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Titolo:
Mechanisms of 1,1-dichloroethylene-induced cytotoxicity in lung and liver
Autore:
Forkert, PG;
Indirizzi:
Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada Queens Univ Kingston ON Canada K7L 3N6 Biol, Kingston, ON K7L 3N6, Canada
Titolo Testata:
DRUG METABOLISM REVIEWS
fascicolo: 1, volume: 33, anno: 2001,
pagine: 49 - 80
SICI:
0360-2532(2001)33:1<49:MO1CIL>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
COVALENT BINDING; VINYLIDENE-CHLORIDE; MURINE LUNG; GLUTATHIONE CONJUGATE; 2-S-GLUTATHIONYL ACETATE; REACTIVE METABOLITES; PULMONARY TOXICITY; FEMALE MICE; RAT-LIVER; HEPATOTOXICITY;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Forkert, PG Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada Queens Univ Kingston ON Canada K7L 3N6 on, ON K7L 3N6, Canada
Citazione:
P.G. Forkert, "Mechanisms of 1,1-dichloroethylene-induced cytotoxicity in lung and liver", DRUG METAB, 33(1), 2001, pp. 49-80

Abstract

Exposure to 1,1-dichloroethylene (DCE) causes lung and liver toxicities inmice. The lesions are characterized by damage preferentially to bronchiolar Clara cells in the lung and necrosis of centrilobular hepatocytes in the liver. The primary metabolites formed from DCE in lung and liver microsomalincubations are the epoxide, 2,2-dichloroacetaldehyde and 2-chloroacetyl chloride, which undergo hydrolysis and/or conjugation with glutathione (GSH). The major products formed are the epoxide-derived GSH conjugates 2-(S-glutathionyl) acetyl glutathione [B] and 2S-glutathionyl acetate [C]. The hydrate of 2,2 dichloroacetaldehyde (acetal) is also detected. These metabolites are detected in vivo in murine lung and liver cytosol and in bile, and importantly, also in human lung and liver microsomal incubations. Formation of the epoxide is mediated mainly by CYP2E1, Immunohistochemical studies localized the epoxide-derived GSH conjugate [C] and cysteine-containing proteins in Clara cells and centrilobular hepatocytes. These findings are consistent with the premise that the lung and liver cytotoxicities induced by DCE are associated with in situ formation of the epoxide within the target cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/08/20 alle ore 04:57:58