Detrimental impacts of fluoride have become a global concern for several decades. Despite its beneficial role which is restricted only in skeletal tissues, deleterious effects are also observed in soft tissues and systems. The generation of enhanced oxidative stress is the commencement of excess fluoride exposure which may lead to cell death. Fluoride causes cell death through autophagy via Beclin 1 and mTOR signaling pathways. Beside these, several organ specific anomalies through different signaling pathways have been documented. Mitochondrial dysfunction, DNA damage, autophagy and apoptosis are the damaging outcomes in case of hepatic disorders. Urinary concentration defects and cell cycle arrest have been reported in renal tissues. Abnormal immune response has been characterized in the cardiac system. Cognitive dysfunction, neurodegenerative condition and learning impairment have also been observed. Altered steroidogenesis, gametogenic abnormalities, epigenetic alterations and birth defect are the major reprotoxic conclusions. Abnormal immune responses, altered immunogenic proliferation, differentiation as well as altered ratio of immune cells are well-defined anomalies in the immune system. Though the mechanistic approach of fluoride toxicity in physiological systems is common, it follows different signaling cascades. This review emphasizes diverse signaling pathways which are the targets of overexposed fluoride.

几十年来，氟化物的有害影响已成为全球关注的问题。尽管其有益作用仅限于骨骼组织，但在软组织和系统中也观察到有害影响。过量的氟化物暴露会导致氧化应激增强，这可能导致细胞死亡。氟化物通过 Beclin 1 和 mTOR 信号通路的自噬导致细胞死亡。除此之外，还记录了通过不同信号传导途径出现的几种器官特异性异常。线粒体功能障碍、DNA 损伤、自噬和细胞凋亡是肝脏疾病的破坏性结果。据报道，肾组织中存在尿浓度缺陷和细胞周期停滞。心脏系统的免疫反应异常。认知功能障碍，还观察到神经退行性疾病和学习障碍。类固醇生成改变、配子发生异常、表观遗传改变和出生缺陷是主要的生殖毒性结论。异常的免疫反应、改变的免疫原性增殖、分化以及免疫细胞比例的改变是免疫系统中明确的异常。尽管生理系统中氟化物毒性的机制很常见，但它遵循不同的信号级联。这篇综述强调了不同的信号通路，这些信号通路是过度暴露的氟化物的目标。免疫细胞的分化和比例改变是免疫系统中明确的异常现象。尽管生理系统中氟化物毒性的机制很常见，但它遵循不同的信号级联。这篇综述强调了不同的信号通路，这些信号通路是过度暴露的氟化物的目标。免疫细胞的分化和比例改变是免疫系统中明确的异常现象。尽管生理系统中氟化物毒性的机制很常见，但它遵循不同的信号级联。这篇综述强调了不同的信号通路，这些信号通路是过度暴露的氟化物的目标。