Should ebselen be considered for the treatment of mercury intoxication? A minireview.

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⁺.