TY  - JOUR
AU  - Ajdžanović, Vladimir
AU  - Miler, Marko
AU  - Šošić-Jurjević, Branka 
AU  - Filipović, Branko
AU  - Milenković, Dragan
AU  - Jakovljević, Vladimir
AU  - Milošević, Verica
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4144
AB  - In a series of our previous works, we revealed the beneficial effects of applied soy isoflavones (genistein or
daidzein) on the wide context of corticosteroidogenesis in vivo, in a rat model of the andropause. Soy isoflavones
decreased the circulating levels of pituitary adrenocorticotropic hormone, inhibited aldosterone secretion, as
well as corticosterone production and secretion, but stimulated dehydroepiandrosterone secretion, all in
andropausal rats. In vitro studies indicate that the mechanism underlying these hormonal changes relies on inhibition of the pituitary tyrosine kinase and adrenocortical 3β-hydroxysteroid dehydrogenase enzymes by soy
isoflavones. Although the clinical studies are in their infancy, the opinion is that genistein and daidzein have
therapeutic potential for the safe treatment of ageing-caused androgen deprivation and glucocorticoid excess
with related metabolic/hemodynamic issues in males. Our accumulated experience and knowledge in the field of
biomedical effects of plant polyphenols have provided a platform for potential recommending the agenda to
organize and accelerate experimental research aimed at producing the optimal supplementation. We hypothesize
that an in vivo approach should first be exploited in the sequence of investigative steps, followed by in vitro
studies and synchronously conducted molecular docking analyses. In vivo research, besides establishing the
margin of exposure safety or adjustment of the correct polyphenol dose, enables identification and quantification
of the metabolites of applied polyphenols in the blood. Subsequent in vitro exploitation of the metabolites and
related docking analyses provide clarification of the molecular mechanisms of action of applied polyphenols.
Chemical modification of the polyphenol structure or coupling it with nanoparticles might be the next step in
optimizing the design of supplementation. Selected, intact or chemically-modified polyphenol molecules should
be included in preclinical studies on a more closely-related species, while clinical studies would finally assess the
safety and effectiveness of a polyphenol-based remedial strategy. The final supplement represents a product of an
appropriate technological process, conducted in accordance with the recommendations derived from the preceding research.
PB  - Elsevir
T2  - Medical Hypotheses
T1  - Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design
VL  - 148
DO  - 10.1016/j.mehy.2021.110516
SP  - 110516
ER  - 

@article{
author = "Ajdžanović, Vladimir and Miler, Marko and Šošić-Jurjević, Branka  and Filipović, Branko and Milenković, Dragan and Jakovljević, Vladimir and Milošević, Verica",
year = "2021",
abstract = "In a series of our previous works, we revealed the beneficial effects of applied soy isoflavones (genistein or
daidzein) on the wide context of corticosteroidogenesis in vivo, in a rat model of the andropause. Soy isoflavones
decreased the circulating levels of pituitary adrenocorticotropic hormone, inhibited aldosterone secretion, as
well as corticosterone production and secretion, but stimulated dehydroepiandrosterone secretion, all in
andropausal rats. In vitro studies indicate that the mechanism underlying these hormonal changes relies on inhibition of the pituitary tyrosine kinase and adrenocortical 3β-hydroxysteroid dehydrogenase enzymes by soy
isoflavones. Although the clinical studies are in their infancy, the opinion is that genistein and daidzein have
therapeutic potential for the safe treatment of ageing-caused androgen deprivation and glucocorticoid excess
with related metabolic/hemodynamic issues in males. Our accumulated experience and knowledge in the field of
biomedical effects of plant polyphenols have provided a platform for potential recommending the agenda to
organize and accelerate experimental research aimed at producing the optimal supplementation. We hypothesize
that an in vivo approach should first be exploited in the sequence of investigative steps, followed by in vitro
studies and synchronously conducted molecular docking analyses. In vivo research, besides establishing the
margin of exposure safety or adjustment of the correct polyphenol dose, enables identification and quantification
of the metabolites of applied polyphenols in the blood. Subsequent in vitro exploitation of the metabolites and
related docking analyses provide clarification of the molecular mechanisms of action of applied polyphenols.
Chemical modification of the polyphenol structure or coupling it with nanoparticles might be the next step in
optimizing the design of supplementation. Selected, intact or chemically-modified polyphenol molecules should
be included in preclinical studies on a more closely-related species, while clinical studies would finally assess the
safety and effectiveness of a polyphenol-based remedial strategy. The final supplement represents a product of an
appropriate technological process, conducted in accordance with the recommendations derived from the preceding research.",
publisher = "Elsevir",
journal = "Medical Hypotheses",
title = "Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design",
volume = "148",
doi = "10.1016/j.mehy.2021.110516",
pages = "110516"
}

Ajdžanović, V., Miler, M., Šošić-Jurjević, B., Filipović, B., Milenković, D., Jakovljević, V.,& Milošević, V.. (2021). Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design. in Medical Hypotheses
Elsevir., 148, 110516.
https://doi.org/10.1016/j.mehy.2021.110516

Ajdžanović V, Miler M, Šošić-Jurjević B, Filipović B, Milenković D, Jakovljević V, Milošević V. Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design. in Medical Hypotheses. 2021;148:110516.
doi:10.1016/j.mehy.2021.110516 .

Ajdžanović, Vladimir, Miler, Marko, Šošić-Jurjević, Branka , Filipović, Branko, Milenković, Dragan, Jakovljević, Vladimir, Milošević, Verica, "Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design" in Medical Hypotheses, 148 (2021):110516,
https://doi.org/10.1016/j.mehy.2021.110516 . .

TY  - CONF
AU  - Potrebić, Milica
AU  - Ajdžanović, Vladimir
AU  - Miler, Marko
AU  - Milenković, Dragan
AU  - Pendoski, Laze
AU  - Jakovljević, Vladimir
AU  - Milošević, Verica
PY  - 2018
UR  - http://www.enea2018.com/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6041
AB  - Objective: The complex process of aging can be defined as progressive loss of the ability to maintain
tissue homeostasis, which may cause many pathological issues, like depression, Alzheimer’s diseases
or cognitive deficits. Due to their various established health effects, citrus flavanones, naringenin
(NAR) and hesperetin (HES), could have important protective role against development and progression of many age-related diseases.The aim of this study was to examine the effects of these flavanones on pituitary-adrenocortical axis in the rat model of old age (24 months old Wistar rats), Methods: The experimental groups included control group, and naringenin and hesperetin treated groups. NAR and HES were administrated orally (15 mg/kg b. m.) during 4 weeks, while control group received sunflower oil as a vehicle. Concentrations of adrenocorticotropic (ACTH) hormone in pituitary ACTH cells (reflected by relative intensity of fluorescence) and blood levels of ACTH and corticosterone in experimental rats were determined semi-quantitatively and by using the immunoassays, respectively. Results: Results have shown that both blood concentrations of ACTH and corticosterone were markedly lower in NAR [51% and 39%, respectively (P<0.05)] and HES treated group [69% and 65%, respectively (P<0.05)] in comparison with the control group. The relative intensity of ACTH immunofluorescence signal was the highest in the control group, while in NAR and HES groups was significantly lower [39% and 65%, respectively (P<0.05)]. Conclusion: This study has shown that citrus flavanones affect pituitary-adrenocortical axis by decreasing ACTH levels in adrenocorticotropic cells and blood concentrations of ACTH and corticosterone, as well. Since the increased activation of this axis in elderly is associated with development of many aging-related neurophysiological issues, bioactive flavanones may be used in their prevention or delay.
PB  - Altdorf: EndoScience Endokrinologie Service GmbH
C3  - 18th Congress of the European Neuroendocrine Association: Abstracts; 2018 Oct 17-20; Wrocław, Poland
T1  - Citrus Flavanones, Naringenin and Hesperetin, decrease ACTH and Corticosterone Levels in Old Rats
SP  - 27
EP  - 28
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6041
ER  - 

@conference{
author = "Potrebić, Milica and Ajdžanović, Vladimir and Miler, Marko and Milenković, Dragan and Pendoski, Laze and Jakovljević, Vladimir and Milošević, Verica",
year = "2018",
abstract = "Objective: The complex process of aging can be defined as progressive loss of the ability to maintain
tissue homeostasis, which may cause many pathological issues, like depression, Alzheimer’s diseases
or cognitive deficits. Due to their various established health effects, citrus flavanones, naringenin
(NAR) and hesperetin (HES), could have important protective role against development and progression of many age-related diseases.The aim of this study was to examine the effects of these flavanones on pituitary-adrenocortical axis in the rat model of old age (24 months old Wistar rats), Methods: The experimental groups included control group, and naringenin and hesperetin treated groups. NAR and HES were administrated orally (15 mg/kg b. m.) during 4 weeks, while control group received sunflower oil as a vehicle. Concentrations of adrenocorticotropic (ACTH) hormone in pituitary ACTH cells (reflected by relative intensity of fluorescence) and blood levels of ACTH and corticosterone in experimental rats were determined semi-quantitatively and by using the immunoassays, respectively. Results: Results have shown that both blood concentrations of ACTH and corticosterone were markedly lower in NAR [51% and 39%, respectively (P<0.05)] and HES treated group [69% and 65%, respectively (P<0.05)] in comparison with the control group. The relative intensity of ACTH immunofluorescence signal was the highest in the control group, while in NAR and HES groups was significantly lower [39% and 65%, respectively (P<0.05)]. Conclusion: This study has shown that citrus flavanones affect pituitary-adrenocortical axis by decreasing ACTH levels in adrenocorticotropic cells and blood concentrations of ACTH and corticosterone, as well. Since the increased activation of this axis in elderly is associated with development of many aging-related neurophysiological issues, bioactive flavanones may be used in their prevention or delay.",
publisher = "Altdorf: EndoScience Endokrinologie Service GmbH",
journal = "18th Congress of the European Neuroendocrine Association: Abstracts; 2018 Oct 17-20; Wrocław, Poland",
title = "Citrus Flavanones, Naringenin and Hesperetin, decrease ACTH and Corticosterone Levels in Old Rats",
pages = "27-28",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6041"
}

Potrebić, M., Ajdžanović, V., Miler, M., Milenković, D., Pendoski, L., Jakovljević, V.,& Milošević, V.. (2018). Citrus Flavanones, Naringenin and Hesperetin, decrease ACTH and Corticosterone Levels in Old Rats. in 18th Congress of the European Neuroendocrine Association: Abstracts; 2018 Oct 17-20; Wrocław, Poland
Altdorf: EndoScience Endokrinologie Service GmbH., 27-28.
https://hdl.handle.net/21.15107/rcub_ibiss_6041

Potrebić M, Ajdžanović V, Miler M, Milenković D, Pendoski L, Jakovljević V, Milošević V. Citrus Flavanones, Naringenin and Hesperetin, decrease ACTH and Corticosterone Levels in Old Rats. in 18th Congress of the European Neuroendocrine Association: Abstracts; 2018 Oct 17-20; Wrocław, Poland. 2018;:27-28.
https://hdl.handle.net/21.15107/rcub_ibiss_6041 .

Potrebić, Milica, Ajdžanović, Vladimir, Miler, Marko, Milenković, Dragan, Pendoski, Laze, Jakovljević, Vladimir, Milošević, Verica, "Citrus Flavanones, Naringenin and Hesperetin, decrease ACTH and Corticosterone Levels in Old Rats" in 18th Congress of the European Neuroendocrine Association: Abstracts; 2018 Oct 17-20; Wrocław, Poland (2018):27-28,
https://hdl.handle.net/21.15107/rcub_ibiss_6041 .

TY  - JOUR
AU  - Ajdžanović, Vladimir
AU  - Jarić, Ivana
AU  - Miler, Marko
AU  - Filipović, Branko
AU  - Šošić-Jurjević, Branka 
AU  - Ristić, Nataša
AU  - Milenković, Dragan
AU  - Milošević, Verica
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6106
AB  - Diosgenin, a steroidal sapogenin of natural origin, has demonstrated benefits when it comes to the treatment of malignancies, cardiovascular issues and menopausal symptoms. In this study, we investigated the histological changes of the adrenal gland after diosgenin application in a rat model of the menopause. Middle-aged, acyclic female Wistar rats were divided into control (C; n = 6) and diosgenin treated (D; n = 6) groups. Diosgenin (100 mg/kg b.w./day) was orally administered for four weeks, while C group received the vehicle alone. A histological approach included design-based stereology, histochemistry and immunohistochemistry. The adrenal cortex volume decreased in D females by 15% (p < 0.05) while the volume of adrenal medulla increased (p < 0.05) by 64%, compared to the same parameters in C group. Volume density of the zona glomerulosa (expressed per absolute adrenal gland volume) in D rats increased (p < 0.05) by 22% in comparison with C animals. Diosgenin treatment decreased (p < 0.05) the volume density of the zona fasciculata (expressed per volume of adrenal cortex) by 15% when compared to C females. Absolute volume of the zona reticularis in D group decreased (p < 0.05) by 38% in comparison with the same parameter in C rats. Also, after diosgenin application, the volume density of the zona reticularis (expressed per volume of adrenal cortex) and the zona reticularis cell volume were decreased by 51% and 20% (p < 0.05) respectively, compared to C animals. Our results, reflecting a decrease in many stereological parameters of the adrenal cortex, indicate that diosgenin took over the role of corticosteroid precursors and became incorporated into steroidogenesis
PB  - Elsevier
T2  - Acta Histochemica
T1  - Diosgenin-caused changes of the adrenal gland histological parameters in a rat model of the menopause
IS  - 1
VL  - 119
DO  - 10.1016/j.acthis.2016.11.006
SP  - 48
EP  - 56
ER  - 

@article{
author = "Ajdžanović, Vladimir and Jarić, Ivana and Miler, Marko and Filipović, Branko and Šošić-Jurjević, Branka  and Ristić, Nataša and Milenković, Dragan and Milošević, Verica",
year = "2017",
abstract = "Diosgenin, a steroidal sapogenin of natural origin, has demonstrated benefits when it comes to the treatment of malignancies, cardiovascular issues and menopausal symptoms. In this study, we investigated the histological changes of the adrenal gland after diosgenin application in a rat model of the menopause. Middle-aged, acyclic female Wistar rats were divided into control (C; n = 6) and diosgenin treated (D; n = 6) groups. Diosgenin (100 mg/kg b.w./day) was orally administered for four weeks, while C group received the vehicle alone. A histological approach included design-based stereology, histochemistry and immunohistochemistry. The adrenal cortex volume decreased in D females by 15% (p < 0.05) while the volume of adrenal medulla increased (p < 0.05) by 64%, compared to the same parameters in C group. Volume density of the zona glomerulosa (expressed per absolute adrenal gland volume) in D rats increased (p < 0.05) by 22% in comparison with C animals. Diosgenin treatment decreased (p < 0.05) the volume density of the zona fasciculata (expressed per volume of adrenal cortex) by 15% when compared to C females. Absolute volume of the zona reticularis in D group decreased (p < 0.05) by 38% in comparison with the same parameter in C rats. Also, after diosgenin application, the volume density of the zona reticularis (expressed per volume of adrenal cortex) and the zona reticularis cell volume were decreased by 51% and 20% (p < 0.05) respectively, compared to C animals. Our results, reflecting a decrease in many stereological parameters of the adrenal cortex, indicate that diosgenin took over the role of corticosteroid precursors and became incorporated into steroidogenesis",
publisher = "Elsevier",
journal = "Acta Histochemica",
title = "Diosgenin-caused changes of the adrenal gland histological parameters in a rat model of the menopause",
number = "1",
volume = "119",
doi = "10.1016/j.acthis.2016.11.006",
pages = "48-56"
}

Ajdžanović, V., Jarić, I., Miler, M., Filipović, B., Šošić-Jurjević, B., Ristić, N., Milenković, D.,& Milošević, V.. (2017). Diosgenin-caused changes of the adrenal gland histological parameters in a rat model of the menopause. in Acta Histochemica
Elsevier., 119(1), 48-56.
https://doi.org/10.1016/j.acthis.2016.11.006

Ajdžanović V, Jarić I, Miler M, Filipović B, Šošić-Jurjević B, Ristić N, Milenković D, Milošević V. Diosgenin-caused changes of the adrenal gland histological parameters in a rat model of the menopause. in Acta Histochemica. 2017;119(1):48-56.
doi:10.1016/j.acthis.2016.11.006 .

Ajdžanović, Vladimir, Jarić, Ivana, Miler, Marko, Filipović, Branko, Šošić-Jurjević, Branka , Ristić, Nataša, Milenković, Dragan, Milošević, Verica, "Diosgenin-caused changes of the adrenal gland histological parameters in a rat model of the menopause" in Acta Histochemica, 119, no. 1 (2017):48-56,
https://doi.org/10.1016/j.acthis.2016.11.006 . .

TY  - CONF
AU  - Miler, Marko
AU  - Ajdžanović, Vladimir
AU  - Jarić, Ivana
AU  - Živanović, Jasmina
AU  - Kardum, Nevena
AU  - Milenković, Dragan
AU  - Milošević, Verica
AU  - Šošić-Jurjević, Branka 
PY  - 2017
UR  - https://www.karger.com/Article/Abstract/477987
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3501
AB  - Polyphenols are class of plant secondary metabolites that exert various beneficial effects. Namely, citrus polyphenols, naringenin (NAR) and hesperetin (HES) are potent antioxidants that may contribute to maintenance of health at old age by improving redox and metabolic status. However, polyphenols also interfere with thyroid peroxidase (TPO) activity and might affect thyroid structure and hormone production. Keeping in mind impaired thyroid function at older age, in this study we tested weather NAR or HES administration could induce structural and immunohistochemical changes in male 24-monthold Wistar rats. NAR or HES were administrated orally (15 mg/kg) during 4 weeks, while control groups received vehicle, sunflower oil. Stereological analyses (absolute and relative volume of epithelium, colloid and interstitium) and qualitative immunohistochemical examination of TPO and vascular endothelial growth factor (VEGF) proteins were performed. Results showed that thyroid structure of both flavanone-treated groups was characterized by lower (p < 0.05) absolute and relative volume of luminal colloid, accompanied by elevated (p < 0.05) relative volume of interstitium in comparison with the controls. These changes were more prominent after NAR even no hypertrophy or absolute thyroid volume change was detected. TPO expression was localized in the cytoplasm and on the apical membrane of the active follicles, showing stronger immunostaining in both flavanone treated group in comparison with the controls. VEGF immunohistochemical expression was localized in the thyrocytes’s cytoplasm of thyrocytes and C cells, being stronger in flavanone-treated animals. In conclusion, both citrus flavanones induced structural alteration of thyroid tissue. Depleted colloid and stronger apical TPO immunostaining in the thyrocytes indicate higher thyroid hormone secretion and production. In line with this, interstitium volume increment, and higher VEGF expression in thyroid parenchyma might be due to a better blood supply and the expansion of microcirculation around active follicles in the thyroid of old-aged males.
PB  - Basel: S. Karger AG
C3  - 40th Annual Meeting of the European Thyroid Association Programme; 2017 Sep 9-12; Belgrade, Serbia (European Thyroid Journal; Vol. 6; No. 1)
T1  - Polyphenols from citrus fruits induce structural and immunohistochemical changes in thyroids of old-aged male Wistar rats
DO  - 10.1159/000477987
SP  - 42
ER  - 

@conference{
author = "Miler, Marko and Ajdžanović, Vladimir and Jarić, Ivana and Živanović, Jasmina and Kardum, Nevena and Milenković, Dragan and Milošević, Verica and Šošić-Jurjević, Branka ",
year = "2017",
abstract = "Polyphenols are class of plant secondary metabolites that exert various beneficial effects. Namely, citrus polyphenols, naringenin (NAR) and hesperetin (HES) are potent antioxidants that may contribute to maintenance of health at old age by improving redox and metabolic status. However, polyphenols also interfere with thyroid peroxidase (TPO) activity and might affect thyroid structure and hormone production. Keeping in mind impaired thyroid function at older age, in this study we tested weather NAR or HES administration could induce structural and immunohistochemical changes in male 24-monthold Wistar rats. NAR or HES were administrated orally (15 mg/kg) during 4 weeks, while control groups received vehicle, sunflower oil. Stereological analyses (absolute and relative volume of epithelium, colloid and interstitium) and qualitative immunohistochemical examination of TPO and vascular endothelial growth factor (VEGF) proteins were performed. Results showed that thyroid structure of both flavanone-treated groups was characterized by lower (p < 0.05) absolute and relative volume of luminal colloid, accompanied by elevated (p < 0.05) relative volume of interstitium in comparison with the controls. These changes were more prominent after NAR even no hypertrophy or absolute thyroid volume change was detected. TPO expression was localized in the cytoplasm and on the apical membrane of the active follicles, showing stronger immunostaining in both flavanone treated group in comparison with the controls. VEGF immunohistochemical expression was localized in the thyrocytes’s cytoplasm of thyrocytes and C cells, being stronger in flavanone-treated animals. In conclusion, both citrus flavanones induced structural alteration of thyroid tissue. Depleted colloid and stronger apical TPO immunostaining in the thyrocytes indicate higher thyroid hormone secretion and production. In line with this, interstitium volume increment, and higher VEGF expression in thyroid parenchyma might be due to a better blood supply and the expansion of microcirculation around active follicles in the thyroid of old-aged males.",
publisher = "Basel: S. Karger AG",
journal = "40th Annual Meeting of the European Thyroid Association Programme; 2017 Sep 9-12; Belgrade, Serbia (European Thyroid Journal; Vol. 6; No. 1)",
title = "Polyphenols from citrus fruits induce structural and immunohistochemical changes in thyroids of old-aged male Wistar rats",
doi = "10.1159/000477987",
pages = "42"
}

Miler, M., Ajdžanović, V., Jarić, I., Živanović, J., Kardum, N., Milenković, D., Milošević, V.,& Šošić-Jurjević, B.. (2017). Polyphenols from citrus fruits induce structural and immunohistochemical changes in thyroids of old-aged male Wistar rats. in 40th Annual Meeting of the European Thyroid Association Programme; 2017 Sep 9-12; Belgrade, Serbia (European Thyroid Journal; Vol. 6; No. 1)
Basel: S. Karger AG., 42.
https://doi.org/10.1159/000477987

Miler M, Ajdžanović V, Jarić I, Živanović J, Kardum N, Milenković D, Milošević V, Šošić-Jurjević B. Polyphenols from citrus fruits induce structural and immunohistochemical changes in thyroids of old-aged male Wistar rats. in 40th Annual Meeting of the European Thyroid Association Programme; 2017 Sep 9-12; Belgrade, Serbia (European Thyroid Journal; Vol. 6; No. 1). 2017;:42.
doi:10.1159/000477987 .

Miler, Marko, Ajdžanović, Vladimir, Jarić, Ivana, Živanović, Jasmina, Kardum, Nevena, Milenković, Dragan, Milošević, Verica, Šošić-Jurjević, Branka , "Polyphenols from citrus fruits induce structural and immunohistochemical changes in thyroids of old-aged male Wistar rats" in 40th Annual Meeting of the European Thyroid Association Programme; 2017 Sep 9-12; Belgrade, Serbia (European Thyroid Journal; Vol. 6; No. 1) (2017):42,
https://doi.org/10.1159/000477987 . .

TY  - JOUR
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Ajdžanović, Vladimir
AU  - Oreščanin Dušić, Zorana
AU  - Milenković, Dragan
AU  - Konić-Ristić, Aleksandra
AU  - Blagojević, Duško
AU  - Milošević, Verica
AU  - Šošić-Jurjević, Branka 
PY  - 2016
UR  - http://linkinghub.elsevier.com/retrieve/pii/S053155651630290X
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2689
AB  - This study aimed to investigate effects of citrus flavanones naringenin (NAR) and hesperetin (HES) on liver antioxidant status and membrane phospholipid composition in 24-month-old rats. NAR and HES (15 mg/kg) were administrated orally to male Wistar rats, once per day, for 4 weeks. Control group received either vehicle (sunflower oil) or remained intact. The results showed decreased (p < 0.05) activity of antioxidant enzymes (AOE), specifically catalase (CAT), superoxide dismutase (SOD) 1 and glutathione reductase (GR) in the liver of intact control old-aged rats in comparison to young intact controls. Flavanone administration to old-aged males increased (p < 0.05) examined AOE activities in comparison to vehicle-administered animals. Namely, NAR was more potent in comparison to HES regarding the increase (p < 0.05) in activities of examined antioxidant enzymes (SOD 1 and 2, glutathione peroxidase-GPx and GR) and the liver glutathione (GSH), while HES elevated (p < 0.05) only activity of CAT and GR. Both flavanones significantly decreased (p < 0.05) TBARS and improved (p < 0.05) membrane phospholipid composition in favor of n-3 PUFA and n-6/n-3 PUFA ratio. Both flavanones did not affect liver histology and reduced (p < 0.05) alanine aminotransferase and aspartate aminotransferase levels in serum. The results of this study indicate beneficial potential of citrus flavanones in the old-aged rat liver.
T2  - Experimental Gerontology
T1  - Citrus flavanones naringenin and hesperetin improve antioxidant status and membrane lipid compositions in the liver of old-aged Wistar rats
VL  - 84
DO  - 10.1016/j.exger.2016.08.014
SP  - 49
EP  - 60
ER  - 

@article{
author = "Miler, Marko and Živanović, Jasmina and Ajdžanović, Vladimir and Oreščanin Dušić, Zorana and Milenković, Dragan and Konić-Ristić, Aleksandra and Blagojević, Duško and Milošević, Verica and Šošić-Jurjević, Branka ",
year = "2016",
abstract = "This study aimed to investigate effects of citrus flavanones naringenin (NAR) and hesperetin (HES) on liver antioxidant status and membrane phospholipid composition in 24-month-old rats. NAR and HES (15 mg/kg) were administrated orally to male Wistar rats, once per day, for 4 weeks. Control group received either vehicle (sunflower oil) or remained intact. The results showed decreased (p < 0.05) activity of antioxidant enzymes (AOE), specifically catalase (CAT), superoxide dismutase (SOD) 1 and glutathione reductase (GR) in the liver of intact control old-aged rats in comparison to young intact controls. Flavanone administration to old-aged males increased (p < 0.05) examined AOE activities in comparison to vehicle-administered animals. Namely, NAR was more potent in comparison to HES regarding the increase (p < 0.05) in activities of examined antioxidant enzymes (SOD 1 and 2, glutathione peroxidase-GPx and GR) and the liver glutathione (GSH), while HES elevated (p < 0.05) only activity of CAT and GR. Both flavanones significantly decreased (p < 0.05) TBARS and improved (p < 0.05) membrane phospholipid composition in favor of n-3 PUFA and n-6/n-3 PUFA ratio. Both flavanones did not affect liver histology and reduced (p < 0.05) alanine aminotransferase and aspartate aminotransferase levels in serum. The results of this study indicate beneficial potential of citrus flavanones in the old-aged rat liver.",
journal = "Experimental Gerontology",
title = "Citrus flavanones naringenin and hesperetin improve antioxidant status and membrane lipid compositions in the liver of old-aged Wistar rats",
volume = "84",
doi = "10.1016/j.exger.2016.08.014",
pages = "49-60"
}

Miler, M., Živanović, J., Ajdžanović, V., Oreščanin Dušić, Z., Milenković, D., Konić-Ristić, A., Blagojević, D., Milošević, V.,& Šošić-Jurjević, B.. (2016). Citrus flavanones naringenin and hesperetin improve antioxidant status and membrane lipid compositions in the liver of old-aged Wistar rats. in Experimental Gerontology, 84, 49-60.
https://doi.org/10.1016/j.exger.2016.08.014

Miler M, Živanović J, Ajdžanović V, Oreščanin Dušić Z, Milenković D, Konić-Ristić A, Blagojević D, Milošević V, Šošić-Jurjević B. Citrus flavanones naringenin and hesperetin improve antioxidant status and membrane lipid compositions in the liver of old-aged Wistar rats. in Experimental Gerontology. 2016;84:49-60.
doi:10.1016/j.exger.2016.08.014 .

Miler, Marko, Živanović, Jasmina, Ajdžanović, Vladimir, Oreščanin Dušić, Zorana, Milenković, Dragan, Konić-Ristić, Aleksandra, Blagojević, Duško, Milošević, Verica, Šošić-Jurjević, Branka , "Citrus flavanones naringenin and hesperetin improve antioxidant status and membrane lipid compositions in the liver of old-aged Wistar rats" in Experimental Gerontology, 84 (2016):49-60,
https://doi.org/10.1016/j.exger.2016.08.014 . .

TY  - CONF
AU  - Ajdžanović, Vladimir
AU  - Spasojević, Ivan
AU  - Konić-Ristić, Aleksandra
AU  - Milenković, Dragan
AU  - Živanović, Jasmina
AU  - Jarić, Ivana
AU  - Milošević, Verica
PY  - 2014
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6241
AB  - Superficial membrane fluidity is related to erythrocyte deformation behavior and affects the hemodynamics, especially in hypertension and atherosclerosis. Grapefruit flavanone naringenin, which is used as alternative therapeutic of cardiovascular conditions, can incorporate cellular membrane and change its fluidity. The aim of this study was to examine the effects of two nutritional doses of naringenin (lower - 0.1 µg/ml and higher - 1 µg/ml) on superficial membrane fluidity in human erythrocytes, which reflects their deformability. We used electron paramagnetic resonance spectroscopy and fatty acid spin probes (5-DS and 7-DS), the spectra of which are dependent on membrane fluidity. The results showed a significant (p=0.029) increase of membrane fluidity near the hydrophilic surface in erythrocytes treated with higher nutritional dose of naringenin, while the lower nutritional dose of naringenin was ineffective (p>0.05) in that membrane region. In the hydrophobic layer just below the erythrocyte membrane phospholipid heads both lower and higher dose of naringenin significantly (p=0.036 and p=0.028, respectively) increased membrane fluidity. These data document the positive and dose dependent effect of naringenin on superficial membrane fluidity in human erythrocytes, recommending its use in the cardiovascular conditions characterized by disturbed hemodynamics.
PB  - Belgrade: Serbian Physiological Society
C3  - Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia
T1  - The positive effect of naringenin on superficial membrane fluidity in human erythrocytes
SP  - 63
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6241
ER  - 

@conference{
author = "Ajdžanović, Vladimir and Spasojević, Ivan and Konić-Ristić, Aleksandra and Milenković, Dragan and Živanović, Jasmina and Jarić, Ivana and Milošević, Verica",
year = "2014",
abstract = "Superficial membrane fluidity is related to erythrocyte deformation behavior and affects the hemodynamics, especially in hypertension and atherosclerosis. Grapefruit flavanone naringenin, which is used as alternative therapeutic of cardiovascular conditions, can incorporate cellular membrane and change its fluidity. The aim of this study was to examine the effects of two nutritional doses of naringenin (lower - 0.1 µg/ml and higher - 1 µg/ml) on superficial membrane fluidity in human erythrocytes, which reflects their deformability. We used electron paramagnetic resonance spectroscopy and fatty acid spin probes (5-DS and 7-DS), the spectra of which are dependent on membrane fluidity. The results showed a significant (p=0.029) increase of membrane fluidity near the hydrophilic surface in erythrocytes treated with higher nutritional dose of naringenin, while the lower nutritional dose of naringenin was ineffective (p>0.05) in that membrane region. In the hydrophobic layer just below the erythrocyte membrane phospholipid heads both lower and higher dose of naringenin significantly (p=0.036 and p=0.028, respectively) increased membrane fluidity. These data document the positive and dose dependent effect of naringenin on superficial membrane fluidity in human erythrocytes, recommending its use in the cardiovascular conditions characterized by disturbed hemodynamics.",
publisher = "Belgrade: Serbian Physiological Society",
journal = "Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia",
title = "The positive effect of naringenin on superficial membrane fluidity in human erythrocytes",
pages = "63",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6241"
}

Ajdžanović, V., Spasojević, I., Konić-Ristić, A., Milenković, D., Živanović, J., Jarić, I.,& Milošević, V.. (2014). The positive effect of naringenin on superficial membrane fluidity in human erythrocytes. in Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia
Belgrade: Serbian Physiological Society., 63.
https://hdl.handle.net/21.15107/rcub_ibiss_6241

Ajdžanović V, Spasojević I, Konić-Ristić A, Milenković D, Živanović J, Jarić I, Milošević V. The positive effect of naringenin on superficial membrane fluidity in human erythrocytes. in Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia. 2014;:63.
https://hdl.handle.net/21.15107/rcub_ibiss_6241 .

Ajdžanović, Vladimir, Spasojević, Ivan, Konić-Ristić, Aleksandra, Milenković, Dragan, Živanović, Jasmina, Jarić, Ivana, Milošević, Verica, "The positive effect of naringenin on superficial membrane fluidity in human erythrocytes" in Abstract book: Molecular, Cellular and Integrative Basis of Health and Disease: transdisciplinary approach: 3rd Congress of Physiological Sciences of Serbia with International Participation; 2014 Oct 29-3; Belgrade, Serbia (2014):63,
https://hdl.handle.net/21.15107/rcub_ibiss_6241 .