Oxygen-induced reperfusion-injury is caused by ROS: Amelioration is possible by recombinant-DNA antioxidant enzymes and mimics in selected tissues.
Billions of years of photolytic cleavage of the water molecule has led to a build-up at sea-level of a "toxic" oxygen concentration in the atmosphere (to 20%). Unfortunately, this dioxygen is likely to be converted in the mitochondria (cell organelles) during cellular respiration to generate reactive oxygen species (ROS); including free-radicals such as superoxide anion (.O2') and hydroxyl radical (.OH) (peroxide O2") a ROS is not a free radical because its electrons are paired). Development of recombinant-DNA improved isoenzyme forms (or mimics) of antioxidant enzymes such as superoxide dismutases is predicted in this hypothesis to be utilised to ameliorate reperfusion-injury (and other oxygen-induced molecular pathology). Introduction into the human genome of the genes for expression of antioxidant enzymes, to order in particular tissues, is imminent. Furthermore, O2 itself will be recognised universally as a harmful gas that can subject the cell to oxidative stress; because it produces ROS, such as the superoxide anion when it acts as the terminal electron acceptor in cellular respiration in the production of water from hydrogen ions in mitochondria. In conclusion, therefore, oxygen-induced injury in humans can no longer be accepted during medical techniques such as reperfusion procedures, because this is associated with reperfusion-injury that can be the cause of several serious medical conditions arising from biomolecular pathology. Some of this is caused by isoforms of cytochromes P450 (CYP; EC 1.14.14.1) such as 3A4, 2D6 and 2C19. These can generate ROS in the liver at low substrate concentrations by futile recycling of oxygen.
Wiseman
Alan
A
School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom. alan@tridgway.wanadoo.co.uk
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000008:administration & dosage* / Q000235:genetics; D004274:DNA, Recombinant; D018716:Molecular Mimicry; D010100:Oxygen / Q000009:adverse effects*; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000139:chemically induced* / Q000517:prevention & control
D004274:DNA, Recombinant; D017382:Reactive Oxygen Species; D003577:Cytochrome P-450 Enzyme System; D010100:Oxygen