Naphthol metabolism: Glucuronide conjugation and transport by the rat intestine in vitro

Abstract

[ 14C]Naphthol was converted to water-soluble 14C-labeled metabolites by everted sacs of rat small intestine. The extent of conversion to metabolites and release to the bathing medium was greater for sacs from cranial (80%) than for sacs from caudal (60%) small intestine. The concentration of metabolites was always greater in serosal than in mucosal fluids. This concentration gradient increased from the cranial to the caudal end of the intestine. Net 14C transport to the serosal fluid was entirely as metabolites and was associated with the volume of water transported. The principal metabolites were glucuronide conjugates of naphthol which were hydrolyzed by β- d-glucuronidase. Naphthyl-β- d-glucuronide appeared to be the principal metabolite in the recovered mucosal and serosal fluids and tissues. The quantities of metabolites synthesized by sacs from the various regions of the intestine were not notably different when either pH 7.4 or pH 6.5 medium was used. The tissue concentration of 14C and quantity of metabolite transferred to serosal fluid in the pH 7.4 and pH 6.5 media were slightly different. The mechanism for the apparent uphill transport of metabolites was not apparent. The results have been compared to those from previous investigations where [ 14C-naphthyl] N-methylcarbamate was studied and provide greater insight into the intestinal metabolism of this naphthol-containing pesticide.