Department of Biology, Stern College for Women, Yeshiva University, 245 Lexington Avenue, New York, NY 10016-4699, USA.
Environ Toxicol Pharmacol. 1998 Mar;5(2):135-44. doi: 10.1016/s1382-6689(97)10071-0.
The cytotoxicity of sodium nitroprusside (SNP) to the human endothelial cell line, ECV304, was studied. The cytotoxicity of SNP was primarily related to the liberation of nitric oxide (NO). S-nitroso-N-acetyl-d-penicillamine (SNAP), an NO donor, was highly toxic. Other degradation products of SNP either exerted much less toxicity (i.e. cyanide and nitrite) or were non-toxic (i.e. ferricyanide and ferrocyanide). SNP induced multinucleation, inhibited cell proliferation, lowered the endogenous level of reduced glutathione (GSH), and induced apoptotic cell death. The plasma membrane was not the prime site of toxic action, as leakage of lactic acid dehydrogenase (LDH) occurred only at a relatively high concentration of SNP. Cells treated with non-toxic levels of the glutathione-depleting agents, 1-chloro-2,4-dinitrobenzene (CDNB), dl-buthionine-[S,R]-sulfoximine (BSO), and 1,3-bis-(chloroethyl)-1-nitrosourea (BCNU), were hypersensitive to subsequent exposure to SNP. The GSH status of the cells was, therefore, a key factor in determining the cytotoxicity of SNP.
我们研究了硝普钠（SNP）对人血管内皮细胞系 ECV304 的细胞毒性。SNP 的细胞毒性主要与一氧化氮（NO）的释放有关。作为一氧化氮供体的 S-亚硝基-N-乙酰-D-青霉胺（SNAP）具有高度毒性。SNP 的其他降解产物要么毒性较小（如氰化物和亚硝酸盐），要么无毒（如铁氰化物和亚铁氰化物）。SNP 诱导多核形成，抑制细胞增殖，降低内源性还原型谷胱甘肽（GSH）水平，并诱导细胞凋亡死亡。细胞膜不是毒性作用的主要部位，因为乳酸脱氢酶（LDH）的泄漏仅在 SNP 的相对高浓度下发生。用谷胱甘肽耗竭剂 1-氯-2,4-二硝基苯（CDNB）、dl-丁硫氨酸-[S,R]-亚砜（BSO）和 1,3-双（氯乙基）-1-亚硝脲（BCNU）处理非毒性水平的细胞后，对随后暴露于 SNP 变得更加敏感。因此，细胞的 GSH 状态是决定 SNP 细胞毒性的关键因素。
