Electrophilic fatty acid nitroalkenes are systemically transported and distributed upon esterification to complex lipids.

ABSTRACT: Electrophilic nitro-fatty acids [NO₂-FAs (fatty acid nitroalkenes)] showed beneficial signaling actions in preclinical studies and safety in phase 1 clinical trials. A detailed description of the pharmacokinetics (PK) of NO₂-FAs is complicated by the capability of electrophilic fatty acids to alkylate thiols reversibly and become esterified in various complex lipids, and the instability of the nitroalkene moiety during enzymatic and base hydrolysis. Herein, we report the mechanism and kinetics of absorption, metabolism, and distribution of the endogenously detectable and prototypical NO₂-FA, 10-nitro-oleic acid (10-NO₂-OA), in dogs after oral administration. Supported by HPLC-high-resolution-MS/MS analysis of synthetic and plasma-derived 10-NO

SUBMITTER: Fazzari M 

PROVIDER: S-EPMC6358300 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature