Synergistic effect of copper and arsenic upon oxidative stress, inflammation and autophagy alterations in brain tissues of Gallus gallus

Arsenic or copper is one of the most highly toxic pollution that can cause dysfunction to brains, however, the exact mechanism remains unclear. The aim of the study is to investigate the mechanisms of arsenic or/and copper-induced oxidative stress, inflammation and autophagy in chicken brains and elucidate the interactions between arsenic and copper. A total of 72 1-day-old Hy-line chickens were divided into four groups (18 chickens per group) treated with 30 mg/kg arsenic trioxide (As2O3) or/and 300 mg/kg copper sulfate (CuSO4) for 12 weeks. Histological signs of inflammation were found in the cerebrum, cerebellum and brainstem exposure to arsenic or/and copper. The malondialdehyde (MDA) content were up-regulation, whereas oxidative damage parameters total antioxidant capacity (T-AOC), glutathione (GSH), the inhibition ability of hydroxyl radical (OH center dot), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly decreased (P < 0.05). The mRNA levels and protein expressions of inflammation markers, such as nuclear factor kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PTGEs) were significantly increased (P < 0.05). The mRNA levels and protein expressions of autophagy markers including phosphatidylinositol 3-kinase (PI3K), Akt, autophagy-related gene 5 (ATG5), microtubule-associated protein light chains 3 (LC3), ATG4B, and Beclinel in different regions of brains were up-regulation (P < 0.05), except the mammalian target of rapamycin complex (mTORC). In conclusion, we speculated that arsenic or copper could induce oxidative stress, inflammation and autophagy in chicken brains, and there may have a synergistic effect between copper and arsenic.