Whole body hyperthermia reduces oxidative stress in the striatum of rats in an animal model of mitochondrial toxicity with 3-nitropropionic acid.
OBJECTIVE
The goal of this study was to determine whether whole body hyperthermia (WBH) could reduce oxidative stress in the striatum produced by 3-nitropropionic acid (3-NP), a mitochondrial toxin that irreversibly inhibits succinate dehydrogenase (SDH), causing impairment of energy metabolism, oxidative stress and a selective degeneration of striatal cells.


METHODS
Rats were subjected to WBH (42 degrees C) or normothermia control conditions for 30 min and then treated with 3-NP. Striatum samples were processed and the levels of protein carbonyl groups, biogenic amines, Hsp72 and salicylate hydroxylation (to probe the hydroxyl radical (OH(*)) intervention) were determined.


RESULTS
WBH significantly reduced oxidative stress in the striatum of animals treated with 3-NP, as judged by reductions in protein carbonyl and salicylate hydroxylation derivative levels, whereas striatal Hsp72 expression was significantly increased. The groups treated with 3-NP presented an increased in the dopamine (DA) derivatives 2,3-dihydroxyphenylacetic acid (DOPAC) and norepinephrine (NE) concentration, whereas the striatal relation DOPAC/DA concentration indicate a reduced dopamine turnover.


CONCLUSIONS
These studies show, for the first time, that a heat shock pretreatment can ameliorate the oxidative stress produced by a metabolic toxin (3-NP) capable of impairing energy supply and produce selective striatal degeneration. These data contribute to a better understanding of the potential for thermal stress to modulate the type of oxidative stress usually present in neurodegenerative disorders associated with metabolic defects.
Department of Experimental Metabolism, Center for Biomedical Research of Michoacán (CIBIMI-IMSS), C.P. 58261, Morelia, Michoacán, México. rafael.medina@imss.gob.mx
Rafael
R
Medina-Navarro
Israel
I
Guerrero-Linares
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D006979:Hyperthermia, Induced; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009043:Motor Activity; D009574:Nitro Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D011422:Propionates / Q000633:toxicity*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D050884:HSP72 Heat-Shock Proteins; D009574:Nitro Compounds; D011422:Propionates; D015102:3,4-Dihydroxyphenylacetic Acid; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid; D004298:Dopamine