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 o f 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 group s were 60%, 30% and 30% as compared with group A at 2 weeks, respectiv ely. 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 f eeding. NADPH-cytochrome P450 reductase activity was also unaffected. The increases of the activities of aniline hydroxylase and 7-ethoxycou marin O-deethylase were observed in group D fed for 9 weeks. At 9 week s iron-deficient diet feeding increase of testosterone 6 beta-hydroxyl ase activity was observed in groups B, C, and D. When Western immunobl ot 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.