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

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.