Candesartan and epigallocatechin-3-gallate ameliorate gentamicin-induced renal damage in rats through p38-MAPK and NF-κB pathways.

This study pointed to estimate the possible protective impacts of candesartan and/or epigallocatechin-3-gallate (EGCG) against gentamicin-induced nephrotoxicity. The current work revealed that gentamicin significantly elevated relative kidney weight and the serum level of creatinine and urea. Also, renal level of malondialdehyde was significantly increased with a concurrent decrease in renal glutathione-S-transferase and superoxide dismutase activities. Moreover, renal levels of nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38-MAPK) were increased together with the elevation of tumor necrosis factor-alpha and interleukin-1 beta levels after gentamicin treatment. In addition, caspase-3 expression was elevated, and histological examination revealed extreme alterations enlightening inflammation, degeneration, and necrosis. Pretreatments with candesartan and/or EGCG attenuated gentamicin-induced nephrotoxicity. Importantly, the altered expression of p38-MAPK and NF-κB may play a significant role in the protective mechanisms exerted by candesartan and EGCG. Coadministration of candesartan and EGCG exhibited more profound response compared with the monotherapy.