In vivo metabolism of CCl/sub 4/ by rats pretreated with chlordecone, mirex, or phenobarbital

Journal Article · Fri Apr 01 04:00:00 EST 1988 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(88)90124-X· OSTI ID:6970363

Mehendale, H M; Klingensmith, J S

The propensity of chlordecone (CD) to potentiate hepatotoxic and lethal effects of CCl4 is well established. Mirex (M), a close structural analogue of CD, or phenobarbital (PB), powerful inducers of hepatic microsomal drug metabolizing enzymes, are much weaker potentiators of CCl4 toxicity. The purpose of this study was to test the possibility that CD potentiates the toxicity of CCl4 by increasing the metabolism of CCl4 to a greater degree than either PB or M. We compared the in vivo metabolism of CCl4 in rats pretreated with CD, M, or PB, by measuring the hepatic content of 14CCl4, the expiration of 14CCl4, expiration of 14CCl4-derived 14CO2, and lipid peroxidation. Male Sprague-Dawley rats (250-270 g) were pretreated with a single oral dose of CD (10 mg/kg), M (10 mg/kg), or corn oil vehicle (1 ml/kg). PB pretreatment consisted of an ip injection of sodium PB (80 mg/kg) in saline (0.9%) for 2 successive days. Twenty-four hours later, 14CCl4 (0.1 ml/kg; sp act: 0.04 mCi/mmol) was administered ip in corn oil and the radioactivity present in the expired air was collected for 6 hr. Excretion of the parent compound as represented by the 14C label in the toluene trap was unchanged by any of the pretreatments. Expiration of 14CO2 measured during the 6 hr after CCl4 administration was increased in animals pretreated with PB or CD. In vivo lipid peroxidation measured as diene conjugation in lipids extracted from the livers was increased to a similar extent in animals pretreated with PB and CD, whereas the serum transaminases (ALT, AST) were significantly elevated only in animals pretreated with CD.M did not affect 14CO2 production and was without a significant effect on the lipid peroxidation.

• Research Organization: Univ. of Mississippi Medical Center, Jackson (USA)
• OSTI ID: 6970363
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 93:2; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINOTRANSFERASES
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AZINES
BARBITURATES
BODY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARBON DIOXIDE
CARBON OXIDES
CARBON TETRACHLORIDE
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHALCOGENIDES
CHLORINATED ALIPHATIC HYDROCARBONS
DIGESTIVE SYSTEM
DRUGS
ENZYME ACTIVITY
ENZYMES
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYPNOTICS AND SEDATIVES
IN VIVO
INSECTICIDES
ISOTOPE APPLICATIONS
KEPONE
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
NITROGEN TRANSFERASES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PESTICIDES
PHENOBARBITAL
PYRIMIDINES
RATS
RODENTS
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES