Cytoprotective effect of reduced glutathione in arsenical-induced endothelial cell injury

Wen Chang Chang, Shu Huie Chen, Hau Lin Wu, Guey Yueh Shi, Sei itsu Murota, Ikuo Morita

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

The effect of four arsenic compounds on cultured endothelial cells isolated from bovine carotid arteries was studied. Only trivalent arsenicals (arsenic trioxide and sodium m-arsenite), but not pentavalent arsenicals (arsenic acid and p-arsenilic acid), induced significant cell injury. Since the intracellular reduced glutathione (GSH) plays an important role in detoxication in mammalian cells, its effect on arsenical-induced cell injury was then studied. Pretreatment of cells with 500 μM GSH not only resulted in several-fold increase in the intracellular level of GSH but also effectively protected them against the injury caused by arsenic trioxide. After a pretreatment of cells with GSH for 3 h, the intracellular GSH reached a plateua. A longer pretreatmentz for 24 h still kept GSH at a very significant level. The cell injury induced by arsenic trioxide was protected by GSH, and then cellular biosynthesis of PGI 2 in culture was also increased. The cytoprotective effect and the stimulatory effect on PGI 2 production, where both were dose-dependent on GSH, were in a strict reverse relationship. Aspirin treatment inhibited the PGi 2 biosynthesis induced by GSH in the arsenic trioxide-induced cell injury, and significantly reduced the cytoprotective effect induced by GSH. These results suggest that the marked stimulation of endogenous PGI 2 biosynthesis by GSH is the mechanism of the latter's cytoprotective effect on arsenic trioxide-induced endothelial cell injury.

Original languageEnglish
Pages (from-to)101-110
Number of pages10
JournalToxicology
Volume69
Issue number1
DOIs
Publication statusPublished - 1991
Externally publishedYes

Keywords

  • Arsenic
  • Endothelial cell injury
  • Prostacyclin
  • Reduced glutathione (GSH)

ASJC Scopus subject areas

  • Toxicology

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