Metabolome evidence of CKDu risks after chronic exposure to simulated Sri Lanka drinking water in zebrafish

作者全名："Jia, Pan-Pan; Li, Yan; Zhang, Lan-Chen; Wu, Ming-Fei; Li, Tian-Yun; Pei, De-Sheng"

作者地址："[Jia, Pan-Pan; Li, Yan; Zhang, Lan-Chen; Wu, Ming-Fei; Pei, De-Sheng] Chongqing Med Univ, Sch Publ Hlth, Chongqing 400016, Peoples R China; [Li, Tian-Yun] Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing 400714, Peoples R China"

通信作者："Pei, DS (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Chongqing 400016, Peoples R China."

来源：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001195833300001

JCR分区：Q1

影响因子：6.2

年份：2024

卷号：273

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：CKDu; Metabolomics analysis; Zebrafish; Environmental factors; Chronic exposure

摘要："It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease."

基金机构："High-level Talents Project of Chongqing Medical University [R4014, R4020]; Research Program of Chongqing Science and Technology Commission [cstc2019jcyj-zdxmX0035, CSTCCXLJRC201714]; National Natural Science Foundation of China [32200386]; Program of China-Sri Lanka Joint Center for Water Technology Research and Demonstration by Chinese Academy of Sciences (CAS) /China-Sri Lanka Joint Center for Education and Research by CAS"

基金资助正文："We thank the support from the High-level Talents Project of Chongqing Medical University (No. R4014 to D.S.P., and R4020 to P.P. J.) , Research Program of Chongqing Science and Technology Commission (No. cstc2019jcyj-zdxmX0035 to D.S.P., and CSTCCXLJRC201714 to D.S.P.) , National Natural Science Foundation of China (No. 32200386 to P.P.J.) , and Program of China-Sri Lanka Joint Center for Water Technology Research and Demonstration by Chinese Academy of Sciences (CAS) /China-Sri Lanka Joint Center for Education and Research by CAS."