Original scientific paper
https://doi.org/10.2478/10004-1254-63-2012-2202
Glutathione Conjugates of Ochratoxin A as Biomarkers of Exposure
Mariana Tozlovanu
; Laboratory of Chemical Engineering, Department of Bioprocess and Microbial System, UMR CNRS/INPT/UPS 5503, ENSA Toulouse, France
Delphine Canadas
; Laboratory of Chemical Engineering, Department of Bioprocess and Microbial System, UMR CNRS/INPT/UPS 5503, ENSA Toulouse, France
Annie Pfohl-Leszkowicz
; Laboratory of Chemical Engineering, Department of Bioprocess and Microbial System, UMR CNRS/INPT/UPS 5503, ENSA Toulouse, France
Christine Frenette
; Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, Canada
Robert J. Paugh
; Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, Canada
Richard A. Manderville
; Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, Canada
Abstract
In the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity.
Keywords
bioactivation; carcinogenicity; DNA adduction; glutathione; metabolism; mutagenicity; N-acetylcysteine
Hrčak ID:
93628
URI
Publication date:
14.12.2012.
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