Spexin alleviates renal injury in streptozotocin induced diabetic nephropathy rat model

Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide and is the strongest single predictor of mortality in diabetic patients. Spexin peptide modulates energy balance, moreover this molecule is closely associated with the inflammatory process. Objective: Within this context, we aimed to clarify the potentially protective impact of spexin peptide on renal damage and inflammatory response genes in a rat model of streptozotocin induced diabetic nephropathy. Methods: The DN model in Sprague-Dawley rats was established by the administration of streptozotocin. Then, rats were treated with saline or spexin peptide (10, 30 and 100 µg/kg different doses). ALT, AST, BUN, and creatinine levels in serum were measured by autoanalyzer. H&E, and Masson's trichrome stainings evaluated histopathological alterations in kidney tissue. mRNA expression levels of IL-1β, IL-18, KIM-1, NGAL, TGFβ1, and TIMP-1 in kidney tissue were measured by qPCR. Results: Spexin administration did not significantly alter routine biochemical parameters, including creatinine, BUN, ALT, AST, or the BUN/creatinine ratio, in diabetic rats. However, High dose spexin treatment significantly reduced tubular and capillary dilatation, as well as collecting duct, tubular, and glomerular defects, compared to the DM group. Also, our results show that TIMP-1, and NGAL upregulated by DM progression compared to vehicle group. Furthermore, IL-18, NGAL, and TIMP-1 were downregulated by dose dependent spexin treatment groups compared to DM group. Conclusion: Our findings revealed that inflammatory response and renal damage genes were regulated by spexin. This peptide may have protective effects on renal failure progression.