Oxidative DNA damage and disturbance of antioxidant capacity by alternariol in Caco-2 cells

Abstract

Oxidative stress occurs as a consequence of an imbalance between the prooxidant/antioxidant systems, causing an increase of intracellular generation of reactive oxygen species. Alternariol (AOH), a mycotoxin produced by Alternaria sp. can alter the action of glutathione (GSH) and the enzymes involved in the redox system, causing damage to cellular macromolecules such as DNA. The aims of this work were to determine the induction of oxidative stress by the antioxidant defenses imbalance in relation to glutathione (GSH), glutathione reductase (GR), glutathione transferase (GST), glutathione peroxidase (GPx) levels and DNA damage in Caco-2 cells derived from adenocarcinoma human colon. Oxidative stress by AOH was confirmed by alteration of GSH levels and the antioxidant defense system after 15, 30 and 60μM AOH exposure during 24h. GSH levels significantly decreased by 43% after treatment with 60μM AOH compared to the control. The activity of GPx and GR was reduced by 30% and 23%, respectively after 60μM AOH. The GST activity was significantly increased (approximately 22%) with 30μM AOH, while 60μM AOH decreased it by 30% in comparison to the control. Analysis of DNA damage was performed using the Comet assay after 24h, where the % of DNA in tail increased from 70% to 85% compared the control.