Influence of dietary selenium and cytochrome P450 modifiers on liver selenium content and cytochrome P450 activity in rats

摘要

The current studies examined the influence of dietary selenium on cytochrome P450 in male Sprague-Dawley rats. Selenium concentration was determined using a gas chromatograph with electron capture (method of McCarthy et al. [1981]), glutathione peroxidase activity by the coupled assay of Paglia and Valentine and the concentration of cytochrome P-450 in microsomal fraction by the method of Omura and Sato [1964]. Increasing dietary Se from 0.01 to 2.0 ppm markedly increased hepatic Se content and elevated GPx activity. It was found that hepatic selenium concentrations were inversely correlated with body weight of rats. Higher concentration of Se was found in the cytosolic than the microsomal fraction of the liver. Se supplementation also increased liver cytochrome P450 activity. Pentobarbital treatment did not alter the concentration of Se in liver or its distribution between the cytosolic and microsomal fractions, but did markedly elevate P450 activity. Comparing with control animals rats given 3-methylcholanthrene had the highest amount of cytochrome P450c and slightly increased concentration of cytochrome P450b. The rats treated with 3-amino-1,2,4-triazol possesed lower amount of hepatic cytochrome P-450b. Cytochrome P450 fraction differences between Se-adequate and Se-supplemented rats disappeared after treatment with pentobarbital, 3-MC, Aroclor 1254 or 3-amino-1,2,4-triazol. Induction of hepatic P-450b cytochrome by Se may explain, in part, its anticarcinogenic properties. Exposure to several cytochrome P450 modifiers can mask the promotion effects of selenium on cytochrome P450.