پيشگيري از تغييرات عملكردي و ساختماني كليه به وسيله نيتريك اكسايد در نفروتوكسيسستي ناشي از جنتامايسين در موش هاي صحرايي

The role of nitric oxide in protection of functional and structural changes in gentamicin nephrotoxicity

Background: In recent years many studies have investigated the role of nitric oxide (NO) in acute renal failure (ARF). in previous investigation, we studied the effects of NO system on changes in urinary enzyme levels, lactate dehydogenase and alkaline phosphatase in a gentamicin (GM) model of ARF.The present study was designed to evaluate the effects of NO induction or inhibition on functional and structural changes in gentamicin-induced ARF. Materials and methods: Kidneys from male Sprague-Dawley rats were perfused for 90 min in situ. To measure glomerular filtration rate (GFR), inulin was added to the perfusate. Tubular cell toxicities were evaluated by measurement of urinary N- acetyl- 13-d-glucosaminidase (NAG) levels. At the end of the experiments, kidneys were transferred to 10% formalin buffer for fixation. The sections were evaluated for histological changes by light microscopy. Six groups (seven in each group) were studied: 1. Control with no treatment; 2. L-arginine (2 mM in perfusate); 3. L-nitro-arginine-methyl ester (L-NAME, 0.1 mM in perfusate); 4. Gentamicin (0.5 mg/ml in perfusate); 5. GM + L-arginine; 6. GM + L-NAME. Results: L-arginine prevented, whereas, L-NAME enhanced GM-induced enzyme release and GFR reduction. Histological studies showed that GM-treated kidneys had clear evidences of tubular damages and these damages were increased by simultaneous administration of L-NAME and GM. Conclusion: This study suggests that NO may have a protective effect on functional and structural changes in gentamicin-induced ARF.