A chelator is required for microsomal lipid peroxidation following reductive ferritin-iron mobilisation.
In the past, antioxidant and chelator studies have implicated a role for iron-dependent oxidative damage in tissues subjected to ischaemia followed by reperfusion. As ferritin is a major source of iron in non-muscular organs and therefore a potential source of the iron required for oxygen radical chemistry, we have determined conditions under which ferritin iron reduction leads to the formation of a pool of iron which is capable of catalysing lipid peroxidation. Under anaerobic conditions and in the presence of rat liver microsomes, flavin mononucleotide (FMN) catalysed the reduction of ferritin iron as shown by both continuous spectrophotometric measurements of tris ferrozine-Fe(II) complex formation and post-reaction Fe(II) determination. The presence of either ferrozine or citrate was not found to alter the time course or extent of ferritin reduction. In contrast, the addition of air to the reactants after a 20 min period of anaerobic reduction resulted in peroxidation of the microsome suspension (as determined with the 2-thiobarbituric acid test) only in the presence of a chelator such as citrate, ADP or nitrilotriacetic acid. These results support the concept that reduced ferritin iron can mediate oxidative damage during reperfusion of previously ischaemic tissues, provided that chelating agents such as citrate or ADP are present.
Goddard
J G
JG
Section of Surgical Research, Clinical Research Centre, Harrow, Middlesex, U.K.
Gower
J D
JD
Green
C J
CJ
D000818:Animals; D002384:Catalysis; D005293:Ferritins / Q000378:metabolism*; D005486:Flavin Mononucleotide / Q000494:pharmacology*; D005609:Free Radicals; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism; D013858:Thiobarbiturates / Q000032:analysis
D005609:Free Radicals; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D013858:Thiobarbiturates; D005486:Flavin Mononucleotide; D005293:Ferritins; C029684:thiobarbituric acid