Purines, free radicals and antioxidant systems : a study in hearts of various species, including humans
ATP is vital for contractility and basal metabolism, i.e. maintenance of ions through membrane pumps. Derangement in high-energy substrates levels due to ischemia could lead to cell death or prolonged post-ischemic dysfunction. Furthermore, other lethal substances, like free radicals, can be formed during reperfusion and cause injury. ATP catabolites might have beneficial or detrimental effects on myocardial function. Hypoxanthine builds up during myocardial ischemia and is broken down to xanthine and urate. The enzyme xanthine oxidoreductase (XOD), which catalyzes this reaction, could be converted during ischemia to the oxidase form which produces superoxide radicals during reperfusion. The first part of chapter 2 deals with free radicals with emphasis on malondialdehyde formation as indirect free radical indicator. Despite the reports of malondialdehyde (MDA) formation in clinical studies, we were unable to measure this compound in explanted human and rat hearts subjected to ischemia (appendix 2). Probably :MDA is only formed under extreme oxidative stress like cumene peroxide. Positive reports in clinical studies could be caused by the non-specific thiobarbituric acid test or an extracardiac source of malondialdehyde. Since the extent of free-radical damage is not only modulated by the sources but also by the defences we investigated the activities of catalase, superoxide dismutase and glutathione-related enzymes. This is described in the second part of chapter 2. Human myocardium is less protected against superoxide radicals in comparison with the other species. Rat hearts have higher glutathione peroxidase activities (appendix 3). Although the various species have different enzyme profiles, there was no relationship between antioxidant levels and xanthine oxidoreductase activity. This suggests that they are not regulated by XOD. In view of these differences in protective capabilities one should be cautious with extrapolation of results from one species towards another. Appendix 2 describes, in addition to malondialdehyde formation, the release of oxidized and reduced glutathione from hearts after a cardioplegic and ischemic period. We conclude that glutathione release after a cardioplegic period could make the hearts more susceptible to oxidative stress upon reperfusion. Furthermore these compounds could be used as indicators of oxidative stress in a clinical setting.
|Keywords||Hypoxanthine, cardiology, myocardial ischemia, purines|
|Promotor||Verdouw, P.D. (Pieter)|
|Publisher||Erasmus MC: University Medical Center Rotterdam|
Janssen, M.. (1993, December). Purines, free radicals and antioxidant systems : a study in hearts of various species, including humans . Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/37813