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Prostaglandins Other Lipid Mediat. 2019 Apr 19:106334. doi: 10.1016/j.prostaglandins.2019.04.004. [Epub ahead of print]

Formation of trans-epoxy fatty acids correlates with formation of isoprostanes and could serve as biomarker of oxidative stress.

Author information

1
Institute for Food Toxicology, University of Veterinary Medicine Hannover, Hannover, Germany; Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany.
2
Rudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, Giessen, Germany.
3
Institute of Toxicology, University Medical Center Mainz, Mainz, Germany.
4
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, Université de Montpellier, ENSCM, France.
5
Nephrology, Hannover Medical School, Hannover, Germany.
6
Rudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, Giessen, Germany; Institute of Toxicology, University Medical Center Mainz, Mainz, Germany.
7
Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
8
Institute for Food Toxicology, University of Veterinary Medicine Hannover, Hannover, Germany; Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany. Electronic address: nils@schebb-web.de.

Abstract

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/cis-epoxy-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.

KEYWORDS:

Biomarker; Eicosanoid; Isoprostane; Oxidative stress; Oxylipin; Trans-epoxy-fatty acid

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