Lipoxins, RevD1 and 9, 13 HODE as the most important derivatives after an early incident of ischemic stroke

Abstract

There is limited information available regarding the association of plasma free fatty acids (FFA) and inflammation mediators with ischemic stroke. At the same time, new treatment strategies are being pursued. The aim of this study was to carry out a thorough analysis of inflammation with multiple FFA-derivative mediators after and ischemic stroke and standard treatment. HPLC separations of 17 eicosanoids were performed using an Agilent Technologies 1,260 liquid chromatograph. The profiles of the esters of fatty acids were labelled by means of gas chromatography. FFA, and eicosanoid profiles in the group of patients after ischemic stroke significantly differed from the profile of the control group. Studies confirmed the involvement of derivative synthesis pathways responsible for the inflammation, especially palmitic acid (9 and 13 HODE), arachidonic acid, EPA and DHA. Arachidonic acid derivatives were synthesised on 5LOX, 15 LOX and COX pathways with the participation of prostaglandins while omega 3 derivatives strengthened the synthesis of resolvins, RevD1 in particular. The ability to accelerate the quenching of inflammation after ischemic stroke seems to be a promising strategy of stroke treatment in its early stage. In this context, our study points to lipoxins, RevD1, and 9, 13 HODE as the most important derivatives.

Figure 1

Synthesis of inflammation mediators, plasma free fatty acid (FFA) derivatives.

Figure 2

Representative GC chromatogram of some statistically significant fatty acids for ischemic stroke (IS) and control group (CG).

Figure 3

Analyzed patterns of inflammatory mediators (A-235; B-280; C-210; D-302 signals).

Figure 4

Representative HPLC chromatogram of statistically significant eicosanoids for ischemic stroke (IS) and control group (CG).

Figure 5

Statistically significant differences in the level of inflammatory mediators (ug/ml).

Figure 6

The synthesis of palmitic acid derivatives and proinflammatory mediators 9 and 13 HODE in ischemic stroke. COX cyclooxygenase, CYP cytochrom P450, DGLA dihomo-γ-linolenic acid, EETs epoxyeicosatetraenoic acids, GLA γ-linolenic acid, HETEs hydroxyeicosatetraenoic acids, HODEs hydroxyoctadecadienoic acids, LOX lipoxygenase, LT leucotrienes, LX lipoxins, MaR1 maresins, PG prostaglandins, Rev(E1,D1)—resolvins, TX thromboxane.

Figure 7

The synthesis of arachidonic acid derivatives and proinflammatory mediators in ischemic stroke. COX cyclooxygenase, CYP cytochrom P450, DGLA dihomo-γ-linolenic acid, EETs epoxyeicosatetraenoic acids, GLA γ-linolenic acid, HETEs hydroxyeicosatetraenoic acids, HODEs hydroxyoctadecadienoic acids, LOX lipoxygenase, LT leucotrienes, LX lipoxins, MaR1 maresins, PG prostaglandins, Rev(E1,D1)—resolvins, TX thromboxane.

Figure 8

The synthesis of omega-3 fatty acid derivatives (EPA, DHA) in ischemic stroke. COX cyclooxygenase, CYP cytochrom P450, DGLA dihomo-γ-linolenic acid, EETs epoxyeicosatetraenoic acids, GLA γ-linolenic acid, HETEs hydroxyeicosatetraenoic acids, HODEs hydroxyoctadecadienoic acids, LOX lipoxygenase, LT leucotrienes, LX lipoxins, MaR1 maresins, PG prostaglandins, Rev(E1,D1)—resolvins, TX thromboxane.