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Titolo:
Pulmonary bioactivation of 1,1-dichloroethylene is associated with CYP2E1 levels in A/J, CD-1, and C57BL/6 mice
Autore:
Forkert, PG; Boyd, SM; Ulreich, JB;
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 Univ Arizona, Dept Surg, Tucson, AZ USA Univ Arizona Tucson AZ USAUniv Arizona, Dept Surg, Tucson, AZ USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 297, anno: 2001,
pagine: 1193 - 1200
SICI:
0022-3565(200106)297:3<1193:PBO1IA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLARA CELL-DAMAGE; COVALENT BINDING; MURINE LUNG; GLUTATHIONE CONJUGATE; METABOLIC-ACTIVATION; VINYLIDENE-CHLORIDE; FEMALE MICE; CYTOCHROME-P-450; LIVER; INJURY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
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 et al., "Pulmonary bioactivation of 1,1-dichloroethylene is associated with CYP2E1 levels in A/J, CD-1, and C57BL/6 mice", J PHARM EXP, 297(3), 2001, pp. 1193-1200

Abstract

1,1 -Dichloroethylene (DCE) elicits lung cytotoxicity and selectively targets Clara cells of bronchioles. The toxic effects are ascribed to CYP2E1-mediated formation of reactive intermediates including the DCE epoxide. Here we tested the hypothesis that differential CYP2E1 levels in the lungs of A/J, CD-1, and C57BL/6 mice lead to differences in the extents of DCE bioactivation and lung damage. Our results showed that lung CYP2E1 levels differedsignificantly in the three murine strains, and followed the rank order A/J> CD-l > C57BL/6, Covalent binding of [C-14]DCE to lung proteins in A/J mice was significantly higher than in either CD-1 or C57BL/6 mice. HPLC analysis of lung cytosol from DCE-treated mice showed that 2-S-glutathionyl] acetate, a glutathione (GSH) conjugate derived from the epoxide (conjugate [CI), was the major metabolite formed. Levels of [C] detected in cytosol from A/J and CD-I mice were significantly higher than in C57BL/6 mice. Immunohistochemical staining for [C] was pronounced in the lungs of A/J mice, was lower in CD-I mice, and was lowest in C57BL/6 mice. Levels of GSH were similar in the lungs of ail untreated mice. However, significant reduction in GSHwas found in DCE-treated mice, with decreases comparable in all three strains. Bronchiolar Clara cell damage was more severe in A/J and CD-l mice than in C57BL/6 mice. These results showed differences in CYP2E1 levels in thelungs of A/J, CD-I, and C57BL/6 mice that correlated with the extent to which the DCE epoxide is formed as well as with the severity of lung cytotoxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 12:59:46