The importance of iron, calcium and free radicals in reperfusion injury: an overview of studies in ischaemic rabbit kidneys.
An overview of a series of experiments attempting to link iron and calcium redistribution and release of free fatty acids with falls in pH and adenine nucleotide levels during cold storage of rabbit kidneys is presented. The data reviewed strongly suggest that these events are inextricably linked to subsequent reperfusion injury. Circumstantial evidence incriminating iron was provided by experiments showing that iron chelation decreased reperfusion injury after warm (WI) and cold ischaemia (CI) in rat skin flap and rabbit kidney models. Evidence for a role for calcium was provided when it was found that a calcium channel blocking agent added to the saline flush solution before storage inhibited lipid peroxidation, whereas chemicals which caused release or influx of calcium into the cell exacerbated oxidative damage. Additional involvement of breakdown products of adenine nucleotides was suggested by the protection from lipid peroxidation afforded by allopurinol. Involvement of calcium-activated phospholipase A2 was strongly suggested by increases in free fatty acids during cold storage and both this increase and lipid peroxidation were inhibited by addition of dibucaine to the storage solution.
Green
C J
CJ
Section of Surgical Research, MRC Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex.
Gower
J D
JD
Healing
G
G
Cotterill
L A
LA
Fuller
B J
BJ
Simpkin
S
S
D000818:Animals; D002118:Calcium / Q000502:physiology*; D005609:Free Radicals; D007501:Iron / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism*
D005609:Free Radicals; D007501:Iron; D002118:Calcium