Fluoride Induces Apoptosis in Mammalian Cells: In Vitro and In Vivo Studies

Abstract

Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

High Fluoride Ingestion Impairs Bone Fracture Healing by Attenuating M2 Macrophage Differentiation

“…The toxicity effect of fluoride in a dose-dependent manner has been previously reported ( Ribeiro et al, 2017 ; Jiang et al, 2020a ). There is still no accurate standard for fluoride ion concentration in the bone tissue of patients with SF, which has led to a blurred relationship between bone damage and bone fluoride concentration.…”

In Vivo Comparison of the Phenotypic Aspects and Molecular Mechanisms of Two Nephrotoxic Agents, Sodium Fluoride and Uranyl Nitrate

“…Under our conditions, UN induced apoptosis after a 72-h period but not after 48 h (data not shown); thus we hypothesize that KIM-1 participates in the protection of the kidney during the acute nephrotoxicity induced by UN after a longer recovery period. F-induced apoptosis was observed after acute exposure in different models, but not in the kidney [29,30,31]. In vitro, NaF induces the downregulation of Bcl-2 in human fibroblasts, stimulating the mitochondrial cell death pathway [25].…”

“…Different mechanisms have been identified in F and U toxicity such as oxidative stress, autophagy, genotoxicity and apoptosis, using in vitro models [21,22,23,24,25]. These mechanisms also seem to be involved in F and U toxicity in vivo in addition to inflammation [26,27,28,29,30,31,32]. Interestingly, the two specific mechanisms of apoptosis and inflammation were implicated in kidney cell toxicity after both U and F exposures in vitro but needed to be demonstrated in vivo.…”

Farrerol Induces Cancer Cell Death via ERK Activation in SKOV3 Cells and Attenuates TNF-α-Mediated Lipolysis

“…Cleaved Caspase-3 acts as an effector caspase that induces apoptosis by degrading proteins such as DNA fragmentation factor and poly ADP ribose polymerase (PARP) that is found in the nucleus and plays an important role in maintaining the survival of cells involved in DNA repair. PARP is a major target protein of Caspase-3 and is inactivated when cleaved by Caspase-3, promoting cell degradation and causing apoptosis [6][7][8][9][10]. Extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK function in protein kinase cascades and play critical roles in the regulation of cell proliferation, differentiation, and apoptosis [11].…”