Journal
TOXICOLOGY IN VITRO
Volume 45, Issue -, Pages 334-339Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2017.04.026
Keywords
Zearalenone; Reactive oxygen species; DNA damage; Glutathione; Enzymatic activity
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Funding
- Spanish Ministry of Economy and Competitiveness [AGL2016-77610-R]
- Academy of Finland [265859]
- Fundacion Seneca-Agencia de Ciencia y Tecnologia de la Region de Murcia [20031/SF/16]
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Mycotoxin contamination of foods and feeds represent a serious problem worldwide. Zearalenone (ZEA) is a secondary metabolite produced by Fusarium species. This study explores oxidative cellular damage and intracellular defense mechanisms (enzymatic and non-enzymatic) in the hepatoma cell line HepG2 after exposure to ZEA and its metabolites (alpha-zearalenol, alpha-ZOL; beta-zearalenol, beta-ZOL). Our results demonstrated that HepG2 cells exposed to ZEA, alpha-ZOL or beta-ZOL at different concentrations (0, 6.25, 12.5 and 25 mu M) showed: (i) elevated ROS levels (1.5- to 7-fold) based on the formation of the highly fluorescent 2',7'-dichlorofluorescein (DCF), (ii) increased DNA damage measured by the comet assay (9-45% higher), (iii) decreased GSH levels and CAT activity (decreased by 54%-25% and by 62%-25% for GSH and CAT, respectively) and (iv) increased GPx and SOD activities (increased by 50%-90% and by 26%-70%, respectively), compared to untreated cells. Our results suggest that mycotoxin-induced oxidative stress and damage may play a major role in the cytotoxic effects of ZEA and its metabolites. GSH and endogenous enzymes function together in protecting cells from ROS and the consequent damage after mycotoxin exposure. ZEA has a lower capacity to induce oxidative stress and damage in HepG2 cells than its metabolites at the tested concentrations.
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