CHRONIC UNPREDICTABLE STRESS INDUCES RENAL DAMAGE IN RATS BY OXIDATIVE STRESS PROVOKED APOPTOSIS AND ALTERING THE FUNCTION OF Na/K-ATPase

Background: Recently, some shocking epidemics of chronic kidney disease of undetermined origin have been reported. In this regard, numerous lines of evidence suggest that socioeconomic and environmental stressors have a key role, an effect that needs further confirmation. The present study was undertaken to explore the effect of Chronic Unpredictable Stress (CUS) on kidney function and structure in rats. Methods: It was a randomized control trial. Rats were divided into control and experimental groups (n=8 each). The experimental group (CUS group) consisted of rats which were exposed to a set of mild stressors for 21 days. After that, biochemical and molecular studies were conducted to measure kidney function tests, renal oxidative stress, inflammatory response, components of intrinsic apoptosis, as well as function of Na/K-ATPase. In addition, renal histopathological study was conducted. Results: Chronic Unpredictable Stress resulted in sever renal damage as indicated by enhanced serum urea and reduced creatinine clearance (Ccr), also evident by the severe glomerular and tubular damage and neutrophils infiltration. Concomitantly, CUS exaggerated oxidative stress and lipid peroxidation by inhibiting activities of endogenous antioxidant enzymes and activating renal inflammatory response. CUS stress resulted in inhibiting activities of renal Na/K-ATPase and induced Na retention. CUS activated intrinsic apoptotic pathway as evident by decrease renal levels of Bcl-2 and enhanced levels of caspase 3 and mRNA levels of p53 and Bax. Conclusion: Chronic Unpredictable Stress causes renal damage by exaggerating oxidative stress, inhibiting Na/K-ATPase pump activity and activation of inflammation and apoptosis.