In vitro characterization of hepatic toxicity of Alternaria toxins

AbstractAlternaria mycotoxins are secondary fungal metabolites which can contaminate food and feed. They are produced byAlternaria species with alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA), and tentoxin (TEN) as the main representatives forAlternaria mycotoxins in food. Once passing the intestinal barrier,Alternaria toxins can reach the liver to exert yet uncharacterized molecular effects. Therefore, hepatic in vitro systems were used to examine selectedAlternaria mycotoxins for their induction of metabolism-dependent cytotoxicity, phosphorylation of the histone H2AX as a surrogate marker for DNA double-strand breaks, and relevant marker genes for hepatotoxicity. Analysis of cell viability as well as the induction of H2AX phosphorylation in the hepatocarcinoma cell line HepG2 revealed a detoxification of 100  μmol/l AME and AOH by pre-treatment with S9 liver homogenate as shown by a decrease in cytotoxicity and H2AX histone phosphorylation to levels observed in control cells. Concentrations up to 100 μmol/l TeA and TEN did not induce H2AX phosphorylation whether metabolized or not. In the metabolica lly competent human hepatoma cell line HepaRG, no cytotoxicity of Alternaria toxins occurred even at high concentrations up to 100 μmol/l, which indicates a low cytotoxic potential. Induction of gene expression associated with liver toxicity was analyzed by quantitative real-time PCR using a speci fic hepatotoxicity PCR array in HepaRG cells: ...
Source: Mycotoxin Research - Category: Toxicology Source Type: research