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  • Title: Temporal effects of 1,1-dichloroethylene on nonprotein sulfhydryl content in murine lung and liver.
    Author: Forkert PG, Moussa M.
    Journal: Drug Metab Dispos; 1993; 21(5):770-6. PubMed ID: 7902234.
    Abstract:
    Administration of 1,1-dichloroethylene (DCE) to mice evokes cytotoxicity involving Clara cells in lung, and at higher doses, centrilobular hepatocytes in liver. Our objective is to investigate temporal alterations in nonprotein sulfhydryl [glutathione (GSH)] content in lung and liver after administration of a dose of DCE (125 mg/kg). Contribution of GSH from whole blood comprised 54% and 14% of the amounts found in lung and liver, respectively, of DCE-treated mice, and were taken into account to determine tissue content of GSH. In lung, a significant decrease in GSH (60% of control) was first detected at 6 hr, and levels remained low from 8 to 12 hr. In liver, a 50% decrease was initially detected at 1 hr after DCE treatment. Progressive increases were found thereafter, 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 staining was more uniform in alveolar septa. Staining was markedly diminished by DCE treatment, and was initially abolished in the alveolar septa, but retained to a limited extent within a small number of Clara cells. These findings suggest that susceptibility of a subpopulation of Clara cells to cytotoxicity may be associated, in part, with low expression of nonprotein sulfhydryl content at the time of DCE treatment.
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