Spin trapping of free radical metabolites of carbon tetrachloride in vitro and in vivo: Effect of acute ethanol administration

Journal Article · Wed Jan 01 04:00:00 EST 1992 · Toxicology and Applied Pharmacology; (United States)

DOI:https://doi.org/10.1016/0041-008X(92)90274-V· OSTI ID:5696225

Reinke, L A; Towner, R A; Janzen, E G ^[1]

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1. Department of Clinical Studies, Ontario Veterinary College, University of Guelph (Canada)

A single dose of ethanol, when administered 18 hr prior to CCl4, potentiates the hepatotoxicity of the halocarbon. In these studies, spin trapping and electron spin resonance (ESR) spectroscopy methods were utilized to determine whether a single ethanol dose increased the metabolism of CCl4 to free radical intermediates. When hepatic microsomes from ethanol-treated or control rats were incubated with CCl4 and the spin trapping agent alpha-phenyl-N-tert-butylnitrone (PBN), the ESR signal of the trichloromethyl radical adduct of PBN was of similar intensity in both groups. The ethanol dose also failed to induce p-nitrophenol hydroxylase activity. When PBN and CCl4 were administered to rats, liver extracts contained ESR signals resulting primarily from the trichloromethyl radical adduct of PBN, and the signals were of similar intensity in both experimental groups. Higher concentrations of the carbon dioxide anion radical adduct of PBN were detected in plasma samples from ethanol-treated rats. However, when hepatocytes from ethanol-treated and control rats were incubated with PBN and CCl4, ESR signals of the carbon dioxide adduct were of similar intensity. These data suggest that the higher concentrations of the carbon dioxide adduct in the blood of ethanol-treated rats may be explained by early CCl4-induced damage to liver cell membranes, rather than increased rates of formation. The data in this report fail to support the hypothesis that a single dose of ethanol stimulates the hepatic metabolism of CCl4 to the trichloromethyl radical. Alternatively, ethanol may potentiate CCl4 toxicity by affecting some critical metabolic step subsequent to trichloromethyl radical formation.

• OSTI ID: 5696225
• Journal Information: Toxicology and Applied Pharmacology; (United States), Journal Name: Toxicology and Applied Pharmacology; (United States) Vol. 112:1; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMALS
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
CARBON TETRACHLORIDE
CELL CONSTITUENTS
CHALCOGENIDES
CHLORINATED ALIPHATIC HYDROCARBONS
DIGESTIVE SYSTEM
DRUGS
ELECTRON SPIN RESONANCE
ENZYME ACTIVITY
ENZYMES
ETHANOL
GLANDS
GLUTATHIONE
HALOGENATED ALIPHATIC HYDROCARBONS
HYDROXY COMPOUNDS
HYDROXYLASES
LIVER
MAGNETIC RESONANCE
MAMMALS
METABOLISM
MICROSOMES
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADICALS
RADIOPROTECTIVE SUBSTANCES
RATS
RESONANCE
RIBOSOMES
RODENTS
SYNTHESIS
TOXICITY
VERTEBRATES