Mediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function.

Autor: Luo KH; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medicine University, Kaohsiung City 807, Taiwan., Tu HP; Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan., Chang HC; Divisions of Pulmonary & Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan., Yang CC; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medicine University, Kaohsiung City 807, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan., Weng WC; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan., Chen TH; Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan., Yang CH; Department of Information Management, Tainan University of Technology, Tainan 71002, Taiwan; Department of Electronic Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 80778, Taiwan., Chuang HY; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medicine University, Kaohsiung City 807, Taiwan; Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Occupational and Environmental Medicine, Kaohsiung Medicine University Hospital, Kaohsiung Medicine University, Kaohsiung 807, Taiwan; Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, and Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address: ericch@kmu.edu.tw.
Jazyk: angličtina
Zdroj: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2024 Sep 15; Vol. 283, pp. 116837. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1016/j.ecoenv.2024.116837
Abstrakt: The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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