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Involvement of cytochrome P4502E1 in the toxicity of dichloropropanol to rat hepatocyte cultures.
Hammond, A H; Fry, J R.
Afiliación
  • Hammond AH; Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, UK.
Toxicology ; 118(2-3): 171-9, 1997 Mar 28.
Article en En | MEDLINE | ID: mdl-9129171
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.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clorhidrinas / Citocromo P-450 CYP2E1 / Alfa-Clorhidrina / Hígado / Mutágenos Límite: Animals Idioma: En Revista: Toxicology Año: 1997 Tipo del documento: Article Pais de publicación: Irlanda
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clorhidrinas / Citocromo P-450 CYP2E1 / Alfa-Clorhidrina / Hígado / Mutágenos Límite: Animals Idioma: En Revista: Toxicology Año: 1997 Tipo del documento: Article Pais de publicación: Irlanda