The effect of phenobarbital pretreatment on the metabolism, covalent binding, and cytotoxicity of aflatoxin B1 in primary cultures of rat hepatocytes
| Autor: | Dennis P. H. Hsieh, David J. Loury, James L. Byard |
|---|---|
| Rok vydání: | 1984 |
| Předmět: |
Male
Aflatoxin Aflatoxin B1 Toxicology Mixed Function Oxygenases chemistry.chemical_compound Aflatoxins Lactate dehydrogenase medicine Animals Drug Interactions Carbon Radioisotopes Cytotoxicity Carcinogen Cells Cultured Glutathione Transferase Oxidase test Rats Inbred Strains Metabolism Glutathione DNA Pollution Rats medicine.anatomical_structure Biochemistry chemistry Liver Hepatocyte Phenobarbital RNA |
| Zdroj: | Journal of toxicology and environmental health. 13(1) |
| ISSN: | 0098-4108 |
| Popis: | The effect of phenobarbital (PB) pretreatment on the metabolism, covalent binding, and cytotoxicity of [14C]aflatoxin B1 (AFB1) was studied in primary hepatocyte cultures. Hepatocytes from control and PB-pretreated rats were isolated from perfused liver biopsies and cultured in a chemically defined, hormone-supplemented medium. [14C]AFB1, dissolved in medium, was added to cultures at 20-22 h. The metabolism of AFB1 to water-soluble products and its binding to trichloroacetic acid-precipitable macromolecules were assessed 0.5 to 24 h later. At 6 h, PB pretreatment reduced total binding to macromolecules by 31% and reduced binding to RNA and DNA by 61% and 66%, respectively. In addition, PB protected cultures from the cytotoxic effects of AFB1, as evidenced by a significantly reduced (p less than 0.05) leakage of lactate dehydrogenase into the medium at 51 h. Elevated mixed-function oxidase and glutathione S-transferase activities, as well as higher levels of AFB1-glutathione conjugate were measured in cultures from rats pretreated with PB. The protective action of PB was concluded to be due to the induction of hepatic glutathione S-transferases responsible for the detoxification of AFB1. |
| Databáze: | OpenAIRE |
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