Nephroprotective effects of Candesartan Cilexetil against Cyclosporine A-induced nephrotoxicity in a rat model.

Abstract

Cyclosporine A (CsA), a well-known immunosuppressive drug, has been prescribed after organ transplantation and in a variety of disorders with an immunological origin. Nephrotoxicity is one of the most frequently stated problems associated with CsA, and therefore the treatment with CsA remains a big challenge. This study sets out to assess the ameliorative influences of Candesartan Cilexetil (CC) on oxidative stress and the nephrotoxic effect of CsA in a rat model. Twenty-four Wister Albino rats, 7-8-week-old, weighing 150-250g, were randomly categorized into three groups (eight animals in each group). These groups were the (1) CsA-treated group, (2) vehicle-treated group, and (3) CC-treated group. Bodyweights were assessed at the start and end of experiments. Renal function test and levels of glutathione peroxidase 1 catalase -CAT (Gpx1), catalase (CAT), superoxide dismutase (SOD), interleukin -2 (IL-2), and malondialdehyde (MDA) were investigated in renal tissues. Histological changes in kidneys were also evaluated. Data showed that levels of urea and creatinine in serum and levels of IL-2 and MDA in renal tissues were elevated in the CsA-treated group, with severe histological changes compared with the control group. Furthermore, tissue levels of Gpx1, CAT, and SOD were significantly decreased in CsA-treated in comparison with the control group. Treatment with CC for the rats subjected to CSA resulted in a marked reduction in levels of serum urea and creatinine and tissue levels of IL-2 and MDA. Levels of Gpx1, CAT, and SOD in renal tissues were greater in the CC-treatment group compared with the CsA-treated group. CC treatment reduced the deterioration of renal morphology compared with CsA treatment. The findings of this study suggest that CC could prevent CSA-induced nephrotoxicity through its anti-inflammatory and antioxidant influences. Considerably more work needs to be done to determine the mechanistic insight behind the ameliorative effect of CC.