The modulatory effects of garlic oil on hepatic cytochrome P450s in mice.
In order to probe into the effects of garlic oil (GO) on the hepatic CYP2E1, CYP1A2 and CYP3A, male Kun-Ming mice were treated with GO (100 mg/kg body weight) or corn oil for 1 day or consecutive 60 days, respectively, and then the protein expressions and the activities of the enzymes were examined. GO did not alter the physical activities of mice and did not induce lesion to the liver. However, it dramatically inhibited the activities and protein levels of hepatic CYP2E1 and 1A2, but not CYP3A. In addition, we noticed that the inhibition of CYP2E1 and 1A2 by GO was more potent in group of 1 day treatment than those in group of 60 days treatment. Compared with the respective control value, the protein levels of CYP2E1 were decreased by 87.40% (p < .01) and 62.26% (p < .01) by 1 day and 60 days of GO treatment, respectively, while the CYP1A2 protein levels were decreased by 70.76% (p < .01) and 41.49% (p < .01), respectively. These data indicated that the mice could adapt to the prolonged treatment, which might be one reasonable explanation for the conflicting data in the literature. The CYP2E1 and 1A2 suppression might contribute to its hepatoprotection, and data about CYP3A indicated that GO was unlikely to alter the metabolism of the concomitantly used drugs.
Zeng
Tao
T
Institute of Toxicology, Shandong University, Shandong, Jinan 250012, P.R. China.
Zhang
Cui-Li
CL
Song
Fu-Yong
FY
Han
Xiao-Ying
XY
Xie
Ke-Qin
KQ
D000410:Alanine Transaminase / Q000097:blood; D000498:Allyl Compounds / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D014176:Protein Biosynthesis / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology* / Q000633:toxicity
D000498:Allyl Compounds; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D013440:Sulfides; C038491:allyl sulfide; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase