The effect of treatment with some phase II substrates on hepatic xenobiotic metabolism and the urinary excretion of metabolites of the d-glucuronic acid pathway in the rat

Abstract

Investigations have been conducted to study the relationship between the activities of certain enzymes of Phase I and Phase II hepatic xenobiotic metabolism and the urinary excretion of some metabolites of the d-glucuronic acid pathway. Male Sprague-Dawley rats were treated for 7 days with daily ip injections of either diphenylacetic acid, guaiacol, 4-hydroxybiphenyl, 2-naphthol, 1-naphthylacetic acid, paracetamol (acetaminophen), 2-phenylpropionic acid, n-propyl gallate, or phenylacetic acid. None of the compounds administered had any effect on a number of parameters of hepatic Phase I xenobiotic metabolism, namely mixed function oxidase enzyme activities, cytochrome P-450 and the microsomal content of protein. However, some of the compounds did stimulate hepatic microsomal UDP-glucuronyltransferase activity. While none of the compounds stimulated the urinary excretion of either d-glucaric acid, l-gulonic acid, or xylitol, all of the compounds except phenylacetic acid increased the urinary excretion of total (free and conjugated) d-glucuronic acid. The results indicate that when hepatic xenobiotic conjugative activity is increased without the stimulation of mixed function oxidases and cytochrome P-450, the urinary excretion of certain metabolites of the d-glucuronic acid pathway, other than d-glucuronic acid, remains unchanged.