Garlic allyl sulfides display differential modulation of rat cytochrome P450 2B1 and the placental form glutathione S-transferase in various organs

Abstract

To investigate whether the regulation of garlic allyl sulfides on biotransformation enzyme expression is tissue-specific, the expression of cytochrome P450 2B1 (CYP 2B1) and the placental form of glutathione S-transferase (PGST) in liver, lung, and intestine, which are the three major organs responsible for drug metabolism, was examined. Rats were orally administrated 0.5 or 2 mmol/kg BW diallyl sulfide (DAS) or 0.5 mmol/kg BW diallyl disulfide (DADS) or diallyl trisulfide (DATS) three times per week for 6 weeks. The final body weights and the body weight ratio of liver and lung were not changed by any of these three allyl sulfide treatments as compared to the control rats. An 11- and 12-fold increase of 7-pentoxyresorufin O-dealkylase (PROD) activities was noted in rats treated with 0.5 or 2 mmol/mg BW DAS, respectively, as compared with the controls (P < 0.05). In contrast, DADS and DATS significantly increased hepatic PGST activity toward ethacrynic acid by 30 and 40%, respectively, as compared with the control rats (P < 0.05). An increase in PGST activity was only noted at 2 mmol/kg BW DAS group (P < 0.05). In addition, similar increases in PGST activity due to DADS and DATS were also noted in lung and jejunum tissue (P < 0.05). Immunoblot assay shows that the changes in CYP 2B1 and PGST proteins due to the three garlic allyl sulfide treatments on liver, lung, and jejunum were consistent with those observed for PROD and PGST activities. Northern blot further revealed that the DADS and DATS increased PGST mRNA levels in both liver (2.9- and 3.0-fold, respectively) and lung (4.1- and 2.6-fold, respectively) and DAS dose-dependently increased CYP 2B1 mRNA levels in the liver. Garlic allyl sulfides differentially induced CYP 2B1 and PGST expression, and this up-regulation of these two biotransformation enzymes is tissue-specific.