Chronic cadmium exposure at environmental-relevant level accelerates the development of hepatotoxicity to hepatocarcinogenesis

doi:10.1016/j.scitotenv.2021.146958

	Chronic cadmium exposure at environmental-relevant level accelerates the development of hepatotoxicity to hepatocarcinogenesis
	Xu, Yajie1,2,3 ; Mu, Wei 4; Li, Jingquan 4; Ba, Qian 4; Wang, Hui 1,4
	2021-08-20
发表期刊	SCIENCE OF THE TOTAL ENVIRONMENT (IF:8.2[JCR-2023],8.6[5-Year])
ISSN	0048-9697
EISSN	1879-1026
卷号	783
DOI	10.1016/j.scitotenv.2021.146958
摘要	Cadmium (Cd) is an environmental heavy metal with long biological half-time and adverse health effects. The long-term toxicity of Cd at low levels remains to be elucidated. Here, we investigated the impact of dietary Cd intake at environmental doses in the full disease cycle from liver injury, fibrosis, inflammation to cancer progression in mouse models and in vitro. We found that chronic low-dose Cd exposure promoted the hepatotoxicity and hepato-pathogenesis in normal and CCl4 mouse models. Cd enhanced liver injury and accelerated liver fibrosis, a key risk factor for cirrhosis and liver cancer, featured as up-regulation of fibrosis-related markers (TGF-beta 1, collagen-1, and TIMP1) and activation of hepatic stellate cells. Consistently, Cd increased the inflammation and the infiltration of macrophages and dendritic cells in liver. At late stage, the angiogenetic factors, VEGF and CD34, were elevated, indicating abnormal angiogenesis. At the end of treatment, Cd promoted CCl4-induced liver cancer formation, including incidence, tumor number and size. These effects were more pronounced in male mice than that in females. The promoting-effects of Cd on fibrosis and angiogenesis were further validated in hepatic stellate cells and liver sinusoidal endothelial cells. PPAR and ERBB signaling pathways were identified as the potential pathways to promote the toxicity of chronic Cd exposure. These findings provide a better understanding about the long-term influence of environmental Cd spanning the entire precancerous lesions-to-cancer formation cycle. (C) 2021 Elsevier B.V. All rights reserved.
关键词	Cadmium Long-term and low-dose exposure Hepatotoxicity Hepatocarcinogenesis
收录类别	SCIE ; EI
语种	英语
WOS研究方向	Environmental Sciences & Ecology
WOS类目	Environmental Sciences
WOS记录号	WOS:000656998900018
出版者	ELSEVIER
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127513
专题	生命科学与技术学院_博士生
通讯作者	Ba, Qian; Wang, Hui
作者单位	1.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai, Peoples R China; 2.Univ Chinese Acad Sci, Beijing, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 4.Shanghai Jiao Tong Univ, Ctr Single Cell Om, State Key Lab Oncogenes & Related Genes, Sch Med,Sch Publ Hlth, Shanghai 200025, Peoples R China
第一作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Xu, Yajie,Mu, Wei,Li, Jingquan,et al. Chronic cadmium exposure at environmental-relevant level accelerates the development of hepatotoxicity to hepatocarcinogenesis[J]. SCIENCE OF THE TOTAL ENVIRONMENT,2021,783.
APA	Xu, Yajie,Mu, Wei,Li, Jingquan,Ba, Qian,&Wang, Hui.(2021).Chronic cadmium exposure at environmental-relevant level accelerates the development of hepatotoxicity to hepatocarcinogenesis.SCIENCE OF THE TOTAL ENVIRONMENT,783.
MLA	Xu, Yajie,et al."Chronic cadmium exposure at environmental-relevant level accelerates the development of hepatotoxicity to hepatocarcinogenesis".SCIENCE OF THE TOTAL ENVIRONMENT 783(2021).