Effect of antipyrine and phenobarbital on renal γ-glutamyltransferase excretion in human urine

Abstract

Serum gamma-glutamyltransferase is used as a marker of hepatic enzyme induction. The kidney contains high activities of gamma-glutamyltransferase in the brush border membrane of the proximal tubule, from which it is released into urine. This study investigated the effect of phenobarbital and antipyrine, two inducers of hepatic monoxygenases and gamma-glutamyltransferase, on the urinary excretion of renal gamma-glutamyltransferase. Three groups (n = 6) of healthy male volunteers received 100 mg phenobarbital for 7 and 14 days and 1200 mg antipyrine for 7 days, respectively. Antipyrine and phenobarbital increased antipyrine elimination, serum gamma-glutamyltransferase, and the urinary excretion of renal gamma-glutamyltransferase, whereas urinary beta-N-acetylglucosaminidase, beta-glucuronidase, and total protein and glucose excretion were unchanged. No correlation was found between serum and urinary gamma-glutamyltransferase or both enzymes and antipyrine elimination. Increases in antipyrine elimination were positively correlated to increases in serum, but not urinary gamma-glutamyltransferase. The findings suggest that antipyrine and phenobarbital increase urinary gamma-glutamyltransferase excretion. However, the increase in urinary gamma-glutamyltransferase does not reflect the magnitude of hepatic enzyme induction.

A Toxicologist's Guide to the Preclinical Assessment of Hepatic Microsomal Enzyme Induction

“…Gamma-glutamyl-transferase (GGT) plasma levels have been reported as being increased in patients on anticonvulsants in the absence of evidence for hepatic dysfunction (Rosalki 1976) and GGT in serum has also been used as a parameter of hepatic enzyme induction in rats (Wensing et al 1990). In a longterm study (29 weeks) on the effects of phenobarbital in dogs, serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) increased significantly, GGT increased transiently, and albumen decreased transiently during the study in the absence of any histopathological damage to the liver (Muller et al 2000).…”

Combining markers of nephrotoxicity and hepatotoxicity for improved monitoring and detection of chronic alcohol abuse

“…Because of variability in urine composition, if the use of 24-h urine collection is not feasible, it is recommended that average results are calculated for samples taken on different days (28) and expressed relative to urinary creatinine. Therefore, the assays were run in two spot urine samples from each patient.…”

Alanine Aminopeptidase Activity in Urine: A New Marker of Chronic Alcohol Abuse?

“…Urine composition shows high inter-and intraindividual variability, which is in part urine flow rate related and can markedly affect the results of the AAP assays, especially when random urine samples are used instead of 24-hr collections. If making such collections is not feasible, the reliability of the results may be improved by averaging data from a number of urine samples taken from a given individual (Taracha et al, 2001;Wensing et al, 1990) and normalizing the results by urine creatinine content. Therefore, both the uAAP and eAAP activities were measured twice in each patient in this study.…”