Ma Feiyang, Wang Mengran, Zhong Gaolong, Liao Jianzhao, Huo Yihui, Wang Zekai, He Shaojun
Anhui Province Key Laboratory of Animal Nutrition Regulation and Health, Anhui Science and Technology University, Chuzhou, 233100, Anhui, People's Republic of China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, People's Republic of China.
Biometals. 2025 May 22. doi: 10.1007/s10534-025-00695-5.
Copper (Cu) is a pervasive element utilized in economic animal production. However, overuse can have toxic effects on animals and threaten public food safety. To gain a deeper understanding of the mechanisms underlying Cu-induced nephrotoxicity, an in-depth analysis was conducted on the effects of Cu on the renal endoplasmic reticulum quality control (ERQC) system. In the course of this experiment, one-day-old chicks were fed diets comprising Cu levels (11, 110, 220 and 330 mg/kg) for 49 days. Our findings indicate that an excess of Cu may result in oxidative stress, which may then induce tissue damage within the kidney. Furthermore, the experimental results indicated that elevated Cu levels may disrupt to the ERQC system in chicken kidneys. The mRNA levels of GRP78, GRP94, ATF4, IRE1, and XBP1, as well as the protein levels of GRP78, GRP94, IRE1, XBP1, and CHOP, were markedly elevated in all treatment groups relative to the control group. Conversely, the mRNA and protein levels of eIF2α and ATF6 exhibited a notable decline with the increase in Cu levels. Similarly, RTN3, ATL1, and ATL2 mRNA levels as well as RTN3 and ATL3 protein levels exhibited a notable elevation in conjunction with an appreciable decline in FAM134B and SEC62 mRNA and protein levels, respectively, as Cu levels increased. Furthermore, bioinformatics analyses indicated a correlation between oxidative damage and ERQC markers. The above results suggest that Cu-induced oxidative damage may injure to chicken kidneys via disturbances in the ERQC system.
铜（Cu）是经济动物生产中广泛使用的一种元素。然而，过度使用会对动物产生毒性作用，并威胁到公众食品安全。为了更深入地了解铜诱导肾毒性的潜在机制，对铜对肾脏内质网质量控制系统（ERQC）的影响进行了深入分析。在本实验过程中，给1日龄雏鸡饲喂含不同铜水平（11、110、220和330毫克/千克）的日粮49天。我们的研究结果表明，过量的铜可能导致氧化应激，进而诱导肾脏组织损伤。此外，实验结果表明，铜水平升高可能会扰乱鸡肾脏中的ERQC系统。与对照组相比，所有处理组中GRP78、GRP94、ATF4、IRE1和XBP1的mRNA水平，以及GRP78、GRP94、IRE1、XBP1和CHOP的蛋白水平均显著升高。相反，随着铜水平的升高，eIF2α和ATF6的mRNA和蛋白水平显著下降。同样，随着铜水平的升高，RTN3、ATL1和ATL2的mRNA水平以及RTN3和ATL3的蛋白水平显著升高，而FAM134B和SEC62的mRNA和蛋白水平则分别显著下降。此外，生物信息学分析表明氧化损伤与ERQC标志物之间存在相关性。上述结果表明，铜诱导的氧化损伤可能通过扰乱ERQC系统对鸡肾脏造成损伤。
