Metabolic sources of reactive oxygen metabolites during oxidant stress and ischemia with reperfusion.
The lung is especially sensitive to a variety of vastly different agents and conditions including hyperoxia, certain drugs and xenobiotics, particulate debris, and ischemia/reperfusion. There is a growing body of experimental data to suggest that most, if not all, of these agents or conditions mediate pulmonary injury by forming reactive O2 metabolites such as O2-., H2O2.OH, HOCl, and RNHCl. The presence mechanisms by which these different agents converge to produce free radical-mediated pulmonary injury is not entirely clear. The lung does contain several metabolic pathways that will produce large amounts of reactive O2 metabolites. For example, hyperoxia-induced pulmonary injury may be mediated by oxidants produced by both mitochondrial and microsomal electron transport. Certain drugs and xenobiotics may be metabolized by nonspecific flavoproteins found in the mitochondrial electron transport chain and associated with microsomal mixed function oxidase system to yield a variety of free radicals and oxidants. Inhalation of particulate debris will activate resident phagocytic leukocytes to produce large quantities of cytotoxic oxidants. Ischemia and reperfusion appear to produce substantial amounts of xanthine oxidase-derived oxy-radicals that recruit and activate inflammatory phagocytes to produce cytotoxic HOCl and N-chlorinated oxidants. Finally, inappropriate metabolism of arachidonate by prostaglandin synthetase in the presence of NADH (NADPH) produces a burst of O2-. The fact that the lung contains so many different metabolic avenues for oxidant and free radical production suggests that this particular organ may be the most sensitive to oxidative insult.
Grisham
M B
MB
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport.
Granger
D N
DN
D000818:Animals; D004798:Enzymes / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D007511:Ischemia / Q000201:enzymology*; D008168:Lung / Q000098:blood supply*; D010101:Oxygen Consumption; D015427:Reperfusion Injury / Q000201:enzymology*
D004798:Enzymes; D005609:Free Radicals