Inflammation May Mediate the Effects of Fluoride on Liver and Kidney Function of Adults: Cross-Sectional Studies in China

doi:10.1007/s12011-025-04583-4

. 2025 Mar 21.

doi: 10.1007/s12011-025-04583-4. Online ahead of print.

Inflammation May Mediate the Effects of Fluoride on Liver and Kidney Function of Adults: Cross-Sectional Studies in China

Minghao Geng¹, Yi Cheng², Leizhen Duan³, Guangshen Dong⁴, Shuo Yang², Xuecheng Jiao⁵, Weihua Jia⁶, Hui Huang², Ming Dou⁷, Xiaoli Fu⁸, Fangfang Yu², Yuhui Du⁹, Guoyu Zhou¹⁰, Yue Ba²

Affiliations

¹ Department of Preventive Medicine, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.
² Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.
³ Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450001, Henan, China.
⁴ Department of Basic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
⁵ Department of Endemic Diseases, Puyang Center for Disease Control and Prevention, Puyang, 457005, Henan, China.
⁶ Department of Endemic Diseases, Zhengzhou Center for Disease Control and Prevention, Zhengzhou, 450006, Henan, China.
⁷ School of Water Conservancy and Transportation, School of Ecology and Environment, Zhengzhou University, Zhengzhou, 450001, Henan, China.
⁸ Department of Preventive Health Care, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁹ National Experimental Teaching Demonstration Center of Public Health and Preventive Medicine, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China. duyuhui@zzu.edu.cn.
¹⁰ Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China. zhouguoyu@zzu.edu.cn.

PMID: 40117029
DOI: 10.1007/s12011-025-04583-4

Inflammation May Mediate the Effects of Fluoride on Liver and Kidney Function of Adults: Cross-Sectional Studies in China

Minghao Geng et al. Biol Trace Elem Res. 2025.

. 2025 Mar 21.

doi: 10.1007/s12011-025-04583-4. Online ahead of print.

Authors

Affiliations

¹ Department of Preventive Medicine, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.
² Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.
³ Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450001, Henan, China.
⁴ Department of Basic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.
⁵ Department of Endemic Diseases, Puyang Center for Disease Control and Prevention, Puyang, 457005, Henan, China.
⁶ Department of Endemic Diseases, Zhengzhou Center for Disease Control and Prevention, Zhengzhou, 450006, Henan, China.
⁷ School of Water Conservancy and Transportation, School of Ecology and Environment, Zhengzhou University, Zhengzhou, 450001, Henan, China.
⁸ Department of Preventive Health Care, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁹ National Experimental Teaching Demonstration Center of Public Health and Preventive Medicine, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China. duyuhui@zzu.edu.cn.
¹⁰ Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China. zhouguoyu@zzu.edu.cn.

PMID: 40117029
DOI: 10.1007/s12011-025-04583-4

Abstract

To assess associations among fluoride exposure, the inflammation, and liver and kidney functions, a total of 1646 adults aged ≥ 18 years were recruited in cross-sectional studies conducted in 2017 and 2022 in fluorosis areas. Questionnaire surveys were administered to obtain the demographic information. Urine and blood samples were collected for determinations of urinary fluoride (UF), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), blood urea nitrogen (BUN), serum creatinine (SCr), serum uric acid (SUA), and white blood cell (WBC) counts. Linear regressions, generalized linear models, and mediation analyses were employed here. We found that AST, BUN, and SUA increased by 0.589, 0.087, and 4.226 with a 1 mg/L increment of UF, and the SCr showed a negative linear association with UF (β = - 0.790) in all. Similar results were also observed in female. However, we only found the positive linear association between UF and AST/ALT in male. We also detected a significant modification by gender on associations between UF and values of AST, ALT, BUN, and SCr. Besides, participants with higher UF levels had higher counts of monocytes (β = 0.014) and neutrophils (β = 0.147) both in all and in stratified analyses of gender. Associations between AST/ALT, TBIL, SCr, SUA, and counts of WBC were revealed. In addition, there were mediator effects of monocytes and neutrophils in associations between UF and BUN (or SUA). We observed similar results in the age group of 46-64 years with those in all participants. This study observed a statistically significant association between UF and adult levels of AST, SCr, BUN, SUA, as well as monocyte and neutrophil counts, particularly in females. Furthermore, alterations in monocyte and neutrophil counts partially mediate the association between UF and BUN (or SUA). Our findings reveal the effects of fluoride exposure on liver and kidney function and provide clues for analyzing the relevant mechanism from an inflammatory perspective.

Keywords: Adult; Fluoride; Kidney; Liver; White blood cells.

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Conflict of interest statement

Declarations. Competing interest: The authors declare no competing interests.

References

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1. Hu Y, Li Y, Li M, Zhao T, Zhang W, Wang Y, He Y, Zhao H, Li H, Wang T, Zhao Y, Wang J, Wang J (2024) Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice. J Hazard Mater 465:133411. https://doi.org/10.1016/j.jhazmat.2023.133411 - DOI - PubMed
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1. Guo X, Wang L, Xuan J, Chen T, Du Y, Qiao H, Zhang S, Sun Z, Wang J, Niu R (2025) Fluoride induces spermatocyte apoptosis by IP3R1/MCU-mediated mitochondrial calcium overload through MAMs. J Hazard Mater 489:137514. https://doi.org/10.1016/j.jhazmat.2025.137514 - DOI - PubMed

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[1] Iheozor-Ejiofor Z, Walsh T, Lewis SR, Riley P, Boyers D, Clarkson JE, Worthington HV, Glenny AM, O’Malley L (2024) Water fluoridation for the prevention of dental caries. Cochrane Database Syst Rev 10:CD010856. https://doi.org/10.1002/14651858.CD010856.pub3 - DOI - PubMed

[2] Iheozor-Ejiofor Z, Walsh T, Lewis SR, Riley P, Boyers D, Clarkson JE, Worthington HV, Glenny AM, O’Malley L (2024) Water fluoridation for the prevention of dental caries. Cochrane Database Syst Rev 10:CD010856. https://doi.org/10.1002/14651858.CD010856.pub3 - DOI - PubMed

[3] Hung M, Hon ES, Mohajeri A, Moparthi H, Vu T, Jeon J, Lipsky MS (2023) A national study exploring the association between fluoride levels and dental fluorosis. JAMA Netw Open 6:e2318406. https://doi.org/10.1001/jamanetworkopen.2023.18406 - DOI - PubMed - PMC

[4] Hung M, Hon ES, Mohajeri A, Moparthi H, Vu T, Jeon J, Lipsky MS (2023) A national study exploring the association between fluoride levels and dental fluorosis. JAMA Netw Open 6:e2318406. https://doi.org/10.1001/jamanetworkopen.2023.18406 - DOI - PubMed - PMC

[5] Hu Y, Li Y, Li M, Zhao T, Zhang W, Wang Y, He Y, Zhao H, Li H, Wang T, Zhao Y, Wang J, Wang J (2024) Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice. J Hazard Mater 465:133411. https://doi.org/10.1016/j.jhazmat.2023.133411 - DOI - PubMed

[6] Hu Y, Li Y, Li M, Zhao T, Zhang W, Wang Y, He Y, Zhao H, Li H, Wang T, Zhao Y, Wang J, Wang J (2024) Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice. J Hazard Mater 465:133411. https://doi.org/10.1016/j.jhazmat.2023.133411 - DOI - PubMed

[7] Tang H, Hou H, Song L, Tian Z, Liu W, Xia T, Wang A (2024) The role of mTORC1/TFEB axis mediated lysosomal biogenesis and autophagy impairment in fluoride neurotoxicity and the intervention effects of resveratrol. J Hazard Mater 467:133634. https://doi.org/10.1016/j.jhazmat.2024.133634 - DOI - PubMed

[8] Tang H, Hou H, Song L, Tian Z, Liu W, Xia T, Wang A (2024) The role of mTORC1/TFEB axis mediated lysosomal biogenesis and autophagy impairment in fluoride neurotoxicity and the intervention effects of resveratrol. J Hazard Mater 467:133634. https://doi.org/10.1016/j.jhazmat.2024.133634 - DOI - PubMed

[9] Guo X, Wang L, Xuan J, Chen T, Du Y, Qiao H, Zhang S, Sun Z, Wang J, Niu R (2025) Fluoride induces spermatocyte apoptosis by IP3R1/MCU-mediated mitochondrial calcium overload through MAMs. J Hazard Mater 489:137514. https://doi.org/10.1016/j.jhazmat.2025.137514 - DOI - PubMed

[10] Guo X, Wang L, Xuan J, Chen T, Du Y, Qiao H, Zhang S, Sun Z, Wang J, Niu R (2025) Fluoride induces spermatocyte apoptosis by IP3R1/MCU-mediated mitochondrial calcium overload through MAMs. J Hazard Mater 489:137514. https://doi.org/10.1016/j.jhazmat.2025.137514 - DOI - PubMed

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Inflammation May Mediate the Effects of Fluoride on Liver and Kidney Function of Adults: Cross-Sectional Studies in China

Affiliations

Inflammation May Mediate the Effects of Fluoride on Liver and Kidney Function of Adults: Cross-Sectional Studies in China

Authors

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Abstract

Conflict of interest statement

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