Day Brian J
Department of Medicine, National Jewish Health, Departments of Medicine, Immunology & Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Biochem Pharmacol. 2009 Feb 1;77(3):285-96. doi: 10.1016/j.bcp.2008.09.029. Epub 2008 Oct 1.
Overproduction of the reactive oxygen species (ROS) superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) are increasingly implicated in human disease and aging. ROS are also being explored as important modulating agents in a number of cell signaling pathways. Earlier work has focused on development of small catalytic scavengers of O(2)(-), commonly referred to as superoxide dismutase (SOD) mimetics. Many of these compounds also have substantial abilities to catalytically scavenge H(2)O(2) and peroxynitrite (ONOO(-)). Peroxides have been increasingly shown to disrupt cell signaling cascades associated with excessive inflammation associated with a wide variety of human diseases. Early studies with enzymatic scavengers like SOD frequently reported little or no beneficial effect in biologic models unless SOD was combined with catalase or a peroxidase. Increasing attention has been devoted to developing catalase or peroxidase mimetics as a way to treat overt inflammation associated with the pathophysiology of many human disorders. This review will focus on recent development of catalytic scavengers of peroxides and their potential use as therapeutic agents for pulmonary, cardiovascular, neurodegenerative and inflammatory disorders.
活性氧(ROS)超氧阴离子(O(2)(-))和过氧化氢(H(2)O(2))的过量产生与人类疾病和衰老的关系日益密切。ROS还被视为多种细胞信号通路中的重要调节因子。早期的研究集中在开发O(2)(-)的小型催化清除剂,通常称为超氧化物歧化酶(SOD)模拟物。这些化合物中的许多还具有催化清除H(2)O(2)和过氧亚硝酸根(ONOO(-))的强大能力。越来越多的研究表明,过氧化物会破坏与多种人类疾病相关的过度炎症相关的细胞信号级联反应。早期使用SOD等酶促清除剂的研究经常报告,在生物模型中几乎没有或没有有益效果,除非SOD与过氧化氢酶或过氧化物酶联合使用。人们越来越关注开发过氧化氢酶或过氧化物酶模拟物,作为治疗与许多人类疾病病理生理学相关的明显炎症的一种方法。本综述将重点关注过氧化物催化清除剂的最新进展及其作为肺部、心血管、神经退行性和炎症性疾病治疗药物的潜在用途。