The inflammatory responses in Cu-mediated elemental imbalance is associated with mitochondrial fission and intrinsic apoptosis in Gallus gallus heart.

Copper (Cu) is an essential trace element for organism of function properly. Overexposure to Cu causes chronic cardiac impairment. The aim of this study was to investigate the change of 28-trace element, inflammatory response, the possible mitochondrial dynamics and apoptosis under Cu exposure in the heart of chickens. Cupric sulfate (CuSO4) (300 mg/kg) was administered in a basal diet to male Hy-line chickens (one-day-old) for 90 days. Results showed the concentrations of Cu in the Cu group were increased by 57.8%, 27.57% and 57.2% at 30, 60 and 90 days, respectively. The Cu supplement caused trace elements imbalance, including reduced concentrations of B, Al, Ni, Ba, Pb and increased Li, Na, Mg, Si, K, Ca, V, Mn, Fe, Co, Zn, As, Mo in the heart of chickens. Exposure to Cu induced the TUNEL positive nuclei, histopathological alterations and ultrastructural apoptotic features. Moreover, Cu exposure activated the NF-κB-mediated pro-inflammatory cytokines, decreased the mRNA levels of opa1, mfn1, mfn2, Bcl-2, increased the mRNA levels of drp1, Bax, caspase-3, caspase-9, P53, while not altered Fas and caspase-8 compared with the control group. Similarly, western blot results showed the same trend of mRNA. Correlation analysis indicated that mitochondrial fission and intrinsic apoptosis might function synergistic. Moreover, mitochondrial network seem to function as cytosolic sensors for the induction of NF-κB mediated inflammatory responses. In summary, we speculated that Cu-induced redistribution of trace elements contributed to inflammatory response and disrupted the mitochondrial network via fission and intrinsic apoptosis in the heart of chickens.