Arsenic-induced cardiotoxicity correlates with mitochondrial damage and trace elements imbalance in broiler chickens

Abstract

Arsenic-based drugs as food additive were used in poultry. However, excessive arsenic exposure can disturb myocardial cell metabolism, which results in the inhibition of growth and development of chickens. Since disordered mitochondria influences cardiac physiology and pathology, a better understanding of the mechanisms modulating cardiomyocyte mitochondria process is critical for identifying the potent detoxication targets under arsenic exposure in chickens. Male Hy-line chickens (1-day-old) were fed either a basal diet or an arsenic trioxide (As2O3)-supplemented diet containing 7.5, 15, and 30 mg/kg As2O3 for 90 d. The concentrations of ions ([Na, Mg, Al, Si, K, Ca, As, Mn, Fe, Zn] and [Cr, Ni, Cu, Ba]) significantly increased and decreased in the heart of chicken under As2O3 exposure, respectively. Moreover, we observed that As2O3 decreased high-density lipoprotein cholesterol concentrations and increased total cholesterol concentrations in the serum. We also observed arterial wall degeneration, biochemical character of mitochondria undergoing either fission or fusion, typical apoptotic cells, typical DNA fragments and TdT-mediated dUTP nick end labeling positive nuclei under As2O3 exposure in the heart. Further quantitative real-time PCR demonstrated that B cell lymphoma/leukemia 2 (Bcl2) were significantly decreased and dynamin-related protein 1 (Drp1), Optic atrophy 1 (Opa1), mitochondrial fission factor 1 (Mfn1), Mfn2, p53, caspase-8, Bcl-2 associated X protein (Bax), caspase-3, caspase-9 and cytochrome C were significantly increased in all As2O3 group. In conclusion, As2O3 can disturb the trace elements homeostasis, which might favor the development of mitochondrial damage. Moreover, we suspected that As2O3-increased mitochondrial dynamics might trigger the apoptosis to limit cell metabolism. These features might identify the role of the mitochondrial dynamics under arsenic-induced cardiovascular disease in the chickens.