The effects of inducible nitric oxide synthase inhibitor L-N6-(1-iminoethyl) lysine in gentamicin-induced acute tubular necrosis in rats.
The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in gentamicin-induced acute tubular necrosis in rats using the iNOS inhibitor L-N6-(1-iminoethyl) lysine (L-NIL). Wistar rats, both sexes (n=18), were equally divided into three groups. Gentamicin group received intraperitoneally (i.p.) gentamicin in 0.9 % NaCl at a dose of 80 mg/kg/day for five consecutive days. L-NIL+gentamicin group received L-NIL at a dose of 3 mg/kg i.p. 36, 24 and 12 h before first dose of gentamicin. Control group received 0.9 % NaCl i.p. for five consecutive days at the equal volume as gentamicin group. Griess reaction was used for determination plasma level of NO. Semiquantitative histological analysis was used for the evaluation of kidney damage level. The plasma NO level and the level of kidney damage were statistically higher in gentamicin group in comparison to the control group (p=0.046). Application of L-NIL prior to gentamicin led to certain decrease in the plasma level of NO as well as in the level of kidney damage. Application of L-NIL, prior to gentamicin administration, did not provide complete protective effects of L-NIL on the kidney, which was demonstrated on kidney sections. The lack of anticipated protective effect of L-NIL on kidney tissue might be explained with the fact that we have used L-NIL prior but not during/after gentamicin administration. It would be necessary to examine the effects of L-NIL administration not only before, but as well during and possibly after the administration of gentamicin.
Institute of Physiology and Biochemistry, Faculty of Medicine, University of Sarajevo, Cekalusa 90, 71000 Sarajevo, Bosnia and Herzegovina.
Nesina
N
Avdagić
Emina
E
Nakas-Ićindić
Senija
S
Rasić
Almira
A
Hadzović-Dzuvo
Asija
A
Zaciragić
Amina
A
Valjevac
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005839:Gentamicins / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D015233:Models, Statistical; D009336:Necrosis / Q000188:drug therapy; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D005839:Gentamicins; C090663:N(6)-(1-iminoethyl)lysine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D008239:Lysine