Role of oxidative stress-mediated cell death and signaling pathways in experimental fluorosis

Babu, Srija; Manoharan, Suryaa; Ottappilakkil, Harsheema; Perumal, Ekambaram

doi:10.1016/j.cbi.2022.110106

Cited by 19 publications

(7 citation statements)

References 195 publications

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“…Excessive fluoride intake might directly attack oxygen, interfere with oxygen metabolism, and lead to increased oxygen free radicals ( 8 , 9 ). Simultaneously, fluoride can also decrease antioxidant enzyme activity and non-enzymatic antioxidant substance content, all of which lead to excessive oxygen free radical generation ( 10 , 11 ). Fluoride free radicals can attack the covalent bond of unsaturated fat acids, which causes lipid peroxidation and increases the free radicals in the body ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Exploration of the SIRT1-mediated BDNF–TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis

Wang,

Li,

Tang

et al. 2023

Front. Public Health

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IntroductionFluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF–TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through in vivo experiments.MethodsThis study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting.ResultsAll rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities.DiscussionCurrently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.

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Section: Introductionmentioning

confidence: 99%

Exploration of the SIRT1-mediated BDNF–TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis

Wang,

Li,

Tang

et al. 2023

Front. Public Health

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“…These findings suggest that oxidative stress plays an important role in the induction of cell death by LOVA treatment. Oxidative stress triggers various types of cell death, including apoptosis, ferroptosis, necroptosis, and autophagy [38,39]. However, the inhibitors of necroptosis, ferroptosis, endoplasmic reticulum stress, and autophagy did not prevent the occurrence of LOVA-induced cell death.…”

Section: Discussionmentioning

confidence: 98%

Lovastatin Treatment Inducing Apoptosis in Human Pancreatic Cancer Cells by Inhibiting Cholesterol Rafts in Plasma Membrane and Mitochondria

Gyoten,

Luo,

Fujiwara-Tani

et al. 2023

IJMS

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Resistance to anticancer drugs is a problem in the treatment of pancreatic ductal carcinoma (PDAC) and overcoming it is an important issue. Recently, it has been reported that statins induce apoptosis in cancer cells but the mechanism has not been completely elucidated. We investigated the antitumor mechanisms of statins against PDAC and their impact on resistance to gemcitabine (GEM). Lovastatin (LOVA) increased mitochondrial oxidative stress in PDAC cells, leading to apoptosis. LOVA reduced lipid rafts in the plasma membrane and mitochondria, suppressed the activation of epithelial growth factor receptor (EGFR) and AKT in plasma membrane rafts, and reduced B-cell lymphoma 2 (BCL2)-Bcl-2-associated X protein (BAX) binding and the translocation of F1F0 ATPase in mitochondrial rafts. In the three GEM-resistant cell lines derived from MIA and PANC1, the lipid rafts in the cell membrane and the mitochondria were increased to activate EGFR and AKT and to increase BCL2-BAX binding, which suppressed apoptosis. LOVA abrogated these anti-apoptotic effects by reducing the rafts in the resistant cells. By treating the resistant cells with LOVA, GEM sensitivity improved to the level of the parental cells. Therefore, cholesterol rafts contribute to drug resistance in PDAC. Further clinical research is warranted on overcoming anticancer drug resistance by statin-mediated intracellular cholesterol regulation.

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“…The increase in the levels of reactive oxygen species (ROS) was reported under the stimulation of F − in cells and organisms. 11,12 Among the ROS, hypochlorous acid (HClO) is a useful biomolecule synthesized from H 2 O 2 and Cl − , which is catalyzed by myeloperoxidase (MPO). 13 During oxidative stress, the elevated level of HClO can damage essential cellular components, resulting in cell dysfunction or death.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Moreover, increased ROS levels have been noted in conditions like skeletal fluorosis, liver damage, and cardiovascular diseases caused by excessive intake of F – . − Some studies imply there is a potential link and the physiological relevance between F – and HClO. The increase in the levels of reactive oxygen species (ROS) was reported under the stimulation of F – in cells and organisms. , Among the ROS, hypochlorous acid (HClO) is a useful biomolecule synthesized from H 2 O 2 and Cl – , which is catalyzed by myeloperoxidase (MPO) . During oxidative stress, the elevated level of HClO can damage essential cellular components, resulting in cell dysfunction or death. , Since HClO is a reliable biomarker for oxidative stress, investigating its level during F – induced oxidative stress is beneficial for comprehensively understanding the biological impact of F – on living organisms.…”

Section: Introductionmentioning

confidence: 99%

Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F^– and HClO in Organisms

Mei,

Hai,

et al. 2024

Anal. Chem.

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Fluoride anions (F − ) play a crucial role in human physiological processes. However, excessive intake of F − would affect oxygen metabolism and promote the generation of oxygenfree radicals. Hence, it is essential to develop a precise and efficient fluorescent probe for visualizing F − -induced oxidative stress. In this work, we developed the first bifunctional BODIPY-based fluorescent probe dfBDP with p-tert-butyldimethylsilanolate benzyl thioether as the sensing site for the detection of F − and HClO via two distinct reactions, the self-immolative removal and the thioether oxidation, which generate the sensing products with two nonoverlap fluorescence bands: 800−1200 and 500−750 nm, respectively. The probe dfBDP displays rapid response, high specificity, and sensitivity for the detection of F − (LOD, 316.2 nM) and HClO (LOD, 33.9 nM) in vitro. Cellular imaging reveals a correlation between F − -induced oxidative stress and the upregulation of HClO. Finally, probe dfBDP was employed to detect F − and HClO in mice under the stimulation of F − . The experimental results display that the level of HClO elevates in the liver of mice.

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Role of oxidative stress-mediated cell death and signaling pathways in experimental fluorosis

Cited by 19 publications

References 195 publications

Exploration of the SIRT1-mediated BDNF–TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis

Exploration of the SIRT1-mediated BDNF–TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis

Lovastatin Treatment Inducing Apoptosis in Human Pancreatic Cancer Cells by Inhibiting Cholesterol Rafts in Plasma Membrane and Mitochondria

Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F^– and HClO in Organisms

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Role of oxidative stress-mediated cell death and signaling pathways in experimental fluorosis

Cited by 19 publications

References 195 publications

Exploration of the SIRT1-mediated BDNF–TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis

Exploration of the SIRT1-mediated BDNF–TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis

Lovastatin Treatment Inducing Apoptosis in Human Pancreatic Cancer Cells by Inhibiting Cholesterol Rafts in Plasma Membrane and Mitochondria

Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F– and HClO in Organisms

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Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F^– and HClO in Organisms