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.