Protection against oxidative damage in cold-stored rabbit kidneys by desferrioxamine and indomethacin.
The storage of rabbit kidneys in hypertonic citrate solution at 0 degree C for 48-72 hr of cold ischemia resulted in oxidative damage to membranes as measured by the in vitro formation of two markers of lipid peroxidation (Schiff's base and thiobarbituric acid (TBA)-reactive material). This damage was further increased when the organs were autografted and reperfused for 60 min. The intravenous (iv) administration of desferrioxamine (a powerful iron-chelating agent) prior to the removal of the kidneys reduced the production of Schiff's bases and TBA-reactive material to low levels in the cortex of stored kidneys and decreased these measures of lipid peroxidation in the medulla by approximately 50%. Intravenous administration of indomethacin (a cyclooxygenase inhibitor) had no effect on the rate of lipid peroxidation in the renal cortex, but significantly reduced the formation of TBA-reactive material and Schiff's bases in the medulla of kidneys following storage for 72 hr. The existence of two separate pathways of lipid peroxidation (one iron-catalyzed and the other cyclooxygenase-catalyzed) in the medulla of stored kidneys was further confirmed when administration of desferrioxamine and indomethacin together resulted in significantly greater protection against lipid peroxidation than when these compounds were administered singly. The value of this combination of agents for protecting kidneys against the damage due to cold ischemia followed by reperfusion was further suggested by a trend toward improved long-term survival of the animals following replantation of the stored kidneys.
Gower
J D
JD
Section of Surgical Research, Clinical Research Centre, Harrow, Middlesex, England.
Healing
G
G
Fuller
B J
BJ
Simpkin
S
S
Green
C J
CJ
D000818:Animals; D003080:Cold Temperature; D003676:Deferoxamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D016030:Kidney Transplantation; D015227:Lipid Peroxidation / Q000187:drug effects; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion; D011817:Rabbits; D014182:Transplantation, Autologous
D003676:Deferoxamine; D007213:Indomethacin