Tea catechin, epigallocatechin-3-gallate, inhibits rubratoxin B-induced apoptosis of hepatocytes through MAPK p38 pathway

Abstract

Epigallocatechin-3-gallate (EGCG), exhibited protective effect against rubratoxin B (RB)-induced apoptosis in cultured rat hepatocytes. In this study, the mechanism of hepatoprotection by EGCG was investigated. Hepatocytes were concomitantly treated with RB and EGCG and then the expression levels of mitogen-activated protein kinase (MAPK) p38, caspase-3 and caspase-8 genes were measured by reverse transcriptase-polymerase chain reaction (RT-PCR). p38 was induced by RB, indicating that RB-induced apoptosis was mediated by p38 pathway. On the contrary, the elevation of p38 by RB was diminished by EGCG co-treatment. The analysis of caspase-3 mRNA expression showed the same tendency as observed for the p38. To further elucidate, the expression level of mitogen-activated kinase kinase 6 (MKK6) gene, upstream signaling factor of p38, was analyzed by RT-PCR. EGCG also suppressed the expression of MKK6 mRNA. These results suggest that EGCG protects hepatocytes from RB toxicity by the suppression of the gene expression in p38 and caspase pathway at any points examined.