Influence of 2,5-hexanedione on rat brain amine synthesis and metabolism.
Sprague-Dawley derived rats were gavaged with daily doses of 2,5-hexanedione, a neurotoxic metabolite of both methyl n-butyl ketone and n-hexane. Seven daily doses of 0, 30, 100 or 300 mg 2,5-hexanedione/kg caused neuromuscular incoordination at the highest dose level while no effect was seen at the lowest level. Intravenous injections of either tritiated tyrosine or tryptophan, followed by exact time-interval sacrifices, facilitated the determination of synthesis rates and metabolism of various brain amines. At a cumulative dose of 210 mg 2,5-hexanedione/kg, the dopamine turnover rate was significantly increased, while precursor and metabolite levels were unchanged. Levels of serotonin as well as the serotonin synthesis rate remained unchanged, but levels of 5-hydroxyindoleacetic acid increased significantly in a dose dependent manner. The rise in 5-hydroxyindoleacetic acid levels inconjunction with no effects on other indoleamione parameters in 2,5-hexanedione-fed animals, suggests a possible inhibition of the energy-dependent 5-hydroxyindoleacetic acid efflux system in the brain.
C H
CH
Farr
C N
CN
Aldous
R P
RP
Sharma
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006588:Hexanones; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D001679:Biogenic Amines; D006588:Hexanones; D012701:Serotonin; C011269:2,5-hexanedione; D004298:Dopamine; D009638:Norepinephrine