Biosynthesis of pyrimidine nucleotides and level of cytochrome P-450 in rat liver and kidney after clofibrate administration (an in vivo study).

Abstract

Like other lipid-soluble xenobiotics, clofibrate (ethyl-2-(4-chlorophenoxy)-2-methylpropanoate) increased the level of microsomal cytochrome P-450 in liver and decreased the utilization of 14C-orotic acid for the synthesis of hepatic cytidine nucleotides. This phenomenon was associated with the increased (a) uptake of 14C-cytidine, (b) total content of cytidine components of the acid-soluble extract and (c) utilization of this nucleoside for the synthesis of RNA. No changes were observed in uridine components. Clofibrate also increased the level of cytochrome P-450 in kidney microsomes; the degree of induction was almost the same as in the liver. The variations of renal pyrimidine metabolism after administration of the drug were analogous to those observed in the liver.