TY - JOUR
T1 - Cytoprotective effect of reduced glutathione in arsenical-induced endothelial cell injury
AU - Chang, Wen Chang
AU - Chen, Shu Huie
AU - Wu, Hau Lin
AU - Shi, Guey Yueh
AU - Murota, Sei itsu
AU - Morita, Ikuo
N1 - Funding Information:
We are greatly indebted to Ms. Y.F. Lu, and Mr. T.F. Tsai for their excellent technical assistance. Thanks are also due to Dr. K.Y. Huang for his critical review of this manuscript and to Ms. Y.J. Chang for her secretarial assistance. This research was supported in part by National Science Council of the Republic of China (NSC 78-0412-B006-46 and NSC 79-0412-B006-31).
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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.
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U2 - 10.1016/0300-483X(91)90157-V
DO - 10.1016/0300-483X(91)90157-V
M3 - Article
C2 - 1926151
AN - SCOPUS:0025988358
VL - 69
SP - 101
EP - 110
JO - Toxicology
JF - Toxicology
SN - 0300-483X
IS - 1
ER -