Urinary excretion of the uraemic toxin p-cresol in the rat: contribution of glucuronidation to its metabolization

Autor: Rita De Smet, Frans M. Belpaire, Gerrit Lesaffer, Marijn Van Hulle, Norbert Lameire, Bruno Van Vlem, Raymond Vanholder, Rita Cornelis
Přispěvatelé: Critical Care
Rok vydání: 2003
Předmět:
Zdroj: Nephrology Dialysis Transplantation. 18:1299-1306
ISSN: 1460-2385
0931-0509
DOI: 10.1093/ndt/gfg107
Popis: BACKGROUND Increasing evidence indicates that lipophilic and/or protein-bound substances such as p-cresol are responsible for adverse physiological alterations in uraemic patients. To better understand the evolution of p-cresol disposition in renal failure and dialysis patients, it is necessary to determine its kinetic characteristics and biotransformation pathways. METHODS We studied the biotransformation of p-cresol after intravenous injection of the compound in eight rats with normal renal function. Urine was collected in four 1 h intervals. To evaluate the presence of p-cresol metabolites, beta-glucuronidase was added to urine samples and the isolated unidentified chromatographic peak observed in previous experiments was submitted to tandem mass spectrometry (MS/MS) analysis. RESULTS Administration of p-cresol produced a p-cresol peak and an unknown peak, suggesting biotransformation of the compound. Addition of beta-glucuronidase to urine samples and incubation at 37 degrees C resulted in a marked decrease in the unidentified peak height (P
Databáze: OpenAIRE