Department of Environmental Medicine, Institute of Community Medicine, University of Tsukuba, 305-8575, Tsukuba, Ibaraki, Japan,
Environ Health Prev Med. 2002 Sep;7(4):141-50. doi: 10.1007/BF02897942.
The cytotoxic effects evoked by exposure to environmental chemicals having electrophilic properties are often attributable to covalent attachment to intracellular macromolecules through sulfhydryl groups or enzyme-mediated redox cycling, leading to the generation of reactive oxygen species (ROS). When huge amounts of ROS form they overwhelm antioxidant defenses resulting in the induction of oxidative stress. Nitric oxide (NO) which plays a crucial role in vascular tone, is formed by endothelial NO synthase (eNOS). Since a decrease in systemic NO production is implicated in the pathophysiological actions of vascular diseases, dysfunction of eNOS by environmental chemicals is associated with cardiopulmonary-related diseases and mortality. In this review, we introduce the mechanism-based toxicities (covalent attachment and redox cycling) of electrophiles. Therefore, this review will focus on the possible mechanisms for the induction of oxidative stress and impairment of NO production caused by environmental chemicals.
暴露于具有亲电性的环境化学物质会引起细胞毒性效应，这通常归因于通过巯基共价结合到细胞内大分子或酶介导的氧化还原循环，从而导致活性氧（ROS）的产生。当大量 ROS 形成时，它们会破坏抗氧化防御系统，导致氧化应激的诱导。一氧化氮（NO）在血管张力中起着至关重要的作用，它是由内皮型一氧化氮合酶（eNOS）形成的。由于全身 NO 生成的减少与血管疾病的病理生理作用有关，因此环境化学物质对 eNOS 的功能障碍与心肺相关疾病和死亡率有关。在这篇综述中，我们介绍了亲电子化合物的基于机制的毒性（共价结合和氧化还原循环）。因此，这篇综述将重点介绍环境化学物质引起氧化应激和 NO 生成损伤的可能机制。
