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.

https://wiadlek.pl/wp-content/uploads/archive/2021/WLek2021121.pdf The aim: The current study was designed to examine the possible Nephroprotective effects of CMN in preventing nephrotoxicity and oxidative stress caused by chronic administration of CsA in rats. Materials and methods: This study consisted of four groups and each group was made up of 8 rats. The first group was considered as a control group (received vehicle (0.9%N/S orally, and olive oil S.C), and the rest included the following: CMN group (received CMN in a dose of 30mg/kg/day orally), CsA group (received CsA in a dose of 20mg/kg/day S.C), and CMN plus CsA combination group (received CMN (30mg/kg/day, orally) plus CsA (20mg/kg/day, S.C) for 21days). For each group, the following variables wereassessed: Serum urea concentration, Serum creatinine concentration, initial body weight, final body weight, Tissue MDA level, Tissue GpX1 level, Tissue CAT level, Tissue SOD level, and tissue IL-2 level, and histopathological examination. Results: Mean levels of serum urea and creatinine, tissue MDA, tissue IL-2, and histopathological scores are significantly (P<0.05) increased in the CsA group compared with the control, and CMN groups (normal renal tissue). Tissue SOD, CAT, and GpX1 activities are significantly (P<0.05) decreased in the CsA group compared with the control, and CMN group. Concomitant administration of CMN with CsA resulted in significantly (P<0.05) lower elevated levels of MDA, serum urea, and creatinine, significantly higher levels of antioxidant enzymes, and normalization of the altered renal morphology compared with CsA treated rats. Conclusions: CMN has antioxidant and anti-inflammatory properties that protect the kidney from CsA’s toxicity.