Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer Building, Room 209, Bronx, NY, 10461, USA.
Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
Neurotox Res. 2020 Jun;38(1):133-144. doi: 10.1007/s12640-020-00194-0. Epub 2020 Mar 31.
Methylmercury (MeHg) is a global pollutant and potent neurotoxin. In humans, MeHg damages the central nervous system (CNS), causing irreversible neuronal shrinkage, and neuronal loss. Most chelators for clinical mercury detoxification are thiol-containing agents. N,N 'bis-(2-mercaptoethyl) isophthalamide (NBMI) is a lipophilic thiol agent synthesized from natural chemicals. NBMI has high affinity for mercury, cadmium and lead, and can decrease their concentrations in polluted water. However, the efficacy of NBMI for MeHg toxicity has yet to be evaluated in intact animals. Here we used the nematode Caenorhabditis elegans (C. elegans) to test the efficacy of NBMI in attenuating MeHg toxicity in vivo in the whole organism. The results showed that NBMI reduced both the acute toxicity (125 μM MeHg, 1 h) and chronic (5 μM MeHg, 24 h) MeHg toxicity. Co-treatment with NBMI achieved maximal efficacy against MeHg toxicity, however delayed treatment 6 days after initiation of exposure was also effective at reducing neurotoxicity. Co-treatment of NBMI reduced the worms' death rate, structural damage in DAergic neurons, and restored antioxidant response levels. While this study provides proof of principle for the therapeutic value of NBMI in MeHg toxicity, future studies are needed to address the cellular and molecular mechanisms and translatability of these effects to humans and other animals.
甲基汞（MeHg）是一种全球性污染物和强效神经毒素。在人类中，MeHg 会损害中枢神经系统（CNS），导致不可逆转的神经元收缩和神经元丧失。大多数用于临床汞解毒的螯合剂都是含巯基的试剂。N,N' - 双（2-巯基乙基）间苯二甲酰胺（NBMI）是一种由天然化学品合成的亲脂性巯基试剂。NBMI 对汞、镉和铅具有高亲和力，并可降低其在污染水中的浓度。然而，NBMI 对 MeHg 毒性的疗效尚未在完整动物中得到评估。在这里，我们使用秀丽隐杆线虫（C. elegans）来测试 NBMI 在体内减轻整个生物体中 MeHg 毒性的功效。结果表明，NBMI 降低了急性毒性（125μM MeHg，1 小时）和慢性毒性（5μM MeHg，24 小时）。NBMI 与 MeHg 共同处理对 MeHg 毒性的疗效达到最大，但在暴露开始后 6 天延迟治疗也能有效降低神经毒性。NBMI 的共同处理降低了蠕虫的死亡率、DA 能神经元的结构损伤，并恢复了抗氧化反应水平。虽然这项研究为 NBMI 在 MeHg 毒性中的治疗价值提供了原理证明，但仍需要进一步的研究来解决这些效应的细胞和分子机制以及对人类和其他动物的可转化性。
