Influence of 2,5-hexanedione on rat brain amine synthesis and metabolism

Autor: C H, Farr, C N, Aldous, R P, Sharma
Rok vydání: 1986
Předmět:
Zdroj: Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer. 6(3-4)
ISSN: 0731-8898
Popis: 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.
Databáze: OpenAIRE