Impact of fluoride on antioxidant activity and mitochondrial homeostasis in fetal rat kidney

Fluoride exposure harms human health. Additionally, recent attention has focused on understanding the impact of an adverse in utero environment on the programming of chronic kidney disease in adult offspring. A previous study has described that fluoride alters kidney development, inducing oligonephronia and promoting the premature maturation of remnant nephrons. Therefore, it is essential to continue researching the potential mechanisms involved in fluoride-induced alterations. Female Wistar rats were administered two doses of fluoride (2.5 or 5.0 mg/kg body weight/day) for 20 days before and after mating. The results showed that fluoride diminished catalase and superoxide dismutase activities while increasing the markers of nuclear factor erythroid 2-related factor 2 (Nrf2) activation, mitochondrial dynamics, autophagy, and biogenesis. Morphometric analysis revealed an increase in mitochondrial size and content. Although the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) increased, the activity of caspase-3 and the immunodetection in the TUNEL assay decreased. Several of these changes were mainly observed with the high fluoride dose. In conclusion, the results suggest that fluoride alters the redox status and mitochondrial homeostasis while decreasing apoptosis. It is essential to recognize that, under normal conditions, apoptosis plays a crucial role in proper kidney development, and its occurrence decreases as the structures mature. Therefore, collectively, these alterations could lead to undesirable effects on postnatal life.