The present study explored the mechanism behind the fluorosis-mediated neurodevelopmental disorder and its intervention by naringin in prenatal and perinatal models in Wistar rats. Both in vitro and in vivo studies were conducted to assess autophagy, oxidative stress, neurogenesis, and impaired molecular dynamics markers. The experiment was conducted over a period of 120 days. Twelve Wistar rats were divided into four groups: control, sodium fluoride (NaF)-treated (10 ppm in drinking water), NaF + naringin-treated (50 mg/kg via oral gavage), and NaF with naringin administered to pups via breastfeeding. Treatments lasted 60 days for adults, with NaF exposure beginning 30 days pre-mating. Pups were evaluated at days 90 (prenatal) and 120 (perinatal) to assess developmental effects. Fluoride was administered by mixing NaF in drinking water at a dose of 10 ppm, and naringin was given via oral gavage at a dose of 50 mg/kg body weight. Fluoride toxicity showed altered behavior in the open field test (OFT), novel object recognition test (NORT), forced swim test (FST), and Morris Water Maze tests and impaired motor coordination in neonatal tests using nest seeking, locomotion, righting reflex, forelimb grasp reflex, cliff avoidance, and negative geotactic reflex. At the end of the experiment, prenatal and natal pups were sacrificed postweaning. Biochemical assays, fluoride concentration estimation, Western blotting, and immunohistochemistry were performed for the brain tissues. Naringin showed improvement in these behavioral studies, probably due to neuroprotection by modulation of SIRT-1, Dnm1L, and Lc3B levels, which were assessed by western blot. These findings highlight naringin as a promising therapeutic agent for mitigating fluoride-induced neurodevelopmental toxicity through pathways involving oxidative stress regulation, autophagy, and mitochondrial dynamics.
Keywords: Autophagy; Cognition; Drinking water; Mitochondrial dynamics; SIRT1; Sodium fluoride.
© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.