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

Abstract

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 anti-oxidant 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-pent-oxyresorufin O-dealkylase activities, whereas DADS in-creased 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 sup-pressed 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.