Protective effect of green tea extract and tea polyphenols against FK506-induced eytotoxicity in renal cells.

Introduction: The nephrotoxicity induced by the immunosuppressive drug FK506, limits its usefulness in widespread application, and the underlying mechanism has not been completely understood. The primary targets of FK506 in the kidney are the proximal tubular epithelial cells. In this study, the protection of green tea extract against FK506-induced cell death of LLC-PK1 cells was investigated. Results: FKS06 caused a significant decrease in survival of the cells, but the addition of green tea extract reduced this effect in a dose-dependent manner. Treatment of the cells with 50 µM FK506 induced a significant increase in annexin V-positive/ PI-negative cells from 2.68 to 14.5%, whereas the addition of 6.25, 12.5, 25 µg/ml of green tea extract caused a significant protective effect in apoptotic cells from 14.5 to 6.51, 3.20 and 3.02%, respectively. The effect of five different constituent tea polyphenols was also examined. Epigallocatechin gallate (EGCG) and epigallocatechin (EGC) significantly reduced FK506-induced cytotoxicity but epicatechin (EC) and catechin (C) had no effect on cell viability. Furthermore, changes in cytochrome c release and caspase activation, which characterize apoptosis, were studied. EGCG and EGC suppressed a significant release of cytochrome c and activation of caspase-3 in FK506-treated LLC-PKI cells. Conclusion: FK506 caused a significant increase in apoptotic cells but the addition of GTE, and particularly its major polyphenolic components EGC and EGCG, suppressed the cell death. [ABSTRACT FROM AUTHOR]