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  • Title: Kava does not display metabolic toxicity in a homogeneous cellular assay.
    Author: Zou L, Harkey MR, Henderson GL, Dike LE.
    Journal: Planta Med; 2004 Apr; 70(4):289-92. PubMed ID: 15095141.
    Abstract:
    To determine whether kava (Kava kava, 'Awa, Yaqona, Piper methysticum Forst.), the popular herbal product associated recently with possible human hepatotoxicity, is bioactivated by cytochrome P450 enzymes to cytotoxic metabolites, three kava lactones (methysticin, yangonin, and desmethoxyyangonin) and an ethanolic extract of dried kava root were incubated over time in culture with MCL-5 cells, a human lymphoblastoid cell line that has been stably transfected with five human P450's (CYP 1A1, 1A2, 2A6, 2E1, and 3A4) and human epoxide hydrolase. Incubations were performed concurrently with a control cell line (cH2) that is derived from the same parental line as MCL-5, but transfected with two empty vectors. The kava compounds displayed varying degrees of toxicity (IC (50) values ranged from 50 to > 100 microM) to the MCL-5 and cH2 cell lines; however, both cell lines were equally sensitive to the test compounds. These results suggest that the parent compound for each of the four test compounds was primarily responsible for the observed cell toxicity and that CYP 1A1, 1A2, 2A6, 2E1, and 3A4 or epoxide hydroxylase did not appear to be involved. Thus, in vitro kava does not appear to be activated to toxic metabolites by enzymes known to be important in metabolic toxicity.
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