Purines, free radicals and antioxidant systems : a study in hearts of various species, including humans
Year: 1993
Type: dissertation
Abstract: ATP is vital for contractility and basal metabolism, i.e. maintenance of ions through \nmembrane pumps. Derangement in high-energy substrates levels due to ischemia \ncould lead to cell death or prolonged post-ischemic dysfunction. Furthermore, other lethal \nsubstances, like free radicals, can be formed during reperfusion and cause injury. ATP \ncatabolites might have beneficial or detrimental effects on myocardial function. \nHypoxanthine builds up during myocardial ischemia and is broken down to xanthine and \nurate. The enzyme xanthine oxidoreductase (XOD), which catalyzes this reaction, could be \nconverted during ischemia to the oxidase form which produces superoxide radicals during \nreperfusion. The first part of chapter 2 deals with free radicals with emphasis on \nmalondialdehyde formation as indirect free radical indicator. Despite the reports of \nmalondialdehyde (MDA) formation in clinical studies, we were unable to measure this \ncompound in explanted human and rat hearts subjected to ischemia (appendix 2). Probably \n:MDA is only formed under extreme oxidative stress like cumene peroxide. Positive reports \nin clinical studies could be caused by the non-specific thiobarbituric acid test or an \nextracardiac source of malondialdehyde. \nSince the extent of free-radical damage is not only modulated by the sources but also \nby the defences we investigated the activities of catalase, superoxide dismutase and \nglutathione-related enzymes. This is described in the second part of chapter 2. Human \nmyocardium is less protected against superoxide radicals in comparison with the other \nspecies. Rat hearts have higher glutathione peroxidase activities (appendix 3). Although the \nvarious species have different enzyme profiles, there was no relationship between \nantioxidant levels and xanthine oxidoreductase activity. This suggests that they are not \nregulated by XOD. In view of these differences in protective capabilities one should be \ncautious with extrapolation of results from one species towards another. \nAppendix 2 describes, in addition to malondialdehyde formation, the release of oxidized \nand reduced glutathione from hearts after a cardioplegic and ischemic period. We conclude \nthat glutathione release after a cardioplegic period could make the hearts more susceptible \nto oxidative stress upon reperfusion. Furthermore these compounds could be u
Author: Maarten Janssen
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2123877472