiss_6333 .

Đurašević, Siniša, Stojković, Maja, Bogdanović, Ljiljana, Grigorov, Ilijana, Bogojević, Desanka, Jasnić, Nebojša, Vujović, Predrag, Dakić, Tamara, Todorović, Zoran, Đorđević, Jelena, "Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats" in Immunology at the Confluence of Multidisciplinary Approaches (2019):86,
https://hdl.handle.net/21.15107/rcub_ibiss_6333 .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Bogdanović, Ljiljana
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3519
AB  - Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to
treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation
to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week
meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our
results showed that meldonium decreased animal body mass gain, food and water intake, and
carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium
increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and
increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1,
causing manganese superoxide dismutase expression and activity to increase, as well as lipid
peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase
activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum
high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in
I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and
serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex
changes in renal lipidomics. Taken together, our results have confirmed that meldonium pretreatment protects against I/R-induced oxidative stress and apoptosis/necrosis.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - The effects of meldonium on the renal acute ischemia/reperfusion injury in rats
IS  - 22
VL  - 20
DO  - 10.3390/ijms20225747
SP  - 5747
ER  - 

@article{
author = "Đurašević, Siniša and Stojković, Maja and Bogdanović, Ljiljana and Pavlović, Slađan and Borković Mitić, Slavica and Grigorov, Ilijana and Bogojević, Desanka and Jasnić, Nebojša and Tosti, Tomislav and Đurović, Saša and Đorđević, Jelena and Todorović, Zoran",
year = "2019",
abstract = "Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to
treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation
to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week
meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our
results showed that meldonium decreased animal body mass gain, food and water intake, and
carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium
increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and
increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1,
causing manganese superoxide dismutase expression and activity to increase, as well as lipid
peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase
activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum
high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in
I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and
serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex
changes in renal lipidomics. Taken together, our results have confirmed that meldonium pretreatment protects against I/R-induced oxidative stress and apoptosis/necrosis.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats",
number = "22",
volume = "20",
doi = "10.3390/ijms20225747",
pages = "5747"
}

Đurašević, S., Stojković, M., Bogdanović, L., Pavlović, S., Borković Mitić, S., Grigorov, I., Bogojević, D., Jasnić, N., Tosti, T., Đurović, S., Đorđević, J.,& Todorović, Z.. (2019). The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences
MDPI., 20(22), 5747.
https://doi.org/10.3390/ijms20225747

Đurašević S, Stojković M, Bogdanović L, Pavlović S, Borković Mitić S, Grigorov I, Bogojević D, Jasnić N, Tosti T, Đurović S, Đorđević J, Todorović Z. The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences. 2019;20(22):5747.
doi:10.3390/ijms20225747 .

Đurašević, Siniša, Stojković, Maja, Bogdanović, Ljiljana, Pavlović, Slađan, Borković Mitić, Slavica, Grigorov, Ilijana, Bogojević, Desanka, Jasnić, Nebojša, Tosti, Tomislav, Đurović, Saša, Đorđević, Jelena, Todorović, Zoran, "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats" in International Journal of Molecular Sciences, 20, no. 22 (2019):5747,
https://doi.org/10.3390/ijms20225747 . .

TY  - CHAP
AU  - Đurašević, Siniša
AU  - Todorović, Zoran
AU  - Pavlović, Slađan
AU  - Pejić, Snežana
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/B9780128144664000276?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3415
AB  - Oxidative stress (OS) represents an imbalance of free radicals production and antioxidant defense in which the extensive pro-oxidant production may cause damage to cell structures. OS is the major event occurring in pathogenesis of liver disorders, ranging from metabolic to proliferative disorders. Cadmium is a highly toxic and widespread toxicant. Cadmium itself is unable to generate free radicals directly, as cadmium does not undergo redox cycling. However, indirect generation of various radicals involving the superoxide radical, hydroxyl radical, and nitric oxide has been reported. One of the biologically most relevant features of C60 fullerene is the ability to quench various free radicals, behaving as a “free radical sponge.” Conversely, photosensitization of C60 yields highly reactive singlet oxygen or superoxide anion. Therefore, the dual property of fullerene to either quench or generate cell-damaging reactive oxygen species could be potentially exploited for their development as cytoprotective or cytotoxic agents.
PB  - Academic Press
T2  - Dietary Interventions in Liver Disease
T1  - Cadmium and Fullerenes in Liver Diseases
DO  - 10.1016/B978-0-12-814466-4.00027-6
SP  - 333
EP  - 344
ER  - 

@inbook{
editor = "Watson, Ronald Ross, Preedy, Victor R.",
author = "Đurašević, Siniša and Todorović, Zoran and Pavlović, Slađan and Pejić, Snežana",
year = "2019",
abstract = "Oxidative stress (OS) represents an imbalance of free radicals production and antioxidant defense in which the extensive pro-oxidant production may cause damage to cell structures. OS is the major event occurring in pathogenesis of liver disorders, ranging from metabolic to proliferative disorders. Cadmium is a highly toxic and widespread toxicant. Cadmium itself is unable to generate free radicals directly, as cadmium does not undergo redox cycling. However, indirect generation of various radicals involving the superoxide radical, hydroxyl radical, and nitric oxide has been reported. One of the biologically most relevant features of C60 fullerene is the ability to quench various free radicals, behaving as a “free radical sponge.” Conversely, photosensitization of C60 yields highly reactive singlet oxygen or superoxide anion. Therefore, the dual property of fullerene to either quench or generate cell-damaging reactive oxygen species could be potentially exploited for their development as cytoprotective or cytotoxic agents.",
publisher = "Academic Press",
journal = "Dietary Interventions in Liver Disease",
booktitle = "Cadmium and Fullerenes in Liver Diseases",
doi = "10.1016/B978-0-12-814466-4.00027-6",
pages = "333-344"
}

Watson, R. R., Preedy, V. R., Đurašević, S., Todorović, Z., Pavlović, S.,& Pejić, S.. (2019). Cadmium and Fullerenes in Liver Diseases. in Dietary Interventions in Liver Disease
Academic Press., 333-344.
https://doi.org/10.1016/B978-0-12-814466-4.00027-6

Watson RR, Preedy VR, Đurašević S, Todorović Z, Pavlović S, Pejić S. Cadmium and Fullerenes in Liver Diseases. in Dietary Interventions in Liver Disease. 2019;:333-344.
doi:10.1016/B978-0-12-814466-4.00027-6 .

Watson, Ronald Ross, Preedy, Victor R., Đurašević, Siniša, Todorović, Zoran, Pavlović, Slađan, Pejić, Snežana, "Cadmium and Fullerenes in Liver Diseases" in Dietary Interventions in Liver Disease (2019):333-344,
https://doi.org/10.1016/B978-0-12-814466-4.00027-6 . .

TY  - CONF
AU  - Đurašević, Siniša
AU  - Jasnić, Nebojša
AU  - Dakić, Tamara
AU  - Jevđović, Tanja
AU  - Lakić, Iva
AU  - Vujović, Predrag
AU  - Đorđević, Jelena
AU  - Mitić-Ćulafić, Dragana
AU  - Nikolić, Biljana
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Pavlović, Slađan
AU  - Prokić, Marko
AU  - Zaletel, Ivan
AU  - Todorović, Zoran
PY  - 2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3423
AB  - We investigated the effect of long-term high-dose virgin coconut oil (VCO) supplementation on rat liver and serum lipid status. Animals were divided into two groups with 8 of them in each: normally fed (Control group) and the group fed with coconut oil at a concentration of 20% in food (VCO group). The experiment lasted for four months. On the last day of the experiment animals were killed, and blood and liver tissue were collected. In serum we measured the levels of total cholesterol (TC), high-density lipoproteins (HDL), non-HDL lipoproteins, triglycerides (TG), aspartate aminotransferase (9\.ST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). We also measured both liver and serum levels of high mobility group protein B 1 (HMGB 1) and haptoglobin (HP), as ,.vell as the liver level of NF-KB p65/ p-NF-KB p65 transcription factor, together with the histopathology analysis on liver slices and liver Comet assay. The results show that coconut oil do not change serum TC and HDL, but reduces non-HDL and TG levels (10% and 50%, respectively) comparing to control. As a result, atherogenic index of serum (AI) is strongly reduced in VCO group versus control. As for the liver status, results show that coconut supplementation increases AST, ALT and ALP levels in VCO group (50%, 30% and 60%, respectively) comparing to control. This effect is caused by the accumulation of coconut oil fat in liver, as confirmed by the histopathology showing signs of mild nonalcoholic steatohepatitis in VCO group, followed with the increased %of DNA in comet tail. The liver inflammation in VCO group is further demonstrated with the liver HP, HMGBl and p-NF-KB p65 level increase, and increase in nuclear level ofNF­kB p65, but not accompanying serum HP and HMGBl increase. In conclusion, our results show that coconut oil supplementation, despite causing mild and localized steatohepatitis, also lowers serum atherogcnic index, a predictor of cardiovascular risk.
PB  - BIT Congress Inc. (BIT Group Global Ltd.)
C3  - BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017
T1  - The effect of long-term high-dose coconut oil supplementation on rat sliver and serum lipids
SP  - 168
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3423
ER  - 

@conference{
author = "Đurašević, Siniša and Jasnić, Nebojša and Dakić, Tamara and Jevđović, Tanja and Lakić, Iva and Vujović, Predrag and Đorđević, Jelena and Mitić-Ćulafić, Dragana and Nikolić, Biljana and Grigorov, Ilijana and Bogojević, Desanka and Pavlović, Slađan and Prokić, Marko and Zaletel, Ivan and Todorović, Zoran",
year = "2017",
abstract = "We investigated the effect of long-term high-dose virgin coconut oil (VCO) supplementation on rat liver and serum lipid status. Animals were divided into two groups with 8 of them in each: normally fed (Control group) and the group fed with coconut oil at a concentration of 20% in food (VCO group). The experiment lasted for four months. On the last day of the experiment animals were killed, and blood and liver tissue were collected. In serum we measured the levels of total cholesterol (TC), high-density lipoproteins (HDL), non-HDL lipoproteins, triglycerides (TG), aspartate aminotransferase (9\.ST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). We also measured both liver and serum levels of high mobility group protein B 1 (HMGB 1) and haptoglobin (HP), as ,.vell as the liver level of NF-KB p65/ p-NF-KB p65 transcription factor, together with the histopathology analysis on liver slices and liver Comet assay. The results show that coconut oil do not change serum TC and HDL, but reduces non-HDL and TG levels (10% and 50%, respectively) comparing to control. As a result, atherogenic index of serum (AI) is strongly reduced in VCO group versus control. As for the liver status, results show that coconut supplementation increases AST, ALT and ALP levels in VCO group (50%, 30% and 60%, respectively) comparing to control. This effect is caused by the accumulation of coconut oil fat in liver, as confirmed by the histopathology showing signs of mild nonalcoholic steatohepatitis in VCO group, followed with the increased %of DNA in comet tail. The liver inflammation in VCO group is further demonstrated with the liver HP, HMGBl and p-NF-KB p65 level increase, and increase in nuclear level ofNF­kB p65, but not accompanying serum HP and HMGBl increase. In conclusion, our results show that coconut oil supplementation, despite causing mild and localized steatohepatitis, also lowers serum atherogcnic index, a predictor of cardiovascular risk.",
publisher = "BIT Congress Inc. (BIT Group Global Ltd.)",
journal = "BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017",
title = "The effect of long-term high-dose coconut oil supplementation on rat sliver and serum lipids",
pages = "168",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3423"
}

Đurašević, S., Jasnić, N., Dakić, T., Jevđović, T., Lakić, I., Vujović, P., Đorđević, J., Mitić-Ćulafić, D., Nikolić, B., Grigorov, I., Bogojević, D., Pavlović, S., Prokić, M., Zaletel, I.,& Todorović, Z.. (2017). The effect of long-term high-dose coconut oil supplementation on rat sliver and serum lipids. in BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017
BIT Congress Inc. (BIT Group Global Ltd.)., 168.
https://hdl.handle.net/21.15107/rcub_ibiss_3423

Đurašević S, Jasnić N, Dakić T, Jevđović T, Lakić I, Vujović P, Đorđević J, Mitić-Ćulafić D, Nikolić B, Grigorov I, Bogojević D, Pavlović S, Prokić M, Zaletel I, Todorović Z. The effect of long-term high-dose coconut oil supplementation on rat sliver and serum lipids. in BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017. 2017;:168.
https://hdl.handle.net/21.15107/rcub_ibiss_3423 .

Đurašević, Siniša, Jasnić, Nebojša, Dakić, Tamara, Jevđović, Tanja, Lakić, Iva, Vujović, Predrag, Đorđević, Jelena, Mitić-Ćulafić, Dragana, Nikolić, Biljana, Grigorov, Ilijana, Bogojević, Desanka, Pavlović, Slađan, Prokić, Marko, Zaletel, Ivan, Todorović, Zoran, "The effect of long-term high-dose coconut oil supplementation on rat sliver and serum lipids" in BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017 (2017):168,
https://hdl.handle.net/21.15107/rcub_ibiss_3423 .

TY  - CONF
AU  - Đurašević, Siniša
AU  - Jasnić, Nebojša
AU  - Dakić, Tamara
AU  - Jevđović, Tanja
AU  - Lakić, Iva
AU  - Vujović, Predrag
AU  - Đorđević, Jelena
AU  - Mitić-Ćulafić, Dragana
AU  - Nikolić, Biljana
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Pavlović, Slađan
AU  - Prokić, Marko
AU  - Zaletel, Ivan
AU  - Todorović, Zoran
PY  - 2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3422
AB  - We investigated the effect of long-term high-dose virgin coconut oil (VCO) supplementation on rat glucose homeostasis. Animals were divided into two groups with 6 of them in each: normally fed (Control group) and the group fed with coconut oil at a concentration of 20% in food (VCO group). The experiment lasted for four months. We measured fasting glycemia once a week during the entire experiment. In the last week of the experiment, we performed an oral glucose tolerance test (OGTT) and an intraperitoneal insulin tolerance test (ITT). On the last day of the experiment the fasting insulin and glyc8mia were measured in the blood of animals. The results show that coconut oil reduces weekly glycemia in VCO animals compared with controls. This effect reaches its maximum after the first two weeks of the experiment, and then slowly decreases and disappears over time of next eight weeks. As a result, the glycemia of control and VCO animals do not differ in last six weeks of the experiment. The area under the curve (AUC) presenting glycemia during whole the experiment is significantly lower in VCO animals than in the controls. The hypoglycemic effect of coconut oil is obviously dose-dependent since the amount of food (and therefore the coconut oil) that the animals eat decreases over the time. The results of the oral glucose tolerance test show that the OGTT AUC of VCO animals is significantly lower than the controls, and same is true for the insulin tolerance test. Finally, glycemia and insulin concentration in serums sampled on the last day of the experiment do not differ between VCO and Control groups, so accordingly neither HOMA-IR I and 2 (Homeostatic model assessment of insulin resistance) nor QUIC.Kl ( Quantitative Insulin Sensitivity Check Index). In conclusion, our results show beneficial effects of long-term high-dose coconut oil supplementation on rat glucose homeostasis.
PB  - BIT Congress Inc. (BIT Group Global Ltd.)
C3  - BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017
T1  - The effect of long-term high-dose coconut oil supplementation on rat glucose homeostasis
SP  - 167
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3422
ER  - 

@conference{
author = "Đurašević, Siniša and Jasnić, Nebojša and Dakić, Tamara and Jevđović, Tanja and Lakić, Iva and Vujović, Predrag and Đorđević, Jelena and Mitić-Ćulafić, Dragana and Nikolić, Biljana and Grigorov, Ilijana and Bogojević, Desanka and Pavlović, Slađan and Prokić, Marko and Zaletel, Ivan and Todorović, Zoran",
year = "2017",
abstract = "We investigated the effect of long-term high-dose virgin coconut oil (VCO) supplementation on rat glucose homeostasis. Animals were divided into two groups with 6 of them in each: normally fed (Control group) and the group fed with coconut oil at a concentration of 20% in food (VCO group). The experiment lasted for four months. We measured fasting glycemia once a week during the entire experiment. In the last week of the experiment, we performed an oral glucose tolerance test (OGTT) and an intraperitoneal insulin tolerance test (ITT). On the last day of the experiment the fasting insulin and glyc8mia were measured in the blood of animals. The results show that coconut oil reduces weekly glycemia in VCO animals compared with controls. This effect reaches its maximum after the first two weeks of the experiment, and then slowly decreases and disappears over time of next eight weeks. As a result, the glycemia of control and VCO animals do not differ in last six weeks of the experiment. The area under the curve (AUC) presenting glycemia during whole the experiment is significantly lower in VCO animals than in the controls. The hypoglycemic effect of coconut oil is obviously dose-dependent since the amount of food (and therefore the coconut oil) that the animals eat decreases over the time. The results of the oral glucose tolerance test show that the OGTT AUC of VCO animals is significantly lower than the controls, and same is true for the insulin tolerance test. Finally, glycemia and insulin concentration in serums sampled on the last day of the experiment do not differ between VCO and Control groups, so accordingly neither HOMA-IR I and 2 (Homeostatic model assessment of insulin resistance) nor QUIC.Kl ( Quantitative Insulin Sensitivity Check Index). In conclusion, our results show beneficial effects of long-term high-dose coconut oil supplementation on rat glucose homeostasis.",
publisher = "BIT Congress Inc. (BIT Group Global Ltd.)",
journal = "BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017",
title = "The effect of long-term high-dose coconut oil supplementation on rat glucose homeostasis",
pages = "167",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3422"
}

Đurašević, S., Jasnić, N., Dakić, T., Jevđović, T., Lakić, I., Vujović, P., Đorđević, J., Mitić-Ćulafić, D., Nikolić, B., Grigorov, I., Bogojević, D., Pavlović, S., Prokić, M., Zaletel, I.,& Todorović, Z.. (2017). The effect of long-term high-dose coconut oil supplementation on rat glucose homeostasis. in BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017
BIT Congress Inc. (BIT Group Global Ltd.)., 167.
https://hdl.handle.net/21.15107/rcub_ibiss_3422

Đurašević S, Jasnić N, Dakić T, Jevđović T, Lakić I, Vujović P, Đorđević J, Mitić-Ćulafić D, Nikolić B, Grigorov I, Bogojević D, Pavlović S, Prokić M, Zaletel I, Todorović Z. The effect of long-term high-dose coconut oil supplementation on rat glucose homeostasis. in BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017. 2017;:167.
https://hdl.handle.net/21.15107/rcub_ibiss_3422 .

Đurašević, Siniša, Jasnić, Nebojša, Dakić, Tamara, Jevđović, Tanja, Lakić, Iva, Vujović, Predrag, Đorđević, Jelena, Mitić-Ćulafić, Dragana, Nikolić, Biljana, Grigorov, Ilijana, Bogojević, Desanka, Pavlović, Slađan, Prokić, Marko, Zaletel, Ivan, Todorović, Zoran, "The effect of long-term high-dose coconut oil supplementation on rat glucose homeostasis" in BIT´s 6th Annual World Congress of Food and Nutrition: Abstract Book. Shenyang, China; September 15-17, 2017 (2017):167,
https://hdl.handle.net/21.15107/rcub_ibiss_3422 .