Effect of various diets on the expression of phase-I drug-metabolizing enzymes in livers of mice.
1. Previous studies have shown that diets can alter the metabolism of drugs; however, it is difficult to compare the effects of multiple diets on drug metabolism among different experimental settings. Phase-I-related genes play a major role in the biotransformation of pro-drugs and drugs. 2. In the current study, effects of nine diets on the mRNA expression of phase-I drug metabolizing enzymes in livers of mice were simultaneously investigated. Compared to the AIN-93M purified diet (control), 73 of the 132 critical phase-I drug-metabolizing genes were differentially regulated by at least one diet. Diet restriction produced the largest number of changed genes (51), followed by the atherogenic diet (27), high-fat diet (25), standard rodent chow (21), western diet (20), high-fructose diet (5), EFA deficient diet (3) and low n-3 FA diet (1). The mRNAs of the Fmo family changed most, followed by Cyp2b and 4a subfamilies, as well as Por (from 1121- to 21-fold increase of theses mRNAs). There were 59 genes not altered by any of these diets. 3. The present results may improve the interpretation of studies with mice and aid in determining effective and safe doses for individuals with different nutritional diets.
Department of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University , Changsha, Hunan , People's Republic of China .
Ying
Y
Guo
Julia Yue
JY
Cui
Hong
H
Lu
Curtis D
CD
Klaassen
D000818:Animals; D016000:Cluster Analysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004032:Diet; D005247:Feeding Behavior; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000201:enzymology*; D008297:Male; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014157:Transcription Factors; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System
Disposition; mRNA level; microarray