Bharathiar University, Coimbatore, Tamilnadu, India.
Biol Trace Elem Res. 2023 Mar;201(3):1214-1236. doi: 10.1007/s12011-022-03242-2. Epub 2022 Apr 30.
Fluoride is one of the major toxicants in the environment and is often found in drinking water at higher concentrations. Living organisms including humans exposed to high fluoride levels are found to develop mild-to-severe detrimental pathological conditions called fluorosis. Fluoride can cross the hematoencephalic barrier and settle in various brain regions. This accumulation affects the structure and function of both the central and peripheral nervous systems. The neural ultrastructure damages are reflected in metabolic and cognitive activities. Hindrances in synaptic plasticity and signal transmission, early neuronal apoptosis, functional alterations of the intercellular signaling pathway components, improper protein synthesis, dyshomeostasis of the transcriptional and neurotrophic factors, oxidative stress, and inflammatory responses are accounted for the fluoride neurotoxicity. Fluoride causes a decline in brain functions that directly influence the overall quality of life in both humans and animals. Animal studies are widely used to explore the etiology of fluoride-induced neurotoxicity. A good number of these studies support a positive correlation between fluoride intake and toxicity phenotypes closely associated with neurotoxicity. However, the experimental dosages highly surpass the normal environmental concentrations and are difficult to compare with human exposures. The treatment procedures are highly dependent on the dosage, duration of exposure, sex, and age of specimens among other factors which make it difficult to arrive at general conclusions. Our review aims to explore fluoride-induced neuronal damage along with associated histopathological, behavioral, and cognitive effects in experimental models. Furthermore, the correlation of various molecular mechanisms upon fluoride intoxication and associated neurobehavioral deficits has been discussed. Since there is no well-established mechanism to prevent fluorosis, phytochemical-based alleviation of its characteristic indications has been proposed as a possible remedial measure.
氟化物是环境中主要的有毒物质之一，通常在饮用水中以较高浓度存在。研究发现，包括人类在内的生物体暴露在高氟水平下会发展出轻度到重度的有害病理状况，称为氟中毒。氟化物可以穿过血脑屏障并在各种大脑区域沉积。这种积累会影响中枢和周围神经系统的结构和功能。神经超微结构损伤反映在代谢和认知活动中。突触可塑性和信号传输受阻、早期神经元凋亡、细胞间信号转导途径成分的功能改变、蛋白质合成不当、转录和神经营养因子的动态平衡失调、氧化应激和炎症反应都被认为是氟化物的神经毒性。氟化物导致大脑功能下降，直接影响人类和动物的整体生活质量。动物研究被广泛用于探索氟化物引起的神经毒性的病因。大量的这些研究支持氟化物摄入与密切相关的神经毒性毒性表型之间的正相关。然而，实验剂量远远超过正常环境浓度，难以与人类暴露相比较。治疗程序高度依赖于剂量、暴露时间、性别和标本年龄等因素，这使得难以得出普遍的结论。我们的综述旨在探讨实验模型中氟化物引起的神经元损伤以及相关的组织病理学、行为和认知效应。此外，还讨论了氟化物中毒和相关神经行为缺陷相关的各种分子机制之间的相关性。由于没有预防氟中毒的既定机制，因此提出了基于植物化学物质的缓解其特征表现的方法作为一种可能的补救措施。
