Abstract The Effect of Inducible Nitric Oxide Synthase Inhibition on Increased Oxidative Stress in the Liver of Endotoxemic Rats Objective: In this study, we aimed to investigate the effect of nitric oxide produced by inducible nitric oxide synthase to oxidative stress in the liver of endotoxemic rats. Method: Male Wistar rats received either saline (4 ml/kg, i.p.) in control group, endotoxin (10 mg/kg, i.p.) in endotoxic shock group and selective inducible nitric oxide synthase inhibitor phenylene-1,3-bis[ethane-2-isothiourea] dihydrobromide (10 mg/kg, i.p.) one hour after saline or endotoxin injection in the other groups. Mean arterial blood pressure was measured within four hours. The liver was isolated from the rats for the measurement of nitrite as an index of nitric oxide production, malondialdehyde for lipid peroxidation and the level of a potent antioxidant reduced glutathione. The activities of the antioxidant enzymes superoxide dismutase and catalase and the activity of myeloperoxidase as an index of neutrophil infiltration were measured. Results: Endotoxin-induced hypotension was prevented by phenylene-1,3-bis [ethane-2-isothiourea] dihydro-bromide (p<0.05). Endotoxin caused an increase in nitrite levels, a decrease in reduced glutathione level and myeloperoxidase, superoxide dismutase and catalase activities (p<0.05). The effects of endotoxin were prevented by phenylene-1,3-bis[ethane-2-isothiourea] dihydrobromide (p<0.05). Conclusion: This study indicates that increased production of nitric oxide by induced nitric oxide synthase during endotoxemia contributes to oxidative stress and the inhibition of nitric oxide synthase restores the decreased antioxidant capacity in the liver.
Türkçe Özet:Amaç: Bu çalışmada, endotoksemik sıçanlardan izole edilen karaciğerde indüklenebilir nitrik oksit sentaz aracılığı ile oluşan nitrik oksitin oksidatif stres üzerindeki etkisinin araştırılması amaçlanmıştır. Yöntem: Erkek Wistar sıçanlara, kontrol grubuna serum fizyolojik (4 ml/kg, i.p.), endotoksik şok grubuna endotoksin (10 mg/kg, i.p.) ve diğer gruplara serum fizyolojik veya endotoksin injeksiyonundan bir saat sonra seçici indüklenebilir nitrik oksit sentaz inhibitörü phenylene-1,3-bis[ethane-2-isothiourea]dihydrobromide (10 mg/kg, i.p.) uygulanmasının ardından, dört saat süre ile kuyruktan ortalama arter basıncı ölçülmüştür. Deneyler sonunda öldürülen sıçanlardan izole edilen karaciğerlerde nitrik oksit oluşumunun bir göstergesi olarak nitrit, lipit peroksidasyonunun bir göstergesi olarak malondialdehit ve güçlü bir antioksidan molekül olarak indirgenmiş glutatyon düzeyleri ölçülmüştür. Antioksidan enzimlerden ise süperoksit dizmutaz ve katalaz enzim aktiviteleri ve nötrofil infiltrasyonunun bir göstergesi olarak miyeloperoksidaz enzim aktivitesi ölçülmüştür. Bulgular: Endotoksinin neden olduğu kan basıncındaki düşmenin karaciğer dokusunda nitrit düzeylerindeki anlamlı artmanın (p<0.05), malondialdehit ve indirgenmiş glutatyon düzeyleri ile miyeloperoksidaz, süperoksit dizmutaz ve katalaz enzim aktivitelerinde anlamlı bir azalma (p<0.05) ile birlikte olduğu gözlenmiştir. Endotoksinin kan basıncı ve karaciğer dokusunda ölçülen parametreler üzerindeki bütün etkileri 1,3-PBIT ile önlenmiştir (p<0.05). Sonuç: Bu çalışma, endotoksemi sırasında indüklenebilir nitrik oksit sentaz aracılığı ile aşırı miktarda üretilen nitrik oksitin karaciğerde oluşan oksidatif strese katkıda bulunabileceğini ve değişmiş olan karaciğer antioksidan kapasitesinin indüklenebilir nitrik oksit sentazın inhibisyonu ile düzeltilebileceğini göstermektedir.
Primary Language | Turkish |
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Journal Section | Articles |
Authors | |
Publication Date | September 1, 2008 |
Submission Date | June 13, 2014 |
Published in Issue | Year 2008 Volume: 1 Issue: 3 |
MEU Journal of Health Sciences Assoc was began to the publishing process in 2008 under the supervision of Assoc. Prof. Gönül Aslan, Editor-in-Chief, and affiliated to Mersin University Institute of Health Sciences. In March 2015, Prof. Dr. Caferi Tayyar Şaşmaz undertook the Editor-in Chief position and since then he has been in charge.
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