Effects of methyl ethyl ketone pretreatment on hepatic mixed-function oxidase activity and on in vivo metabolism of n-hexane
| Autor: | J. S. Bus, P. Robertson, E. L. White |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Male
Time Factors Health Toxicology and Mutagenesis Metabolite Pharmacology In Vitro Techniques Toxicology Biochemistry Mixed Function Oxygenases chemistry.chemical_compound Cytochrome P-450 Enzyme System medicine Neurotoxin Animals Hexanes Inhalation exposure Neurotoxicity General Medicine medicine.disease Butanones Rats Inbred F344 Rats chemistry Liver Toxicity Microsome Sciatic nerve Benzphetamine medicine.drug Subcellular Fractions |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 19(7) |
| ISSN: | 0049-8254 |
| Popis: | 1. Male Fischer-344 rats were given methyl ethyl ketone (MEK; 1.87 ml/kg), a potentiator of the neurotoxicity of n-hexane, by gavage for 4 days prior to a single inhalation exposure to n-hexane (1000 ppm). 2. Samples of blood, liver, testis and sciatic nerve were obtained and analysed for n-hexane, MEK and their metabolites by g.l.c.-mass spectrometry. 3. Pretreatment with MEK increased the concentrations of 2,5-hexanedione (2,5-HD; the proximal neurotoxin) in blood, sciatic nerve and testis relative to concentrations in the tissues in sham-treated controls. 4. Concentrations of 2,5-dimethylfuran, a metabolite of 2,5-HD, were increased in all four tissues tested. 5. After 1-7 days treatment with MEK, the activity of 7-ethoxycoumarin O-deethylase was increased (up to 500%), but benzphetamine N-demethylase activity was virtually unaffected. 6. Hence, the potentiating effects of MEK on the neurotoxicity of n-hexane appear to arise, at least in part, from the activating effects of MEK on selected microsomal enzymes responsible for n-hexane activation. |
| Databáze: | OpenAIRE |
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