The individual and combined effects of dietary fat and garlic oil on two drug-metabolizing enzymes, cytochrome P450 2B1 and the placental form of glutathione (GSH) S-transferase (PGST), in rat liver were examined in this study. Rats were fed a low corn oil, high corn oil or high fish oil diet and received various amount of garlic oil (0, 30, 80, 200 mg/kg body) orally three times per week for 6 wk. The fat energy in the low and high fat diets accounted for 11.6 and 45.7% of total energy, respectively. Final body weights did not differ among the three dietary fat groups and were not affected by garlic oil treatment. The fatty acid profile in hepatic phospholipids revealed higher eicosapentaenoic acid [20:5(n-3)] and docosahexaenoic acid [22:6(n-3)] levels in the fish oil–fed group than in the low and high corn oil–fed groups (P < 0.05). In contrast, the corn oil–fed groups had greater hepatic phospholipid arachidonic acid [20:4(n-6)] levels (P < 0.05). Both dietary fat and garlic oil significantly affected hepatic cytochrome 7-pentoxyresorufin O-dealkylase (PROD) activity and GST activity toward ethacrynic acid. Rats fed the high fish oil diet had 85 and 51% higher PROD activity compared with those fed the low or the high corn oil diet, respectively (P < 0.05). The GST activity in the high fish oil and the high corn oil groups was 33 and 18% higher than that in the low corn oil group (P < 0.05), respectively, and the GST activity in rats fed the high fish oil diet was higher than in those fed the high corn oil diet (P < 0.05). Garlic oil dose-dependently increased GST activity. No interaction between dietary fat and garlic oil on PROD or GST activity was noted. Northern and Western blot analysis revealed that dietary fish oil increased both cytochrome P450 2B1 and PGST mRNA and protein levels. Cytochrome P450 2B1 and PGST mRNA and protein levels were also dose-dependently increased by garlic oil treatment. The effects of garlic oil and dietary fat on P450 2B1 and PGST mRNA and protein expression were independent. These results indicate that dietary fat and garlic oil independently modulate P450 2B1 and PGST expression at transcriptional and/or post-transcriptional stages.
The American Society for Nutritional Sciences(131),1438-1443