The importance of lipid peroxidation and iron for the ischaemia-reperfusion injury of kidneys

Abstract

All over the world, scientists are studying the possible role of oxygen free radicals (OFR) in numerous pathological conditions, including ischaemia- reperfusion (I/R). The final step in the radical damage is lipid peroxidation. The radical damage is considerably increased in the presence of iron.Aims of the present study:1. To examine the effects of pre-treatment with desferrioxamine or H290/51 on the production of radicals at reperfusion after ischaemia.2. To examine the effects of pre-treatment with desferrioxamine or H290/51 on the kidney function and survival after ischaemia-reperfusion.3. To study the effects of ischaemia and reperfusion on lipid peroxidation as reflected in TBARS production in vivo and in vitro and to elucidate the effects of pre-treatment with H290/51 in this respect.4. To study the effect of ischaemia and reperfusion on mitochondrial bioenergetics and intracellular pH measured with volume-selective 31P NMR spectroscopy (OSIRIS) and to elucidate the effects of pretreat-ment with H290/51 in these respects. Methods: New Zealand white rabbits and Sprague-Dawley rats were used. In the ESR experiments, OXANOH was used as spin trap. In the TBARS experiment, the kidneys were sliced after ischaemia and put into Krebs solution and reoxygenated in a 37°C waterbath. Then the slices were chopped and frozen for later analyses of TBARS. In the NMR experiments, the rabbit was placed in a magnetic tube during the experiments and could therefore not be touched. An experimental model in which the blood supply to the renal artery could be clamped at a distance by means of a Fogarty-catheter was developed. Results: In the ESR studies, pre-treatment with desferrioxamine reduced the production of radicals to 30% compared with pre-ischaemic values, but pre-treatment with H290/51 completely abolished the increase in the production of radicals seen after ischaemia. Pre-treatment with desferrioxamine improved glomerular function, but had no effect on tubular function after I/R. Pre-treatment with H290/51 improved both glomerular and tubular functions after I/R. Lipid peroxidation as reflected in TBARS-production was reduced after pre-treatment with H290/51 to near pre-ischaemic values. Mitochondrial function after I/R, as reflected in ATP and pH increase, was greatly improved after pre-treatment with H290/51. Conclusions: Desferrioxamine and H290/51 diminish the production of radicals and protect renal function after I/R. H290/51 diminishes lipid peroxidation, as reflected in TBARS production, and protects the mitochondrial function after I/R.