Effect of Dietary (‐)‐epigallocatechin‐3‐gallate (EGCG) Pretreatment on the Hepatotoxicity of Acute High Dose EGCG (270.3)

Green tea based dietary supplements containing high levels of (‐)‐epigallocatechin‐3‐gallate (EGCG) have become popular for weight loss. Case‐studies have reported hepatotoxicity associated with consumption of green tea‐based supplements and laboratory studies have demonstrated the potential hepatotoxicity of EGCG. We examined the effect of pretreatment with dietary EGCG on the bioavailability and hepatotoxicity of high oral bolus EGCG in CF‐1 mice. EGCG (750 mg/kg, i.g., once daily) for 3 d increased plasma alanine aminotransferase by 80‐fold compared to controls. High dose EGCG also decreased hepatic levels of reduced (59% decrease) and total glutathione (33% decrease), and increased hepatic phosphorylation of histone 2AX compared to vehicle‐treated control mice. Pretreatment with dietary EGCG (3.2 mg/g) for 2 wk blunted these changes. EGCG pretreatment also raised the levels of several oxidative stress‐related genes. Analysis of plasma and liver levels of EGCG showed that pretreatment with dietary EGCG reduced the peak plasma (38% reduction) and hepatic (57% reduction) EGCG concentrations following oral bolus dosing. In conclusion, EGCG appears to modulate its own bioavailability and chronic exposure to dietary EGCG may reduce the hepatotoxic potential of high oral bolus EGCG. These data may help explain the variation in sensitivity of human subjects to green tea‐containing supplements.Grant Funding Source: NIH AT004678