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Arsenic trioxide and/or copper sulfate induced apoptosis and autophagy associated with oxidative stress and perturbation of mitochondrial dynamics in the thymus of Gallus gallus

Liu, Juanjuan, Zhao, Hongjing, Wang, Yu, Shao, Yizhi, Zong, Hui, Zeng, Xiangwei, Xing, Mingwei
Chemosphere 2019 v.219 pp. 227-235
chickens, copper sulfate, diet, oxidative toxicity, copper, malondialdehyde, thymus gland, arsenic, Gallus gallus, models, autophagy, genes, mitochondria, pollution, chromatin, antioxidants, apoptosis, arsenic oxide
Arsenic (As) and copper (Cu) are ubiquitous environmental contaminants that are hazardous to the immune system. Our objective was to investigate the toxicity and potential mechanisms of thymus exposure to As and/or Cu. A chicken model was established by adding arsenic trioxide (As₂O₃; 30 mg/kg), copper sulfate (CuSO₄; 300 mg/kg), and simultaneously both elements in the basal diet. After the chickens were fed for 12 weeks, a significant reduction in antioxidant enzyme levels or production of malondialdehyde (MDA) emphasized the occurrence of oxidative stress. Furthermore, an imbalance in mitochondrial dynamics along with its abnormal structure certified mitochondrial dysfunction. Additionally, elevated levels of pro-apoptotic and autophagy genes and decreased levels of antiapoptotic genes were found in treated groups. Karyopyknosis and chromatin peripheral condensation were accompanied by an increased apoptosis ratio, as well as accumulation of autophagosomes, thus indicating that apoptosis and autophagy are involved in immune cell death. All of the above thymus lesions and index abnormalities occurred in a time-dependent manner, and the Cu and As co-administered groups showed more deteriorating effects than the Cu and As groups alone. Moreover, in the As or Cu group, the thymus tissue suffered different susceptibilities in oxidative toxicity, which needs further study. Collectively, our results manifested that co-exposure to As and Cu increased the oxidative burden and exacerbated mitochondrial dysfunction on the thymus. Additionally, apoptosis and autophagy may act as partners in inducing cell death in a cooperative manner in chicken thymus after As and/or Cu exposure.