Abstract
Nitrated fatty acids are endogenously present in human and animal tissues, as well as in plant-derived oils. In particular, 10-nitro oleic acid (10-NO 2 -OA) potently induces Nrf2-dependent antioxidant gene expression and inhibits TLR4/NF-κB signaling, thus promoting an overall cyto-protective and anti-inflammatory response. 10-NO 2 -OA has been extensively tested in animal models and is currently undergoing clinical evaluation in humans. Quantitative radiochromatographic/MS analysis indicated that the renal and fecal pathways are the main routes for 10-NO 2 -OA excretion in rats, and allowed the identification of 4-nitro-octanedioic acid (NO 2 -8:0-diCOOH) as the most abundant metabolite in rat urine. In addition, high resolution LC-MS/MS analysis revealed the presence of a novel series of urinary metabolites including ω-carboxylation and β-oxidation products, as well as N-acetylcysteine, taurine and sulfo-conjugates in both rats and humans. Overall, the findings reported herein not only provide valuable tools for the experimental evaluation of 10-NO 2 -OA levels in vivo, but importantly they also set the basis for monitoring its metabolism during potential clinical interventions in humans.
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