Effects of dietary zinc deficiency on the expression of hepatic microsomal cytochrome P450 2E1 in rats

Abstract

The objective of this study was to investigate if the altered 2E1 drug metabolism capacity in rats is due to effects of dietary zinc deficiency on the expression of hepatic microsomal P450 2E1 in rats. Rats were 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 also included. At the end of the feeding trial, each dietary group was further divided into the drug control and ethanol treatment group. Ethanol (EtOH, 8 mL/kg body weight, intubation) was given once a day for 3 consecutive days. Within the drug control group, zinc deficiency reduced total P450 concentration but had no effect on the level of NADPH-P450 reductase, 2E1 protein, and 2E1 mRNA. 2E1 activity, which was indicated by N-nitrosodimethylamine demethylase (NDMA), aniline hydroxylase (AH), and p-nitrophenol hydroxylase (NH) activity, was also not affected by dietary zinc deficiency. The NDMA demethylase activity and 2E1 mRNA level were higher in zinc pair-fed rats than in zinc-adequate rats. EtOH treatment induced total P450 concentration in zinc-adequate and zinc-deficient rats and NADPH-P450 reductase level in zinc-adequate rats. 2E1 activity was induced by EtOH, while the level of 2E1 protein and 2E1 mRNA was unchanged. In conclusion, the constitutive expression 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 EtOH treatment markedly induced 2E1 activity without affecting the level of 2E1 protein and mRNA. ( J. Nutr. Biochem. 5:308–313, 1994.)