Fluoride-Induced Oxidative Stress in Non-Skeletal Tissues: A Systematic Review and Meta-Analysis

Purpose: Several studies have investigated the oxidative stress parameters in non-skeletal tissues of animals exposed to fluoride, however, the findings from these studies are inconsistent. We conducted a systematic review and meta-analysis to evaluate the levels of oxidative stress biomarkers in experimental animals treated with fluoride compared with the control group. Methods: The PubMed, Cochrane Library, EBSCO, and JSTOR databases were searched for studies reporting oxidative stress biomarkers in non-skeletal tissues of animals exposed to fluoride. A random effects model with the standardized mean difference (SMD) was used for meta-analyses. The heterogeneity of the studies was evaluated using Higgin's 12 statistics. The risk of bias was assessed using the SYRCLE's risk of bias tool and publication bias using Egger's test Results: Compared to the control, the levels of ROS, LPO, and NO were significantly elevated and the levels of SOD, CAT, GSH-Px, and GSH significantly reduced in the studied tissues. The level of GST however showed no significant difference. The test for subgroup differences suggested that different animal species and tissues have varying susceptibilities and tolerance to fluoride. Furthermore, the extent of fluoride-induced oxidative stress damage can be modified by the intervention period. Meta-regression analysis indicated that the studies' effect size for LPO was influenced by animal species. Conclusions: This meta-analysis's findings demonstrated the presence of oxidative stress and depletion of antioxidants in the non-skeletal tissues of experimental animals exposed to fluoride. More studies in humans are recommended to strengthen the current evidence.