EFFECTS OF DIETARY ZINC-DEFICIENCY ON THE EXPRESSION OF HEPATIC-MICROSOMAL CYTOCHROME-P450 2E1 IN RATS

The objective of this study was to investigate if the altered 2E1 drug metabolism capacity in rats is due to effects of dietary zinc deficie ncy on the expression of hepatic microsomal P450 2E1 in rats. Rats wer e given free access to either a zinc-adequate diet or a zinc-deficient diet for 3 weeks. A second control group, the pair-fed control, was a lso included At the end of the feeding trial, each dietary group was f urther divided into the drug control and ethanol treatment group. Etha nol (EtOH, 8 mL/kg body weight, intubation) ac as given once a day for 3 consecutive days. Within the drug control group, zinc deficiency re duced total P450 concentration but had no effect on the level of NADPH -P450 reductase, 2E1 protein, and 2E1 mRNA. 2E1 activity, which was in dicated by N-nitrosodimethylamine demethylase (NDMA), aniline hydroxyl ase (AH), and p-nitrophenol hydroxylase (NH) activity, was also not af fected by dietary zinc deficiency. The NDMA demethylase activity and 2 E1 mRNA level were higher in zinc pair-fed rats than in zinc-adequate rats. EtOH treatment induced total P350 concentration in zinc-adequate and zinc-deficient rats and NADPH-P450 reductase level in zinc-adequa te rats. 2E1 activity was induced by EtOH, while the level of 2E1 prot ein and 2E1 mRNA was unchanged. In conclusion, the constitutive expres sion of hepatic microsomal 2E1 was not affected by zinc deficiency per se; however; the prolonged severe depression of feed intake caused by zinc deficiency increased the level of 2E1 mRNA in rats. An acute EtO H treatment markedly induced 2E1 activity without affecting the level of 2E1 protein and mRNA.