Ascorbic acid and reducing agents regulate the fates and functions of S-nitrosothiols

Area of Science:

• Biochemistry
• Pharmacology
• Physiology

Background:

• S-nitrosothiols (RS-NO), including S-nitrosoglutathione (GS-NO), are known nitric oxide (NO) donors.
• The metabolic pathways and biological roles of RS-NO require further investigation.

Purpose of the Study:

• To elucidate the metabolic fate and functional significance of GS-NO and related RS-NO.
• To investigate the influence of physiological conditions and reducing agents on RS-NO stability and activity.

Main Methods:

• Analysis of GS-NO stability in plasma, liver, and kidney fractions under physiological conditions.
• Assessment of the impact of reducing agents (ascorbic acid, cysteine, reduced glutathione) on GS-NO decomposition.
• Evaluation of the effects of NO, GS-NO, and RS-NO on Ehrlich ascites tumor cell respiration.
• Investigation of the in vivo depressor action of intravenously administered GS-NO.

Main Results:

• GS-NO demonstrated stability in plasma but rapid decomposition in liver and kidney homogenates/supernatants.
• Reducing agents, particularly ascorbic acid, significantly enhanced GS-NO decomposition.
• GS-NO inhibited tumor cell respiration, an effect potentiated by reducing agents.
• Intravenous GS-NO administration induced a depressor response, potentially mediated by ascorbic acid.

Conclusions:

• The metabolism and biological functions of GS-NO and related RS-NO are significantly influenced by reducing agents like ascorbic acid.
• Ascorbic acid may play a key role in modulating the in vivo effects of RS-NO.