Beigi Harchegani Asghar, Khor Abolfazl, Tahmasbpour Eisa, Ghatrehsamani Mahdi, Bakhtiari Kaboutaraki Hamid, Shahriary Alireza
a Chemical Injuries Research Center, Systems biology and poisonings institute, Baqiyatallah University of Medical Sciences , Tehran , Iran.
b Laboratory of Regenerative Medicine & Biomedical Innovations , Pasteur Institute of Iran , Tehran , Iran.
Cutan Ocul Toxicol. 2019 Mar;38(1):9-17. doi: 10.1080/15569527.2018.1495230. Epub 2018 Sep 10.
Sulfur mustard (SM) is a chemical compound that preferentially targets ocular, cutaneous and pulmonary tissues. Although pathologic effect of SM has been extensively considered, molecular and cellular mechanism of its toxicity, especially at the chronic phase of injury is not well-understood. Excessive production of reactive oxygen species (ROS) and oxidative stress (OS) appears to be involved in SM-induced injuries. SM may trigger several molecular and cellular pathways linked to OS and inflammation that can subsequently result in cell death and apoptosis. At the acute phase of injury, SM can enhance ROS production and OS by reducing the activity of antioxidants, depletion of intercellular glutathione (GSH), decreasing the productivity of GSH-dependent antioxidants, mitochondrial deficiency, accumulation of leukocytes and pro-inflammatory cytokines. Overexpression of ROS producing enzymes and down-regulation of antioxidant enzymes are probably the major events by which SM leads to OS at the chronic phase of injury. Therefore, antioxidant therapy with potent antioxidants such as N-acetylcysteine and curcumin may be helpful to mitigate SM-induced OS damages. This review aims to discuss the proposed cellular and molecular mechanisms of acute and delayed SM toxicity, the importance of OS and mechanisms by which SM increases OS either at the acute or chronic phases of injuries along with research on antioxidant therapy as a suitable antidote.
硫芥（SM）是一种化学化合物，它优先作用于眼部、皮肤和肺部组织。尽管人们已经广泛研究了硫芥的病理效应，但其毒性的分子和细胞机制，尤其是在损伤的慢性阶段，仍未得到充分理解。活性氧（ROS）的过度产生和氧化应激（OS）似乎与硫芥诱导的损伤有关。硫芥可能触发与氧化应激和炎症相关的多种分子和细胞途径，随后可导致细胞死亡和凋亡。在损伤的急性期，硫芥可通过降低抗氧化剂活性、消耗细胞内谷胱甘肽（GSH）、降低GSH依赖性抗氧化剂的生成、线粒体功能障碍、白细胞和促炎细胞因子的积累来增强ROS的产生和氧化应激。在损伤的慢性阶段，ROS生成酶的过度表达和抗氧化酶的下调可能是硫芥导致氧化应激的主要事件。因此，使用N-乙酰半胱氨酸和姜黄素等强效抗氧化剂进行抗氧化治疗可能有助于减轻硫芥诱导的氧化应激损伤。本综述旨在讨论硫芥急性和延迟毒性的细胞和分子机制、氧化应激的重要性以及硫芥在损伤的急性或慢性阶段增加氧化应激的机制，以及作为合适解毒剂的抗氧化治疗研究。
