Biochemical changes in the intestine associated with anoxia and reoxygenation: in vivo and in vitro studies.
In ischemia/reperfusion injury, it is hypothesized that superoxide is responsible for the component of injury due to reperfusion. The superoxide is hypothesized to result from the aerobic oxidation of purines produced by the ischemia-mediated breakdown of high-energy phosphates. This oxidation is catalyzed by xanthine oxidase proposed to be rapidly formed as a result of ischemia-mediated protease conversion from xanthine dehydrogenase. In vivo experiments with the intestine of either rats or guinea pigs were unable to confirm the rapid conversion of xanthine dehydrogenase to xanthine oxidase as a result of ischemia. In vitro experiments with isolated guinea pig enterocytes did show a significant increase in xanthine oxidase activity after these cells were first placed in an anaerobic environment for 60 min and then reoxygenated; however, the magnitude of the increase is such that the biological importance of this finding remains uncertain. Using a variety of techniques, including spin trapping, hydroxylamine oxidation, and vanadate NADPH oxidation, we explored the possibility that superoxide was produced as a result of anoxia followed by reoxygenation in the in vitro enterocyte system. From these experiments, we determined that superoxide is generated as a result of anoxia/reoxygenation. However, from xanthine oxidase inhibition experiments using pterinaldehyde, only a small percentage of the total superoxide produced comes from the action of this enzyme on purines.
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013481:Superoxides / Q000096:biosynthesis*; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D005609:Free Radicals; D011687:Purines; D013481:Superoxides; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D007658:Ketone Oxidoreductases; D010100:Oxygen