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.