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Mechanisms of Kava‐Associated Hepatic Toxicity
Author(s) -
Lim Steven Tai Shun,
Nerurkar Pratibha Vivek
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a940
Subject(s) - kava , oxidative stress , pharmacology , cyp2e1 , cyp1a2 , toxicity , cytochrome p450 , chemistry , biochemistry , biology , metabolism , organic chemistry
Kava‐kava (Piper methysticum) has been used for centuries in the South Pacific Islands as a religious, recreational and ceremonial beverage. Kava gained popularity as an anti‐anxiety herb in the 1990's, but was banned from most major markets by 2003 due to alleged hepatotoxicity. Although traditionally kava was prepared from rootstock, in recent years stem peelings may have been included in industrial preparations, due to the high demand by pharmaceutical companies. Studies indicate that the kava alkaloid pipermethystine (PM) is present in higher quantities in stem peelings as compared to rootstock. Mechanistic studies from our laboratory indicated that PM‐associated cytotoxicity in human hepatoma cell line, HepG2, correlated with a significant decrease in cellular ATP, mitochondrial membrane potential and increase in reactive oxygen species (ROS) production. Short‐term administration of PM (10mg/kg) and/or acetonic kava extracts (100mg/kg) to F‐344 Fisher rats, significantly increased the hepatic antioxidant status and hepatic microsomal cytochrome P‐450 (CYP) enzymes such as CYP1A2, CYP2E1 and CYP2D6, indicating a potential for kava‐drug interactions. CYP2E1 is known to be involved in alcohol metabolism. We are therefore currently investigating the potential role of kava‐ethanol interaction to induce hepatic toxicities. Taken together our data indicates that increases in oxidative stress and changes in drug metabolizing enzymes may in part contribute towards reported hepatic toxicity associated with kava. [Supported by USDA CSREES (2003‐34135‐14033) grant]