The role of glutathione and cysteine conjugates in the nephrotoxicity of o-xylene in rats
Details
Serval ID
serval:BIB_92867854060A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The role of glutathione and cysteine conjugates in the nephrotoxicity of o-xylene in rats
Journal
Archives of Toxicology
ISSN
0340-5761 (Print)
Publication state
Published
Issued date
09/1998
Volume
72
Number
9
Pages
553-8
Notes
Journal Article --- Old month value: Sep
Abstract
Moderate nephrotoxicity was induced in male and female rats exposed to o-xylene for 4 h at atmospheric concentrations of approximately 3000 ppm. The xylene in vivo nephrotoxicity resulted in low enzyme leakage from the kidney into the urine. This low leakage was confirmed in 24-h urine by an increase in gamma-glutamyltranspeptidase (gammaGT), N-acetyl-beta-D-glucosaminidase (NAG) and alkaline phosphatase (ALP) activities. Compared to the control, both the 24-h urine output and the glucose excretion increased in male and female rats. These increases were probably a result of damage to the renal proximal tubules. The role of the metabolic pathway of glutathione in the emergence of the renal damage observed with o-xylene was investigated in rats. Recent studies indicate that the metabolic pathway of glutathione may be a bioactivation pathway, which is responsible for nephrotoxic effects with several drugs or chemicals. The renal toxicity of three synthesized o-xylene thio-conjugates was investigated in several groups of female rats. Administration of S-(o-methylbenzyl)glutathione (i.p., 1 mmol/kg), S-(o-methylbenzyl)cysteine (per os, 1 mmol/kg) or N-acetyl-S-(o-methylbenzyl)cysteine (i.p., 0.75 mmol/kg) to female rats did not induce renal toxicity, as monitored by urinary biochemical parameters (gammaGT, NAG, ALP, glucose). The data obtained suggest that the glutathione pathway would appear to be only detoxication, and probably does not contribute to the renal toxicity of o-xylene in female rats. Thus, either another metabolic pathway or other intermediate metabolites are probably involved in the nephrotoxic action of o-xylene.
Keywords
Administration, Inhalation
Animals
Cysteine/*analogs & derivatives/chemical synthesis/metabolism/toxicity
Female
Glutathione/*analogs & derivatives/chemical synthesis/metabolism/toxicity
Glycosuria/etiology
Kidney Diseases/*chemically induced/enzymology/urine
Male
Rats
Rats, Sprague-Dawley
Xylenes/*toxicity
Pubmed
Web of science
Create date
28/01/2008 10:36
Last modification date
20/08/2019 15:55