Chang W C, Chen S H, Wu H L, Shi G Y, Murota S, Morita I
Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Toxicology. 1991;69(1):101-10. doi: 10.1016/0300-483x(91)90157-v.
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.
研究了四种砷化合物对从牛颈动脉分离的培养内皮细胞的作用。只有三价砷化合物（三氧化二砷和间亚砷酸钠），而不是五价砷化合物（砷酸和对氨基苯砷酸），能诱导显著的细胞损伤。由于细胞内还原型谷胱甘肽（GSH）在哺乳动物细胞解毒中起重要作用，因此研究了其对砷诱导的细胞损伤的影响。用500微摩尔/升GSH预处理细胞，不仅使细胞内GSH水平增加了几倍，而且有效地保护它们免受三氧化二砷引起的损伤。用GSH预处理细胞3小时后，细胞内GSH达到平台期。24小时的更长时间预处理仍使GSH保持在非常显著的高水平。三氧化二砷诱导的细胞损伤受到GSH的保护，培养物中PGI2的细胞生物合成也增加。GSH的细胞保护作用和对PGI2产生的刺激作用均呈剂量依赖性，且二者呈严格的反向关系。阿司匹林处理抑制了GSH在三氧化二砷诱导的细胞损伤中诱导的PGI2生物合成，并显著降低了GSH诱导的细胞保护作用。这些结果表明，GSH对内源性PGI2生物合成的显著刺激是其对三氧化二砷诱导的内皮细胞损伤具有细胞保护作用的机制。
