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

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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.

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