N2O3 Nitrosative Stress

The term nitrosative stress emphasises a close relationship to oxidative stress, where among other targets, metals and thiols are modified by oxidation. Oxidants and nitrosants can interact to form other oxidising/nitrosating species, which in turn can potentiate the toxicity of either species is capable of imposing by itself. 

Dinitrogen trioxide (N2O3) can be derived from several sources the reaction of NO with O2, acidic nitrite, or from the NO/Oj-reaction (Wink et al. 1993). The primary mode of chemistry is to nitro-sate amines and thiols to form nitrosamines and S-nitrosothiols (Williams 1988). 

It was proposed that nitrosation of the exocyclic amide group resulted in a primary nitrosamine  

This was then followed by rapid deamination resulting in hydroxy group  

Nitrosylated albumin was detected in activated macrophage supernatants using an anti-NO-acetyl-ated cysteine antibody (Gobert et al. 1999). It was estimated that 10 % of N2O3 produced by activated cells participate in extracellular nitrosylation. N2O3 thus appears to be a new effector molecule of the immune system, as an agent for the nitrosylation of albumin, the main nitric oxide carrier in vivo. 

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In 1991, it was found that in addition to nitrosamine formation, NO and RNS could also modify DNA and resulting in deamination via nitrosation (Wink et al. 1991 Nguyen et al. 1992). These results suggested that N2O3 and nitrosative stress can lead to deamination of purines and cytosine/methylcytosine. There are a number of chemical mechanisms such as deamination (hydrolysis), depurination,... 

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