Superoxide Radicals (SR) in the Pathophysiology of Ischemic Acute Renal Failure (ARF)
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Several factors including hypoxia,lysomal enzymes release, endotoxins and kinins have been involved in the pathogenesis of ARF1. Among these, hypoxia represents the initiating event of a series of biochemical reactions which culminate in the production of oxidative radicals. The most important are the superoxide ions (O2 −) and the free radicals which result from their interactions with other molecules. These substances can injure cells by peroxidating the lipid membranes. The organism however has efficient enzymatic and non enzymatic systems which can oppose and control the production of free radicals and superoxide anion. These systems are represented by superoxide dismutase, catalase and glutathione peroxidase which can detoxicate the SR, the hydrogenperoxide and the lipid peroxides3,4 Among the other physiological scavangers glutathion vitamin E and C, cysteine and probably uric acid have great importance5. The biological sequence occurring during ischemia is schematically represented in Fig.1. During hypoxia there is a rapid consumption of ATP with a rise in intracellular AMP concentration, subsequently metabolized to adenosine, inosine and finally hypoxanthine,which accumulates in the ischemic tissue and represents the substrate of xanthine(X) dehydrogenase and X- oxidase Certain authors postulate that the fundamental biochemical phase during hypoxia, is represented by X-dehydrogenase activity, while in the reoxygenation phase the activity of Xoxidase prevails, producing hydrogen peroxide and SR, responsible for the maintenance of the ischemic damage.
KeywordsUric Acid Glomerular Filtration Rate Renal Artery Acute Renal Failure Ischemic Damage
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- 1.J.M. McCord, Oxygen-derived free radicals in post-ischemic tissue injury, New Eng.J.Med 312: 159 (1984).Google Scholar
- 4.B.E.Leibovitz, B.V.Siegel, Aspects of free radical reactions in biological system: aging, J.Gerontol. 35: 45 (1980).Google Scholar
- 6.M.Shlaper, P.F.Kane, V.Y.Wiggins, M.M.Kirsh, Possible role for cytotoxic oxygen metabolites in the pathogenesis of cardiac ischémic injury, Circulation 66:85 suppl. 1 (1982).Google Scholar
- 7.J.R.Stewart, W.H.Blackwell, S.L.Crute, V.Loughlin, M.L.Hess, L.S. Greenfield, Prevention of myocardial ischemia: reperfusion injury with oxygen free radical scavengers, Surg.Forum 33: 317 (1982).Google Scholar
- 8.A.S.Casale, G.B.Bulkley, B.H. Bulkley, J.T. Flaherty, V.L.Gott, T.S. Oxygen free radical scavengers protect the arrested, globally ischemic heart upon reperfusion, Surg.Forum 34: 313 (1983).Google Scholar
- 11.J.M.McCord, I.Fridovich, The reduction of cytochrome C by milk xanthine-oxidase, J.Biol.Chem. 243: 5753 (1968).Google Scholar
- 12.C.E.Jones, J.W.Crowell, E.E.Smith, Significance of increased blood uric acid following extensive hemorrhage, Am.J.Physiol. 214: 1374 (1968).Google Scholar
- 13.D.A.Parks, G.B.Bulkley, N.D.Granger, S.R.Hamilton, J.M.McCord, Ischemic injury in the cat small intestine: Role of superoxide radicals, Gastroenterology 82: 9 (1982).Google Scholar