Prospects for the Role of Ferroptosis in Fluorosis

Zhang, Yi; Wu, Jing; Jiang, Lai; Lu, Chenkang; Huang, Zhengwei; Liu, Bin

doi:10.3389/fphys.2021.773055

Cited by 15 publications

(7 citation statements)

References 46 publications

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“…Since the discovery of ferroptosis, its toxic mechanism regarded as exogenous chemicals has attracted extensive attention. However, the pathogenesis of ferroptosis in fluorosis is not clear, and the key genes and pathways related to ferroptosis in fluorosis need to be further discovered [ 19 ]. In this study, 35 differentially expressed genes (17 upregulated and 18 downregulated) related to ferroptosis in fluorosis were obtained by analyzing the gene expression profile of the fluoride exposure model for the first time and were used to indicate that ferroptosis-related genes are involved in the pathogenesis of fluorosis, suggesting potential pharmacological targets.…”

Section: Discussionmentioning

confidence: 99%

“…Our recent KEGG pathway analysis found that the differential expression of ferroptosis-related genes in fluorosis is mainly involved in ferroptosis, fatty acid metabolism, and glutathione metabolism. Besides that, in a fluoride-containing medium, the degree of ferroptosis of sub-cultivating MC3T3-E1 (WT) cells was higher than that of fluoride-resistant MC3T3-E1 (FR) cells, indicating that there is a potential link between fluorosis and ferroptosis [ 19 ]. In addition, a cross-sectional study of schoolchildren reported that Glutathione S-Transferase (GST) levels were positively associated with the degree of fluorosis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Ferroptosis cells have typical necrotic morphology, accompanied by small abnormal mitochondria, reduced cristae, membrane condensation, rupture of the outer membrane, and no apoptotic characteristics [ 16 , 17 , 18 ]. A large number of studies indicate that fluoride can induce oxidative stress by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and further lead to ferroptosis [ 19 , 20 ]. The discovery of ferroptosis in fluorosis suggests that ferroptosis is a new mechanism of fluorosis, and the targeted intervention of ferroptosis is expected to be an effective method for the treatment of fluorosis.…”

Section: Introductionmentioning

confidence: 99%

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In Silico Analysis of Ferroptosis-Related Genes and Its Implication in Drug Prediction against Fluorosis

Liu

et al. 2023

IJMS

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Fluorosis is a serious global public health problem. Interestingly, so far, there is no specific drug treatment for the treatment of fluorosis. In this paper, the potential mechanisms of 35 ferroptosis-related genes in U87 glial cells exposed to fluoride were explored by bioinformatics methods. Significantly, these genes are involved in oxidative stress, ferroptosis, and decanoate CoA ligase activity. Ten pivotal genes were found by the Maximal Clique Centrality (MCC) algorithm. Furthermore, according to the Connectivity Map (CMap) and the Comparative Toxicogenomics Database (CTD), 10 possible drugs for fluorosis were predicted and screened, and a drug target ferroptosis-related gene network was constructed. Molecular docking was used to study the interaction between small molecule compounds and target proteins. Molecular dynamics (MD) simulation results show that the structure of the Celestrol–HMOX1 composite is stable and the docking effect is the best. In general, Celastrol and LDN-193189 may target ferroptosis-related genes to alleviate the symptoms of fluorosis, which may be effective candidate drugs for the treatment of fluorosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Silico Analysis of Ferroptosis-Related Genes and Its Implication in Drug Prediction against Fluorosis

Liu

et al. 2023

IJMS

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“…Alteration of the iAs methylation pattern may be influenced by GSH depletion reported by iF exposure [ 39 ]. It has already been shown that GSH depletion could be a potential mechanism associated with altered methylation capacity [ 17 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Decreased Arsenic Disposition and Alteration of its Metabolic Profile in mice Coexposed to Fluoride

Peña

Hernández

Razo

2023

Biol Trace Elem Res

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Inorganic arsenic (iAs) and fluoride (iF) are ubiquitous elements whose coexistence is frequent in several regions of the world due to the natural contamination of water sources destined for human consumption. It has been reported that coexposure to these two elements in water can cause toxic effects on health, which are controversial since antagonistic and synergistic effects have been reported. However, there is little information on the possible toxicological interaction between concurrent exposure to iAs and iF on the iAs metabolism profile.The goal of this study was to determine the effect of iF exposure on iAs methylation patterns in the urine and the tissues of female mice of the C57BL/6 strain, which were divided into four groups and exposed daily for 10 days through drinking water as follows: purified water (control); arsenite 1 mg/L, fluoride 50 mg/L and arsenite & fluoride 1:50 mg/L.To characterize the iAs methylation pattern in concomitant iF exposure, iAs and its methylated metabolites (MAs and DMAs) were quantified in the tissues and the urine of mice was exposed to iAs alone or in combination. Our results showed a statistically significant decrease in the arsenic species concentrations and altered relative proportions of arsenic species in tissues and urine in the As-iF coexposure group compared to the iAs-exposed group. These findings show that iF exposure decreases arsenic disposition and alters methylation capacity.Nevertheless, additional studies are required to elucidate the mechanisms involved in the iAs-iF interaction through iF exposure affecting iAs disposition and metabolism.

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“…Ferroptosis activators like erastin or RSL3 cease the antioxidant system once they enhance the deposition of iron inside the cell [ 129 ]. The iron deposited over here will directly produce excessive ROS via the Fenton reaction, leading to an increase in OD [ 130 ]. Moreover, the activity of enzymes namely LOX or Egg-laying defective nine (EGLN) prolyl hydroxylases is increased by iron accumulation, where the roles of the enzymes are LiPr and oxygen homeostasis respectively [ 49 , 94 , 131 , 132 ].…”

Section: Hallmarks Features Of Ferroptosismentioning

confidence: 99%

Deeper insight into ferroptosis: association with Alzheimer’s, Parkinson’s disease, and brain tumors and their possible treatment by nanomaterials induced ferroptosis

Yadav,

Choudhary,

Gacem

et al. 2023

Redox Report

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Ferroptosis is an emerging and novel type of iron-dependent programmed cell death which is mainly caused by the excessive deposition of free intracellular iron in the brain cells. This deposited free iron exerts a ferroptosis pathway, resulting in lipid peroxidation (LiPr). There are mainly three ferroptosis pathways viz. iron metabolism-mediated cysteine/glutamate, and LiPr-mediated. Iron is required by the brain as a redox metal for several physiological activities. Due to the iron homeostasis balance disruption, the brain gets adversely affected which further causes neurodegenerative diseases (NDDs) like Parkinson's and Alzheimer's disease, strokes, and brain tumors like glioblastoma (GBS), and glioma. Nanotechnology has played an important role in the prevention and treatment of these NDDs. A synergistic effect of nanomaterials and ferroptosis could prove to be an effective and efficient approach in the field of nanomedicine. In the current review, the authors have highlighted all the latest research in the field of ferroptosis, specifically emphasizing on the role of major molecular key players and various mechanisms involved in the ferroptosis pathway. Moreover, here the authors have also addressed the correlation of ferroptosis with the pathophysiology of NDDs and theragnostic effect of ferroptosis and nanomaterials for the prevention and treatment of NDDs.

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Prospects for the Role of Ferroptosis in Fluorosis

Cited by 15 publications

References 46 publications

In Silico Analysis of Ferroptosis-Related Genes and Its Implication in Drug Prediction against Fluorosis

In Silico Analysis of Ferroptosis-Related Genes and Its Implication in Drug Prediction against Fluorosis

Decreased Arsenic Disposition and Alteration of its Metabolic Profile in mice Coexposed to Fluoride

Deeper insight into ferroptosis: association with Alzheimer’s, Parkinson’s disease, and brain tumors and their possible treatment by nanomaterials induced ferroptosis

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