The influence of some foreign compounds on hepatic xenobiotic metabolism and the urinary excretion of D-glucuronic acid metabolites in the rat

Abstract

A gas-liquid chromatographic method has been developed for the determination of some d-glucuronic acid metabolites in rat urine. A sequential study was conducted on the effect of sodium phenobarbital (PB) treatment and subsequent reversal of a number of parameters of hepatic xenobiotic metabolism and the urinary excretion of some metabolites of the d-glucuronic acid pathway. A good correlation was obtained between the levels of activity of hepatic microsomal xenobiotic metabolizing enzymes and the urinary excretion of l-gulonic, d-glucaric, and d-glucuronic acids. Studies were also conducted with 20-methylcholanthrene (MC), dichlorodiphenyltrichloroethane (DDT), pregnenolone-16α-carbonitrile (PCN), and butylated hydroxytoluene (BHT). All of these agents enhanced hepatic microsomal xenobiotic-metabolizing enzymes and the urinary excretion of some metabolites of the d-glucuronic acid pathway. For example, the urinary excretion of d-glucaric and l-gulonic acids was enhanced by PB and MC treatments, but the former remained unaffected by the administration of either DDT, PCN, or BHT. Furthermore, none of the other urinary indices measured, namely, d-glucuronic acid, l-gulonic acid, l-ascorbic acid, and xylitol, was consistently enhanced by all five agents studied. However, when the urinary concentrations of the d-glucuronic acid metabolites were summated, significant increases in the total urinary excretion of the metabolites were observed with all compounds. The results suggest that in order to obtain a valid urinary index of the induction of hepatic xenobiotic-metabolizing enzymes in the rat it is necessary to measure a spectrum of metabolites of the d-glucuronic acid pathway.