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Abstract
1. The effects of garlic oil (GO) on the expression of P4502E1, glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) were assessed by metabolic activities, immunoblot and RNA blot analyses in the rat.
2. p-Nitrophenol (PNP) hydroxylase activity decreased in the hepatic microsomes isolated from rats treated with GO at 200mg/kg b.w. by 10–30% as compared with control. Pyrazine-inducible P4502E1 expression was decreased by approximately 40% following concomitant treatment of animals with GO at the dose of 200mg/kg from day 1 to 3 post-treatment, as evidenced by PNP hydroxylase activity. The rates of aniline hydroxylase and NDMA demethylase activities in GO-treated animals were consistent with those of PNP hydroxylase activity. Treatment of animals with 500mg/kg GO resulted in suppression of P4502E1-mediated catalytic activities, as monitored by both PNP and aniline hydroxylase activities, whereas the effects at the dose of 1000mg/kg were identical with those at 500mg/kg b.w.
3. Immunoblot analyses of hepatic microsomes, using an anti-P4502E1 antibody, showed that GO minimally suppressed constitutive P4502E1 expression at 24, 48 and 72 h post-treatment at the daily doses from 200 to 1000mg/kg b.w., as compared with vehicle-treated animals. Time-dependent pyrazine induction of P4502E1, however, was substantially blocked by concomitant treatment of animals with 200mg/kg GO to the levels of control. Treatment at the dose of 1000mg/kg failed to further suppress P4502E1 levels. GO treatment caused no changes in the levels of P4502E1 mRNA, as assessed by slot blot analyses.
4. Cytosol produced from the GO-treated rat showed ∼ 40% increases in GST conjugating activity toward 1-chloro-2,4-dinitrobenzene, whereas mEH protein levels were 1·5–2·0-fold greater than control with similar increases in the mRNA levels noted.
5. These results demonstrate that GO suppresses inducible P4502E1 expression more significantly than constitutive expression, and that GO induces GST and mEH expression to a certain extent.