2-Methylfuran toxicity in rats--role of metabolic activation in vivo
Administration of a single ip dose of 2-methylfuran (2-MF) to male Sprague-Dawley rats at a dose of 100 mg/kg produced centrilobular necrosis of the liver and bronchial injury of the lung, the severity of the lesions increasing with increasing doses up to 400 mg/kg. Kidneys, however, showed no visible evidence of tissue damage even at the highest dose. Liver injury was also evidenced by an increase in serum glutamic pyruvic transaminase (SGPT) levels. Tissue distribution and covalent binding studies conducted over a dose of 50-200 mg/kg of (/sup 14/C)2-MF indicated that the total radioactivity present per gram of wet tissue was in the order of liver greater than kidney greater than lung greater than blood. Covalent binding of the label to protein was greatest in the liver followed by kidney and the lung. Radioactivity bound covalently per milligram of DNA was also highest in the liver followed by kidney. Tissue distribution and covalent binding studies were conducted over a period of 0.5 to 24 hr after an ip dose of 100 mg/kg of (/sup 14/C)2-MF. Maximal covalent binding was observed in the liver at 4 hr. At all time points binding of the label was greatest in liver, followed by kidney. Liver glutathione levels were depressed following 2-MF administration. Pretreatment of rats with phenobarbital markedly increased the covalent binding to protein and DNA and caused a twofold increase in SGPT compared to rats treated with 2-MF alone. Pretreatment with 3-methylcholanthrene had no effect on either parameter. Administration of N-octylimidazole, an inhibitor of cytochrome P-450, prior to administration of the radiolabeled 2-MF decreased the covalent binding of the label to protein and DNA. Moreover, the SGPT levels remained the same in the pretreated rats compared to the rats treated with vehicle alone.
- OSTI ID:
- 5117072
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 1; ISSN TXAPA
- Country of Publication:
- United States
- Language:
- English
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550601 -- Medicine-- Unsealed Radionuclides in Diagnostics
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AROMATICS
AZINES
BARBITURATES
BODY
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CYTOCHROMES
DIGESTIVE SYSTEM
DISTRIBUTION
DNA
DRUGS
ENZYMES
FURANS
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYPNOTICS AND SEDATIVES
ISOTOPE APPLICATIONS
KIDNEYS
LABELLED COMPOUNDS
LIVER
LUNGS
MAMMALS
METABOLIC ACTIVATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PHENOBARBITAL
PIGMENTS
POLYCYCLIC AROMATIC HYDROCARBONS
PROTEINS
PYRIMIDINES
RATS
RESPIRATORY SYSTEM
RODENTS
TISSUE DISTRIBUTION
TOXICITY
TRACER TECHNIQUES
VERTEBRATES