Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303,United States.
Proterris, Inc., Boston, MA,United States.
Curr Top Med Chem. 2021;21(32):2890-2908. doi: 10.2174/1568026621666211116090917.
The quest to find novel strategies to tackle respiratory illnesses has led to the exploration of the potential therapeutic effects of carbon monoxide (CO) as an endogenous signaling molecule and a cytoprotective agent. Further, several studies have demonstrated the pharmacological efficacy of CO in animal models of respiratory disorders, such as acute lung injury and pulmonary hypertension. Because of the gaseous nature of CO and its affinity for multiple targets, its controlled delivery has been a challenge. Past studies have employed different delivery modalities, including CO gas, HO-1 inducers, and CO donors, sometimes leading to substantive variations in the resulting pharmacological effects for various reasons. Herein, this review summarizes and analyzes the differences among the profiles of various CO-delivery modalities in terms of their efficacy, dosing regimen, and pharmacokinetics in airways models. We believe that analysis of these issues will help in understanding the fundamental roles of CO in airways, and eventually, contribute to its development as a medicine for respiratory diseases.
为了寻找应对呼吸系统疾病的新策略,研究人员开始探索一氧化碳(CO)作为内源性信号分子和细胞保护剂的潜在治疗效果。此外,多项研究表明,CO 在急性肺损伤和肺动脉高压等呼吸疾病动物模型中具有药理功效。由于 CO 的气体性质及其与多个靶点的亲和力,其受控输送一直是一个挑战。过去的研究采用了不同的输送方式,包括 CO 气体、HO-1 诱导剂和 CO 供体,由于各种原因,这导致各种输送方式的药理效果存在实质性差异。在此,本综述总结和分析了在气道模型中,各种 CO 输送方式在疗效、剂量方案和药代动力学方面的差异。我们相信,对这些问题的分析将有助于了解 CO 在气道中的基本作用,并最终促进其作为治疗呼吸系统疾病的药物的开发。