Publication: The effects of L-arginine nitric oxide metabolites and renal lipid proxidation in cisplatin treated rats
Abstract
Ratlarda sisplatin uygulanmasına bağlı olarak böbrek lipid peroksidasyon düzeyinin ve indirgenmiş glutatyon (GSH) tüketiminin arttığı gözlenmiştir. Bu çalışmada, nitrik oksit sentazın (NOS) substratı olan L-arjininin sisplatine bağlı böbrek hasarı oluşturulmuş ratlarda böbrek hasarına, böbrek lipid peroksidasyonuna, idrar nitrit (NO2)+nitrat (NO3) düzeylerine etkisi araştırılmıştır. Sisplatin (3 mg/kg) intraperitonal olarak günde bir kez 5 gün uygulandı. L-arjinin (0.2g/kg) ve N°-nitro-L-arjinin metil ester (L-NAME, NOS inhibitörü, 20 mg/kg) sisplatin uygulanmasından 1 saat önce uygulandı. Sisplatin plazma kreatinin, üre düzeylerinde, günlük idrar hacminde ve idrar gama-glutamil transferaz (GGT) düzeyinde artışa neden olurken kreatinin klirensinde ve idrar NO2'+NO3' atılımında azalmaya neden oldu. Sisplatin uygulanmasından önce düşük doz intraperitonal L-arjinin verilmesi plazma kreatinin ve üre düzeylerindeki artışı engelledi. Sisplatin böbrek lipid peroksit düzeylerini artırırken GSH içeriğinin de azalmasına neden oldu. L-arjinin bu etkileri tersine çevirdi. L-arjinin günlük idrar atılımının ve idrar nitrik oksit metabolitlerinin normale dönmesini sağladı. Diğer taraftan, L-NAME sisplatine bağlı renal hasarda koruyucu etki göstermedi. Bulgularmıza göre intraperitonal L-arjinin uygulanması NO üretimini içine alan mekanizma ile sisplatine bağlı böbrek hasarında koruyucu etki göstermektedir.
Increase of lipid peroxidation and glutathione (GSH) depletion in kidney tissues have been observed in rats with cisplatin-(CDDP) induced nephrotoxicity. This investigation elucidates the role of L-arginine, the substrate of nitric oxide synthase (NOS), on renal injury, lipid peroxidation and urinary excretion of nitrite (NO2')+ nitrate (NO3~) in rats with CDDP induced renal failure. CDDP (3 mg/kg, once a day) was injected intraperitoneally for 5 days. In subgroups, daily L-arginine (0.2g/kg) or N°-nitro-L-arginine methyl ester (L-NAME) (NOS inhibitor, 20 mg/kg) were administrated intraperitonally 1 hour prior to CDDP treatment. Treatment with CDDP resulted in significant increase plasma creatinine (Cr), urea levels, daily urine volume, urinary gamma glutamyl transferase (GGT) levels and significant decrease creatinine clearance and urinary NO2~ +NO3 excretion. Intraperitoneal administration of L-arginine in the low dose prevented the CDDP induced elevation of plasma Cr and urea levels. When compared with controls, CDDP administration resulted in increased lipid peroxidation and decreased GSH levels in the kidney; L-arginine reversed these effects. In addition, pretreatment of L-arginine was effective in the normalization of daily urine volume and urinary excretion ofNO2'+NO3'. On the other hand, the administration of L-NAME resulted in no protection agonist CDDP-induced renal damage. The findings of this study suggest that intraperitoneal L-arginine administration can prevent the CDDP-induced renal damage by a mechanism which involves the production of NO.
Increase of lipid peroxidation and glutathione (GSH) depletion in kidney tissues have been observed in rats with cisplatin-(CDDP) induced nephrotoxicity. This investigation elucidates the role of L-arginine, the substrate of nitric oxide synthase (NOS), on renal injury, lipid peroxidation and urinary excretion of nitrite (NO2')+ nitrate (NO3~) in rats with CDDP induced renal failure. CDDP (3 mg/kg, once a day) was injected intraperitoneally for 5 days. In subgroups, daily L-arginine (0.2g/kg) or N°-nitro-L-arginine methyl ester (L-NAME) (NOS inhibitor, 20 mg/kg) were administrated intraperitonally 1 hour prior to CDDP treatment. Treatment with CDDP resulted in significant increase plasma creatinine (Cr), urea levels, daily urine volume, urinary gamma glutamyl transferase (GGT) levels and significant decrease creatinine clearance and urinary NO2~ +NO3 excretion. Intraperitoneal administration of L-arginine in the low dose prevented the CDDP induced elevation of plasma Cr and urea levels. When compared with controls, CDDP administration resulted in increased lipid peroxidation and decreased GSH levels in the kidney; L-arginine reversed these effects. In addition, pretreatment of L-arginine was effective in the normalization of daily urine volume and urinary excretion ofNO2'+NO3'. On the other hand, the administration of L-NAME resulted in no protection agonist CDDP-induced renal damage. The findings of this study suggest that intraperitoneal L-arginine administration can prevent the CDDP-induced renal damage by a mechanism which involves the production of NO.