Lecithinized superoxide dismutase reduces cold ischemia-induced chronic allograft dysfunction.

Abstract

BACKGROUND:

Chronic renal allograft failure (CAF) is influenced by both allo-dependent and independent factors and is a major cause of graft loss in clinical renal transplantation. We evaluated a novel membrane-bound free radical scavenger, lecithinized superoxide dismutase (lec-SOD), to determine its potential in limiting the harmful effects of ischemia/reperfusion injury on CAF.

METHODS:

Fisher rat kidneys were stored for either 1 hour or 18 hours in cold Marshall's preservation solution either with or without lec-SOD and transplanted into Lewis recipients.

RESULTS:

Within 3 days of transplantation, an early inflammatory response involving granulocytes and macrophages was detected in renal allografts exposed to 18 hours cold ischemia that was significantly reduced by preservation with lec-SOD. By 24 weeks post-transplantation, elevated proteinuria and detection of apoptotic cells was observed in kidneys exposed to 18 hours of cold ischemia, that was attenuated by preservation with lec-SOD (P < 0.05). However, up-regulated expression of intracellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) Class II together with a T lymphocyte infiltration were observed at 24 weeks that was not prevented by preservation with lec-SOD.

CONCLUSIONS:

These results demonstrate that ischemia/reperfusion injury, apoptotic cell death and allo-immune responses may be exacerbated by cold ischemia and accelerate the development of CAF. Preservation with lec-SOD may protect against the early damage induced by cold ischemia and reperfusion injury.

• Authors: Ken Nakagawa, Dicken D H Koo, David R Davies, Derek W R Gray, Andrew J McLaren, Kenneth I Welsh, Peter J Morris, Susan V Fuggle
• Journal: Kidney international (Kidney Int) Vol. 61 Issue 3 Pg. 1160-9 (Mar 2002) ISSN: 0085-2538 [Print] United States
• PMID: 11849471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Free Radical Scavengers
• Histocompatibility Antigens Class I
• Phosphatidylcholines
• Recombinant Proteins
• Intercellular Adhesion Molecule-1
• Superoxide Dismutase
• lecithinized superoxide dismutase

Topics

• Animals
• Apoptosis (drug effects)
• Cryopreservation
• Free Radical Scavengers (pharmacology)
• Histocompatibility Antigens Class I (metabolism)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Ischemia (pathology, physiopathology)
• Kidney (drug effects, pathology, physiopathology)
• Kidney Transplantation
• Leukocytes (pathology)
• Male
• Phosphatidylcholines (pharmacology)
• Rats
• Rats, Inbred F344
• Rats, Inbred Lew
• Recombinant Proteins (pharmacology)
• Renal Circulation
• Reperfusion Injury (pathology, physiopathology)
• Superoxide Dismutase (pharmacology)