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.
