Changes in the rat liver drug metabolizing system during a short thiobenzamide feeding cycle

The changes in the hepatic drug metabolizing enzymes induced by the liver tumor promoter thiobenzamide (TB) were investigated. Feeding of TB to rats at a promoting regimen (1 g/kg of diet for 2 weeks) resulted in a significant decrease in the amount of liver microsomal cytochrome P-450 and of total...

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Bibliographic Details
Published in:Archives of toxicology 1987-12, Vol.61 (2), p.150-154
Main Authors: CHIELI, E, SAVIOZZI, M, MALVALDI, G
Format: Article
Language:English
Subjects:
Adaptation, Biological - drug effects
Amides - toxicity
Animals
Biological and medical sciences
Body Weight - drug effects
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
Cytochrome P-450 Enzyme System - metabolism
DNA - metabolism
Liver - enzymology
Liver - metabolism
Male
Medical sciences
Mitosis - drug effects
Mixed Function Oxygenases - metabolism
NADH Dehydrogenase - metabolism
Organ Size - drug effects
Rats
Rats, Inbred Strains
Thioamides - toxicity
Tumors
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Summary:The changes in the hepatic drug metabolizing enzymes induced by the liver tumor promoter thiobenzamide (TB) were investigated. Feeding of TB to rats at a promoting regimen (1 g/kg of diet for 2 weeks) resulted in a significant decrease in the amount of liver microsomal cytochrome P-450 and of total heme. Also, the activity of cytochrome P-450 dependent monooxygenases (aminopyrine demethylase, arylhydrocarbonmonooxygenase and ethoxycoumarindeethylase) and FAD-containing monoxygenase (N,N-dimethylaniline N-oxidase and TB S-oxidase) were depressed. By contrast, phase II enzymes such as epoxide hydrase, UDP-glucuronyl transferase and GSH-transferase were significantly induced. This overall change in the drug metabolizing system was associated with tolerance of the liver towards a high necrogenic dose of TB itself as well as with an increase of mitoses and apoptosis of the hepatocytes. The findings suggest a possible relationship between this TB-induced adaptive response and the promoting activity of the compound on liver carcinogenesis.
ISSN:0340-5761
1432-0738
DOI:10.1007/BF00661374