Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway

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 hepatoto...

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Main Authors: Ding Zhang, Jiayi Liu, Jingru Liu, Maryam Fatima, Lu Yang, Yingze Qin, Wei Li, Zilong Sun, Bo Yang
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325004361
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author Ding Zhang
Jiayi Liu
Jingru Liu
Maryam Fatima
Lu Yang
Yingze Qin
Wei Li
Zilong Sun
Bo Yang
author_facet Ding Zhang
Jiayi Liu
Jingru Liu
Maryam Fatima
Lu Yang
Yingze Qin
Wei Li
Zilong Sun
Bo Yang
author_sort Ding Zhang
collection DOAJ
description 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.
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issn 0147-6513
language English
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publisher Elsevier
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spelling doaj-art-a56e173f28254f8e8be00871dc35e9552025-08-20T02:09:07ZengElsevierEcotoxicology and Environmental Safety0147-65132025-04-0129411810010.1016/j.ecoenv.2025.118100Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathwayDing Zhang0Jiayi Liu1Jingru Liu2Maryam Fatima3Lu Yang4Yingze Qin5Wei Li6Zilong Sun7Bo Yang8College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR China; Corresponding authors.College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR ChinaSecond hospital of Shanxi Medical University, Taiyuan 030001, PR ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, PR China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S0147651325004361CadmiumExerciseIntestinal damageLiver damageNrf2TLR2/NF-κB
spellingShingle Ding Zhang
Jiayi Liu
Jingru Liu
Maryam Fatima
Lu Yang
Yingze Qin
Wei Li
Zilong Sun
Bo Yang
Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway
Ecotoxicology and Environmental Safety
Cadmium
Exercise
Intestinal damage
Liver damage
Nrf2
TLR2/NF-κB
title Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway
title_full Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway
title_fullStr Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway
title_full_unstemmed Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway
title_short Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway
title_sort exercise antagonizes cadmium caused liver and intestinal injury in mice via nrf2 and tlr2 nf κb signalling pathway
topic Cadmium
Exercise
Intestinal damage
Liver damage
Nrf2
TLR2/NF-κB
url http://www.sciencedirect.com/science/article/pii/S0147651325004361
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