title: Mechanisms of oxidant stress-induced acute tissue injury.
abstract: During the last 25 years, a large body of experimental evidence has accumulated from pharmacological intervention studies that suggests an important role for reactive oxygen species in numerous pathophysiological processes. While a variety of chemical mechanisms of reactive oxygen-induced damage to lipids, proteins, and DNA is fairly well understood, the molecular pathology of oxidant stress-induced tissue injury in vivo remains unclear in most cases. Recent advances indicate that the direct destructive potential of reactive oxygen in vivo is limited by the extensive detoxification capacity of most cells and may be restricted to a small fraction of cells exposed to a locally high oxidant stress. However, reactive oxygen species can participate in recruitment of inflammatory cells by upregulation of adhesion molecules and generation of chemotactic factors, and are necessary for protease-mediated cell injury in vivo. Reactive oxygen species can also scavenge other biologically active molecules (e.g., nitric oxide), thereby modulating indirectly their effector cells. In addition to the discussed effects relevant for acute injury, other oxidant stress-induced mechanisms (e.g., DNA modifications) may be relevant in chronic disease states. A solid mechanistic understanding of the role of reactive oxygen species in the overall pathophysiology is critical for providing a rationale for antioxidant therapy and the targeted development of new antioxidant drugs.
authors.affiliation: Upjohn Company, Kalamazoo, Michigan 49001, USA.
authors.forename: H
authors.initials: H
authors.lastname: Jaeschke
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D006801:Humans; D008054:Lipid Peroxides; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species