Renal Oxidative Stress and Inflammatory Response in Perinatal Cyclosporine-A Exposed Rat Progeny and its Relation to Gender

Abstract

Background and Aim of the Work: The current study postulated that cyclosporine A (CSA) could induce gender-specific renal damage. Hence, the current study aims to investigate the nephrotoxic effect of perinatal exposure of male and female rat progeny to CSA. Moreover, it aims to evaluate the oxidative stress and inflammation as a possible pathophysiologic mechanism. Materials and Methods: Female rats were randomly allocated to two groups of four and assigned to undergo either CSA (15 mg/kg/day; the 6th day after conception and continuing until the progeny were weaned) or vehicle treatment as control groups. At the age of 6 weeks, the progeny were divided into the following four groups: male progeny of control-group mothers (M-vehicle, 7); male progeny of CSA-treated mothers (M-CSA, 9); female progeny of control-group mothers (F-vehicle, 7); and female progeny of CSA-treated mothers (F-CSA, 6). Serum adiponectin, tumor necrosis factor-α (TNF-α) and creatinine, creatinine clearance, and urinary 8-isoprostane were measured. Histopathological examination by hematoxylin and eosin stain of Kidney was carried out. Results: Proteinuria and decreased creatinine clearance are significant in M-CSA than M-vehicle and F-CSA. 8-isoprostane is lower in F-CSA than F-vehicle. Increased TNF-α and decreased adiponectin levels in M-CSA than M-vehicle were observed. No significant differences were found in female rat groups. Conclusion: From the current study, it could be concluded that CSA could induce renal inflammation as well as oxidative stress that may explain the impaired renal function. The sex difference was a prominent finding in their vulnerability to CSA effects.