Oxidative damage under As and/or Cu stress leads to apoptosis and autophagy and may be cross-talking with mitochondrial disorders in bursa of Fabricius.

Arsenic (As) exists in many forms in the whole natural environment, with As the highest toxicity. Herein our study demonstrated that arsenic trioxide (AsO) at a dose of 30 mg/kg caused serious oxidative damage to chickens' bursa of Fabricius (BF) in a time-dependent manner. Copper (Cu) is a necessary micronutrient and a key catalytic cofactor of many enzymes. We found excessive Cu (in the form of 300 mg/kg copper sulfate (CuSO)) also induced severe oxidative stress (OxS), and its co-exposure with As had a greater destructive power against oxidative system. Under electron microscope, swollen mitochondria, disappeared cristae and agglutinated chromatin were observed, accompanied by myeloid structure and autophagosome. The results showed apoptosis and autophagy occurred under the action of As and Cu, and the situation was more serious in combined exposure group, which was further explained by terminal deoxynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine 5'-Triphosphate (dUTP) Nick-End Labeling (TUNEL). By quantitative real time polymerase chain reaction (RT-qPCR) and western blot, we found that mitochondrial dynamics were disordered under OxS, and the abnormal changes of B-cell lymphoma (Bcl)-2, p53, Bcl-2-interacting protein (Beclin)-1 and autophagy-related gene (ATG) 4B indicated the crosstalk between apoptosis and autophagy. In conclusion, apoptosis and autophagy of BF induced by As and Cu and mitochondrial disorder are closely related to the collapse of antioxidant system, and their connections are inseparable. Our results provide a reference for environmental risk prevention and selection of poultry feed additives and pesticides to avoid the health risks caused by As and Cu exposure.