Similarity and dissimilarity of thiols as anti-nitrosative agents in the nitric oxide–superoxide system

Concomitant production of nitric oxide and superoxide in biological systems has been proposed to generate numerous reactive oxygen and nitrogen species that cause oxidative and nitrosative stress. Thiols, especially glutathione, play an important role in cellular defense against radical species. In the present study, we investigated and compared the anti-nitrosative activity of a wide range of thiols in a simplified chemical system of co-generated nitric oxide and superoxide. Of the 13 thiols studied, three groups of thiols are distinguishable: (i) Group I includes cysteine and its four congeners (cysteine methyl ester, cysteine ethyl ester, homocysteine, cysteamine); they are subject to rapid oxidative decomposition and have the least anti-nitrosative activity. (ii) Group II consists of glutathione, penicillamine, tiopronin and mesna; they have the greatest effect on delaying the nitrosation reaction. (iii) Group III comprises N-acetylcysteine, N-acetylpenicillamine, captopril, and thioglycolate; they all have high pKa for the mercapto group and show the strongest inhibitory effect on the rate and extent of nitrosation in the system studied.

Research highlights
► The anti-nitrosative activity of 13 thiols in a concurrent nitric oxide–superoxide system is compared. Three groups of thiols have to be distinguished.
► Group I includes cysteine, cysteine methyl ester, cysteine ethyl ester, homocysteine, and cysteamine; they are subject to rapid oxidative decomposition and have the least anti-nitrosative activity.
► Group II consists of GSH, penicillamine, tiopronin and mesna; they have the greatest effect on delaying the nitrosation reaction.
► Group III comprises N-acetylcysteine, N-acetylpenicillamine, captopril, and thioglycolate; they all have high pKa for the mercapto group and show the strongest inhibitory effect on the rate and extent of nitrosation.