The investigation of the effects of epigallocatechin gallate (EGCG) in cisplatin-induced nephrotoxicity in rats

Cisplatin (CDDP)-induced nephrotoxicity is related to an increase in oxidative stress in the kidney and limits clinical use of CDDP. Epigallocatechin gallate (EGCG), a very potent antioxidant derived from green tea. In the present study, we investigated the effect of EGCG against CDDP-induced lipid peroxidation and nephrotoxicity in rats.Male wistar rats (n=28, 8 wk-old, between 200-215 g) were divided into four groups: (i) control rats, (ii) EGCG (100 mgkg-1, daily)-control rats, (iii) CDDP-injected rats, CDDP group (7 mgkg?1 i.p, single dose) (iv) EGCG-treated (100 mgkg?1, daily) CDDP-injected rats (EGCG+CDDP group). CDDP administration resulted in significant increase in serum urea nitrogen and creatinine (p<0.001). Serum creatinine and urea nitrogen levels were lower in rats treated with EGCG+CDDP compared with rats treated with CDDP alone (p<0.001). The serum from the CDDP-treated rats showed a significant increase in malondialdehyde (MDA) levels in comparison to the values (p<0.05). EGCG prevented the rise of MDA (p<0.05). Renal Bax protein expression was significantly higher in CDDP-treated rats compared with control rats, and EGCG treatment significantly reduced the levels of Bax (p<0.05). Bcl?2 protein expression was higher in EGCG+CDDP administered rats than CDDP-injected rats (p<0.05). The expression of renal Hsp60 and Hsp70 was significantly lower in EGCG+CDDP group compared with rats treated with CDDP alone (p<0.001). CDDP-induced renal histopathological changes were significantly improved with EGCG.These results show that CDDP produces oxidative stress and renal damage. In conclusion, our study show that EGCG, which reduces oxidative stress and changes the expression of Bax and Bcl-2 protein, has signi ? cant potential as a therapeutic intervention for CDDP-induced renal injury.Key words: cisplatin, nephrotoxicity, EGCG, MDA, Bax/bcl-2, Hsp60-70