Ma Feiyang, Huo Yihui, Liao Jianzhao, Xu Guangqing, Wang Zhekai, He Shaojun
College of Animal Science, Anhui Science and Technology University, Chuzhou, Anhui 233100, PR China.
College of Veterinary Medicine, China Agricultural University, Beijing 100091, PR China.
Poult Sci. 2025 Jul 15;104(10):105549. doi: 10.1016/j.psj.2025.105549.
Copper (Cu) is widely used in both agriculture and industry and may pose toxic risks to animals and public safety if overused. In order to gain a more profound insight into the nephrotoxic effects of Cu, a detailed analysis was performed of its impact on renal PANoptosis, with particular attention being paid to the possible involvement of lipid metabolism disorders in the kidney. In this study, one-day-old chicks were fed diets with varying Cu levels (11, 110, 220, and 330 mg/kg) over a period of 49 days. Our findings indicated that excessive Cu exposure led to vacuolar degeneration, fibrosis and mitochondrial damage in the kidney. Moreover, the assay results demonstrated that elevated Cu levels led to disturbances in lipid synthesis and catabolism, as well as the activation of lipophagy in broiler kidneys. Concurrently, genetic and protein analysis demonstrated that excess Cu triggered pyroptosis (IL-18, NLRP3, GSDMD, Caspase-1), necrosis (MLKL, Caspase-7, Caspase-8) and apoptosis (Bcl-2, Cleaved-Caspase-9/Caspase-9, Cleaved-Caspase-9/Caspase-9), ultimately resulting in PANoptosis in the chicken kidney. Furthermore, the bioinformatics analysis indicated a correlation between lipid metabolism and PANoptosis-related markers. The aforementioned results indicate that Cu-induced disruption to lipid metabolism may contribute to the process of PANoptosis in broiler kidneys.
铜（Cu）在农业和工业中都有广泛应用，如果过度使用，可能会对动物和公共安全构成毒性风险。为了更深入地了解铜的肾毒性作用，对其对肾脏PAN凋亡的影响进行了详细分析，特别关注肾脏脂质代谢紊乱可能的参与情况。在本研究中，一日龄雏鸡在49天的时间里被喂食不同铜水平（11、110、220和330毫克/千克）的日粮。我们的研究结果表明，过量接触铜会导致肾脏出现空泡变性、纤维化和线粒体损伤。此外，检测结果表明，铜水平升高会导致脂质合成和分解代谢紊乱，以及肉鸡肾脏中脂噬的激活。同时，基因和蛋白质分析表明，过量的铜会引发细胞焦亡（IL-18、NLRP3、GSDMD、Caspase-1）、坏死（MLKL、Caspase-7、Caspase-8）和凋亡（Bcl-2、Cleaved-Caspase-9/Caspase-9、Cleaved-Caspase-9/Caspase-9），最终导致鸡肾脏中的PAN凋亡。此外，生物信息学分析表明脂质代谢与PAN凋亡相关标志物之间存在相关性。上述结果表明，铜诱导的脂质代谢紊乱可能促成了肉鸡肾脏中PAN凋亡的过程。
