Potentiation of CCl/sub 4/ hepatotoxicity by chlordecone: evidence of increased metabolism of CCl/sub 4/ in vivo

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5431030

Dolak, J A; Britton, R S; Glende, Jr, E A; Recknagel, R O

Chlordecone (CD) has been shown to dramatically increase CCl/sub 4/ hepatotoxicity, but the mechanisms by which this effect occurs are not clear. Dose-response studies were performed to determine the size of CD's potentiating action on CCl/sub 4/-induced liver enzyme release and loss of hepatic microsomal enzymatic functions. Rats were pretreated with 15 mg CD/kg BW i.g., or vehicle. After 48 hrs, 0-250 ..mu..1 CCl/sub 4//100g BW were given i.p., and the rats were killed 24 hrs later. In CD-treated rats, 6 ..mu..1 CCl/sub 4//100 resulted in a mean SGOT level similar to that found after administration of 100 ..mu..1/100g to control animals. CD also potentiated the CCl/sub 4/-dependent loss of cytochrome P-450 and glucose-6-phosphatase, with the 6 ..mu..1 CCl/sub 4//100g dose in the CD-treated rats being equieffective to the 100 ..mu..1/100g dose in the controls. Since CD treatment increased cytochrome P-450 content by 67%, an experiment was performed to see if this induction increased the metabolism of /sup 14/CCl/sub 4/ to reactive products (/sup 14/C covalently bound to microsomal protein and lipid after 1 hr). An increase in the metabolism of the 6 ..mu..1/100g dose of CCl/sub 4/ was observed in the CD-treated rats with binding of /sup 14/C to both protein and lipid being increased 2.7- and 1.7-fold, respectively; there was no difference in binding at the 100 ..mu..1/100g dose. These results suggest that an increase in CCl/sub 4/ metabolism may contribute to the potentiation of CCl/sub 4/ hepatotoxicity by CD.

• Research Organization: Case Western Reserve Univ., Cleveland, OH
• OSTI ID: 5431030
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
CARBON 14 COMPOUNDS
CARBON TETRACHLORIDE
CELL CONSTITUENTS
CHLORINATED ALIPHATIC HYDROCARBONS
COVALENCE
CYTOCHROMES
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
ENZYMES
ESTERASES
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
HYDROLASES
INSECTICIDES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
MICROSOMES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
PESTICIDES
PHOSPHATASES
PIGMENTS
PROTEINS
RATS
REACTION KINETICS
RODENTS
TOXICITY
TRACER TECHNIQUES
VERTEBRATES