TY - JOUR
T1 - Analysis of gene expression changes of drug metabolizing enzymes in the livers of F344 rats following oral treatment with kava extract
AU - Guo, Lei
AU - Li, Quanzhen
AU - Xia, Qingsu
AU - Dial, Stacey
AU - Chan, Po Chuen
AU - Fu, Peter
PY - 2009/2
Y1 - 2009/2
N2 - The association of kava product use with liver-related risks has prompted regulatory action in many countries. We studied the changes in gene expression of drug metabolizing enzymes in the livers of Fischer 344 male rats administered kava extract by gavage for 14 weeks. Analysis of 22,226 genes revealed that there were 14, 41, 110, 386, and 916 genes significantly changed in the 0.125, 0.25, 0.5, 1.0, and 2.0 g/kg treatment groups, respectively. There were 16 drug metabolizing genes altered in all three high-dose treatment groups, among which seven genes belong to cytochrome P450 isozymes. While gene expression of Cyp1a1, 1a2, 2c6, 3a1, and 3a3 increased; Cyp 2c23 and 2c40 decreased, all in a dose-dependent manner. Real-time PCR analyses of several genes verified these results. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, particularly the CYP isozymes, which could cause herb-drug interactions and may potentially lead to hepatotoxicity.
AB - The association of kava product use with liver-related risks has prompted regulatory action in many countries. We studied the changes in gene expression of drug metabolizing enzymes in the livers of Fischer 344 male rats administered kava extract by gavage for 14 weeks. Analysis of 22,226 genes revealed that there were 14, 41, 110, 386, and 916 genes significantly changed in the 0.125, 0.25, 0.5, 1.0, and 2.0 g/kg treatment groups, respectively. There were 16 drug metabolizing genes altered in all three high-dose treatment groups, among which seven genes belong to cytochrome P450 isozymes. While gene expression of Cyp1a1, 1a2, 2c6, 3a1, and 3a3 increased; Cyp 2c23 and 2c40 decreased, all in a dose-dependent manner. Real-time PCR analyses of several genes verified these results. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, particularly the CYP isozymes, which could cause herb-drug interactions and may potentially lead to hepatotoxicity.
KW - Drug metabolizing enzyme
KW - Drug metabolizing gene
KW - Gene expression
KW - Kava extract
KW - Microarray
KW - TaqMan assay
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U2 - 10.1016/j.fct.2008.11.037
DO - 10.1016/j.fct.2008.11.037
M3 - Article
C2 - 19100306
AN - SCOPUS:58149512737
SN - 0278-6915
VL - 47
SP - 433
EP - 442
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
IS - 2
ER -