Superoxide Radicals (SR) in the Pathophysiology of Ischemic Acute Renal Failure (ARF)

Abstract

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 peroxides^3,4 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.