Elucidating environmental factors and their combined effects on CKDu in Sri Lanka using zebrafish*

作者全名："Jia, Pan-Pan; Chandrajith, Rohana; Junaid, Muhammad; Li, Tian-Yun; Li, Yong-Zhi; Wei, Xing-Yi; Liu, Li; Pei, De-Sheng"

作者地址："[Jia, Pan-Pan; Pei, De-Sheng] Chongqing Med Univ, Sch Publ Hlth, Chongqing, Peoples R China; [Chandrajith, Rohana; Junaid, Muhammad; Li, Tian-Yun; Li, Yong-Zhi; Wei, Xing-Yi; Liu, Li] Chongqing Inst Green & Intelligent Technol, Chinese Acad Sci, Chongqing 400714, Peoples R China; [Chandrajith, Rohana] Univ Peradeniya, Fac Sci, Dept Geol, Peradeniya, Sri Lanka"

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

来源：ENVIRONMENTAL POLLUTION

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001023307800001

JCR分区：Q1

影响因子：7.6

年份：2023

卷号：332

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Environmental factors; Kidney damages; Omics analysis; Combined exposure; Zebrafish models

摘要："Chronic kidney disease with uncertain etiology (CKDu) in Sri Lanka has attracted much attention as a global health issue. However, how environmental factors in local drinking water induce kidney damage in organisms is still elusive. We investigated multiple environmental factors including water hardness and fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM) to elucidate their toxic effects on CKDu risk in zebrafish. Acute exposure affected renal development and inhibited the fluorescence of Na, KATPase alpha1A4:GFP zebrafish kidney. Chronic exposure influenced the body weight of both genders of adult fish and induced kidney damage by histopathological analyses. Furthermore, the exposure significantly disturbed differential expression genes (DEGs), diversity and richness of gut microbiota, and critical metabolites related to renal functions. The transcriptomic analysis revealed that kidney-related DEGs were linked with renal cell carcinoma, proximal tubule bicarbonate reclamation, calcium signaling pathway, and HIF-1 signaling pathway. The significantly disrupted intestinal microbiota was closely related to the environmental factors and H & E score, which demonstrated the mechanisms of kidney risks. Notably, the Spearman correlation analysis indicated that the changed bacteria such as Pseudomonas, Paracoccus, and ZOR0006, etc were significantly connected to the DEGs and metabolites. Therefore, the assessment of multiple environmental factors provided new insights on ""bio-markers"" as potential therapies of the target signaling pathways, metabolites, and gut bacteria to monitor or protect residents from CKDu."

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 (NSFC) [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 sincerely thank Prof. Ying Cao for the kind gift of Na, K-ATPase alpha1A4:GFP zebrafish. This work was supported by 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 (NSFC, 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."