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Titolo:
Early events in naphthalene-induced acute Clara cell toxicity - II. Comparison of glutathione depletion and histopathology by airway location
Autore:
Plopper, CG; Van Winkle, LS; Fanucchi, MV; Malburg, SRC; Nishio, SJ; Chang, AM; Buckpitt, AR;
Indirizzi:
Univ Calif Davis, Sch Vet Med, Dept Anat, Davis, CA 95616 USA Univ Calif Davis Davis CA USA 95616 t Med, Dept Anat, Davis, CA 95616 USA Univ Calif Davis, Sch Vet Med, Dept Physiol & Cell Biol, Davis, CA 95616 USA Univ Calif Davis Davis CA USA 95616 siol & Cell Biol, Davis, CA 95616 USA Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA Univ Calif Davis Davis CA USA 95616 Dept Mol Biosci, Davis, CA 95616 USA Univ Calif Davis, Sch Med, Dept Epidemiol & Prevent Med, Davis, CA 95616 USA Univ Calif Davis Davis CA USA 95616 ol & Prevent Med, Davis, CA 95616 USA
Titolo Testata:
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
fascicolo: 3, volume: 24, anno: 2001,
pagine: 272 - 281
SICI:
1044-1549(200103)24:3<272:EEINAC>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
BLEB FORMATION; CYTOCHROME-P-450 ACTIVITY; MURINE LUNG; METABOLISM; PULMONARY; CYTOTOXICITY; HEPATOCYTES; INJURY; LIVER; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Plopper, CG Univ Calif Davis, Sch Vet Med, Dept Anat, 1331 Haring Hall, Davis, CA 95616 USA Univ Calif Davis 1331 Haring Hall Davis CA USA 95616 95616 USA
Citazione:
C.G. Plopper et al., "Early events in naphthalene-induced acute Clara cell toxicity - II. Comparison of glutathione depletion and histopathology by airway location", AM J RESP C, 24(3), 2001, pp. 272-281

Abstract

One of the presumed roles of intracellular glutathione (GSH) is the protection of cells from injury by reactive intermediates produced by the metabolism of xenobiotics. To establish whether GSH depletion is a critical step in the initiation of events that lead to cytotoxicity by P450-activated cytotoxicants, naphthalene, a well-defined Clara cell cytotoxicant, was administered to mice (200 mg/kg) by intraperitoneal injection. Shortly after injection (1, 2, and 3 h), intracellular GSH content was assessed by high performance liquid chromatography or quantitative epifluorescent imaging microscopy and compared with the degree of cytotoxicity as assessed by high resolution histopathology. In highly susceptible airways (distal bronchioles), GSHdecreased by 50% in 1 h. Cytoplasmic vacuolization was not visible until 2h, when GSH had decreased by an additional 50%. By 3 h, cytoplasmic blebbing was extensive. In minimally susceptible airways (lobar and proximal bronchi), GSH depletion varied widely within the population; a small proportionof the cells lost greater than 50% of their GSH by 2 h and a significant percentage of the cells retained most of their GSH throughout the entire 3 h. Cytoplasmic vacuolization was apparent in some of the cells at 2 h but not visible in any cells at 3 h. We conclude that (1) loss of intracellular GSH is an early event that precedes initial signs of cellular damage in Clara cell cytotoxicity; (2) this pattern of loss in relation to early injury is found both in highly susceptible and minimally susceptible airway sites; (3) there is wide cell-to-cell heterogeneity in the response; (4) the heterogeneity in the response profile varies between populations in highly susceptible and minimally susceptible sites; and (5) once the intracellular GSH concentration within the entire cell population drops below a certain threshold, the initial phase of injury becomes irreversible.

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Documento generato il 04/04/20 alle ore 13:20:19