Long-term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal-splenic axis

Copper is an essential micro-element in animal growth. Tribasic copper chloride (TBCC), as an important source of animal feed copper, is widely used in agricultural production. Multiple studies have shown that excessive intake of copper can affect the immune function of animals and lead to disease o...

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Main Authors: Jinwen Quan, Xiaoyue Chang, Siying Liu, Ting He, Gaolong Zhong, Zhonghua Liu, Wenlan Yu
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324014994
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author Jinwen Quan
Xiaoyue Chang
Siying Liu
Ting He
Gaolong Zhong
Zhonghua Liu
Wenlan Yu
author_facet Jinwen Quan
Xiaoyue Chang
Siying Liu
Ting He
Gaolong Zhong
Zhonghua Liu
Wenlan Yu
author_sort Jinwen Quan
collection DOAJ
description Copper is an essential micro-element in animal growth. Tribasic copper chloride (TBCC), as an important source of animal feed copper, is widely used in agricultural production. Multiple studies have shown that excessive intake of copper can affect the immune function of animals and lead to disease or death. The intestine-spleen axis, which is the interaction between the spleen, intestines and gut microbiota, is closely linked to immune function in the body. However, the mechanism of intestine-spleen axis affecting TBCC induced immune dysfunction in rats has not been revealed. In this study, we analyzed the impacts of different doses of TBCC on the intestine, gut microbiota and spleen of rats, and investigated their relationship in the process. Our results demonstrated that under copper exposure, the structural integrity of the intestinal epithelium was compromised, resulting in a significant downregulation of genes and proteins expression levels related to the intestinal barrier (Zonula occludens-1, Claudin-1 and Occludin). Additionally, copper perturbed the composition of the rat intestinal microbiota, altered the abundance and diversity of the microbial community. Copper entered the spleen via the intestine-spleen axis, leading to structural damage in the spleen and activation of the NFκB signaling pathway, and increased pro-inflammatory cytokines (IFN-γ, TNF-α, IL-18, and IL-1β), ultimately causing pyroptosis and inflammation in the spleen. These findings offer a novel perspective on how copper may induce spleen injury through the intestine-spleen axis.
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spelling doaj-art-92bb536cbd874e3197b1f70ae44b96ca2025-01-23T05:25:29ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117423Long-term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal-splenic axisJinwen Quan0Xiaoyue Chang1Siying Liu2Ting He3Gaolong Zhong4Zhonghua Liu5Wenlan Yu6College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, PR China; Laboratory Animal Center, South China Agriculture University, Guangzhou, Guangdong 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, PR China; Laboratory Animal Center, South China Agriculture University, Guangzhou, Guangdong 510642, PR China; Corresponding author at: College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, PR China.Copper is an essential micro-element in animal growth. Tribasic copper chloride (TBCC), as an important source of animal feed copper, is widely used in agricultural production. Multiple studies have shown that excessive intake of copper can affect the immune function of animals and lead to disease or death. The intestine-spleen axis, which is the interaction between the spleen, intestines and gut microbiota, is closely linked to immune function in the body. However, the mechanism of intestine-spleen axis affecting TBCC induced immune dysfunction in rats has not been revealed. In this study, we analyzed the impacts of different doses of TBCC on the intestine, gut microbiota and spleen of rats, and investigated their relationship in the process. Our results demonstrated that under copper exposure, the structural integrity of the intestinal epithelium was compromised, resulting in a significant downregulation of genes and proteins expression levels related to the intestinal barrier (Zonula occludens-1, Claudin-1 and Occludin). Additionally, copper perturbed the composition of the rat intestinal microbiota, altered the abundance and diversity of the microbial community. Copper entered the spleen via the intestine-spleen axis, leading to structural damage in the spleen and activation of the NFκB signaling pathway, and increased pro-inflammatory cytokines (IFN-γ, TNF-α, IL-18, and IL-1β), ultimately causing pyroptosis and inflammation in the spleen. These findings offer a novel perspective on how copper may induce spleen injury through the intestine-spleen axis.http://www.sciencedirect.com/science/article/pii/S0147651324014994RatCopperIntestinal microbiotaIntestine-spleen axisPyroptosis
spellingShingle Jinwen Quan
Xiaoyue Chang
Siying Liu
Ting He
Gaolong Zhong
Zhonghua Liu
Wenlan Yu
Long-term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal-splenic axis
Ecotoxicology and Environmental Safety
Rat
Copper
Intestinal microbiota
Intestine-spleen axis
Pyroptosis
title Long-term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal-splenic axis
title_full Long-term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal-splenic axis
title_fullStr Long-term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal-splenic axis
title_full_unstemmed Long-term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal-splenic axis
title_short Long-term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal-splenic axis
title_sort long term copper exposure induced pyroptosis and inflammation of rat spleen through intestinal splenic axis
topic Rat
Copper
Intestinal microbiota
Intestine-spleen axis
Pyroptosis
url http://www.sciencedirect.com/science/article/pii/S0147651324014994
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