Regulation of xanthine dehydrogenase in rat liver in response to peroxisome proliferators

Previously we found a depression in the activity of hepatic xanthine dehydrogenase in rats fed clofibrate or di(2-ethylhexyl)phthalate. The present study further demonstrated that dietary addition of other peroxisome proliferators, including bezafibrate, dehydroepiandrosterone and perfluoro-n-octanoic acid also depressed activity of hepatic xanthine dehydrogenase in rats. Western and Northern blot analyses indicated the depression in hepatic xanthine dehydrogenase protein and mRNA by feeding bezafibrate. These results suggest that administration of a wide variety of peroxisome proliferators depresses the activity of hepatic xanthine dehydrogenase in rats and that the depression in activity of this enzyme by the proliferator might be mediated by decreased mRNA of the enzyme. Further, nuclear run-on analysis revealed no influence of feeding bezafibrate on the transcriptional activity of hepatic xanthine dehydrogenase gene, suggesting increased degradation of the enzyme mRNA by the chemical.