title: Increased stability of S-nitrosothiol solutions via pH modulations.
abstract: S-nitrosothiol (RSNO) solutions represent a valuable source of nitric oxide and could be used as topical vasodilators, but their fast decomposition rate poses a serious obstacle to their potentially widespread therapeutic use. Our aim was to characterize and quantify the effect of pH on S-nitrosothiol formation and decomposition in simple aqueous solutions of S-nitrosoglutathione (GSNO), S-nitroso-N-acetylcysteine (SNAC) and S-nitroso-3-mercaptopropionic acid (SN3MPA). Furthermore, we investigated the effect of storage pH on the stability of GSNO incorporated in poly(ethylene glycol)/ poly(vinyl alcohol) matrices. S-nitrosothiol concentrations were measured spectrophotometrically and laser Doppler scanning method was used to assess dermal blood flow. GSH and NAC solutions reached a complete transformation to nitrosothiols when synthesized using acidic NaNO(2) solution. The initial concentration of all investigated RSNOs decreased more slowly with pH adjusted to mildly basic values (8.4-8.8) for the storage period. Polymer gels of PVA/PEG compositions at mildly basic storage pH further reduced the decomposition rate succeeding to contain 46.8% of the initial GSNO concentration for 25 days. This amount of topically administered GSNO was still capable of increasing the dermal blood flow over 200% in human subjects.
authors.affiliation: Semmelweis University, Department of Human Physiology and Clinical Experimental Research, Budapest, Hungary. istvan.hornyak@eok.sote.hu
authors.forename: István
authors.initials: I
authors.lastname: Hornyák
authors.forename: Krisztina
authors.initials: K
authors.lastname: Marosi
authors.forename: Levente
authors.initials: L
authors.lastname: Kiss
authors.forename: Pál
authors.initials: P
authors.lastname: Gróf
authors.forename: Zsombor
authors.initials: Z
authors.lastname: Lacza
mesh_terms: D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D002374:Catalase / Q000737:chemistry; D004355:Drug Stability; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009603:Nitroso Compounds / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012039:Regional Blood Flow / Q000187:drug effects; D026422:S-Nitrosoglutathione / Q000737:chemistry* / Q000494:pharmacology; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D012996:Solutions; D013482:Superoxide Dismutase / Q000737:chemistry; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D005609:Free Radicals; D009603:Nitroso Compounds; D011108:Polymers; C572263:S-nitroso-3-mercaptopropionic acid; D012996:Solutions; D014665:Vasodilator Agents; C024940:S-nitroso-N-acetylcysteine; D026422:S-Nitrosoglutathione; D015097:3-Mercaptopropionic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D000111:Acetylcysteine