Gene expression profiling in male B6C3F1 mouse livers exposed to kava identifies--changes in drug metabolizing genes and potential mechanisms linked to kava toxicity.
The association of kava products with liver-related health risks has prompted regulatory action in many countries. We used a genome-wide gene expression approach to generate global gene expression profiles from the livers of male B6C3F1 mice administered kava extract by gavage for 14 weeks, and identified the differentially expressed drug metabolizing genes in response to kava treatments. Analyses of gene functions and pathways reveal that the levels of significant numbers of genes involving drug metabolism were changed and that the pathways involving xenobiotics metabolism, Nrf2-mediated oxidative stress response, mitochondrial functions and others, were altered. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, potentially leading to herb-drug interactions and hepatotoxicity.
Guo
Lei
L
Division of Systems Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA. lei.guo@fda.hhs.gov
Shi
Qiang
Q
Dial
Stacey
S
Xia
Qingsu
Q
Mei
Nan
N
Li
Quan-zhen
QZ
Chan
Po-Chuen
PC
Fu
Peter
P
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008658:Inactivation, Metabolic / Q000235:genetics*; D020901:Kava / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000378:metabolism / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism
D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System