IN-VITRO TOXICITY OF SODIUM-NITROPRUSSIDE TO HUMAN ENDOTHELIAL ECV304CELLS

The cytotoxicity of sodium nitroprusside (SNP) to the human endothelia l cell line, ECV304, was studied. The cytotoxicity of SNP was primaril y related to the liberation of nitric oxide (NO). S-nitroso-N-acetyl-D -penicillamine (SNAP), an NO donor, was highly toxic. Other degradatio n products of SNP either exerted much less toxicity (i.e. cyanide and nitrite) or were non-toxic (i.e. ferricyanide and ferrocyanide). SNP i nduced multinucleation: inhibited cell proliferation, lowered the endo genous 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 relative ly high concentration of SNP. Cells treated with non-toxic levels of t he glutathione-depleting agents, 1-chloro-2,4-dinitrobenzene (CDNB), D L-buthionine-[S,R]-sulfoximine (BSQ), and 1,3-bis-(chloroethpl)-1-nitr osourea (BCNU), were hypersensitive to subsequent exposure to SNP. The GSH status of the cells was, therefore, a key factor in determining t he cytotoxicity of SNP. (C) 1998 Elsevier Science B.V. All rights rese rved.