Modulation of phase I and phase II xenobiotic‐metabolizing enzymes by selenium‐enriched garlic in rats

Abstract

Previous research showed that treatment with selenium‐enriched garlic (Se‐garlic) was able to inhibit the initiation phase of mammary carcinogenesis in the dimethyl‐benz[a]anthracene (DMBA) model in rats. The present study was designed to investigate the following parameters: 1) DMBA‐DNA adduct formation in liver and mammary gland, 2) urinary excretion of DMBA metabolites, 3) phase I and phase II xenobiotic‐metabolizing enzymes, and 4) tissue selenium levels as a function of Se‐garlic supplementation. Prior feeding with an Se‐garlic‐containing diet (at 3 ppm Se) for two weeks resulted in a consistent reduction of all DMBA adducts in liver and mammary gland. This was accompanied by a 40% increase in urinary excretion of DMBA metabolites over a two‐day period. Several liver P‐450 enzymes were examined in rats fed a diet supplemented with 1, 2, or 3 ppm Se. Compared with controls receiving 0.1 ppm Se, no significant alteration in activity was detected with respect to P‐450 1A1 (responsible for DMBA activation), 1A2, 2B1, 2E1, and 3A4: In contrast, glutathione S‐transferase and uridine 5'‐diphosphate‐glucuronyltransferase activities were elevated to a maximum of 2‐ to 2.5‐fold in liver and kidney. As expected, there was a dose‐dependent elevation of selenium concentrations in liver, kidney, mammary gland, and plasma as a function of the level of Se‐garlic supplementation. Our data seem to suggest that an increased detoxification of carcinogen via the phase II conjugating enzymes might represent a mechanism of tumor suppression by Se‐garlic.