TY  - JOUR
A1  - Rund, Katharina M.
A1  - Heylmann, Daniel
A1  - Seiwert, Nina
A1  - Wecklein, Sabine
A1  - Oger, Camille
A1  - Galano, Jean-Marie
A1  - Durand, Thierry
A1  - Chen, Rongjun
A1  - Güler, Faikah
A1  - Fahrer, Jörg
A1  - Bornhorst, Julia
A1  - Schebb, Nils Helge
T1  - Formation of trans-epoxy fatty acids correlates with formation of isoprostanes and could serve as biomarker of oxidative stress
JF  - Prostaglandins & Other Lipid Mediators
N2  - In mammals, epoxy-polyunsaturated fatty acids (epoxy-PUFA) are enzymatically formed from naturally occurring all-cis PUFA by cytochrome P450 monooxygenases leading to the generation of cis-epoxy-PUFA (mixture of R,S- and S,R-enantiomers). In addition, also non-enzymatic chemical peroxidation gives rise to epoxy-PUFA leading to both, cis- and trans-epoxy-PUFA (mixture of R,R- and S,S-enantiomers). Here, we investigated for the first time trans-epoxy-PUFA and the trans/cis-epoxy-PUFA ratio as potential new biomarker of lipid peroxidation. Their formation was analyzed in correlation with the formation of isoprostanes (IsoP), which are commonly used as biomarkers of oxidative stress. Five oxidative stress models were investigated including incubations of three human cell lines as well as the in vivo model Caenorhabditis elegans with tert-butyl hydroperoxide (t-BOOH) and analysis of murine kidney tissue after renal ischemia reperfusion injury (IRI). A comprehensive set of IsoP and epoxy-PUFA derived from biologically relevant PUFA (ARA, EPA and DHA) was simultaneously quantified by LC-ESI(-)-MS/MS. Following renal IRI only a moderate increase in the kidney levels of IsoP and no relevant change in the trans/cis-epoxy-PUFA ratio was observed. In all investigated cell lines (HCT-116, HepG2 and Caki-2) as well as C. elegans a dose dependent increase of both, IsoP and the trans/cis-epoxy-PUFA ratio in response to the applied t-BOOH was observed. The different cell lines showed a distinct time dependent pattern consistent for both classes of autoxidatively formed oxylipins. Clear and highly significant correlations of the trans/cisepoxy-PUFA ratios with the IsoP levels were found in all investigated cell lines and C. elegans. Based on this, we suggest the trans/cis-epoxy-PUFA ratio as potential new biomarker of oxidative stress, which warrants further investigation.
KW  - Isoprostane
KW  - Trans-epoxy-fatty acid
KW  - Oxidative stress
KW  - Biomarker
KW  - Oxylipin
KW  - Eicosanoid
Y1  - 2019
U6  - https://doi.org/10.1016/j.prostaglandins.2019.04.004
SN  - 1098-8823
SN  - 2212-196X
VL  - 144
PB  - Elsevier
CY  - New York
ER  -