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Selective and Non-Selective Inhibition of Nitric Oxide Synthase in the In-Vitro Model of Gentamicin-Induced Acute Renal Failure in Rats
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Ghaznavi R *   , Kadkhodaei M |
| , rghaznav @ sina.tums.ac.ir |
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Abstract: (9293 Views) |
| Background: All the three nitric oxide synthase (NOS) isoforms are presented in the kidney. Some data provided evidences that eNOS activity leads to restoration of renal function after injury, but activation of iNOS aggravates renal failure. In the present study, we investigated that whether in gentamicin-induced renal failure selective iNOS blockade is beneficial. Materials and Methods: Four groups of rats were studied: Control with saline injections gentamicin (GM) with GM injections only (iv, 4 mg/kg) GM + L-NAME : N-omega -L-arginine methyl ester (L-NAME) administrated simultaneously with (iv, 30 mg/kg) or two and four hours after GM (ip,30 mg/kg) GM + L-NIL: N-imino-ethyil lysine (L-NIL) administrated simultaneously with (iv, 3 mg/kg) or two and four hours after GM(ip,3 mg/kg). In all groups, serum and urine creatinine were measured. Creatinine clearance were calculated and considered as GFR. Urine N-acethyle-b-D –glocose aminidase (NAG) was assayed. After surgery, kidney sections were histologically studied. Results: GFR was significantly lower in GM group compared to control and L-NIL groups (P<0.01). It was also lower in L-NAME group compared to GM group (P<0.05). Creatinine levels were significantly higher in GM group compared to that of control ones (P<0.01). L-NIL group had lower creatinine levels when compared to GM group. NAG had higher activities in the urine of GM group when compared to the controls (P<0.01). Enzyme activities in L-NIL group were numerically between the control and GM groups. L-NAME increased GM-induced enzyme release (P<0.05). Histological studies showed that GM-treated kidneys had clear evidences of tubular damages and these damages were decreased by simultaneous administration of L-NIL and GM, although not significant. Conclusion: Selective inhibition of iNOS by L-NIL may prevent whereas, non-selective inhibition of NOS by L-NAME aggravates GM-induced renal failure |
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| Keywords: Gentamicin, Nephrotoxicity, L-NIL, NAG, GFR |
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Full-Text [PDF 362 kb]
(1438 Downloads)
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Type of Study: Original |
Subject:
Medicine
Received: 2017 | Accepted: 2017 | Published: 2017
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