Glutathione Conjugates of Ochratoxin A as Biomarkers of Exposure

  • Mariana Tozlovanu
  • Delphine Canadas
  • Annie Pfohl-Leszkowicz
  • Christine Frenette
  • Robert J. Paugh
  • Richard A. Manderville
Keywords: bioactivation, carcinogenicity, DNA adduction, glutathione, metabolism, mutagenicity, N-acetylcysteine

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 signifi cantly 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 detoxifi cation 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.
How to Cite
1.
Tozlovanu M, Canadas D, Pfohl-Leszkowicz A, Frenette C, Paugh RJ, Manderville RA. Glutathione Conjugates of Ochratoxin A as Biomarkers of Exposure. Arh Hig Rada Toksikol [Internet]. 1 [cited 2024Mar.29];63(4). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/21
Section
Scientific Paper