Department of Physiology, College of Wildlife Resources, Northeast Forestry University, Harbin, 150040, Heilongjiang, People's Republic of China.
Environ Sci Pollut Res Int. 2018 Nov;25(33):33172-33182. doi: 10.1007/s11356-018-3163-z. Epub 2018 Sep 25.
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 CuSO (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.
作为几种酶的辅助因子，铜（Cu）参与许多重要的代谢过程。此外，作为一种重金属，如果过量，它对生物体表现出高度的毒性。本研究旨在检测鸡空肠在 90 天内受到 CuSO（300mg/kg 饮食）刺激后的病理生理变化。结果表明，微量元素代谢紊乱，表现为 90 天内大量下调（Na、Al、Li、B、Cr、Ni、Sn、Sb、Ba）和上调（Cu、Si、As、Cd、Se 和 Tl）。同时，观察到 TdT 介导的 dUTP 缺口末端标记（TUNEL）阳性核和明显的超微结构凋亡特征增加。同时，在 30、60 和 90 天，检测氧化应激、凋亡、自噬和线粒体动力学的指标，以揭示这些病理变化背后的分子机制。结果表明，与对照组相比，Cu 组抗氧化能力受到抑制，同时促凋亡和线粒体分裂激活基因的 mRNA 和蛋白水平升高（P<0.05）。此外，自噬长链 3（LC3-II/LC3-I）、Bcl-2 相互作用蛋白（beclin-1）和自噬相关基因（ATG4B 和 ATG5）的标志物在 30、60 和 90 天期间呈时间依赖性增加。我们推测，在微量元素重新分布的背景下，亚慢性铜中毒诱导氧化应激，并级联诱导凋亡、自噬和线粒体紊乱，导致鸡空肠毒性。总之，我们的研究为家禽亚慢性 Cu 暴露提供了基础评估，对人为活动引起的铜污染表示关注。
