Toxicology (Amsterdam), 1997-03, Vol.118 (2), p.171-179
1997
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- Autor(en) / Beteiligte
- Titel
- Involvement of cytochrome P4502E1 in the toxicity of dichloropropanol to rat hepatocyte cultures
- Ist Teil von
- Toxicology (Amsterdam), 1997-03, Vol.118 (2), p.171-179
- Ort / Verlag
- Shannon: Elsevier Ireland Ltd
- Erscheinungsjahr
- 1997
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- Hepatocytes were isolated and cultured from untreated rats and rats treated with isoniazid to induce cytochrome P4502E1. Isoniazid selectively increased p-nitrophenol hydroxylase activity in 2-h cultures, and increased the toxicity of both 1,3- and 2,3-dichloropropanol. Isoniazid also increased the rate and extent of glutathione depletion by the dichloropropanols. There was no effect of isoniazid on the toxicity of 1,3-dichloroacetone, precocene II or allyl alcohol. In addition, diethyldithiocarbamate selectively inhibited p-nitrophenol hydroxylase in 2-h cultures from untreated and isoniazid-treated rats, as well as abolishing toxicity of the dichloropropanols. In 24-h cultures from isoniazid-treated rats diethyldithiocarbamate inhibited high affinity MCOD activity by 55% and there was also a small but significant inhibition of precocene II toxicity. These results indicate that isoniazid-inducible P4502E1 can mediate the toxicity of dichloropropanol.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0300-483XeISSN: 1879-3185DOI: 10.1016/S0300-483X(96)03604-9Titel-ID: cdi_proquest_miscellaneous_15964268
- Format
- –
- Schlagworte
- 1-Propanol - toxicity, Acetone - analogs & derivatives, Acetone - toxicity, alpha-Chlorohydrin - analogs & derivatives, alpha-Chlorohydrin - metabolism, alpha-Chlorohydrin - toxicity, Analysis of Variance, Animals, Antidotes - pharmacology, Benzopyrans - toxicity, Biological and medical sciences, Cell Death - drug effects, Cells, Cultured, Chemical and industrial products toxicology. Toxic occupational diseases, Chlorohydrins - metabolism, Chlorohydrins - toxicity, Cytochrome P-450 CYP2E1 - biosynthesis, Cytochrome P-450 CYP2E1 - metabolism, Cytochrome P-450 Enzyme System - metabolism, Dichloropropanol, Diethyldithiocarbamate, Ditiocarb - pharmacology, Drug Interactions, Enzyme Activation - drug effects, Enzyme Induction - drug effects, Glutathione - metabolism, Hepatocytes, Hepatotoxicity, Insecticides - toxicity, Isoniazid, Isoniazid - toxicity, L-Lactate Dehydrogenase - metabolism, Liver - cytology, Liver - drug effects, Liver - enzymology, Male, Medical sciences, Mutagens - metabolism, Mutagens - toxicity, Plants, Propanols, Rats, Rats, Wistar, Toxicology, Various organic compounds