Oxidative damage to rat brain in iron and copper overloads.
This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.
Department of General and Inorganic Chemistry, University of Buenos Aires, Buenos Aires, Argentina. mrepetto@ffyb.uba.ar.
Rosario
R
Musacco-Sebio
Nidia
N
Ferrarotti
Christian
C
Saporito-Magriñá
Jimena
J
Semprine
Julián
J
Fuda
Horacio
H
Torti
Alberto
A
Boveris
Marisa G
MG
Repetto
D000818:Animals; D001921:Brain / Q000473:pathology*; D003300:Copper / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003300:Copper; D007501:Iron