3-Nitropropionic acid (3-NPA) produces hypothermia and inhibits histochemical labeling of succinate dehydrogenase (SDH) in rat brain.
3-Nitropropionic acid (3-NPA) is a toxin sometimes produced on moldy crops (sugarcane, peanuts, etc.) in amounts sufficient to cause severe neurological disorders when consumed by humans. In vitro, 3-NPA irreversibly inactivates SDH, a Complex II respiratory enzyme required for mitochondrial energy production. A single dose of 3-NPA (30 mg/kg s.c.) was given to singly-caged adult male Sprague-Dawley rats. Rectal temperature was measured after dosing as a potential biomarker of exposure to 3-NPA, and animals were sacrificed at various times after 3-NPA exposure for histochemical visualization of SDH activity. 3-NPA-treated rats experienced a progressive hypothermia, which reached a loss of 3 degrees C or more in core body temperature by 3 hours after dosing. The optical density of the SDH stain in brain was reduced according to a similar time-course, most prominently in the cerebellum and least sharply in the thalamus. The caudate nucleus had the greatest density of SDH staining that we measured in brain; it also has been reported to be the region most consistently lesioned by 3-NPA. However, within other areas of brain such as subdivisions of the hippocampus, neither endogenous SDH activity nor its sensitivity to inhibition by 3-NPA could predict the susceptibility to neurodegenerative changes. Although SDH activity remained significantly reduced in most areas of brain (except thalamus) for up to 5 days after dosing, core temperatures had returned to control values by 5 days suggesting that animals can utilize an alternate method of heat production to withstand insult by 3-NPA.
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National Center for Toxicological Research, USFDA, Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Jefferson 72079, USA.
Scallet
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Rountree
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Binienda
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D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D006651:Histocytochemistry; D007035:Hypothermia / Q000139:chemically induced*; D007202:Indicators and Reagents; D008297:Male; D009574:Nitro Compounds; D009580:Nitroblue Tetrazolium; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013385:Succinate Dehydrogenase / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects
D007202:Indicators and Reagents; D009574:Nitro Compounds; D011422:Propionates; D009580:Nitroblue Tetrazolium; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid