Effects of garlic oil and its organosulfur compounds on the activities of hepatic drug-metabolizing and antioxidant enzymes in rats fed high- and low-fat diets.
We examined the effects of garlic oil (GO) and two of its organosulfur compounds, diallyl sulfide (DAS) and diallyl disulfide (DADS), on the drug-metabolizing and antioxidant systems in rats and sought to determine whether these effects are associated with dietary fat. Rats were fed a high-fat diet and received GO or DADS (200 mg/kg body wt) or DAS (100 mg/kg) orally three times a week for seven weeks. Control animals received corn oil alone. Another group of rats was fed a low-fat diet, with or without GO. GO and DADS significantly reduced the body weight gain of rats (p < 0.05). GO, however, dramatically increased the spleen weight and spleen weight-to-body weight ratio (p < 0.05). DAS increased glutathione S-transferase (GST) and 7-pentoxyresorufin O-dealkylase activities, whereas DADS increased only GST activity (p < 0.05). Immunoblot assay showed GO-, DAS-, and DADS-enhanced expression of the placental form of GST and cytochrome P-450 IIBI but suppressed cytochrome P-450 IIEI expression. Hepatic antioxidant enzyme activities were also modulated by these garlic components. GO and DADS inhibited glutathione peroxidase activity (p < 0.05), and DADS and DAS enhanced glutathione reductase activity (p < 0.05). Only GO enhanced the superoxide dismutase activity (p < 0.05). All these garlic components increased glutathione levels in red blood cells (p < 0.05) but did not influence hepatic glutathione levels. Although the amount of fat in the diet modulated drug-metabolizing and antioxidant functions, no interactions between GO and dietary fat were observed. These results indicate that GO and its allyl sulfide components, as well as dietary lipid, modulate drug-metabolizing and antioxidant enzyme activities. The action of GO appears to be independent of dietary lipid content.
Sheen
L Y
LY
Department of Nutrition, China Medical College, Taichung, Taiwan.
Chen
H W
HW
Kung
Y L
YL
Liu
C T
CT
Lii
C K
CK
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000008:administration & dosage*; D004912:Erythrocytes / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology*; D013457:Sulfur Compounds / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D000498:Allyl Compounds; D000975:Antioxidants; D004041:Dietary Fats; D013440:Sulfides; D013457:Sulfur Compounds; C038491:allyl sulfide; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019362:Cytochrome P-450 CYP2B1; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase; D005980:Glutathione Reductase; D005982:Glutathione Transferase