Protective effect of oral L-arginine administration on gentamicin-induced renal failure in rats.
We investigated the effects of orally supplemented L-arginine, the substrate of nitric oxide (NO) and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g/l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or gentamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group developed marked renal failure, characterized by a significantly decreased creatinine clearance and increased blood creatinine, fractional excretion of sodium, fractional excretion of lithium, urine gamma glutamyl transferase, systolic blood pressure and daily urine volume when compared to controls. Renal histological analysis confirmed tubular necrosis. L-arginine administration caused normalization of these parameters, whereas L-NAME led to aggravation of the failure. Concomitant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to the rats receiving gentamicin alone. We conclude that L-arginine supplementation has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME.
Can
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C
Department of Pharmacology, Faculty of Medicine, Ege University, 35100 Izmir, Turkey.
Sen
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S
Boztok
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N
Tuglular
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I
D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008094:Lithium / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D051437:Renal Insufficiency / Q000139:chemically induced / Q000517:prevention & control*; D012964:Sodium / Q000652:urine; D014554:Urination / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000187:drug effects / Q000652:urine
D004791:Enzyme Inhibitors; D005839:Gentamicins; D001120:Arginine; D008094:Lithium; D012964:Sodium; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D019331:NG-Nitroarginine Methyl Ester