TY  - JOUR
AU  - Đurđević, Dragan
AU  - Đukić, Mirjana
AU  - Ninković, Milica
AU  - Stevanović, Ivana
AU  - Jovanović, Marina
AU  - Vasić, Una
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2062
AB  - Diquat (DQ) neurotoxicity mechanisms are unknown, although, it's systemic toxicity is mediated by free radical reactions. The role of glutathione cycle was assessed by glutathione reductase (GR) applied in the pre-treatment of DQ poisoning. Wistar rats were used and tested compounds were administered intrastriatally (i.s.) in one single dose. Total glutathione (tGSH), glutathione disulfide (GSSG) and glutathione peroxidase (GPx) were measured in the vulnerable brain regions (VBRs) (striatum, hippocampus and cortex), at 30 minutes, 24 hours and 7 days post treatment. Results from the intact and the sham operated groups were not statistically different. Rapid spatial spreading of oxidative stress was confirmed in the examined VBRs.. Mortality (30-40%, within 24hrs) and signs of lethargy were observed in the DQ group. Activity of GPx activity was elevated and GSSG/GSH was higher in the examined VBRs during the experiment, compared to the controls. The i.s. pre-treatment with GR achieved neuroprotective role against DQ induced neurotoxicity, based on animal survival, absence of lethargy and decreased GPx activity and GSSG/GSH in the examined VBRs during the experiment, compared to the DQ group. Our results confirmed that oxidation of GSH was the reason for the reduced antioxidative defense against DQ neurotoxicity.
AB  - Mehanizmi neurotoksičnosti dikvata (DK) su nepoznati, mada se zna da je sistemska toksičnost posredovana reakcijama slobodnih radikala. Uloga glutationskog ciklusa je isptivana primenom glutation reduktaze (GR) u predtretmanu trovanja DK. Wistar pacovi su korišćeni i testirana jedinjenja intrastrjiatalno (i.s.) primenjena u jednokratnoj dozi. Ukupni glutation (tGSH), glutation-disulfid (GSSG) i aktivnost glutation peroksidaze (GPx) su mereni u selektivno osetljivim regionima mozga (strijatum, hipokampus i korteks), 30. minuta, 24. sata i 7. dana posle tretmana. Rezultati netretiranih (intaktna grupa) i lažno operisanih pacova se ne razlikuju statistički. Vremensko i prostorno širenje oksidativnog stresa je potvrđeno kod ispitivanih moždanih struktura. Mortalitet (30-40%, u roku od 24 casa) i znaci letargije su uočeni u samo u DK grupi. Statistički povećana aktivnost GPx, kao i odnosa GSSG/GSH u ispitivanim moždanim strukturama tokom eksperimenta, potvrđuje oksidativno narušenu ravnotežu i oštećenja moždanog tkiva. Predtretman i.s. sa GR je ispoljio neurozaštitni efekat od neurotoksičnosti DK, bazirano na preživljavanju životinja, odsustvu letargije i smanjenoj aktivnost GPx i odnosa GSSG / GSH ispitivanih moždanih struktura tokom eksperimenta, u odnosu na DK grupu. Naši rezultati ukazuju da je oksidacija GSH kljucna za smanjenje antioksidativne odbrane od DK neurotoksicnosti.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria
T1  - Glutathione cycle in diquat neurotoxicity: Assessed by intrastriatal pre-treatment with glutathione reductase
T1  - Uloga glutationskog ciklusa u neurotoksičnosti dikvata - ispitivano primenom intrastrijatalnog predtretmana sa glutation reduktazom
VL  - 63
IS  - 2-3
SP  - 159
EP  - 175
DO  - 10.2298/AVB1303159D
ER  - 

@article{
author = "Đurđević, Dragan and Đukić, Mirjana and Ninković, Milica and Stevanović, Ivana and Jovanović, Marina and Vasić, Una",
year = "2013",
abstract = "Diquat (DQ) neurotoxicity mechanisms are unknown, although, it's systemic toxicity is mediated by free radical reactions. The role of glutathione cycle was assessed by glutathione reductase (GR) applied in the pre-treatment of DQ poisoning. Wistar rats were used and tested compounds were administered intrastriatally (i.s.) in one single dose. Total glutathione (tGSH), glutathione disulfide (GSSG) and glutathione peroxidase (GPx) were measured in the vulnerable brain regions (VBRs) (striatum, hippocampus and cortex), at 30 minutes, 24 hours and 7 days post treatment. Results from the intact and the sham operated groups were not statistically different. Rapid spatial spreading of oxidative stress was confirmed in the examined VBRs.. Mortality (30-40%, within 24hrs) and signs of lethargy were observed in the DQ group. Activity of GPx activity was elevated and GSSG/GSH was higher in the examined VBRs during the experiment, compared to the controls. The i.s. pre-treatment with GR achieved neuroprotective role against DQ induced neurotoxicity, based on animal survival, absence of lethargy and decreased GPx activity and GSSG/GSH in the examined VBRs during the experiment, compared to the DQ group. Our results confirmed that oxidation of GSH was the reason for the reduced antioxidative defense against DQ neurotoxicity., Mehanizmi neurotoksičnosti dikvata (DK) su nepoznati, mada se zna da je sistemska toksičnost posredovana reakcijama slobodnih radikala. Uloga glutationskog ciklusa je isptivana primenom glutation reduktaze (GR) u predtretmanu trovanja DK. Wistar pacovi su korišćeni i testirana jedinjenja intrastrjiatalno (i.s.) primenjena u jednokratnoj dozi. Ukupni glutation (tGSH), glutation-disulfid (GSSG) i aktivnost glutation peroksidaze (GPx) su mereni u selektivno osetljivim regionima mozga (strijatum, hipokampus i korteks), 30. minuta, 24. sata i 7. dana posle tretmana. Rezultati netretiranih (intaktna grupa) i lažno operisanih pacova se ne razlikuju statistički. Vremensko i prostorno širenje oksidativnog stresa je potvrđeno kod ispitivanih moždanih struktura. Mortalitet (30-40%, u roku od 24 casa) i znaci letargije su uočeni u samo u DK grupi. Statistički povećana aktivnost GPx, kao i odnosa GSSG/GSH u ispitivanim moždanim strukturama tokom eksperimenta, potvrđuje oksidativno narušenu ravnotežu i oštećenja moždanog tkiva. Predtretman i.s. sa GR je ispoljio neurozaštitni efekat od neurotoksičnosti DK, bazirano na preživljavanju životinja, odsustvu letargije i smanjenoj aktivnost GPx i odnosa GSSG / GSH ispitivanih moždanih struktura tokom eksperimenta, u odnosu na DK grupu. Naši rezultati ukazuju da je oksidacija GSH kljucna za smanjenje antioksidativne odbrane od DK neurotoksicnosti.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria",
title = "Glutathione cycle in diquat neurotoxicity: Assessed by intrastriatal pre-treatment with glutathione reductase, Uloga glutationskog ciklusa u neurotoksičnosti dikvata - ispitivano primenom intrastrijatalnog predtretmana sa glutation reduktazom",
volume = "63",
number = "2-3",
pages = "159-175",
doi = "10.2298/AVB1303159D"
}

Đurđević, D., Đukić, M., Ninković, M., Stevanović, I., Jovanović, M.,& Vasić, U.. (2013). Glutathione cycle in diquat neurotoxicity: Assessed by intrastriatal pre-treatment with glutathione reductase. in Acta veterinaria
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 63(2-3), 159-175.
https://doi.org/10.2298/AVB1303159D

Đurđević D, Đukić M, Ninković M, Stevanović I, Jovanović M, Vasić U. Glutathione cycle in diquat neurotoxicity: Assessed by intrastriatal pre-treatment with glutathione reductase. in Acta veterinaria. 2013;63(2-3):159-175.
doi:10.2298/AVB1303159D .

Đurđević, Dragan, Đukić, Mirjana, Ninković, Milica, Stevanović, Ivana, Jovanović, Marina, Vasić, Una, "Glutathione cycle in diquat neurotoxicity: Assessed by intrastriatal pre-treatment with glutathione reductase" in Acta veterinaria, 63, no. 2-3 (2013):159-175,
https://doi.org/10.2298/AVB1303159D . .

TY  - JOUR
AU  - Đukić, Mirjana
AU  - Jovanović, Marina
AU  - Ninković, Milica
AU  - Stevanović, Ivana
AU  - Đurđević, Dragan
AU  - Vasić, Una
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1792
AB  - In this study we examined if the response of the cortex against diquat (DQ), intrastriatally (i.s.) applied to Wistar rats, was mediated by oxidative/nitrosative stress (OS/NS). In particular, we were focused on the glutathione (GSH) antioxidative role, thus we applied i.s. glutathione reductase (GR) in the pre-treatment of DQ administration. Superoxide anion radical (O2 •-), nitrate (NO3 -), malondialdehyde (MDA) and superoxide dismutase (SOD), were measured in ipsi- and contra- lateral sides of the cortex, at 30 minutes, 24 hours and 7 days post treatment. The redox balance was not significantly changed in the cortex of sham operated and intact groups. Also, no differences were observed between the ipsi- and contra- lateral side of the cortex. Lethargy and mortality (30-40%) of the animals in the DQ group within 24 hrs, coincided with rapidly developed lipid peroxidation supported by OS/NS upon i.s. DQ administration. Strong redox potential of DQ probably resulted in a huge deprivation of molecular oxygen. The pretreatment with GR acted neuro-protectively, based on animal survival and absence of lethargy, although, lipid peroxidation was not developed in the GR+DQ group, OS was documented by a high concentration of O2 •- (within 24 hrs), descending and eventually inhibiting SOD activity (at 7 days).
AB  - U ovoj studiji smo ispitali da li je oksidativni/nitrosativni stres (OS/NS), uključen u odgovor korteksa Wistar pacova nakon intrastrijatalne (i.s.) izloženosti dikvatu (DK). Posebno smo ispitivali značaj antioksidativne uloge glutationa (GSH), zbog čega smo primenili glutation reduktazu (GR) u predtretmanu davanja DK. Superoksid anjon radikal (O2•¯), nitrati (NO3¯), malondialdehid (MDA) i superoksid dismutaza (SOD), su mereni u obostranom korteksu (ipsi- i kontrastrana), nakon 30 minuta, 24 sati i 7 dana od tretmana. Redoks balans se nije značajno promenio u korteksu lažno operisanih i netretiranih pacova. Takođe, ne postoji statistički značajna razlika između ipsi- i kontra- strane korteksa. Letargija i mortalitet (30-40%) kod životinja u DK grupi su uočene tokom 24 časa od i.s. trovanja DK, što se poklopilo sa naglim razvojem OS/NS i lipidne peroksidacije. Visok redoks potencijal DK verovatno rezultira opsežnim utroškom molekularnog kiseonika. Zaključeno je da je ostvaren neuroprotektivni učinak predtretmana sa GR, na osnovu preživljavanja životinja i odsustva letargije. Lipidna peroksidacija nije bila razvijena u grupi predtretiranoj sa GR ali je ipak izmerena visoka koncentracija O2•¯ (tokom 24 sata) koja zatim opada i na kraju 7. dana u potpunosti inhibira aktivnost SOD.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria
T1  - Influence of glutathione reductase on diquat neurotoxcity assessed by oxidative/nitrosative stress in the cortex of intrastriatally treated rats
T1  - Uticaj glutation reduktaze na neurotoksičnost dikvata - ispitivan je oksidativni/nitrozativni stres u korteksu intrastrijatalno tretiranih pacova
VL  - 62
IS  - 5-6
SP  - 553
EP  - 568
DO  - 10.2298/AVB1206553D
ER  - 

@article{
author = "Đukić, Mirjana and Jovanović, Marina and Ninković, Milica and Stevanović, Ivana and Đurđević, Dragan and Vasić, Una",
year = "2012",
abstract = "In this study we examined if the response of the cortex against diquat (DQ), intrastriatally (i.s.) applied to Wistar rats, was mediated by oxidative/nitrosative stress (OS/NS). In particular, we were focused on the glutathione (GSH) antioxidative role, thus we applied i.s. glutathione reductase (GR) in the pre-treatment of DQ administration. Superoxide anion radical (O2 •-), nitrate (NO3 -), malondialdehyde (MDA) and superoxide dismutase (SOD), were measured in ipsi- and contra- lateral sides of the cortex, at 30 minutes, 24 hours and 7 days post treatment. The redox balance was not significantly changed in the cortex of sham operated and intact groups. Also, no differences were observed between the ipsi- and contra- lateral side of the cortex. Lethargy and mortality (30-40%) of the animals in the DQ group within 24 hrs, coincided with rapidly developed lipid peroxidation supported by OS/NS upon i.s. DQ administration. Strong redox potential of DQ probably resulted in a huge deprivation of molecular oxygen. The pretreatment with GR acted neuro-protectively, based on animal survival and absence of lethargy, although, lipid peroxidation was not developed in the GR+DQ group, OS was documented by a high concentration of O2 •- (within 24 hrs), descending and eventually inhibiting SOD activity (at 7 days)., U ovoj studiji smo ispitali da li je oksidativni/nitrosativni stres (OS/NS), uključen u odgovor korteksa Wistar pacova nakon intrastrijatalne (i.s.) izloženosti dikvatu (DK). Posebno smo ispitivali značaj antioksidativne uloge glutationa (GSH), zbog čega smo primenili glutation reduktazu (GR) u predtretmanu davanja DK. Superoksid anjon radikal (O2•¯), nitrati (NO3¯), malondialdehid (MDA) i superoksid dismutaza (SOD), su mereni u obostranom korteksu (ipsi- i kontrastrana), nakon 30 minuta, 24 sati i 7 dana od tretmana. Redoks balans se nije značajno promenio u korteksu lažno operisanih i netretiranih pacova. Takođe, ne postoji statistički značajna razlika između ipsi- i kontra- strane korteksa. Letargija i mortalitet (30-40%) kod životinja u DK grupi su uočene tokom 24 časa od i.s. trovanja DK, što se poklopilo sa naglim razvojem OS/NS i lipidne peroksidacije. Visok redoks potencijal DK verovatno rezultira opsežnim utroškom molekularnog kiseonika. Zaključeno je da je ostvaren neuroprotektivni učinak predtretmana sa GR, na osnovu preživljavanja životinja i odsustva letargije. Lipidna peroksidacija nije bila razvijena u grupi predtretiranoj sa GR ali je ipak izmerena visoka koncentracija O2•¯ (tokom 24 sata) koja zatim opada i na kraju 7. dana u potpunosti inhibira aktivnost SOD.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria",
title = "Influence of glutathione reductase on diquat neurotoxcity assessed by oxidative/nitrosative stress in the cortex of intrastriatally treated rats, Uticaj glutation reduktaze na neurotoksičnost dikvata - ispitivan je oksidativni/nitrozativni stres u korteksu intrastrijatalno tretiranih pacova",
volume = "62",
number = "5-6",
pages = "553-568",
doi = "10.2298/AVB1206553D"
}

Đukić, M., Jovanović, M., Ninković, M., Stevanović, I., Đurđević, D.,& Vasić, U.. (2012). Influence of glutathione reductase on diquat neurotoxcity assessed by oxidative/nitrosative stress in the cortex of intrastriatally treated rats. in Acta veterinaria
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 62(5-6), 553-568.
https://doi.org/10.2298/AVB1206553D

Đukić M, Jovanović M, Ninković M, Stevanović I, Đurđević D, Vasić U. Influence of glutathione reductase on diquat neurotoxcity assessed by oxidative/nitrosative stress in the cortex of intrastriatally treated rats. in Acta veterinaria. 2012;62(5-6):553-568.
doi:10.2298/AVB1206553D .

Đukić, Mirjana, Jovanović, Marina, Ninković, Milica, Stevanović, Ivana, Đurđević, Dragan, Vasić, Una, "Influence of glutathione reductase on diquat neurotoxcity assessed by oxidative/nitrosative stress in the cortex of intrastriatally treated rats" in Acta veterinaria, 62, no. 5-6 (2012):553-568,
https://doi.org/10.2298/AVB1206553D . .