Research and Scientific Studies Unit, College of Nursing, Jazan University, Jazan 45142, Saudi Arabia.
Molecules. 2022 Aug 28;27(17):5542. doi: 10.3390/molecules27175542.
Chronic obstructive pulmonary disease (COPD) is an increasing and major global health problem. COPD is also the third leading cause of death worldwide. Oxidative stress (OS) takes place when various reactive species and free radicals swamp the availability of antioxidants. Reactive nitrogen species, reactive oxygen species (ROS), and their counterpart antioxidants are important for host defense and physiological signaling pathways, and the development and progression of inflammation. During the disturbance of their normal steady states, imbalances between antioxidants and oxidants might induce pathological mechanisms that can further result in many non-respiratory and respiratory diseases including COPD. ROS might be either endogenously produced in response to various infectious pathogens including fungi, viruses, or bacteria, or exogenously generated from several inhaled particulate or gaseous agents including some occupational dust, cigarette smoke (CS), and air pollutants. Therefore, targeting systemic and local OS with therapeutic agents such as small molecules that can increase endogenous antioxidants or regulate the redox/antioxidants system can be an effective approach in treating COPD. Various thiol-based antioxidants including fudosteine, erdosteine, carbocysteine, and N-acetyl-L-cysteine have the capacity to increase thiol content in the lungs. Many synthetic molecules including inhibitors/blockers of protein carbonylation and lipid peroxidation, catalytic antioxidants including superoxide dismutase mimetics, and spin trapping agents can effectively modulate CS-induced OS and its resulting cellular alterations. Several clinical and pre-clinical studies have demonstrated that these antioxidants have the capacity to decrease OS and affect the expressions of several pro-inflammatory genes and genes that are involved with redox and glutathione biosynthesis. In this article, we have summarized the role of OS in COPD pathogenesis. Furthermore, we have particularly focused on the therapeutic potential of numerous chemicals, particularly antioxidants in the treatment of COPD.
慢性阻塞性肺疾病（COPD）是一个日益严重的全球性健康问题。COPD 也是全球第三大致死原因。当各种活性物质和自由基超过抗氧化剂的可用性时，就会发生氧化应激（OS）。活性氮物种、活性氧（ROS）及其对应的抗氧化剂对于宿主防御和生理信号通路以及炎症的发展和进展非常重要。在它们正常稳态受到干扰时，抗氧化剂和氧化剂之间的平衡可能会引发病理机制，从而导致许多非呼吸系统和呼吸系统疾病，包括 COPD。ROS 可能是由于各种感染病原体（包括真菌、病毒或细菌）产生的内源性物质，也可能是由于几种吸入的颗粒或气态物质（包括一些职业性粉尘、香烟烟雾（CS）和空气污染物）产生的外源性物质。因此，用小分子等治疗剂靶向全身和局部 OS，这些治疗剂可以增加内源性抗氧化剂或调节氧化还原/抗氧化剂系统，可以成为治疗 COPD 的有效方法。各种基于巯基的抗氧化剂，包括福多司坦、厄多司坦、卡巴司坦和 N-乙酰-L-半胱氨酸，具有增加肺部巯基含量的能力。许多合成分子，包括蛋白羰基化和脂质过氧化抑制剂/阻滞剂、超氧化物歧化酶模拟物等催化抗氧化剂、自旋捕获剂，可以有效地调节 CS 诱导的 OS 及其导致的细胞改变。许多临床前和临床研究表明，这些抗氧化剂具有降低 OS 和影响几个促炎基因和涉及氧化还原和谷胱甘肽生物合成的基因表达的能力。本文总结了 OS 在 COPD 发病机制中的作用。此外，我们特别关注了许多化学物质，特别是抗氧化剂在 COPD 治疗中的治疗潜力。
