Iron release and membrane damage in erythrocytes exposed to oxidizing agents, phenylhydrazine, divicine and isouramil.
Mouse erythrocytes were incubated with oxidizing agents, phenylhydrazine, divicine and isouramil. With all the oxidants a rapid release of iron in a desferrioxamine (DFO)-chelatable form was seen and it was accompanied by methaemoglobin formation. If the erythrocytes were depleted of GSH by a short preincubation with diethyl maleate, the release of iron was accompanied by lipid peroxidation and, subsequently, haemolysis. GSH depletion by itself did not induce iron release, methaemoglobin formation, lipid peroxidation or haemolysis. Rather, the fate of the cell in which iron is released depended on the intracellular availability of GSH. In addition, iron release was higher in depleted cells than in native ones, suggesting a role for GSH in preventing iron release when oxidative stress is imposed by the oxidants. Iron release preceded lipid peroxidation. The latter was prevented when the erythrocytes were preloaded with DFO in such a way (preincubation with 10 mM-DFO) that the intracellular concentration was equivalent to that of the released iron, but not when the intracellular DFO was lower (preincubation with 0.1 mM-DFO). Extracellular DFO did not affect lipid peroxidation and haemolysis, suggesting again that the observed events occur intracellularly (intracellular chelation of released iron). The relevance of iron release from iron complexes in the mechanisms of cellular damage induced by oxidative stress is discussed.
Ferrali
M
M
Istituto di Patologia Generale, Università di Siena, Italy.
Signorini
C
C
Ciccoli
L
L
Comporti
M
M
D000818:Animals; D001463:Barbiturates / Q000633:toxicity*; D003676:Deferoxamine / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006461:Hemolysis; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008706:Methemoglobin / Q000096:biosynthesis; D051379:Mice; D016877:Oxidants / Q000633:toxicity*; D010659:Phenylhydrazines / Q000633:toxicity*; D011744:Pyrimidinones / Q000633:toxicity*
D001463:Barbiturates; D016877:Oxidants; D010659:Phenylhydrazines; D011744:Pyrimidinones; C030299:phenylhydrazine; C026511:divicine; C032211:isouramil; D008706:Methemoglobin; D007501:Iron; D005978:Glutathione; D003676:Deferoxamine