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 NaNO2 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.
Acknowledgments
The authors are thankful to Professor László Poppe and Anna Tomin at the Department of Organic Chemistry at the Budapest University of Technology and Economics.
Declaration of interests
This work was supported by GVOP KMA 0124, TÁMOP 4.2.2-08/1/KMR-2008-0004, TÉT ARG and SIN, the Baross G and Irinyi programs and the Bolyai and Öveges Fellowships.
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
This paper was first published online on Early Online on 9 January 2012.