Radical releasing properties of nitric oxide donors GEA 3162, SIN-1 and S-nitroso-N-acetylpenicillamine.
The nitric oxide (NO)-, superoxide anion (O2.-)- and peroxynitrite (ONOO-)-releasing properties of 1,2,3,4-oxatriazolium,5-amino-3-(3,4-dichlorophenyl)-chloride (GEA 3162) were characterized and compared with the known NO-donors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine. All the three compounds released NO in aqueous solutions in a dose-dependent manner as measured by ozone-chemiluminescence. GEA 3162 produced more NO than SIN-1, but less than S-nitroso-N-acetylpenicillamine during a 45 min incubation time. SIN-1 reduced nitro blue tetrazolium and the effect was inhibitable by superoxide dismutase. Reduction of nitro blue tetrazolium was not detected in the solutions of GEA 3162 and S-nitroso-N-acetylpenicillamine suggesting that SIN-1 but not GEA 3162 and S-nitroso-N-acetylpenicillamine release O2.- in their decomposition process. Formation of ONOO- in solutions of GEA 3162, SIN-1 and S-nitroso-N-acetylpenicillamine was estimated indirectly by measuring the formation of nitrotyrosine. The data indicate that ONOO- was produced in the presence of SIN-1 but not in solutions of GEA 3162 and S-nitroso-N-acetylpenicillamine. The results suggest that GEA 3162 produces negligible amounts of O2.- and ONOO- as compared to SIN-1. This adds the value of GEA 3162 as an useful tool in NO research and could well explain the earlier findings on the superior NO-like biological activity of oxatriazole derivatives as compared to SIN-1.
Holm
P
P
Medical School, University of Tampere, Tampere University Hospital, Finland.
Kankaanranta
H
H
Metsä-Ketelä
T
T
Moilanen
E
E
D008981:Molsidomine / Q000031:analogs & derivatives* / Q000737:chemistry; D009569:Nitric Oxide / Q000138:chemical synthesis*; D010100:Oxygen / Q000737:chemistry; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000737:chemistry; D013481:Superoxides / Q000138:chemical synthesis; D014230:Triazoles / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000138:chemical synthesis
C110881:S-nitro-N-acetylpenicillamine; D014230:Triazoles; D013481:Superoxides; D009569:Nitric Oxide; D014443:Tyrosine; C002385:linsidomine; C082874:GEA 3162; D008981:Molsidomine; D010396:Penicillamine; D010100:Oxygen