Green Tea Extract Exposure Pattern Differenzially Affects Acetaminophen-Induced Hepatotoxicity

Abstract

Green tea extract (GTE) is a widely used dietary supplement and has been promoted for a wide range of uses such as anticancer, antioxidant, and weight loss. There are conflicting reports about the safety of GTE. Some studies have shown that GTE (or one or more of its major constituents) is safe and can even provide protection against various toxic insults or diseases; whereas, other studies have shown that GTE itself can cause hepatotoxicity and toxicity in other tissues. This study was conducted to determine if GTE alters the toxicity of the widely-used over-the-counter analgesic acetaminophen (APAP). APAP was chosen since it is the leading cause of acute liver failure in the US and the high incidence may be partly due to exacerbation of APAP hepatotoxicity by concomitant dietary factors such as GTE consumption. Two different exposure scenarios were tested. The first exposure scenario involved administering an oral dose of APAP (150 or 300mg/kg) followed 6h later by an oral dose of GTE (500–2000mg/kg). The second exposure scenario involved administering 3 once-daily oral doses of GTE (1500mg/kg/day) followed by an oral dose of APAP (300mg/kg) on the 4th day. Mice were fasted overnight before the APAP dose, and hepatotoxicity was assessed 24h after the APAP dose. Based on serum ALT and AST levels and survival, GTE potentiated APAP-induced hepatotoxicity when administered 6h after the APAP dose. In contrast, GTE decreased APAP-induced hepatotoxicity when administered for 3 days prior to the APAP dose. Further mechanistic studies are underway to determine the molecular mechanisms of potentiation and protection that were observed for the different exposure scenarios. These results might help explain the wide range of effects noted with green tea, GTE, and major green tea constituents in the peer-reviewed literature. These results also highlight the potential for drug-dietary supplement interactions even with widely used over-the-counter drugs.