Inducible Nitric Oxide Synthase (Inos) Mediates Ethanol-Induced Redox Imbalance And Upregulation Of Inflammato Cytokines In The Kidney

Overexpression of the inducible isoform of the enzyme nitric oxide synthase (iNOS) has been associated to pathological processes in the kidney. Ethanol consumption induces the renal expression of iNOS; however, the contribution of this enzyme to the deleterious effects of ethanol in the kidney remains elusive. We examined whether iNOS plays a role in the renal dysfunction and oxidative stress induced by ethanol consumption. With this purpose, male C57BL/6 wild-type (WI) or iNOS-deficient (iNOS(-/-)) mice were treated with ethanol (20% WO for 10 weeks. Treatment with ethanol increased the expression of Nox4 as well as the concentration of thiobarbituric acid reactive substances and the levels of tumor necrosis factor a in the renal cortex of ANT but not iNOS(-/-) mice. Augmented serum levels of creatinine and increased systolic blood pressure were found in ANT and iNOS(-/-) mice treated with ethanol. WT mice treated with ethanol showed increased production of reactive oxygen species and myeloperoxidase activity, but these responses were attenuated in iNOS(-/-) mice. We concluded that iNOS played a role in ethanol-induced oxidative stress and pro-inflammatory cytokine production in the kidney. These are mechanisms that may contribute to the renal toxicity induced by ethanol.