Association between metal exposure and oxidative stress in preschool children and the moderating role of urinary creatinine

The association between childhood metal exposure and oxidative stress levels is of paramount importance, as children are a susceptible group to metal toxicity and elevated oxidative damage has been linked to a variety of diseases. Despite the fact that urinary creatinine is commonly used to account for variations in urine dilution, it may introduce analytical bias if creatinine excretion is influenced by the same factors that affect urinary metal excretion or if metal exposure compromises kidney function. In this study, we evaluated the individual and joint association between urinary metal ion concentrations and the oxidative stress biomarker 8-hydroxy-2 ' -deoxyguanosine in preschool children and assessed the moderation role of urinary creatinine. Multiple linear regression showed that copper and selenium were negatively correlated with 8-hydroxy-2 ' -deoxyguanosine, arsenic and antimony were positively correlated with 8-hydroxy-2 ' -deoxyguanosine. Restricted cubic spline demonstrated the non-linear relationship between lithium, nickel, arsenic, tin, and antimony and 8-hydroxy-2 ' -deoxyguanosine. Bayesian kernel machine regression and quantile g-computation analyses showed a positive association between urinary metal ion concentration and 8-hydroxy-2 ' -deoxyguanosine levels, with selenium being the most significant metal ion contributing to elevated oxidative stress levels. Moderation analyses revealed that the association between urinary metal ions and 8-hydroxy-2 ' -deoxyguanosine is more significant at high urinary creatinine levels. The results indicated the importance of adequately accounting for urinary creatinine levels to avoid overestimation of metal exposure and distortion of the true association between metal exposure and oxidative damage.