Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains.
Since hydrogen peroxide (H2O2) can react with ferrous iron (FE++) to form the more toxic hydroxyl radical (OH) in vitro, and since H2O2 is generated brain xanthine oxidase (XO) during ischemia/reperfusion (I/R), we hypothesized that gerbils depleted of iron by dietary restriction or treated with iron chelators would be less susceptible to I/R injury. We found that gerbils fed a low iron diet for 8 weeks had decreased brain and serum iron levels, less neurologic deficits, and decreased brain edema after temporary unilateral carotid ligation (ischemia) and then reperfusion than gerbils fed a control standard iron diet. In addition, brains from gerbils treated with iron-free deferoxamine (an iron chelator), but not iron-loaded deferoxamine, had decreased (P less than .05) brain edema following ischemia and reperfusion. The results indicate that iron may contribute to cerebral ischemia/reperfusion damage.
Patt
A
A
Department of Medicine, University of Colorado Health Sciences Center, Denver.
Horesh
I R
IR
Berger
E M
EM
Harken
A H
AH
Repine
J E
JE
D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry; D001929:Brain Edema / Q000517:prevention & control*; D002545:Brain Ischemia / Q000503:physiopathology; D003676:Deferoxamine / Q000494:pharmacology*; D005260:Female; D005849:Gerbillinae; D006400:Hematocrit; D007501:Iron / Q000032:analysis / Q000097:blood / Q000502:physiology; D000090463:Iron Deficiencies; D008297:Male; D015427:Reperfusion Injury / Q000517:prevention & control*; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D007501:Iron; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D003676:Deferoxamine