Cyclic Hydroxylamines as Monitors of Peroxynitrite and Superoxide-Revisited.

There is a considerable need for methods that allow quantitative determination in vitro and in vivo of transient oxidative species such as peroxynitrite (ONOOH/ONOO) and superoxide (HO/O). Cyclic hydroxylamines, which upon oxidation yield their respective stable nitroxide radicals, have been suggested as spin probes of peroxynitrite and superoxide. The present study investigated this approach by following the kinetics of peroxynitrite decay in the absence and presence of various 5-membered and 6-membered ring hydroxylamines, and comparing the yield of their respective nitroxides using electron paramagnetic spectroscopy.

The nitroxide/antioxidant 3-carbamoyl proxyl attenuates disease severity in murine models of severe asthma.

Asthma is characterized by airway inflammation, hyper-responsiveness, symptoms of dyspnea, wheezing and coughing. In most patients, asthma is well controlled using inhaled corticosteroids and bronchodilators. A minority of patients with asthma develop severe disease, which is frequently only partially responsive or even resistant to treatment with corticosteroids.

3-Carbamoyl-proxyl nitroxide radicals attenuate bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a poor prognosis and limited treatment options. Oxidative and nitrosative stress is implicated as one of the main pathogenic pathways in IPF. The rationale for the use of antioxidants to treat lung fibrosis is appealing, however to date a consistent beneficial effect for such an approach has not been observed.

Hydroxylamines inhibit tyrosine oxidation and nitration: The role of their respective nitroxide radicals.

In vivo, nitroxide antioxidants distribute within minutes throughout all tissues, but are reduced to their respective hydroxylamines due to the cellular reducing environment, which apparently limits their application. To distinguish their antioxidative activity from that of their respective nitroxides, the kinetics and mechanism of their inhibitory effect on the enzymatic oxidation and nitration of tyrosine have been studied. The inhibitory effect of the hydroxylamines on the oxidation and nitration of tyrosine induced by HRP/HO and HRP/HO/nitrite was investigated by following the kinetics of the formation of their respective nitroxides, HO decomposition, release of O and accumulation of tyrosine oxidation and nitration products.

Mechanistic insight into the catalytic inhibition by nitroxides of tyrosine oxidation and nitration.

Background: Nitroxide antioxidants (RNO) protect from injuries associated with oxidative stress. Tyrosine residues in proteins are major targets for oxidizing species giving rise to irreversible cross-linking and protein nitration, but the mechanisms underlying the protective activity of RNO on these processes are not sufficiently clear.

Methods: Tyrosine oxidation by the oxoammonium cation (RN=O) was studied by following the kinetics of RNO formation using EPR spectroscopy.