Oxidative damage to kidney membranes during cold ischemia. Evidence of a role for calcium.
Storage of rabbit kidneys at 0 degrees C for periods of 72 hr after flushing with hypertonic citrate solution, or 24 hr when flushed with isotonic saline, resulted in significant increases in Schiff base and thiobarbituric acid-reactive markers of lipid peroxidation in vitro. The extent of lipid peroxidation was not significantly altered by addition of verapamil (100 microM), a Ca++ channel blocking agent, or calcium 1 mM (CaCl2) to the HCA storage solution. In contrast, verapamil significantly reduced the extent of lipid peroxidation in kidneys stored in saline solution, and a significant increase in oxidative damage occurred when CaCl2 was added to this storage solution. Thus the extent of lipid peroxidation in kidneys stored in saline was significantly mediated by extracellular Ca++, whereas in HCA this was probably chelated by the large excess of citrate (55 mM) in this medium that prevented, or at least slowed, its entry into the renal cells. Lipid peroxidation was however significantly increased in kidneys stored in both HCA and saline solutions by addition of the calcium ionophore A23187 (10 microM) or the polysaccharide dye ruthenium red (5 microM) that inhibits mitochondrial uptake of Ca++. This strongly suggested that altered intracellular Ca++ homeostasis during the storage period played an important role in the development of oxidative damage to kidneys stored in both these media.
Cotterill
L A
LA
Section of Surgical Research, Northwick Park Hospital, Harrow, Middlesex.
Gower
J D
JD
Fuller
B J
BJ
Green
C J
CJ
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003080:Cold Temperature; D007511:Ischemia; D007668:Kidney; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D009926:Organ Preservation / Q000379:methods*; D010084:Oxidation-Reduction; D011817:Rabbits; D012430:Ruthenium Red / Q000494:pharmacology; D012545:Schiff Bases; D014700:Verapamil / Q000494:pharmacology
D008054:Lipid Peroxides; D012545:Schiff Bases; D012430:Ruthenium Red; D000001:Calcimycin; D014700:Verapamil; D002118:Calcium