Effects of nitric oxide on gentamicin toxicity in isolated perfused rat kidneys.

Abstract:

BACKGROUND:There have been many studies in recent years concerning the role of nitric oxide (NO) in acute renal failure (ARF). In this study, the effects of the inhibition or the induction of NO synthase (NOS) on gentamicin-induced ARF was investigated in isolated perfused rat kidneys. METHODS:Kidneys from male Sprague-Dawley rats were perfused in situ for 90 min. Perfusion was conducted in the presence of inulin (60 mg/dL in perfusion buffer) as a glomerular filtration rate (GFR) marker. Six groups (total: 42 rats) were studied: group 1, controls with no treatment; group 2, L-arginine (2 mM in perfusate); group 3, L-nitro-arginine-methyl ester (L-NAME, 0.1 mM in perfusate); group 4, gentamicin (GM, 0.5 mg/mL in perfusate); group 5, GM + L-arginine (same dose as groups 2 and 4) and; group 6, GM + L-NAME (same dose as groups 3 and 4). Cell injury was assessed by measuring N-acetyl-beta-D-glucosaminidase (NAG), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activity in urine. RESULTS:L-arginine prevented, whereas L-NAME enhanced, GM-induced enzyme release and GFR reduction. Histological studies showed that GM-treated kidneys had clear signs of tubular damage and this damage was increased by simultaneous L-NAME and GM administration. CONCLUSION:This study suggests that NO formation could prevent the GM-induced nephrotoxicity in this ARF model.

journal_name

J Nephrol

journal_title

Journal of nephrology

authors

Ghaznavi R,Faghihi M,Kadkhodaee M,Shams S,Khastar H

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

548-52

issue

5

eissn

1121-8428

issn

1724-6059

journal_volume

18

pub_type

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