TY  - JOUR
AU  - Jelenković, Ankica V.
AU  - Jovanović, Marina D.
AU  - Bokonjić, Dubravko
AU  - Maksimović, Milan
AU  - Bošković, Bogdan
PY  - 2012
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/444
AB  - Background/Aim. Despite years of research in a number of experimental models the question whether nitric oxide (NO) and methylene blue (MB) have pro- or anticonvulsant effects remains to be fully resolved. Methods. In adult Wistar rats the influence of a nonselective inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (LNAME, 10µg) on clinical and biochemical effects of MB (10µg) given before the intraperitoneally administered chemical convulsant pentylenetetrazole (PTZ, 80 mg/kg) was examined. MB and L-NAME were applied intracerebroventricularly. PTZ application was followed by a 4- minute observation time, after which rats were sacrificed and elements of oxido-reductive balance were measured in a crude mitochondrial fraction of forebrain cortex, hippocampus and striatum. Results. Convulsive responses (forelimb dystonia - FLD, generalised clonic- and clonic-tonic convulsions - GCC and GCTC respectively) were observed in all rats received PTZ, together with significantly decreased lipid peroxidation in the forebrain cortex and striatum and increased superoxide dismutase activity in the hippocampus, in comparison to controls (saline treated). It was registered anticonvulsant effects of L-NAME pretreatment. However, these effects were insignificant. In the hippocampus of these animals there was decreased lipid peroxidation (p < 0.01, p < 0.05 vs saline-treated and PTZ-treated rats, respectively) and reverted PTZ-induced increase of superoxide dismutase activity. But MB individually pretreatment significantly decreased the incidence of CTCs and GCCs (FLD: p = 0.0513), prolonged the convulsive latent time for FLD, GCTCs and GCCs, in all the examined brain regions increased lipid peroxidation and decreased the level of superoxide anion. Administration of L-NAME 10 minutes before MB reverted all MB-evoked clinical and biochemical effects. Conclusion. Methylene blue applied individually before PTZ has strong anticonvulsant effects that were eliminated by L-NAME pretreatment. These effects and changed biochemical parameters in the brains of animals treated by L-NAME before MB in comparison to MBtreated group suggest involvement of NO in MB's effects in the animal model of PTZ-evoked convulsions.
AB  - Uvod/Cilj. I pored višegodišnjeg istraživanja na različitim eksperimentalnim modelima, nije potpuno odgovoreno na pitanje da li azot-oksid (NO) i metilen plavo (MP) deluju konvulzivno ili antikonvulzivno. Metode. Na odraslim pacovima Vistar soja ispitivan je uticaj NG-nitro-L-arginin metil estra (L-NAME, 10 µg), neselektivnog inhibitora azot oksid sintaze, na kliničke i biohemijske efekte metilen plavog (MP, 10 µg) datog intracerebroventrikularno pre hemijskog konvulziva pentilentetrazola (PTZ, 80 mg/kg), primenjenog intraperitonealno. Pacovi su posmatrani četiri minuta posle davanja PTZ-a, posle čega su žrtvovani i u neprečišćenoj mitohondrijskoj frakciji prednjeg mozga, hipokampusa i strijatuma određivani su parametri oksidoreduktivne ravnoteže. Rezultati. Posle primene PTZ-a, konvulzivni odgovor (distonija prednjih nogu - DPN, generalizovane klonične - GKK i generalizovane kloničnotonične konvulzije - GKTK) bio je ispoljen kod svih životinja, kao i statistički značajno sniženje lipidne peroksidacije u kori prednjeg mozga i strijatuma, i povećanje aktivnosti superoksid dizmutaze (SOD) u hipokampusu, u poređenju sa kontrolnom grupom (dobila fiziološki rastvor NaCl). Registrovani su antikonvulzivni efekti L-NAME koji nisu bili statistički značajni. U hipokampusu ovih životinja bila je snižena lipidna peroksidacija (p < 0,01 u poređenju sa kontrolnom grupom, p < 0,05 u poređenju sa životinjama koje su dobile PTZ), kao i aktivnost SOD u poređenju sa životinjama koje su dobile PTZ. Samo metilen plavo dovelo je do statistički značajnog smanjenja incidencije GKK I GKTK (DPN: p = 0,0513), produžilo je latentni period DPN, GKK i GKTK, a u svim ispitivanim strukturama mozga bila je povećana lipidna peroksidacija i smanjen nivo superoksidnog anjona. Svi klinički i biohemijski efekti izazvani primenom MP u potpunosti su odstranjeni primenom L-NAME 10 minuta pre davanja MP. Zaključak. Metilen plavo, dat samostalno pre PTZ, ispoljio je snažne antikonvulzivne efekte. Nestanak ovih efekata i izmenjeni biohemijski parametri u mozgovima pacova koji su pre MP dobili L-NAME, sugerišu da je NO uključen u efekte MP ispoljene na životinjskom modelu konvulzija izazvanih primenom PTZ-a.
T2  - Vojnosanitetski pregled
T1  - Uticaj NG-nitro-L-arginin metil estra na kliničke i biohemijske efekte metilen plavog kod konvulzija izazvanih pentilentetrazolom
T1  - Influence of NG-nitro-L-arginine methyl ester on clinical and biochemical effects of methylene blue in pentylenetetrazole-evoked convulsions
IS  - 6
VL  - 69
SP  - 481
EP  - 487
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_444
ER  - 

@article{
author = "Jelenković, Ankica V. and Jovanović, Marina D. and Bokonjić, Dubravko and Maksimović, Milan and Bošković, Bogdan",
year = "2012, 2012",
abstract = "Background/Aim. Despite years of research in a number of experimental models the question whether nitric oxide (NO) and methylene blue (MB) have pro- or anticonvulsant effects remains to be fully resolved. Methods. In adult Wistar rats the influence of a nonselective inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (LNAME, 10µg) on clinical and biochemical effects of MB (10µg) given before the intraperitoneally administered chemical convulsant pentylenetetrazole (PTZ, 80 mg/kg) was examined. MB and L-NAME were applied intracerebroventricularly. PTZ application was followed by a 4- minute observation time, after which rats were sacrificed and elements of oxido-reductive balance were measured in a crude mitochondrial fraction of forebrain cortex, hippocampus and striatum. Results. Convulsive responses (forelimb dystonia - FLD, generalised clonic- and clonic-tonic convulsions - GCC and GCTC respectively) were observed in all rats received PTZ, together with significantly decreased lipid peroxidation in the forebrain cortex and striatum and increased superoxide dismutase activity in the hippocampus, in comparison to controls (saline treated). It was registered anticonvulsant effects of L-NAME pretreatment. However, these effects were insignificant. In the hippocampus of these animals there was decreased lipid peroxidation (p < 0.01, p < 0.05 vs saline-treated and PTZ-treated rats, respectively) and reverted PTZ-induced increase of superoxide dismutase activity. But MB individually pretreatment significantly decreased the incidence of CTCs and GCCs (FLD: p = 0.0513), prolonged the convulsive latent time for FLD, GCTCs and GCCs, in all the examined brain regions increased lipid peroxidation and decreased the level of superoxide anion. Administration of L-NAME 10 minutes before MB reverted all MB-evoked clinical and biochemical effects. Conclusion. Methylene blue applied individually before PTZ has strong anticonvulsant effects that were eliminated by L-NAME pretreatment. These effects and changed biochemical parameters in the brains of animals treated by L-NAME before MB in comparison to MBtreated group suggest involvement of NO in MB's effects in the animal model of PTZ-evoked convulsions., Uvod/Cilj. I pored višegodišnjeg istraživanja na različitim eksperimentalnim modelima, nije potpuno odgovoreno na pitanje da li azot-oksid (NO) i metilen plavo (MP) deluju konvulzivno ili antikonvulzivno. Metode. Na odraslim pacovima Vistar soja ispitivan je uticaj NG-nitro-L-arginin metil estra (L-NAME, 10 µg), neselektivnog inhibitora azot oksid sintaze, na kliničke i biohemijske efekte metilen plavog (MP, 10 µg) datog intracerebroventrikularno pre hemijskog konvulziva pentilentetrazola (PTZ, 80 mg/kg), primenjenog intraperitonealno. Pacovi su posmatrani četiri minuta posle davanja PTZ-a, posle čega su žrtvovani i u neprečišćenoj mitohondrijskoj frakciji prednjeg mozga, hipokampusa i strijatuma određivani su parametri oksidoreduktivne ravnoteže. Rezultati. Posle primene PTZ-a, konvulzivni odgovor (distonija prednjih nogu - DPN, generalizovane klonične - GKK i generalizovane kloničnotonične konvulzije - GKTK) bio je ispoljen kod svih životinja, kao i statistički značajno sniženje lipidne peroksidacije u kori prednjeg mozga i strijatuma, i povećanje aktivnosti superoksid dizmutaze (SOD) u hipokampusu, u poređenju sa kontrolnom grupom (dobila fiziološki rastvor NaCl). Registrovani su antikonvulzivni efekti L-NAME koji nisu bili statistički značajni. U hipokampusu ovih životinja bila je snižena lipidna peroksidacija (p < 0,01 u poređenju sa kontrolnom grupom, p < 0,05 u poređenju sa životinjama koje su dobile PTZ), kao i aktivnost SOD u poređenju sa životinjama koje su dobile PTZ. Samo metilen plavo dovelo je do statistički značajnog smanjenja incidencije GKK I GKTK (DPN: p = 0,0513), produžilo je latentni period DPN, GKK i GKTK, a u svim ispitivanim strukturama mozga bila je povećana lipidna peroksidacija i smanjen nivo superoksidnog anjona. Svi klinički i biohemijski efekti izazvani primenom MP u potpunosti su odstranjeni primenom L-NAME 10 minuta pre davanja MP. Zaključak. Metilen plavo, dat samostalno pre PTZ, ispoljio je snažne antikonvulzivne efekte. Nestanak ovih efekata i izmenjeni biohemijski parametri u mozgovima pacova koji su pre MP dobili L-NAME, sugerišu da je NO uključen u efekte MP ispoljene na životinjskom modelu konvulzija izazvanih primenom PTZ-a.",
journal = "Vojnosanitetski pregled",
title = "Uticaj NG-nitro-L-arginin metil estra na kliničke i biohemijske efekte metilen plavog kod konvulzija izazvanih pentilentetrazolom, Influence of NG-nitro-L-arginine methyl ester on clinical and biochemical effects of methylene blue in pentylenetetrazole-evoked convulsions",
number = "6",
volume = "69",
pages = "481-487",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_444"
}

Jelenković, A. V., Jovanović, M. D., Bokonjić, D., Maksimović, M.,& Bošković, B.. (2012). Uticaj NG-nitro-L-arginin metil estra na kliničke i biohemijske efekte metilen plavog kod konvulzija izazvanih pentilentetrazolom. in Vojnosanitetski pregled, 69(6), 481-487.
https://hdl.handle.net/21.15107/rcub_ibiss_444

Jelenković AV, Jovanović MD, Bokonjić D, Maksimović M, Bošković B. Uticaj NG-nitro-L-arginin metil estra na kliničke i biohemijske efekte metilen plavog kod konvulzija izazvanih pentilentetrazolom. in Vojnosanitetski pregled. 2012;69(6):481-487.
https://hdl.handle.net/21.15107/rcub_ibiss_444 .

Jelenković, Ankica V., Jovanović, Marina D., Bokonjić, Dubravko, Maksimović, Milan, Bošković, Bogdan, "Uticaj NG-nitro-L-arginin metil estra na kliničke i biohemijske efekte metilen plavog kod konvulzija izazvanih pentilentetrazolom" in Vojnosanitetski pregled, 69, no. 6 (2012):481-487,
https://hdl.handle.net/21.15107/rcub_ibiss_444 .

TY  - CONF
AU  - Jelenković, Ankica V.
AU  - Jovanović, Marina D
AU  - Ninković, Milica B
AU  - Maksimović, Milan
AU  - Bosković, Bogdan
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1663
C3  - Epilepsia
T1  - Influence of superoxide dismutase on convulsions evoked by pentylenetetrazol
IS  - null
VL  - 47
EP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1663
ER  - 

@conference{
author = "Jelenković, Ankica V. and Jovanović, Marina D and Ninković, Milica B and Maksimović, Milan and Bosković, Bogdan",
year = "2006",
journal = "Epilepsia",
title = "Influence of superoxide dismutase on convulsions evoked by pentylenetetrazol",
number = "null",
volume = "47",
pages = "77",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1663"
}

Jelenković, A. V., Jovanović, M. D., Ninković, M. B., Maksimović, M.,& Bosković, B.. (2006). Influence of superoxide dismutase on convulsions evoked by pentylenetetrazol. in Epilepsia, 47(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1663

Jelenković AV, Jovanović MD, Ninković MB, Maksimović M, Bosković B. Influence of superoxide dismutase on convulsions evoked by pentylenetetrazol. in Epilepsia. 2006;47(null):null-77.
https://hdl.handle.net/21.15107/rcub_ibiss_1663 .

Jelenković, Ankica V., Jovanović, Marina D, Ninković, Milica B, Maksimović, Milan, Bosković, Bogdan, "Influence of superoxide dismutase on convulsions evoked by pentylenetetrazol" in Epilepsia, 47, no. null (2006),
https://hdl.handle.net/21.15107/rcub_ibiss_1663 .

TY  - JOUR
AU  - Jelenković, Ankica V.
AU  - Jovanović, Marina D.
AU  - Ninković, Milica
AU  - Maksimović, Milan
AU  - Bošković, Bogdan
PY  - 2003
PY  - 2003
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/465
AB  - Controversy about proconvulsant and anticonvulsant nitric oxide (NO) effects and the place of oxidative stress in convulsions, are still a matter of research. We investigated the interaction between 2-amino-5-phosphonovaleric acid (APV), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist and Nw-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) antagonist, in pentylenetetrazole (PTZ)-induced convulsions. Pentylenetetrazole was applied to adult Wistar rats intraperitoneally (ip) in a single dose of 80 mg/kg, and L-NAME (10 µg/10 µl) or APV (20 µg/10 µl) intracerebroventricularly (icv), 30 and 10 minutes before PTZ, respectively. In the same manner, another group received both antagonists. Control animals were given 0.9% saline. Nw-nitro-L-arginine methyl ester exerted a weak anticonvulsant effect, preventing generalized clonic (GCC) and clonic-tonic convulsions (CTC) in 17% of cases. With APV protection against GCC and CTC was 100%, forelimb dystonia (FLD) was decreased in 33% of cases, and time to onset of all convulsive patterns was prolonged (p<0.05 to 0.01). All effects of APV, except in CTC, were reversed by L-NAME applied prior to APV. In APV-PTZ treated animals, superoxide anion content was increased in the forebrain cortex, striatum and hippocampus, without an overwhelmed antioxidative superoxide dismutase (SOD) defense system in the other treatments. When the APV-PTZ group was treated with L-NAME, both SOD activity and superoxide anion content were additionally decreased indicating that the NOS-NO system was involved in the metabolism of superoxide anions. It is suggested that clinical and biochemical effects of NO strongly depend upon the pretreatment and might lead to a wrong impression of NO contradictory activity.
AB  - Kontroverzni nalazi o prokonvulzivnim kao i antikonvulzivnim efektima azot oksida (NO) i značaju oksidativnog stresa u konvulzijama, i dalje su predmet istraživanja. U konvulzijama izazvanim primenom pentilentetrazola (PTZ) ispitivali smo interakciju između 2-amino-5-fosfovalerinske kiseline (APV) kompetitivnog antagoniste N-metil-D-aspartat (NMDA) receptora i Nw-nitro-L-arginin metil estra (L-NAME), neselektivnog antagoniste azot oksid sintaze (NOS). Odraslim pacovima Wistar soja, PTZ je ubrizgavan intraperitonealno (ip) u jednoj dozi od 80 mg/kg. Ostale supstance, L-NAME (10 µg/10 µl) i APV (20 µg/10 µl), primenjivale su se intracerebroventrikularno (icv), i to L-NAME 30, a APV 10 minuta pre PTZ. Po istom vremenskom principu, jedna grupa dobila je oba antagonista, a kontrolna fiziološki rastvor NaCl. Nw-nitro-L-arginin metil estar ispoljio je slabo antikonvulzivno dejstvo, smanjujući incidenciju generalizovanih kloničnih (GCC) i klonično-toničnih konvulzija (CTC) za 17%. Za razliku od L-NAME, APV je sprečila nastanak GCC i CTC kod svih životinja (100%), a incidencija klonusa prednjih nogu (FLD) smanjena je za 33%. Istovremeno primenom APV produženo je vreme od aplikacije PTZ do pojave svih konvulzivnih tipova (p<.05 do 0.01). Primenom L-NAME pre APV, umanjeni su efekti APV, pri čemu je došlo do povećanja incidencije FLD i GCC za 16% odnosno 50%. U kori prednjeg mozga, strijatumu i hipokampusu, životinja koje su dobile APV+PTZ, došlo do povećanja koncentracije superoksidnog anjona. Aktivnost superoksid dizmutaze ne prati ovaj skok. Njen dodatni pad u grupi tretiranoj sa L-NAME pre APV+PTZ, ukazuje da je sistem NOS-NO uključen u metabolizam superoksidnog anjona. Dobijeni rezultati ukazuju da klinički i biohemijski efekti NO u velikoj meri zavise od prethodno primenjenih supstanci i promena izazvanih njima, što može da doprinose sticanju pogrešnog utiska o kontradiktornim dejstvima NO.
T2  - Acta veterinaria
T1  - Azot oksid (NO) i antagonist NMDA receptora u konvulzijama izazvanim pentilenetetrazolom
T1  - Nitric oxide (NO) and an NMDA receptor antagonist in pentylenetetrazole-induced convulsions
IS  - 2-3
VL  - 53
SP  - 103
EP  - 112
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_465
ER  - 

@article{
author = "Jelenković, Ankica V. and Jovanović, Marina D. and Ninković, Milica and Maksimović, Milan and Bošković, Bogdan",
year = "2003, 2003",
abstract = "Controversy about proconvulsant and anticonvulsant nitric oxide (NO) effects and the place of oxidative stress in convulsions, are still a matter of research. We investigated the interaction between 2-amino-5-phosphonovaleric acid (APV), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist and Nw-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) antagonist, in pentylenetetrazole (PTZ)-induced convulsions. Pentylenetetrazole was applied to adult Wistar rats intraperitoneally (ip) in a single dose of 80 mg/kg, and L-NAME (10 µg/10 µl) or APV (20 µg/10 µl) intracerebroventricularly (icv), 30 and 10 minutes before PTZ, respectively. In the same manner, another group received both antagonists. Control animals were given 0.9% saline. Nw-nitro-L-arginine methyl ester exerted a weak anticonvulsant effect, preventing generalized clonic (GCC) and clonic-tonic convulsions (CTC) in 17% of cases. With APV protection against GCC and CTC was 100%, forelimb dystonia (FLD) was decreased in 33% of cases, and time to onset of all convulsive patterns was prolonged (p<0.05 to 0.01). All effects of APV, except in CTC, were reversed by L-NAME applied prior to APV. In APV-PTZ treated animals, superoxide anion content was increased in the forebrain cortex, striatum and hippocampus, without an overwhelmed antioxidative superoxide dismutase (SOD) defense system in the other treatments. When the APV-PTZ group was treated with L-NAME, both SOD activity and superoxide anion content were additionally decreased indicating that the NOS-NO system was involved in the metabolism of superoxide anions. It is suggested that clinical and biochemical effects of NO strongly depend upon the pretreatment and might lead to a wrong impression of NO contradictory activity., Kontroverzni nalazi o prokonvulzivnim kao i antikonvulzivnim efektima azot oksida (NO) i značaju oksidativnog stresa u konvulzijama, i dalje su predmet istraživanja. U konvulzijama izazvanim primenom pentilentetrazola (PTZ) ispitivali smo interakciju između 2-amino-5-fosfovalerinske kiseline (APV) kompetitivnog antagoniste N-metil-D-aspartat (NMDA) receptora i Nw-nitro-L-arginin metil estra (L-NAME), neselektivnog antagoniste azot oksid sintaze (NOS). Odraslim pacovima Wistar soja, PTZ je ubrizgavan intraperitonealno (ip) u jednoj dozi od 80 mg/kg. Ostale supstance, L-NAME (10 µg/10 µl) i APV (20 µg/10 µl), primenjivale su se intracerebroventrikularno (icv), i to L-NAME 30, a APV 10 minuta pre PTZ. Po istom vremenskom principu, jedna grupa dobila je oba antagonista, a kontrolna fiziološki rastvor NaCl. Nw-nitro-L-arginin metil estar ispoljio je slabo antikonvulzivno dejstvo, smanjujući incidenciju generalizovanih kloničnih (GCC) i klonično-toničnih konvulzija (CTC) za 17%. Za razliku od L-NAME, APV je sprečila nastanak GCC i CTC kod svih životinja (100%), a incidencija klonusa prednjih nogu (FLD) smanjena je za 33%. Istovremeno primenom APV produženo je vreme od aplikacije PTZ do pojave svih konvulzivnih tipova (p<.05 do 0.01). Primenom L-NAME pre APV, umanjeni su efekti APV, pri čemu je došlo do povećanja incidencije FLD i GCC za 16% odnosno 50%. U kori prednjeg mozga, strijatumu i hipokampusu, životinja koje su dobile APV+PTZ, došlo do povećanja koncentracije superoksidnog anjona. Aktivnost superoksid dizmutaze ne prati ovaj skok. Njen dodatni pad u grupi tretiranoj sa L-NAME pre APV+PTZ, ukazuje da je sistem NOS-NO uključen u metabolizam superoksidnog anjona. Dobijeni rezultati ukazuju da klinički i biohemijski efekti NO u velikoj meri zavise od prethodno primenjenih supstanci i promena izazvanih njima, što može da doprinose sticanju pogrešnog utiska o kontradiktornim dejstvima NO.",
journal = "Acta veterinaria",
title = "Azot oksid (NO) i antagonist NMDA receptora u konvulzijama izazvanim pentilenetetrazolom, Nitric oxide (NO) and an NMDA receptor antagonist in pentylenetetrazole-induced convulsions",
number = "2-3",
volume = "53",
pages = "103-112",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_465"
}

Jelenković, A. V., Jovanović, M. D., Ninković, M., Maksimović, M.,& Bošković, B.. (2003). Azot oksid (NO) i antagonist NMDA receptora u konvulzijama izazvanim pentilenetetrazolom. in Acta veterinaria, 53(2-3), 103-112.
https://hdl.handle.net/21.15107/rcub_ibiss_465

Jelenković AV, Jovanović MD, Ninković M, Maksimović M, Bošković B. Azot oksid (NO) i antagonist NMDA receptora u konvulzijama izazvanim pentilenetetrazolom. in Acta veterinaria. 2003;53(2-3):103-112.
https://hdl.handle.net/21.15107/rcub_ibiss_465 .

Jelenković, Ankica V., Jovanović, Marina D., Ninković, Milica, Maksimović, Milan, Bošković, Bogdan, "Azot oksid (NO) i antagonist NMDA receptora u konvulzijama izazvanim pentilenetetrazolom" in Acta veterinaria, 53, no. 2-3 (2003):103-112,
https://hdl.handle.net/21.15107/rcub_ibiss_465 .