The effect of a synthetic hexadentate iron chelator (CP130) and desferrioxamine on rabbit kidneys exposed to cold and warm ischaemia.
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.
Gower
J D
JD
Section of Surgical Research, MRC Clinical Research Centre, Harrow, Middlesex, UK.
Ambrose
I J
IJ
Manek
S
S
Bright
J
J
Dobbin
P S
PS
Hider
R C
RC
Goddard
J G
JG
Thorniley
M S
MS
Green
C J
CJ
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007511:Ischemia / Q000473:pathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D011728:Pyridones / Q000494:pharmacology*; D011817:Rabbits; D015424:Reperfusion; D012545:Schiff Bases / Q000378:metabolism; D013696:Temperature; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D007502:Iron Chelating Agents; D011728:Pyridones; D012545:Schiff Bases; D017392:Thiobarbituric Acid Reactive Substances; C086585:CP 130; D003676:Deferoxamine