Zhang Ding, Liu Jiayi, Liu Jingru, Fatima Maryam, Yang Lu, Qin Yingze, Li Wei, Sun Zilong, Yang Bo
College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR China.
College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR China.
Ecotoxicol Environ Saf. 2025 Apr 1;294:118100. doi: 10.1016/j.ecoenv.2025.118100. Epub 2025 Mar 30.
Cadmium (Cd) causes a health risk to humans and animals. Exercise can prevent and treat a variety of diseases, but the effect and mechanism of exercise on cadmium poisoning are still unclear. The present research aims to investigate the antagonistic impacts of exercise on enterotoxicity and hepatotoxicity caused by Cd. The results indicated that exercise, both before and during Cd exposure, can reduce Cd caused pathological damages in the liver and duodenum of mice, suppressing the expression levels of the IL-1β, IL-6 and TNF-α genes. In mice exposed to Cd, exercise significantly decreased blood ALT and AST levels, alleviating oxidative stress in the liver by reducing MDA synthesis and enhancing SOD and GSH-PX activities. Exercise inhibited nuclear damage and hepatocyte apoptosis caused by Cd by increasing Bcl-2 protein expression and preventing the release of pro-apoptotic proteins such as caspase-3, Cytc, Bax, caspase-8and cleaved-caspase-3. Exercise before or during Cd exposure can increase the protein and gene expression of HO-1, NQO-1 and Nrf2 in the liver of mice exposed to Cd. These findings suggested that the Nrf2 signaling pathway may have contributed to the exercise-induced partial attenuation of Cd-induced hepatic injury. Exercise also promoted the expression of the occludin gene in the duodenum of Cd-exposed mice, decreasing the structural damage and inflammatory cell infiltration induced by Cd. NF-κB and TLR2 protein expression levels were elevated in mice exposed to Cd. However, exercise mitigated the increase in NF-κB and TLR2 expression in the duodenum of Cd-intoxicated mice, suggesting that the protective effects of exercise on the intestinal tract in Cd-exposed mice may be mediated through modulation of the NF-κB/TLR2 signaling pathway. In conclusion, this study elucidated the protective effects of exercise against Cd-induced hepatotoxicity and intestinal injury in mice. The protective mechanisms of exercise on Cd-exposed liver and intestinal tract were partially realized through the regulation of Nrf2 and NF-κB/TLR2 signaling pathways.
镉（Cd）对人类和动物的健康构成风险。运动可以预防和治疗多种疾病，但运动对镉中毒的影响及机制仍不清楚。本研究旨在探讨运动对镉所致肠毒性和肝毒性的拮抗作用。结果表明，在镉暴露之前和期间进行运动，均可减轻镉对小鼠肝脏和十二指肠造成的病理损伤，抑制白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）基因的表达水平。在镉暴露小鼠中，运动显著降低血液中谷丙转氨酶（ALT）和谷草转氨酶（AST）水平，通过减少丙二醛（MDA）合成、增强超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）活性减轻肝脏氧化应激。运动通过增加Bcl-2蛋白表达、阻止半胱天冬酶-3（caspase-3）、细胞色素C（Cytc）、Bax、半胱天冬酶-8（caspase-8）和裂解的半胱天冬酶-3等促凋亡蛋白的释放，抑制镉所致的核损伤和肝细胞凋亡。在镉暴露之前或期间进行运动，可增加镉暴露小鼠肝脏中血红素加氧酶-1（HO-1）、醌氧化还原酶-1（NQO-1）和核因子E2相关因子2（Nrf2）的蛋白和基因表达。这些发现提示，Nrf2信号通路可能参与了运动诱导的镉所致肝损伤的部分减轻过程。运动还促进镉暴露小鼠十二指肠中闭合蛋白基因的表达，减少镉所致的结构损伤和炎性细胞浸润。镉暴露小鼠中核因子κB（NF-κB）和Toll样受体2（TLR2）蛋白表达水平升高。然而，运动减轻了镉中毒小鼠十二指肠中NF-κB和TLR2表达的增加，提示运动对镉暴露小鼠肠道的保护作用可能是通过调节NF-κB/TLR2信号通路介导的。总之，本研究阐明了运动对镉所致小鼠肝毒性和肠道损伤的保护作用。运动对镉暴露肝脏和肠道的保护机制部分是通过调节Nrf2和NF-κB/TLR2信号通路实现的。
