Oxidative stress in septic shock and disseminated intravascular coagulation.
Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidant stress plays a major role in several aspects of septic shock and disseminated intravascular coagulation (DIC), and it is the subject of this review. Immunohistochemical and biochemical evidence demonstrate the significant role of reactive oxygen species (ROS) in endotoxic and hemorrhagic shock, and in endothelial injury associated with DIC syndrome. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+/K+ ATP-ase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of ROS. In addition, reactive oxygen species are potent triggers of DNA strand breakage, with subsequent activation of the nuclear enzyme poly-ADP ribosyl synthetase, with eventual severe energy depletion of the cells. Pharmacological evidence suggests that the peroxynitrite-poly-ADP ribosyl synthetase pathway contributes to the cellular injury in shock and endothelial injury. Treatment with superoxide dismutase mimetics (SODms), which selectively mimic the catalytic activity of the human superoxide dismutase enzymes, have been shown to prevent in vivo shock and the cellular energetic failure associated with shock.
Salvemini
Daniela
D
Metaphore Pharmaceuticals, St. Louis, MO 63114, USA. dsalvemini@metaphore.com
Cuzzocrea
Salvatore
S
D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000378:metabolism* / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
D005609:Free Radicals; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase