| Abstract: | Oxidative stresses associated with ischemia/reperfusion, neutrophil activation, and anesthesia with certain volatile agents, etc., are thought to play an important role in the development of acute organ failure in critical illnesses, such as acute lung injury, acute coronary artery insufficiency, acute liver failure, acute renal failure, and multiple organ dysfunction syndrome. Such oxidative stressors provoke a set of cellular responses, particularly those that participate in the defense against tissue injuries. Free heme, which can be rapidly released from hemeproteins, may constitute a major threat in the oxidant stress because it catalyzes the formation of reactive oxygen species. To counteract such insults, cells respond by inducing the 33‐kDa heat shock protein, heme oxygenase (HO)‐1, the rate‐limiting enzyme in heme degradation. Induced HO‐1 as such removes free heme by an enzymatic process. In addition, HO‐1 induction itself confers protection to tissues from further oxidative injuries. In contrast, the abrogation of HO‐1 induction, or chemical ablation of HO activity abolishes the beneficial effect of HO‐1, and results in the aggravation of tissue injuries. In this article, we review recent advances in the essential role of HO‐1 in tissue protection in various models of experimental oxidative tissue injuries as well as in human disorders, which is related to critically ill conditions, with special emphasis on the role of its induction in tissue defense and its potential therapeutic implications. Drug Dev. Res. 67:130–153, 2006. © 2006 Wiley‐Liss, Inc. |
