The effect of
CP130 (a synthetic hexadentate pyridinone
iron chelator) on the formation of two markers of lipid peroxidation (TBA-reactive material and Schiff's bases) in rabbit kidneys following a 72 h period of cold (0-4 degrees C) ischaemia was investigated by either adding
CP130 to the flush/storage
solution (hypertonic citrate solution) or by administering the agent intravenously 15 min before removal of the organs. In both cases,
CP130 blocked the adverse rises in lipid peroxidation caused by ischaemia and subsequent reoxygenation of the homogenates in vitro. Both
CP130 and
desferrioxamine (DFX) (administered intravenously 15 min before ischaemia and 5 min before reperfusion) were also found to significantly reduce post-ischaemic rates of in vitro lipid peroxidation in kidneys rendered warm ischaemic for 90 min followed by reperfusion for 5 or 60 min in situ. Kidneys exposed to warm ischaemia and reperfusion developed interstitial and intracellular oedema, congestion and haemorrhage. DFX administration had little effect on the histological outcome, whereas
CP130 significantly reduced interstitial oedema (at 5 min reperfusion compared to the DFX-treated group), intracellular oedema (at 60 min reperfusion compared to the DFX-treated group) and congestion (at 5 min reperfusion compared with a control group not given any agent). It is concluded that while
CP130 and DFX exhibited similar
antioxidant properties,
CP130 provided better protection from ischaemia/
reperfusion injury at the histological level. Synthetic
iron chelators may therefore be of benefit in clinical
organ transplantation by protecting against tissue damage caused by prolonged ischaemia.