Department of Neurology, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
Chem Biol Interact. 2024 Nov 1;403:111223. doi: 10.1016/j.cbi.2024.111223. Epub 2024 Sep 3.
Carbon monoxide (CO) poisoning presents a substantial public health challenge that necessitates the identification of its pathological mechanisms and therapeutic targets. CO toxicity arises from tissue hypoxia-ischemia secondary to carboxyhemoglobin formation, and cellular damage mediated by CO at the cellular level. The mitochondria are the major targets of neuronal damage caused by CO. Under normal physiological conditions, mitochondria produce reactive oxygen species (ROS), which are byproducts of aerobic metabolism. While low ROS levels are crucial for essential cellular functions, including signal transduction, differentiation, responses to hypoxia and immunity, transcriptional regulation, and autophagy, excess ROS become pathological and exacerbate CO poisoning. This review presents the evidence of elevated ROS being associated with the progression of CO poisoning. Antioxidant treatments targeting ROS removal have been proven effective in mitigating CO poisoning, underscoring their therapeutic potential. In this review, we highlight the latest advances in the understanding of the role and the clinical implications of ROS in CO poisoning. We focus on cellular sources of ROS, the molecular mechanisms underlying mitochondrial oxidative stress, and potential therapeutic strategies for targeting ROS in CO poisoning.
一氧化碳（CO）中毒对公共健康构成了重大挑战，因此需要确定其病理机制和治疗靶点。CO 毒性源于形成碳氧血红蛋白后引起的组织缺氧-缺血，以及 CO 在细胞水平引起的细胞损伤。线粒体是 CO 引起的神经元损伤的主要靶标。在正常生理条件下，线粒体产生活性氧（ROS），这是有氧代谢的副产物。虽然低 ROS 水平对于包括信号转导、分化、对缺氧和免疫的反应、转录调节和自噬在内的基本细胞功能至关重要，但过量的 ROS 会变得病理性并加剧 CO 中毒。本综述介绍了 ROS 升高与 CO 中毒进展相关的证据。针对 ROS 清除的抗氧化治疗已被证明可有效减轻 CO 中毒，突出了其治疗潜力。在本综述中，我们强调了对 ROS 在 CO 中毒中的作用和临床意义的最新认识。我们重点介绍了 ROS 的细胞来源、线粒体氧化应激的分子机制以及针对 CO 中毒中 ROS 的潜在治疗策略。
