Alterations of antioxidant indexes and inflammatory cytokine expression aggravated hepatocellular apoptosis through mitochondrial and death receptor-dependent pathways in Gallus gallus exposed to arsenic and copper.

Abstract

In this study, we sought to investigate the effects of sub-chronic exposure of arsenic (As) and copper (Cu) on oxidative stress, inflammatory response, and mitochondria and death receptor apoptosis pathways in chicken liver. Seventy-two 1-day-old male Hy-line chickens were treated with basal diet, 30mg/kg arsenic trioxide (As2O3), or/and 300mg/kg copper sulfate (CuSO4) for 4, 8, and 12weeks. Study revealed that exposure to As or/and Cu undermined the antioxidant function and increased lipid peroxidation. Worse yet, liver cell swollen, vacuolar degeneration, and inflammatory cell infiltration were accompanied by an increase of the nuclear factor-κB (NF-κB) and its downstream inflammation-related genes after exposure to As or/and Cu. Furthermore, mitochondria swollen and chromatin condensation were found in As and Cu groups, and hepatocyte nuclear membrane rupture and markedly increased (P< 0.01) apoptosis index were observed in As combined with Cu group. Meanwhile, the transcription and protein expression levels of Bcl-2-associated X protein (Bax), p53, cytochrome c (Cyt c), and caspase-3, 8, 9 were upregulated and B cell lymphoma-2 (Bcl-2) was downregulated in As, Cu, and As + Cu groups in the liver tissues (P< 0.05, P< 0.01). Our results indicated that exposure to As or/and Cu could lead to oxidative stress, inflammatory response, and tissue damage and aggravate hepatocellular apoptosis through mitochondrial and death receptor-dependent pathways in chicken liver. And As and Cu showed a possible synergistic relationship in liver damage.