PMID- 38461577 OWN - NLM STAT- MEDLINE DCOM- 20240329 LR - 20240329 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 274 DP - 2024 Apr 1 TI - Joint and interactive effects of metal mixtures on liver damage: Epidemiological evidence from repeated-measures study. PG - 116178 LID - S0147-6513(24)00253-7 [pii] LID - 10.1016/j.ecoenv.2024.116178 [doi] AB - BACKGROUND: The impact of heavy metals on liver function has been examined in numerous epidemiological studies. However, these findings lack consistency and longitudinal validation. METHODS: In this study, we conducted three follow-up surveys with 426 participants from Northeast China. Blood and urine samples were collected, along with questionnaire information. Urine samples were analyzed for concentrations of four metals (chromium [Cr], cadmium [Cd], lead [Pb], and manganese [Mn]), while blood samples were used to measure five liver function indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin [ALB], globulin [GLB], and total protein [TP]). We utilized a linear mixed-effects model (LME) to explore the association between individual heavy metal exposure and liver function. Joint effects of metal mixtures were investigated using quantile g-computation and Bayesian kernel machine regression (BKMR). Furthermore, we employed BKMR and Marginal Effect models to examine the interaction effects between metals on liver function. RESULTS: The LME results demonstrated a significant association between urinary heavy metals (Cr, Cd, Pb, and Mn) and liver function markers. BKMR results indicated positive associations between heavy metal mixtures and ALT, AST, and GLB, and negative associations with ALB and TP, which were consistent with the g-comp results. Synergistic effects were observed between Cd-Cr on ALT, Mn-Cr and Cr-Pb on ALB, while an antagonistic effect was found between Mn-Pb and Mn-Cd on ALB. Additionally, synergistic effects were observed between Mn-Cr on GLB and Cd-Cr on TP. Furthermore, a three-way antagonistic effect of Mn-Pb-Cr on ALB was identified. CONCLUSION: Exposure to heavy metals (Cr, Cd, Mn, Pb) is associated with liver function markers, potentially leading to liver damage. Moreover, there are joint and interaction effects among these metals, which warrant further investigation at both the population and mechanistic levels. CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Yin, Guohuan AU - Yin G AD - Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. FAU - Zhao, Shuanzheng AU - Zhao S AD - Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. FAU - Zhao, Meiduo AU - Zhao M AD - Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. FAU - Xu, Jing AU - Xu J AD - Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. FAU - Ge, Xiaoyu AU - Ge X AD - Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. FAU - Wu, Jingtao AU - Wu J AD - Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. FAU - Zhou, Yifan AU - Zhou Y AD - Civil Aviation Medicine Center, Civil Aviation Administration of China, Beijing 100123, China. FAU - Liu, Xiaolin AU - Liu X AD - Department of Epidemiology and Biostatistics, Jinzhou Medical University, Jinzhou, Liaoning 121001, China. FAU - Wei, Lanping AU - Wei L AD - Jinzhou Central Hospital, Jinzhou, Liaoning 121001, China. FAU - Xu, Qun AU - Xu Q AD - Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. Electronic address: xuqun@ibms.cams.cn. LA - eng PT - Journal Article DEP - 20240310 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 00BH33GNGH (Cadmium) RN - 2P299V784P (Lead) RN - 0 (Metals, Heavy) RN - 42Z2K6ZL8P (Manganese) RN - 0R0008Q3JB (Chromium) SB - IM MH - Humans MH - *Cadmium/toxicity MH - Bayes Theorem MH - Lead/pharmacology MH - *Metals, Heavy/pharmacology MH - Manganese/toxicity MH - Chromium/pharmacology MH - Liver OTO - NOTNLM OT - Heavy metal OT - Interaction OT - Joint effect OT - Liver damage OT - Longitudinal study COIS- 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. EDAT- 2024/03/11 00:42 MHDA- 2024/03/29 06:47 CRDT- 2024/03/10 19:01 PHST- 2023/12/04 00:00 [received] PHST- 2024/03/01 00:00 [revised] PHST- 2024/03/03 00:00 [accepted] PHST- 2024/03/29 06:47 [medline] PHST- 2024/03/11 00:42 [pubmed] PHST- 2024/03/10 19:01 [entrez] AID - S0147-6513(24)00253-7 [pii] AID - 10.1016/j.ecoenv.2024.116178 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2024 Apr 1;274:116178. doi: 10.1016/j.ecoenv.2024.116178. Epub 2024 Mar 10.