Current Developments in the Therapeutic Potential of S-Nitrosoglutathione, an Endogenous NO-Donor Molecule

Istvan      Hornyak; Eszter      Pankotai; Levente      Kiss; Zsombor      Lacza

Abstract

Nitric oxide (NO) has a role in many physiological processes and its decreased concentration can lead to several pathophysiological events, therefore it is of considerable importance to find and to characterize suitable NO-donors for clinical use. S-nitrosothiols (RSNOs) are promising candidates for such therapeutics because these molecules do not appear to induce tolerance and were shown to be effective in several disease models. One of the main endogenous nitrosothiols is S-nitrosoglutathione (GSNO), which was tested as a therapeutic agent in 15 human investigations with good results. Despite the proven benefits of GSNO this molecule is not yet present in any pharmaceutical composition. The problem with the use of nitrosothiols is their fast and often unpredictable rate of decomposition in aqueous solutions. In this article we review current developments in the field which relate to the clinical applications of GSNO and other nitrosothiols in indications such as asthma, cystic fibrosis, embolization prevention or diabetic leg ulcers. The review focuses on the chemical and biological data which support the therapeutic use of GSNO and highlights areas where further research is needed.

Keywords: Diabetic neuropathy, GSNO, S-nitrosoglutathione, nitrosothiols, percutan transcutaneous carotid angioplasty, platelet activation, venous ulcer, endogenous nitrosothiols, cystic fibrosis, S-nitroso-N-acetylcysteine, Snitrosothiol complexes, glutathione, nitric oxide (NO), mitochondrial environment, S-nitrosylated mitochondrial proteins