Cotterill, Lisa Ann;
(1990)
The role of calcium and oxygen-derived free radicals in reperfusion injury to the ischaemic kidney.
Doctoral thesis (Ph.D.), University College London.
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Abstract
The objective of this thesis was to investigate the possible roles of calcium and oxygen derived free radicals in tissue damage resulting from ischaemia and reperfusion using the rabbit kidney as a model. Kidneys were flushed and stored at 0°C for 24-72 hours (cold ischaemia) in either hypertonic citrate solution (a good storage medium) or isotonic saline (a poor storage medium) and the extent of free radical induced lipid peroxidation was subsequently measured in vitro in tissue homogenates. The effects of a number of agents which affect calcium homeostasis or inhibit calcium-dependent processes were investigated. The results strongly suggested that altered calcium homeostasis during the ischaemic period, involving both extracellular influx and intracellular redistribution played an important role in the development of oxidative membrane damage upon reoxygenation. Free fatty acids (FFAs), the products of phospholipase action were analysed by glc and a rise in unsaturated FFAs, particularly arachidonic acid, was found to occur in renal tissue during the storage period. Further studies implicated the involvement of a calcium-dependent phospholipase A2 in the mediation of increased lipid peroxidation following ischaemia. Experiments were designed to test the hypothesis that hypoxia/reoxygenation may alter the turnover of the phosphatidylinositol (PI) secondary messenger system. Reoxygenation of rabbit kidney cortical slices exposed to hypoxia in vitro resulted in a rapid increase in PI hydrolysis to secondary messenger products. This effect appeared to be calcium-dependent and paralleled the increase in lipid peroxidation observed upon reoxygenation of hypoxic slices. The results of this investigation strongly suggest that altered calcium homeostasis and the production of oxygen-derived free radicals act synergistically and contribute significantly to the pathogenesis of renal damage resulting from ischaemia and reperfusion. Modulators of calcium-dependent processes may therefore be of therapeutic value in preventing organ damage during renal transplantation.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | The role of calcium and oxygen-derived free radicals in reperfusion injury to the ischaemic kidney. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis Digitised by Proquest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10124754 |
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