Deoxynivalenol induces carp neutrophil apoptosis and necroptosis via CYP450s/ROS/PI3K/AKT pathway

Abstract Deoxynivalenol (DON) is a mycotoxin that seriously pollutes feed and the environment at a high risk to livestock and fish. Excessive DON could trigger oxidative stress and cause toxicity in non-target organisms. However, the impact of various concentrations of DON exposure on immune cells and the mechanism in it remain unknown. In the present test, the carp was a study object, the neutrophils were isolated and treated with different concentrations of DON (0, 20, 40 and 80 μg/mL). Cell death analysis found that an obvious increase of the apoptosis and necrosis rates exposed to DON, and aggravation in a dose-dependent manner. Moreover, DON exposure induced the expression of Cytochrome P450 (CYP450) family genes and triggered oxidative stress, including increased levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), reduced the catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)’s activities and glutathione (GSH) contents. Besides, inhibited PI3K/AKT signal and activated BCL2/BAX/Cyt-c/Caspase-3 and RIP1/RIP3/MLKL pathway were obvious and in a DON dose-dependent manner. In summary, the results indicate DON exposure could cause neutrophil death via activating CYP450s/ROS signal, inhibiting RI3K/AKT pathway, and inducing apoptosis and necroptosis. These data provide new insights for revealing the toxicological effects of mycotoxin.