Cytoprotective effect of reduced glutathione in arsenical-induced endothelial cell injury.
The effect of four arsenic compounds on cultured endothelial cell 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 microM 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 plateau. A longer pretreatment for 24 h still kept GSH at a very significant high level. The cell injury induced by arsenic trioxide was protected by GSH, and then cellular biosynthesis of PGI2 in culture was also increased. The cytoprotective effect and the stimulatory effect on PGI2 production, where both were dose-dependent on GSH, were in a strict reverse relationship. Aspirin treatment inhibited the PGI2 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 PGI2 biosynthesis by GSH is the mechanism of the latter's cytoprotective effect on arsenic trioxide-induced endothelial cell injury.
Chang
W C
WC
Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Chen
S H
SH
Wu
H L
HL
Shi
G Y
GY
Murota
S
S
Morita
I
I
D000818:Animals; D001151:Arsenic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001241:Aspirin / Q000494:pharmacology; D002417:Cattle; D002477:Cells; D002478:Cells, Cultured; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction
D005978:Glutathione; D001151:Arsenic; D001241:Aspirin