| Objective: To analyze the relationship between low-to-moderate fluoride exposure and oxidative stress level among children,and further explore the role of oxidative stress indicator in the associations between fluoride exposure and dental fluorosis(DF).Methods: In this study,a total of 593 children aged 7-13 years were recruited in Tianjin with stratified multi-stage random sampling method.A-face-to-face interview was performed to complete a questionnaire and collected the general demographic data of the children and their parents.The status of dental fluorosis in children was diagnosed by professional doctors.The drinking water and urine samples of the children were collected to measure water fluoride and urine fluoride content,and the fluoride concentrations of water and urine samples were determined using the ion selective electrode method.8-Hydroxy-2’-deoxyguanosine(8-OHd G)in urine was determined by enzyme-linked immunosorbent assay(ELISA)as an indicator of oxidative stress.Multivariate linear regression model and log-binomial regression model were used to analyze the associations between fluoride exposure,8-OHd G levels and DF prevalence,and the potential role of 8-OHd G in the relationship between fluoride and DF was analyzed through mediation analysis and modification analysis.Results: The contents of water fluoride and urine fluoride in this study ranged from 0.20 to 3.90 mg/L and 0.01 to 5.54 mg/L;with an average(± standard deviation)of 1.42(± 1.00)mg/L and 1.36(± 1.30)mg/L;and the interquartile range was 0.70～2.20 mg/L,0.16～2.29 mg/L,respectively.8-OHd G level ranged from 5.72～17.12 μg/L,with an average(± standard deviation)of 11.46(± 2.36)μg/L,and the interquartile range was 9.72～13.51 μg/L.The multiple linear regression analysis showed that for evey 1 mg/L increase in water fluoride concentration,the urine 8-OHd G content increased by 0.69 μg/L(β = 0.69,95%CI: 0.50,0.87).For evey 1 mg/L increase in urine fluoride content,urinary 8-OHd G content increased by 0.68 μg/L(β = 0.68,95%CI: 0.53,0.82).Both water fluoride and urine fluoride concentrations had a dose-response relationship with children’s urine 8-OHd G concentrations(Both trend P value < 0.001).For evey 1 mg/L increase in water fluoride was associated with increments of 50%(95%CI: 1.42,1.59),87%(95%CI: 1.65,2.12),74%(95%CI: 1.62,1.87),3.25-fold(95%CI: 3.14,5.76)in the risks of total DF,very mild DF,mild DF and moderate DF,respectively.For evey 1 mg/L increase in urine fluoride was associated with increments of 42%(95%CI: 1.34,1.50),67%(95%CI: 1.47,1.89),59%(95%CI: 1.47,1.72),2.03-fold(95%CI: 2.33,3.93)in the risks of total DF,very mild DF,mild DF and moderate DF,respectively.For every 1 μg/L increase in urine 8-OHd G levels was associated with increments of 11%(95% CI: 1.08,1.15),15%(95% CI: 1.06,1.24),18%(95% CI: 1.13,1.23),25%(95% CI: 1.08,1.44)in the risks of total DF,very mild DF,mild DF and moderate DF,respectively.The mediation analysis indicated that 8-OHd G mediated partly in the associations between water fluoride and total DF,very mild DF and mild DF with the ratios of 8.1%(95%CI: 4.6,14.0),9.1%(95%CI: 3.3,22.3)and 12.6%(95%CI: 7.6,20.2).And 8-OHd G only mediated partly in the relationships between urine fluoride and total DF and mild DF with the ratios of 7.1%(95%CI: 3.8,12.9)and 10.5%(95%CI: 5.8,18.3).In addition,the stratified analysis showed that water fluoride and urine fluoride concentrations had stronger effects in the risk of mild DF in children in the middle and highest tertile of the 8-OHd G group compared with children in the lowest tertile group,and the interactions are statistically significant(Interaction P values were 0.0031 and 0.0288,respectively)Conclusions: Low-to-moderate fluoride exposure is positively associated with urine 8-OHd G levels among children.Urine 8-OHd G level is positively correlated with dental fluorosis risk.In addition,8-OHd G might mediate and moderate the association between fluoride and mild DF. |
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