Effects of various nitric oxide synthase inhibitors on quinolinic acid-induced neuronal injury in rats
Efekti različitih inhibitora azot oksid sintaze na oštećenje neurona indukovano hinolinskom kiselinom kod pacova
2004
Authors
Vasiljević, Ivana D.Jovanović, Marina
Čolić, Miodrag
Mihajlović, Rosa
Đukić, Mirjana
Ninković, Milica
Maličević, Živorad
Article (Published version)
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The aetiology of neuronal death in neurodegenerative diseases, including Huntington-s disease, is still unknown. There could be a complex interplay among altered energy metabolism, excitotoxicity and oxidative stress. Our aim was to examine the effects of intrastriatal injection of a selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, and a non-specific potent nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester, in order to study the possible involvement of glutathione, an important antioxidant, in quinolinic acid-induced striatal toxicity in the rat. Unilateral administration of quinolinic acid to rat striatum in a single dose of 150 nmol/L was used as a model of Huntington-s disease. The other group of animals were pretreated with 7- nitroindazole and Nw-nitro-L-arginine methyl ester, respectively. Control groups were treated with saline solution and olive oil, respectively. Content of total glutathione, was increased in the ipsi- and contralateral s...triatum, forebrain cortex, basal forebrain and hippocampus in the groups treated with nitric oxid synthase inhibitors and quinolinic acid compared to the quinolinic acid-treated animals. These results support the hypothesis that oxygen free radicals contribute to excitotoxic neuronal injury, and also that nitric oxide synthase inhibitors could be potential neuroprotective agents in Huntington-s disease.
Etiologija selektivnog umiranja neurona u neurodegenerativnim bolestima je nepoznata, iako postoje dokazi o defektu energetskog metabolizma, ekscitotoksičnosti i oksidativnom oštećenju. Verovatno je da ključnu ulogu ima kompleksna interakcija između ovih mehanizama. Cilj ovog rada bio je da se ispitaju efekti intrastrijatne primene selektivnog inhibitora neuronske azot oksid sintaze, 7-nitroindazola, kao i nespecifičnog inhibitora azot oksid sintaze, Nw-nitro-l-arginin metil estra, zbog moguće uključenosti glutationa, ključnog antioksidansa, u toksičnost strijatuma izazvanu hinolinskom kiselinom, kod pacova. Unilateralna aplikacija hinolinske kiseline, u strijatum pacova u pojedinačnoj dozi od 150 nmol/L korišćena je kao model Hantingtonove bolesti. Druge grupe životinja tretirane su 7-nitroindazolom, odnosno Nw-nitro-l-arginin metil estrom. Kontrolne grupe dobijale su fiziološki rastvor, odnosno maslinovo ulje. Sadržaj ukupnog glutationa je povećan u ipsi- i kontralateralnom strijatum...u, kori prednjeg mozga, bazalnom prednjem mozgu i hipokampusu grupa životinja koje su pored hinolinske kiseline primile i odgovarajući inhibitor neuronske azot oksid sintaze, u poređenju sa grupom tretiranom samo neurotoksinom. Ovi podaci pokazuju da kiseonični slobodni radikali učestvuju u ekscitotoksičnom oštećenju neurona, kao i da inhibitori azot oksid sintaze mogu biti potencijalni neuroprotektivni agensi u Hantingtonovoj bolesti.
Keywords:
Huntington-s disease / quinolinic acid / Nw-nitro-L-arginine methyl ester / 7-nitroindazole / glutathione / Hantingtonova bolest / hinolinska kiselina / Nw-nitro-l-arginin metil estar / 7-nitroindazol / glutationSource:
Jugoslovenska medicinska biohemija, 2004, 23, 1, 11-18Publisher:
- Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd
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PharmacyTY - JOUR AU - Vasiljević, Ivana D. AU - Jovanović, Marina AU - Čolić, Miodrag AU - Mihajlović, Rosa AU - Đukić, Mirjana AU - Ninković, Milica AU - Maličević, Živorad PY - 2004 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/562 AB - The aetiology of neuronal death in neurodegenerative diseases, including Huntington-s disease, is still unknown. There could be a complex interplay among altered energy metabolism, excitotoxicity and oxidative stress. Our aim was to examine the effects of intrastriatal injection of a selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, and a non-specific potent nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester, in order to study the possible involvement of glutathione, an important antioxidant, in quinolinic acid-induced striatal toxicity in the rat. Unilateral administration of quinolinic acid to rat striatum in a single dose of 150 nmol/L was used as a model of Huntington-s disease. The other group of animals were pretreated with 7- nitroindazole and Nw-nitro-L-arginine methyl ester, respectively. Control groups were treated with saline solution and olive oil, respectively. Content of total glutathione, was increased in the ipsi- and contralateral striatum, forebrain cortex, basal forebrain and hippocampus in the groups treated with nitric oxid synthase inhibitors and quinolinic acid compared to the quinolinic acid-treated animals. These results support the hypothesis that oxygen free radicals contribute to excitotoxic neuronal injury, and also that nitric oxide synthase inhibitors could be potential neuroprotective agents in Huntington-s disease. AB - Etiologija selektivnog umiranja neurona u neurodegenerativnim bolestima je nepoznata, iako postoje dokazi o defektu energetskog metabolizma, ekscitotoksičnosti i oksidativnom oštećenju. Verovatno je da ključnu ulogu ima kompleksna interakcija između ovih mehanizama. Cilj ovog rada bio je da se ispitaju efekti intrastrijatne primene selektivnog inhibitora neuronske azot oksid sintaze, 7-nitroindazola, kao i nespecifičnog inhibitora azot oksid sintaze, Nw-nitro-l-arginin metil estra, zbog moguće uključenosti glutationa, ključnog antioksidansa, u toksičnost strijatuma izazvanu hinolinskom kiselinom, kod pacova. Unilateralna aplikacija hinolinske kiseline, u strijatum pacova u pojedinačnoj dozi od 150 nmol/L korišćena je kao model Hantingtonove bolesti. Druge grupe životinja tretirane su 7-nitroindazolom, odnosno Nw-nitro-l-arginin metil estrom. Kontrolne grupe dobijale su fiziološki rastvor, odnosno maslinovo ulje. Sadržaj ukupnog glutationa je povećan u ipsi- i kontralateralnom strijatumu, kori prednjeg mozga, bazalnom prednjem mozgu i hipokampusu grupa životinja koje su pored hinolinske kiseline primile i odgovarajući inhibitor neuronske azot oksid sintaze, u poređenju sa grupom tretiranom samo neurotoksinom. Ovi podaci pokazuju da kiseonični slobodni radikali učestvuju u ekscitotoksičnom oštećenju neurona, kao i da inhibitori azot oksid sintaze mogu biti potencijalni neuroprotektivni agensi u Hantingtonovoj bolesti. PB - Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd T2 - Jugoslovenska medicinska biohemija T1 - Effects of various nitric oxide synthase inhibitors on quinolinic acid-induced neuronal injury in rats T1 - Efekti različitih inhibitora azot oksid sintaze na oštećenje neurona indukovano hinolinskom kiselinom kod pacova VL - 23 IS - 1 SP - 11 EP - 18 DO - 10.2298/JMH0401011V ER -
@article{ author = "Vasiljević, Ivana D. and Jovanović, Marina and Čolić, Miodrag and Mihajlović, Rosa and Đukić, Mirjana and Ninković, Milica and Maličević, Živorad", year = "2004", abstract = "The aetiology of neuronal death in neurodegenerative diseases, including Huntington-s disease, is still unknown. There could be a complex interplay among altered energy metabolism, excitotoxicity and oxidative stress. Our aim was to examine the effects of intrastriatal injection of a selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, and a non-specific potent nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester, in order to study the possible involvement of glutathione, an important antioxidant, in quinolinic acid-induced striatal toxicity in the rat. Unilateral administration of quinolinic acid to rat striatum in a single dose of 150 nmol/L was used as a model of Huntington-s disease. The other group of animals were pretreated with 7- nitroindazole and Nw-nitro-L-arginine methyl ester, respectively. Control groups were treated with saline solution and olive oil, respectively. Content of total glutathione, was increased in the ipsi- and contralateral striatum, forebrain cortex, basal forebrain and hippocampus in the groups treated with nitric oxid synthase inhibitors and quinolinic acid compared to the quinolinic acid-treated animals. These results support the hypothesis that oxygen free radicals contribute to excitotoxic neuronal injury, and also that nitric oxide synthase inhibitors could be potential neuroprotective agents in Huntington-s disease., Etiologija selektivnog umiranja neurona u neurodegenerativnim bolestima je nepoznata, iako postoje dokazi o defektu energetskog metabolizma, ekscitotoksičnosti i oksidativnom oštećenju. Verovatno je da ključnu ulogu ima kompleksna interakcija između ovih mehanizama. Cilj ovog rada bio je da se ispitaju efekti intrastrijatne primene selektivnog inhibitora neuronske azot oksid sintaze, 7-nitroindazola, kao i nespecifičnog inhibitora azot oksid sintaze, Nw-nitro-l-arginin metil estra, zbog moguće uključenosti glutationa, ključnog antioksidansa, u toksičnost strijatuma izazvanu hinolinskom kiselinom, kod pacova. Unilateralna aplikacija hinolinske kiseline, u strijatum pacova u pojedinačnoj dozi od 150 nmol/L korišćena je kao model Hantingtonove bolesti. Druge grupe životinja tretirane su 7-nitroindazolom, odnosno Nw-nitro-l-arginin metil estrom. Kontrolne grupe dobijale su fiziološki rastvor, odnosno maslinovo ulje. Sadržaj ukupnog glutationa je povećan u ipsi- i kontralateralnom strijatumu, kori prednjeg mozga, bazalnom prednjem mozgu i hipokampusu grupa životinja koje su pored hinolinske kiseline primile i odgovarajući inhibitor neuronske azot oksid sintaze, u poređenju sa grupom tretiranom samo neurotoksinom. Ovi podaci pokazuju da kiseonični slobodni radikali učestvuju u ekscitotoksičnom oštećenju neurona, kao i da inhibitori azot oksid sintaze mogu biti potencijalni neuroprotektivni agensi u Hantingtonovoj bolesti.", publisher = "Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd", journal = "Jugoslovenska medicinska biohemija", title = "Effects of various nitric oxide synthase inhibitors on quinolinic acid-induced neuronal injury in rats, Efekti različitih inhibitora azot oksid sintaze na oštećenje neurona indukovano hinolinskom kiselinom kod pacova", volume = "23", number = "1", pages = "11-18", doi = "10.2298/JMH0401011V" }
Vasiljević, I. D., Jovanović, M., Čolić, M., Mihajlović, R., Đukić, M., Ninković, M.,& Maličević, Ž.. (2004). Effects of various nitric oxide synthase inhibitors on quinolinic acid-induced neuronal injury in rats. in Jugoslovenska medicinska biohemija Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd., 23(1), 11-18. https://doi.org/10.2298/JMH0401011V
Vasiljević ID, Jovanović M, Čolić M, Mihajlović R, Đukić M, Ninković M, Maličević Ž. Effects of various nitric oxide synthase inhibitors on quinolinic acid-induced neuronal injury in rats. in Jugoslovenska medicinska biohemija. 2004;23(1):11-18. doi:10.2298/JMH0401011V .
Vasiljević, Ivana D., Jovanović, Marina, Čolić, Miodrag, Mihajlović, Rosa, Đukić, Mirjana, Ninković, Milica, Maličević, Živorad, "Effects of various nitric oxide synthase inhibitors on quinolinic acid-induced neuronal injury in rats" in Jugoslovenska medicinska biohemija, 23, no. 1 (2004):11-18, https://doi.org/10.2298/JMH0401011V . .