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1,1-二氯乙烯对小鼠肺和肝脏中非蛋白巯基含量的时间效应。

Temporal effects of 1,1-dichloroethylene on nonprotein sulfhydryl content in murine lung and liver.

作者信息

Forkert P G, Moussa M

机构信息

Department of Anatomy, Queen's University, Kingston, Ontario, Canada.

出版信息

Drug Metab Dispos. 1993 Sep-Oct;21(5):770-6.

PMID: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.

摘要

给小鼠施用1,1 - 二氯乙烯(DCE)会引发细胞毒性,涉及肺部的克拉拉细胞,在更高剂量时,还会影响肝脏的小叶中心肝细胞。我们的目标是研究施用一定剂量的DCE(125 mg/kg)后,肺和肝脏中非蛋白质巯基[谷胱甘肽(GSH)]含量的时间变化。在DCE处理的小鼠中,全血中GSH对肺和肝脏中GSH含量的贡献分别为54%和14%,在确定组织GSH含量时已将其考虑在内。在肺中,6小时时首次检测到GSH显著下降(降至对照的60%),8至12小时时水平持续较低。在肝脏中,DCE处理后1小时最初检测到下降了50%。此后发现有逐渐增加,24小时时恢复到对照水平。肝脏中GSH的组织化学染色显示小叶内肝细胞呈均匀标记;DCE处理使所有肝细胞的染色均匀减弱。在对照肺中,细支气管上皮和肺泡隔呈现组织化学反应性。克拉拉细胞染色程度最大且差异较大,而肺泡隔的染色更均匀。DCE处理使染色明显减弱,最初肺泡隔中的染色消失,但在少数克拉拉细胞中仍有有限程度的保留。这些发现表明,一部分克拉拉细胞对细胞毒性的易感性可能部分与DCE处理时非蛋白质巯基含量的低表达有关。

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