Effects on the activities of drug metabolizing enzymes and on the cytochrome P450 3A isozyme in the liver of rats fed on different levels of iron-deficient diet

The effects of different levels of iron deficiency on the activities of drug metabolizing enzymes and on the cytochrome P450 (P450) isozymes were examined in male rats. Weanling rats were fed diet A (control) : 38.8 mg Fe/kg diet, B : 17.5 mg Fe/kg diet, C : 6.6 mg Fe/kg diet, and D : 3.8 mg Fe/kg diet for 2 or 9 weeks. The decreases of hemoglobin (Hb) and hematocrit (Ht) were noted significantly in C and D groups after 2 weeks of feeding. The hepatic iron contents in the B, C, and D groups were 60%, 30% and 30% as compared with group A at 2 weeks, respectively. This low level of iron concentration was maintained for 9 weeks. P450 and cytochrome b5 (b5) contents were not considerably changed in all experimental stages of the iron-deficient diet within 9 weeks of feeding. NADPH-cytochrome P450 reductase activity was also unaffected. The increases of the activities of aniline hydroxylase and 7-ethoxycoumarin O-deethylase were observed in group D fed for 9 weeks. At 9 weeks iron-deficient diet feeding increase of testosterone 6β-hydroxylase activity was observed in groups B, C, and D. When Western immunoblot analysis in groups A and D using CYP 3A2 antibody was performed, an about 2-fold induction of CYP 3A2 protein was observed in group D as compared with group A at 9 weeks.