El-Ghiaty Mahmoud A, El-Kadi Ayman O S
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada; email:
Annu Rev Pharmacol Toxicol. 2023 Jan 20;63:341-358. doi: 10.1146/annurev-pharmtox-051921-020936. Epub 2022 Sep 13.
Arsenic is a naturally occurring hazardous element that is environmentally ubiquitous in various chemical forms. Upon exposure, the human body initiates an elimination pathway of progressive methylation into relatively less bioreactive and more easily excretable pentavalent methylated forms. Given its association with decreasing the internal burden of arsenic with ensuing attenuation of its related toxicities, biomethylation has been applauded for decades as a pure route of arsenic detoxification. However, the emergence of detectable trivalent species with profound toxicity has opened a long-standing debate regarding whether arsenic methylation is a detoxifying or bioactivating mechanism. In this review, we approach the topic of arsenic metabolism from both perspectives to create a complete picture of its potential role in the mitigation or aggravation of various arsenic-related pathologies.
砷是一种天然存在的有害元素，在环境中以各种化学形式广泛存在。人体接触砷后，会启动一条逐步甲基化的消除途径，将其转化为生物活性相对较低、更易排泄的五价甲基化形式。鉴于其与降低体内砷负担以及随之减轻相关毒性有关，几十年来，生物甲基化一直被赞誉为砷解毒的纯粹途径。然而，具有高毒性的可检测三价砷物种的出现引发了一场长期争论，即砷甲基化是一种解毒机制还是生物活化机制。在本综述中，我们从这两个角度探讨砷代谢的话题，以全面了解其在减轻或加重各种砷相关病症中可能发挥的作用。
