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.

This study examined the arachidonic acid metabolism and immune response in rats administered orally (p.o.) with either garlic oil (GO), diallyl disulfide (DADS) (200 mg/kg of body weight), or corn oil (control) three times a week for 7 weeks. Both GO and DADS were found to modify the hepatic membrane fatty acid composition:  the linoleic acid was increased, and the arachidonic acid was decreased (P < 0.05). GO but not DADS suppressed the Δ6 desaturase activity (P < 0.05). Neither treatment affected the phospholipase A2 activity or plasma prostaglandin E2 level. GO increased the spleen/body weight ratio (P < 0.05) and enhanced concanavalin A-stimulated splenocyte proliferation. However, the systemic contact hypersensitivity response as detected by the extent of ear swelling was suppressed by 74% in the GO-treated rats (P < 0.05). The findings indicate that GO inhibits Δ6 desaturase activity and changes membrane arachidonic acid content, both of which show immunomodulatory potential. Keywords: Garlic oil; diallyl disulfide; arachidonic acid metabolism; Δ6 desaturase; immune response