Evaluation of 10-Nitro Oleic Acid Bio-Elimination in Rats and Humans

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 -OA) potently induces Nrf2-dependent antioxidant gene expression and inhibits TLR4/NF-κB signaling, thus promoting an overall cyto-protective and ant...

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Bibliographic Details
Published in:Scientific reports 2017-01, Vol.7 (1), p.39900, Article 39900
Main Authors: Salvatore, Sonia R, Vitturi, Dario A, Fazzari, Marco, Jorkasky, Diane K, Schopfer, Francisco J
Format: Article
Language:English
Subjects:
Acetylcysteine
Adult
Animal models
Animals
Antioxidants - administration & dosage
Antioxidants - metabolism
Antioxidants - pharmacokinetics
Carboxylation
Clinical trials
Excretion
Fatty acids
Female
Gene expression
Humans
Inflammation
Intestinal Elimination
Kidneys
Male
Metabolites
Middle Aged
NRF2 protein
Oils & fats
Oleic acid
Oleic Acids - administration & dosage
Oleic Acids - metabolism
Oleic Acids - pharmacokinetics
Oxidation
Plants
Randomized Controlled Trials as Topic
Rats
Rats, Sprague-Dawley
Renal Elimination
Rodents
Taurine
TLR4 protein
Toll-like receptors
Urine
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Summary: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 -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 -OA has been extensively tested in animal models and is currently undergoing clinical evaluation in humans. Bio-elimination pathways for 10-NO -OA were evaluated in rats (30 mg/kg·day) and in humans (0.34 mg/kg) using samples obtained from a double-blind, dose-rising clinical trial. Quantitative radiochromatographic/MS analysis indicated that the renal and fecal pathways are the main routes for 10-NO -OA excretion in rats, and allowed the identification of 4-nitro-octanedioic acid (NO -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 -OA levels in vivo, but importantly they also set the basis for monitoring its metabolism during potential clinical interventions in humans.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep39900