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, Volume 40, Issue 1–2, pp 96–105 | Cite as

The effect of a synthetic hexadentate iron chelator (CP130) and desferrioxamine on rabbit kidneys exposed to cold and warm ischaemia

  • J. D. Gower
  • I. J. Ambrose
  • S. Manek
  • J. Bright
  • P. S. Dobbin
  • R. C. Hider
  • J. G. Goddard
  • M. S. Thorniley
  • C. J. Green
Inflammation

Abstract

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°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 homogenatesin 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 ofin vitro lipid peroxidation in kidneys rendered warm ischaemic for 90 min followed by reperfusion for 5 or 60 minin 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 6 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.

Keywords

Lipid Peroxidation Schiff Iron Chelator Citrate Solution Warm Ischaemia 

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Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • J. D. Gower
    • 1
  • I. J. Ambrose
    • 1
  • S. Manek
    • 1
  • J. Bright
    • 2
  • P. S. Dobbin
    • 3
  • R. C. Hider
    • 3
  • J. G. Goddard
    • 1
  • M. S. Thorniley
    • 1
  • C. J. Green
    • 1
  1. 1.Section of Surgical ResearchMRC Clinical Research CentreHarrowUK
  2. 2.Section of Medical StatisticsMRC Clinical Research CentreHarrowUK
  3. 3.Chelsea Department of PharmacyKing's CollegeLondonUK

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