Hemeoxygenase and Nitric Oxide: A Cross Talk in Cold Stress-Induced Injury

Background and aim: Hemeoxygenase-1 (HO-1) is a stress responsive protein induced by various oxidative stress agents. It has protective effects in several organs including liver and kidney against oxidative stress injury however, the mechanisms underlying the effects of HO-1 remains poorly defined. This study investigated the effect of HO-1 inducer (Hemin) on liver and kidney tissues in rats exposed to cold restraint stress (CRS) and the possible contribution of nitric oxide in this effect. Methods: Male Wistar rats were divided into 5 groups, normal control group, CRS non treated group, CRS + hemin (50 mg/kg i.p.) group, CRS + aminioguanidine (inhibitor of inducible nitric oxide synthase (iNOS)) (50 mg/kg s.c.) group and CRS + hemin + aminoguanidine group. Liver and kidney tissues injuries were assessed biochemically and histopathologically. Samples from liver and kidney were used for estimation of oxidative stress markers. Results: Exposure to CRS caused injury of liver and kidney manifested by elevated serum alanine aminotransferase (ALT), and serum urea and creatinine, and confirmed by histopathological changes. Liver and kidney injuries were associated with elevation of oxidative stress markers. Pre-treatment with either hemin or aminoguanidine restored the levels of oxidative stress to near normal values with improvement of the hisopathological changes. No further protection was noticed when hemin coadministered with iNOS inhibitor (aminoguandine). Conclusion: The results of this study suggest that release of HO-1 in CRS tissue injury exhibits a protective antioxidant effect probably via inhibition of iNOS.