Evaluation of the stability of oxytocin and vasopressin under oxidative stress conditions

Oxytocin and vasopressin are neuropeptides produced in the hypothalamus that play a well-known role in social and emotional behavior, as well as in the regulation of body fluids tonicity. From a chemical point of view, both are cyclic nonapeptides with similar sequence of CYIQNCPLG and CYFQNCPRG respectively. The cysteine residues cyclize the structure through a disulfide bond and the C-terminus is found as a primary amide. In recent studies, oxytocin was suggested to act as a neuroprotective factor by inhibiting neuro inflammation, oxidative stress, free radical formation and neuronal apoptosis, preventing mitochondrial dysfunction, activating free radical scavengers and several antioxidant enzymes. The mechanism for neuroprotection remains, however, almost unclear.[1] In this work, we have investigated the stability of oxytocin and vasopressin under oxidative stress conditions, such as UV irradiation, treatment with reactive oxygen and nitrogen species and lipoxidation byproducts, similarly to our previous study on other neuropeptides.[2] Although oxytocin was suggested as a neuroprotective factor, we were quite surprised to find out that the molecule itself, and vasopressin as well, are very unstable under reactive conditions. In particular, the generation of oxygen radicals by UV irradiation of peptide solutions produced a marked variation of CD spectra in both aqueous buffers and trifluoroethanol, showing a significant variation of the positive band at 228 nm and the negative band at 195 nm. Similar results were observed after treatment with reactive aldehydes, while nitrogen radicals did not provide significant spectroscopical changes. The analysis of peptide solutions after oxidative stress treatment via mass spectroscopy showed the formation of monomeric species related to the desulfurization under UV irradiation and the formation of adducts with dialdehydes, which were not detected in previous reports.[3]