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

Abstract

This study was conducted to investigate whether the effects of zinc deficiency on the in vitro and in vivo drug metabolism in rats results from an altered expression of hepatic microsomal P450, particularly P450 2B (2B), in rats. Three-week-old, male Wistar rats were randomly assigned to three groups: a zinc-adequate ad libitum (ZnAL), zinc-adequate pair-fed (ZnPF), and zinc-deficient (ZnDF) group. After 3 weeks on the diet, each dietary group was further divided into drug control and phenobarbital (PB, 100 mg/kg, 3 days, ip) group. Within the drug control group, total microsomal P450 concentration was lower in both ZnPF and ZnDF than in ZnAL. Zinc deficiency resulted in a decreased aminopyrine N-demethylase (AD) activity expressed per milligram protein, with no effect on benzphetamine N-demethylase (BD) activity. The constitutive level of 2B protein and mRNA was not affected by dietary treatments. The level of NADPH–P450 reductase in ZnDF was significantly higher than in ZnAL and ZnPF. PB treatment significantly induced total microsomal P450 concentration, AD and BD activities expressed per milligram protein, 2B protein and mRNA levels, and NADPH–P450 reductase level in all dietary groups. In summary, the constitutive level of AD activity, but not BD activity, was decreased in dietary zinc deficient rats. The constitutive levels of 2B protein and mRNA were not affected by dietary zinc deficiency. PB-induced expression of 2B, both transcriptionally and translationally, and the induction of AD and BD activity by PB were not affected by zinc deficiency in rats. Severe feed restriction had no effect on the levels of both constitutively and inductively expressed AD and BD activities, 2B protein, and 2B mRNA.Key words: dietary zinc deficiency, 2B protein and mRNA, 2B activity, induction of 2B, phenobarbital.