Glucuronidation of 1-naphthol and excretion into the vein in perfused rat kidney

Abstract

UDP-glucuronosyltransferase is expressed in the proximal convoluted tubular cells of rat kidney. Kidney perfusion with a Krebs-Henseleit buffer containing 1-naphthol was performed to estimate the dynamics and disposition of the glucuronide conjugate formed in the epithelial cells of the renal tubules. When 1-naphthol was injected into the renal artery, and the perfusate from the renal vein was returned to a reservoir and recirculated through the kidney preparation (recirculating perfusion), most of the 1-napthol was immediately excreted into the vein as a glucuronide conjugate and its concentration increased rapidly. In contrast, the 1-napthol glucuronide appeared more slowly in the urine. 1-Naphthol was also injected during the initial 5 min of perfusion under single-pass perfusion conditions (single-pass perfusion) in situ, and the metabolite and parent compound in the venous perfusate and in urine were assayed. Under this condition, most of the 1-naphthol glucuronide was excreted into the renal vein, and not urine. Phenol UDP-glucuronosyltransferase was highly induced in the rat kidney by beta-naphthoflavone treatment. Moreover, the amount of 1-naphthol glucuronide excreted in the renal vein was increased 2.7-fold in the perfused kidney of beta-naphthoflavone-treated rats, but the amount in the urine was not significantly increased under singlepass perfusion conditions. These results indicate that the kidney can glucuronidate phenolic xenobiotics in epithelial cells of the tubules and excrete the resultant glucuronide into the renal vein.