Human cultured IMR-32 neuronal-like and U87 glial-like cells have different patterns of toxicity under fluoride exposure

Abstract

Background Fluoride (F) is a naturally exists in nature but several studies have indicated it as an environmental toxicant to all leaving beings. Human F exposure has increased over the years since this ion has been used by industry on foods, beverages, toothpastes and on water supply. Although F is safe at optimal concentrations in water supply, human exposure to high levels could trigger neurofunctional deficits. Materials and methods In this study, human glial-like (U87) and neuronal-like (IMR-32) cells lineages were used to access F toxicity and CNS cell sensibility on both cell facing the same protocol. Cells were exposed to F over 3, 5 and 10 days on two different F concentrations. Fluoride exposed cells were evaluated by standard toxicity assays to cell viability, apoptosis, necrosis and general cell metabolism. Oxidative stress parameters were evaluated by ATP and ROS levels, lipid peroxidation, GSH/GSSG ratio and comet assay. Results No changes were observed in IMR-32 at any given time while after 10 days of exposure to 0.22μg/mL, U87 glial-like cells showed signs of toxicity such as decreased cell viability by necrosis while general cell metabolism was increased. Oxidative stress parameters were next evaluated only on U87 glial-like cells after 10 days of exposure. F induced a decrease on ATP levels while no changes were observed on reactive oxygen species and lipid peroxidation. GSH/GSSG ratio was decreased followed by DNA damage both on 0.22μg/mL F. Conclusions Our results suggest an important differential behavior of the distinct types of cells exposed to the different fluoride concentrations, pointing that the U87 glial-like cells as more susceptible to damage triggered by this ion.

Prolonged exposure to high fluoride levels during adolescence to adulthood elicits molecular, morphological, and functional impairments in the hippocampus

“…The neuron density decrease is an important feature to be highlighted and further investigated regarding the time-window and fluoride levels exposure mainly because it is suggestive of a neurodegenerative pattern, featured in some neurological diseases such as Alzheimer’s diseases 36 . However, the cause of the density decrease must be first elucidated, whether is caused by a direct cell death already shown in previous studies 37 – 39 , whether is due to an impairment on the remarkable neurogenic role of hippocampus, especially the latter, considering the period of fluoride exposure ended with the CNS fully developed 29 , with 81-days-old, which corroborates with the dual suggestive pathways of our findings regarding the developmental fluoride neurotoxicity 30 , 40 .…”

Biocompatible and Oxidation‐Resistant Ti3C2Tx MXene with Halogen‐Free Surface Terminations

“…This result can be attributed to necrotic cell death by halogen ion‐induced toxicity of MILD‐Ti 3 C 2 T x . [ 86,87 ] Taken together, the data shown above support that NaOH‐Ti 3 C 2 T x is biocompatible regardless of the degree of oxidation even at high concentrations, and the contrasting toxicity of MLID‐Ti 3 C 2 T x possibly arising from the halogen species emerging from its oxidative degradation.…”

Effect of Fluoride on Cytotoxicity Involved in Mitochondrial Dysfunction: A Review of Mechanism

“…Fluorosis can cause mitochondrial dysfunction, which is partly due to the disruption of the balance between mitochondrial fission and fusion, which leads to changes in the morphology of mitochondria, which in turn leads to mitochondrial dysfunction ( 122 ). The neurotoxicity of fluoride is related to the destruction of mitochondria ( 123 ). Mitochondrial fission / fusion kinetics is very important for maintaining functional mitochondria ( 124 ).…”