Wang Xin, Ling Weikang, Zhu Yang, Ji Chengweng, An Xiaoguang, Qi Yuxin, Li Shuo, Zhang Chengye, Tong Ruixue, Jiang Dongmei, Kang Bo
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, P. R. China.
FASEB J. 2025 Mar 31;39(6):e70453. doi: 10.1096/fj.202403002R.
Copper exposure poses potential detrimental effects on both public and ecosystem health. Spermidine, an antioxidant, has shown promise in reducing oxidative stress and inflammation within the liver. However, its specific role in mitigating copper-induced hepatic cuproptosis and disturbances in copper metabolism remains unexplored. Consequently, this research aims to investigate to examine the impact of spermidine on hepatic cuproptosis and the related disturbances in copper metabolism. In the study, we established a model of copper-induced liver toxicity by feeding C57BL/6 mice a high-copper diet for three months. Histopathological and biochemical analyses revealed that copper exposure induced hepatic inflammatory cell infiltration, hepatocyte degeneration, elevated levels of MDA, ROS, and Cu accumulation in the liver, and increased ALT and AST activities in serum (p < .05). Regarding inflammation, copper exposure significantly increased serum levels of IL-1β, IL-6, and TNF-α (p < .05), upregulated TNF-α and IFN-γ expression, and downregulated IL-10 expression in the liver (p < .05). Meanwhile, copper exposure inhibited the expression of copper metabolism and Fe-S cluster-related proteins (p < .05). Exogenous spermidine administration effectively reduced ROS, MDA, and Cu accumulation in the liver, while also decreasing ALT and AST activites, IL-1β, IL-6, and TNF-α levels in the serum (p < .05), and downregulated TNF-α and IFN-γ expression (p < .001). Additionally, spermidine combined with CuSO treatment significantly promotes the expression of copper metabolism and Fe-S cluster-related proteins, compared to the CuSO group (p < .05). In summary, spermidine reduces Cu accumulation in the liver, alleviates hepatic cuproptosis, oxidative damage, and inflammation, and exerts a protective effect on the liver.
铜暴露对公众健康和生态系统健康都具有潜在的有害影响。亚精胺作为一种抗氧化剂，已显示出在减轻肝脏内氧化应激和炎症方面的潜力。然而，其在减轻铜诱导的肝脏铜死亡和铜代谢紊乱中的具体作用仍未得到探索。因此，本研究旨在调查亚精胺对肝脏铜死亡及铜代谢相关紊乱的影响。在该研究中，我们通过给C57BL/6小鼠喂食高铜饮食三个月，建立了铜诱导的肝毒性模型。组织病理学和生化分析表明，铜暴露诱导了肝脏炎症细胞浸润、肝细胞变性、肝脏中丙二醛（MDA）、活性氧（ROS）水平升高以及铜积累增加，并且血清中谷丙转氨酶（ALT）和谷草转氨酶（AST）活性升高（p < 0.05）。关于炎症，铜暴露显著增加了血清白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平（p < 0.05），上调了肝脏中TNF-α和干扰素-γ（IFN-γ）的表达，并下调了白细胞介素-10（IL-10）的表达（p < 0.05）。同时，铜暴露抑制了铜代谢和铁硫簇相关蛋白的表达（p < 0.05）。外源性给予亚精胺有效地降低了肝脏中的ROS、MDA和铜积累，同时还降低了血清中的ALT和AST活性、IL-1β、IL-6和TNF-α水平（p < 0.05），并下调了TNF-α和IFN-γ的表达（p < 0.001）。此外，与硫酸铜（CuSO）组相比，亚精胺与CuSO联合处理显著促进了铜代谢和铁硫簇相关蛋白的表达（p < 0.05）。总之，亚精胺减少了肝脏中的铜积累，减轻了肝脏铜死亡、氧化损伤和炎症，并对肝脏发挥了保护作用。
