Kidney Protection Effect of Ginsenoside Re and Its Underlying Mechanisms on Cisplatin-Induced Kidney Injury

摘要

Background/Aims Cisplatin (CDDP) was the first platinum-containing anti-cancer drug. However, CDDP causes nephrotoxicity as a side effect, which limits its clinic application. The aim of this study was to investigate the renoprotective effect of ginsenoside Re (G-Re) in a murine model of CDDP-induced acute kidney injury. Methods Male ICR mice were divided into 4 groups. G-Re was administered to the mice by oral gavage once a day at a dose of 25 mg/kg for 10 days. On the 7th day, a single injection of CDDP (25 mg/kg) was given at 1 h after G-Re treatment. Results CDDP administration resulted in renal dysfunction, as evidenced by an increase in the serum levels of creatinine and urea nitrogen. Oxidative stress in the CDDP group was reflected by an increase of malondialdehyde and a depletion of reduced glutathione and catalase in renal tissue. These findings were supported by increased 4-hydroxynonenal expression, which was significantly reduced by G-Re. Simultaneously, the overexpression of cytochrome P450 E1 was inhibited. G-Re inhibited the inflammatory response by the reduction of the protein expression of cyclooxygenase-2 and inducible nitric oxide synthase. Furthermore, CDDP increased the expression of Bax and decreased Bcl-2 expression in renal tissue. Hematoxylin and eosin, Hoechst 33258, and TUNEL staining also confirmed the presence of acute tubular necrosis and apoptosis. G-Re significantly decreased the levels of indicators of renal dysfunction, inflammatory cytokines, apoptosis, and malondialdehyde in the kidney and also significantly attenuated the histopathological changes associated with acute renal failure. Conclusions Collectively, the results of this study suggest that the nephroprotective potential of G-Re may, in part, be related to its anti-oxidant, anti-inflammatory, and anti-apoptotic effects.