Deciphering the ionic homeostasis, oxidative stress, apoptosis, and autophagy in chicken intestine under copper(II) stress

Zhao, Hongjing; Wang, Yu; Shao, Yizhi; Liu, Juanjuan; Liu, Yanhua; Xing, Mingwei

Deciphering the ionic homeostasis, oxidative stress, apoptosis, and autophagy in chicken intestine under copper(II) stress

2018

As cofactors of several enzymatic, copper (Cu) participates in many essential metabolic processes. Also, as a heavy metal, it exhibits highly toxic to the organism if excessive. This study endeavored to detect the pathophysiological changes in the jejunum of chickens, which were insulted by CuSO₄ (300 mg/kg diet) for 90 days. Results showed metabolic disorders of trace elements evidenced by their significant downregulations (Na, Al, Li, B, Cr, Ni, Sn, Sb, Ba) and upregulations (Cu, Si, As, Cd, Se, and Tl) in 90 days. Simultaneously, increased TdT-mediated dUTP nick end labeling (TUNEL)-positive nuclei and distinct ultrastructural apoptotic features were observed. Meanwhile, in 30, 60, and 90 days, indicators of oxidative stress, apoptosis, autophagy, and mitochondrial dynamic were detected to uncover the molecular mechanism behind these pathological changes. The results showed that suppressed antioxidant ability was companied by increased mRNA and protein levels of proapoptosis and mitochondrial fission activating genes in the Cu group compared with chickens in the control group (P < 0.05). Moreover, the markers of autophagy long-chain 3 (LC3-II/LC3-I), Bcl-2-interacting protein (beclin-1), and autophagy-related gene (ATG4B and ATG5) displayed a time-dependent increase during 30, 60, and 90 days. We conjectured that subchronic copper poisoning, under the background of redistribution of trace elements, induced oxidative stress and cascaded apoptosis, autophagy, and mitochondrial disorder, which contributed to jejunotoxicity in chicken. Collectively, our study provides a basic assessment of subchronic Cu exposure on poultry, voicing concerns about copper pollution by anthropogenic activities.

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