Nilda V Barbosa, Michael Aschner, Alexey A Tinkov, Marcelo Farina, João Batista Teixeira da Rocha
{"title":"Should ebselen be considered for the treatment of mercury intoxication? A minireview.","authors":"Nilda V Barbosa, Michael Aschner, Alexey A Tinkov, Marcelo Farina, João Batista Teixeira da Rocha","doi":"10.1080/15376516.2023.2258958","DOIUrl":null,"url":null,"abstract":"<p><p>Mercury is a ubiquitous environmental contaminant and can be found in inorganic (Hg<sup>0</sup>, Hg<sup>+</sup> and Hg<sup>2+</sup>) and organic forms (chiefly CH<sub>3</sub>Hg<sup>+</sup> or MeHg<sup>+</sup>). The main route of human, mammals and bird exposure occurs <i>via</i> predatory fish ingestion. Occupational exposure to Hg<sup>0</sup> (and Hg<sup>2+</sup>) can also occur; furthermore, in gold mining areas the exposure to inorganic Hg can also be high. The toxicity of electrophilic forms of Hg (E<sup>+</sup>Hg) is mediated by disruption of thiol (-SH)- or selenol (-SeH)-containing proteins. The therapeutic approaches to treat methylmercury (MeHg<sup>+</sup>), Hg<sup>0</sup> and Hg<sup>2+</sup> are limited. Here we discuss the potential use of ebselen as a potential therapeutic agent to lower the body burden of Hg in man. Ebselen is a safe drug for humans and has been tested in clinical trials (for instance, brain ischemia, noise-induce hearing loss, diabetes complications, bipolar disorders) at doses varying from 400 to 3600 mg per day. Two clinical trials with ebselen in moderate and severe COVID are also approved. Ebselen can be metabolized to an intermediate with -SeH (selenol) functional group, which has a greater affinity to electrophilic Hg (E<sup>+</sup>Hg) forms than the available thiol-containing therapeutic agents. Accordingly, as observed <i>in vitro</i> and rodent models <i>in vivo,</i> Ebselen exhibited protective effects against MeHg<sup>+</sup>, indicating its potential as a therapeutic agent to treat MeHg<sup>+</sup> overexposure. The combined use of ebselen with thiol-containing molecules (e.g. N-acetylcysteine and enaramide)) is also commented, because they can have synergistic protective effects against MeHg<sup>+</sup>.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841883/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology Mechanisms and Methods","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15376516.2023.2258958","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
Abstract
Mercury is a ubiquitous environmental contaminant and can be found in inorganic (Hg0, Hg+ and Hg2+) and organic forms (chiefly CH3Hg+ or MeHg+). The main route of human, mammals and bird exposure occurs via predatory fish ingestion. Occupational exposure to Hg0 (and Hg2+) can also occur; furthermore, in gold mining areas the exposure to inorganic Hg can also be high. The toxicity of electrophilic forms of Hg (E+Hg) is mediated by disruption of thiol (-SH)- or selenol (-SeH)-containing proteins. The therapeutic approaches to treat methylmercury (MeHg+), Hg0 and Hg2+ are limited. Here we discuss the potential use of ebselen as a potential therapeutic agent to lower the body burden of Hg in man. Ebselen is a safe drug for humans and has been tested in clinical trials (for instance, brain ischemia, noise-induce hearing loss, diabetes complications, bipolar disorders) at doses varying from 400 to 3600 mg per day. Two clinical trials with ebselen in moderate and severe COVID are also approved. Ebselen can be metabolized to an intermediate with -SeH (selenol) functional group, which has a greater affinity to electrophilic Hg (E+Hg) forms than the available thiol-containing therapeutic agents. Accordingly, as observed in vitro and rodent models in vivo, Ebselen exhibited protective effects against MeHg+, indicating its potential as a therapeutic agent to treat MeHg+ overexposure. The combined use of ebselen with thiol-containing molecules (e.g. N-acetylcysteine and enaramide)) is also commented, because they can have synergistic protective effects against MeHg+.
期刊介绍:
Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy.
Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including:
In vivo studies with standard and alternative species
In vitro studies and alternative methodologies
Molecular, biochemical, and cellular techniques
Pharmacokinetics and pharmacodynamics
Mathematical modeling and computer programs
Forensic analyses
Risk assessment
Data collection and analysis.