TEMPORAL EFFECTS OF 1,1-DICHLOROETHYLENE ON NONPROTEIN SULFHYDRYL CONTENT IN MURINE LUNG AND LIVER

Citation
Pg. Forkert et M. Moussa, TEMPORAL EFFECTS OF 1,1-DICHLOROETHYLENE ON NONPROTEIN SULFHYDRYL CONTENT IN MURINE LUNG AND LIVER, Drug metabolism and disposition, 21(5), 1993, pp. 770-776
Citations number
23
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00909556
Volume
21
Issue
5
Year of publication
1993
Pages
770 - 776
Database
ISI
SICI code
0090-9556(1993)21:5<770:TEO1ON>2.0.ZU;2-M
Abstract
Administration of 1,1-dichloroethylene (DCE) to mice evokes cytotoxici ty involving Clara cells in lung, and at higher doses, centrilobular h epatocytes in liver. Our objective is to investigate temporal alterati ons in nonprotein sulfhydryl [glutathione (GSH)] content in lung and l iver after administration of a dose of DCE (125 mg/kg). Contribution o f GSH from whole blood comprised 54% and 14% of the amounts found in l ung and liver, respectively, of DCE-treated mice, and were taken into account to determine tissue content of GSH. In lung, a significant dec rease in GSH (60% of control) was first detected at 6 hr, and levels r emained low from 8 to 12 hr. In liver, a 50% decrease was initially de tected at 1 hr after DCE treatment. Progressive increases were found t hereafter, with a return to the control level at 24 hr. Histochemical staining for GSH in liver revealed homogeneous labeling in hepatocytes across the lobule; DCE treatment diminished staining uniformly in all hepatocytes. In control lung, histochemical reactivity was exhibited in bronchiolar epithelium and alveolar septa. Clara cells were stained to the greatest extent and with considerable variability, whereas sta ining was more uniform in alveolar septa. Staining was markedly dimini shed by DCE treatment, and was initially abolished in the alveolar sep ta, but retained to a limited extent within a small number of Clara ce lls. These findings suggest that susceptibility of a subpopulation of Clara cells to cytotoxicity may be associated, in part, with low expre ssion of nonprotein sulfhydryl content at the time of DCE treatment.