Investigation of the effects of T-2 toxin in chicken-derived three-dimensional hepatic cell cultures

Abstract

Despite being one of the most common contaminants of poultry feed, the molecular effects of T-2 toxin on the liver of the exposed animals are still not fully elucidated. To gain more accurate understanding, the effects of T-2 toxin were investigated in the present study in chicken-derived three-dimensional (3D) primary hepatic cell cultures. 3D spheroids were treated with three concentrations (100, 500, 1000 nM) of T-2 toxin for 24 h. Cellular metabolic activity declined in all treated groups as reflected by the Cell Counting Kit-8 assay, while extracellular lactate dehydrogenase activity was increased after 500 nM T-2 toxin exposure. The levels of oxidative stress markers malondialdehyde and protein carbonyl were reduced by the toxin, suggesting effective antioxidant compensatory mechanisms of the liver. Concerning the pro-inflammatory cytokines, IL-6 concentration was decreased, while IL-8 concentration was increased by 100 nM T-2 toxin exposure, indicating the multifaceted immunomodulatory action of the toxin. Further, the metabolic profile of hepatic spheroids was also modulated, confirming the altered lipid and amino acid metabolism of toxin-exposed liver cells. Based on these results, T-2 toxin affected cell viability, hepatocellular metabolism and inflammatory response, likely carried out its toxic effects by affecting the oxidative homeostasis of the cells.