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.
Medina-Navarro
Rafael
R
Department of Experimental Metabolism, Center for Biomedical Research of Michoacán (CIBIMI-IMSS), C.P. 58261, Morelia, Michoacán, México. rafael.medina@imss.gob.mx
Guerrero-Linares
Israel
I
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