Antioxidant Phytochemicals for the Prevention of Fluoride-Induced Oxidative Stress and Apoptosis: a Review

Angwa, Linet Musungu; Jiang, Yuting; Pei, Junrui; Sun, Dianjun

doi:10.1007/s12011-021-02729-8

Cited by 22 publications

(10 citation statements)

References 246 publications

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“…Mitochondrial regulation of apoptosis and oxidative stress are closely related, as repeatedly reported in the literature [65][66][67], and the correlation between oxidative stress and apoptosis has been demonstrated. Therefore, simultaneous detection of mitochondrial superoxide generation (detected by MitoSOX Red membrane-penetrating dye) and expression of phosphatidylserine on the cell surface of apoptotic cells (assessed by binding of annexin V) in the same cell sample provides an accurate evaluation of the ability of the test compound to initiate oxidative stress in cell culture and induce apoptosis.…”

Section: Cytotoxicity Assaysupporting

confidence: 63%

Natural Acetogenins, Chatenaytrienins-1, -2, -3 and -4, Mitochondrial Potential Uncouplers and Autophagy Inducers—Promising Anticancer Agents

Dzhemileva,

Tuktarova,

Dzhemilev

et al. 2023

Antioxidants

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The present paper details the complete stereoselective synthesis of four natural acetogenins, chatenaytrienins-1, -2, -3 and -4, previously isolated from the roots of fruit trees of the family Annonaceae (A. nutans and A. muricata), as an inseparable mixture. The novel organometallic reactions, developed by the authors, of Ti-catalyzed cross-cyclomagnesiation of O-containing and aliphatic allenes using available Grignard reagents were applied at the key stage of synthesis. We have studied the biological activity of the synthesized individual chatenaytrienins-1, -2, -3 and -4 in vitro, including their cytotoxicity in a panel of tumor lines and their ability to induce apoptosis, affect the cell cycle and mitochondria, and activate the main apoptotic signaling pathways in the cell, applying modern approaches of flow cytometry and multiplex analysis with Luminex xMAP technology. It has been shown that chatenaytrienins affect mitochondria by uncoupling the processes of mitochondrial respiration, causing the accumulation of ROS ions, followed by the initiation of apoptosis. The most likely mechanism for the death of cortical neurons from the consumption of tea from the seeds of Annona fruit is long-term chronic hypoxia, which leads to the development of an atypical form of Parkinson’s disease that is characteristic of the indigenous inhabitants of Guam and New Caledonia.

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Section: Cytotoxicity Assaysupporting

confidence: 63%

Natural Acetogenins, Chatenaytrienins-1, -2, -3 and -4, Mitochondrial Potential Uncouplers and Autophagy Inducers—Promising Anticancer Agents

Dzhemileva,

Tuktarova,

Dzhemilev

et al. 2023

Antioxidants

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show abstract

“…When considering the indirect exposure protocol and blood plasma F levels in offspring, oxidative biochemical changes triggered by the concentrations used in this study could be expected, even if more subtly, since previous studies in adult animals with direct exposure have shown that these same concentrations can modulate molecular and biochemical aspects of salivary glands for a longer time [17,18]. In this regard, evidence shows that increased bioavailability of F in blood plasma may be associated with an imbalance in the redox system caused by F, which can be considered the key mechanism for these changes [27]. Therefore, GSH activity was evaluated in this study, as it is the main antioxidant defense pathway [28], in addition to malondialdehyde (MDA) dosage to assess possible oxidative damage caused by an imbalance in the redox system [29].…”

Section: Discussionmentioning

confidence: 68%

Maternal Fluoride Exposure Exerts Different Toxicity Patterns in Parotid and Submandibular Glands of Offspring Rats

Santos

Ferreira

Bittencourt

et al. 2022

IJMS

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There is currently a controversial and heated debate about the safety and ethical aspects of fluoride (F) used for human consumption. Thus, this study assessed the effects of prenatal and postnatal F exposure of rats on the salivary glands of their offspring. Pregnant rats were exposed to 0, 10, or 50 mg F/L from the drinking water, from the first day of gestation until offspring weaning (42 days). The offspring rats were euthanized for the collection of the parotid (PA) and submandibular (SM) glands, to assess the oxidative biochemistry and to perform morphometric and immunohistochemical analyses. F exposure was associated with a decrease in the antioxidant competence of PA in the 10 mg F/L group, contrasting with the increase observed in the 50 mg F/L group. On the other hand, the antioxidant competence of the SM glands was decreased at both concentrations. Moreover, both 10 and 50 mg F/L groups showed lower anti-α-smooth muscle actin immunostaining area in SM, while exposure to 50 mg F/L was associated with changes in gland morphometry by increasing the duct area in both glands. These findings demonstrate a greater susceptibility of the SM glands of the offspring to F at high concentration in comparison to PA, reinforcing the need to adhere to the optimum F levels recommended by the regulatory agencies. Such findings must be interpreted with caution, especially considering their translational meaning.

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“…In this study, we constructed the protein interaction network of ferroptosis-related genes in fluorosis for the first time and screened the targeted therapeutic drugs of fluorosis. Although it has been reported that chronic symptoms of skeletal fluorosis are irreversible and permanent [ 60 ], a double-blind controlled trial in children found that treatment with ascorbic acid, calcium, and vitamin D3 significantly improved children’s dental, clinical, and skeletal fluorosis and related biochemical indicators. This shows that fluorosis can be reversed [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

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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Antioxidant Phytochemicals for the Prevention of Fluoride-Induced Oxidative Stress and Apoptosis: a Review

Cited by 22 publications

References 246 publications

Natural Acetogenins, Chatenaytrienins-1, -2, -3 and -4, Mitochondrial Potential Uncouplers and Autophagy Inducers—Promising Anticancer Agents

Natural Acetogenins, Chatenaytrienins-1, -2, -3 and -4, Mitochondrial Potential Uncouplers and Autophagy Inducers—Promising Anticancer Agents

Maternal Fluoride Exposure Exerts Different Toxicity Patterns in Parotid and Submandibular Glands of Offspring Rats

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

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