Abstract
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.
Highlights
Nitric oxide (NO) is free radical gas with unique properties
Using multiple comparison test the only significant difference was found between the control and gentamicin group (p=, ) while no significant difference was found between control and L-N -( -iminoethyl) lysine (L-NIL)+gentamicin group and between gentamicin and L-NIL+gentamicin group (Figure )
Our results have shown that plasma NO level in animals, which were treated with inducible nitric oxide synthase (iNOS) inhibitor (L-NIL) before the induction of ATN by gentamicin, was lower in the comparison with the plasma NO level in animals with ATN caused by gentamicin without the use of iNOS inhibitor, but the observed difference was not statistically significant
Summary
Nitric oxide (NO) is free radical gas with unique properties. NO can diffuse rapidly across membranes and transmit a signal over many cell lengths. NO is involved in the regulation of many physiological processes, as well as in the pathophysiology of a number of diseases ( ) It is synthesized enzymatically from L-arginine in numerous tissues and cell types by three structurally distinct isoforms of the enzyme, nitric oxide synthase (NOS). These constitutive forms of NOS generate low, transient levels of NO in response to intracellular calcium concentrations These low levels of NO act to regulate blood pressure, platelet adhesion, gastrointestinal motility, bronchomotore tone and neurotransmission ( , ). L-NIL was found to be orally active and produces marked efficacy at doses that did not produce an elevation in systemic blood pressure, demonstrating in vivo selectivity This suggests that selective iNOS inhibitor may have therapeutic potential for the treatment of diseases mediated by overproduction of NO ( , ). NO plays a fundamental role in both physiology and pathophysiology of the proximal tubule ( )
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