Hesperidin Protects Against Sodium Fluoride-Induced Molecular, Stereological, and Behavioral Alterations in the Rat Cerebellum Publisher Pubmed



Talebinasab A ; Javanbakht P ; Mojaverrostami S ; Ragerdi Kashani I ; Keshavarz L ; Hashemi M ; Amirizadeh S ; Shabani M ; Asadigolshan R
Source: Nutritional Neuroscience Published:2025

Abstract

Objectives: Exposure to elevated levels of fluoride from environmental or dietary sources can lead to toxic effects on the nervous system. This work examined the potential of hesperidin, a citrus-derived flavonoid recognized for its neuroprotective actions, to counteract NaF-induced toxicity in the rat cerebellum. Methods: Male rats (n = 10 per group) were divided into four groups receiving either normal water, NaF (200 ppm) alone, NaF plus hesperidin (200 mg/kg/day), or hesperidin alone for 4 weeks. Neurobehavioral assessments, including the beam walking, ladder rung walking, inclined plane, and accelerating rotarod tests, were performed, followed by neurochemical and quantitative stereological analysis of the cerebellum. Results: NaF-treated rats exhibited deficits in coordination, balance, learning, and adaptation as assessed by behavioral testing. However, co-treatment with hesperidin significantly prevented these motor deficits. Molecular findings indicated that hesperidin may have lessened NaF-induced neurotoxicity by helping to maintain brain-derived neurotrophic factor (BDNF) mRNA expression and preserving antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)], while simultaneously lowering malondialdehyde (MDA) levels and suppressing p53 expression. Stereological analysis showed that hesperidin prevented NaF-related reductions in total cerebellar, cortical, and white matter volumes, as well as in Purkinje cell number. Discussion: Prolonged NaF exposure is linked to cerebellar structural alterations and motor deficits, likely mediated by oxidative stress, apoptosis, and disrupted neurotrophic signaling. In this experimental model, appeared to mitigate these effects by enhancing antioxidant defenses and supporting neuroprotective mechanisms, suggesting its potential to preserve cerebellar structure and function under fluoride-induced toxicity. © 2025 Elsevier B.V., All rights reserved.