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


CONCLUSIONS
This study suggests that NO formation could prevent the GM-induced nephrotoxicity in this ARF model.
Ghaznavi
Rana
R
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran--Iran.
Faghihi
Mahdieh
M
Kadkhodaee
Mehri
M
Shams
Sedigheh
S
Khastar
Hossein
H
D000118:Acetylglucosaminidase / Q000378:metabolism; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D005839:Gentamicins / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D005839:Gentamicins; D009569:Nitric Oxide; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D000469:Alkaline Phosphatase; D000118:Acetylglucosaminidase; D019331:NG-Nitroarginine Methyl Ester