Relevance of 4-F4t-neuroprostane and 10-F4t-neuroprostane to neurological diseases

Abstract

F-neuroprostanes (F-NeuroPs) are non-enzymatic oxidized products derived from docosahexaenoic acid (DHA) and are suggested to be oxidative damage biomarkers of neurological diseases. However, 128 isomers can be formed from DHA oxidation and among them, 4(RS)-4-F-NeuroP (4-F-NeuroP) and 10(RS)-10-F-NeuroP (10-F-NeuroP) are the most studied. Here, we report the identification and the clinical relevance of 4-F-NeuroP and 10-F-NeuroP in plasma of four different neurological diseases, including multiple sclerosis (MS), autism spectrum disorders (ASD), Rett syndrome (RTT), and Down syndrome (DS). The identification and the optimization of the method were carried out by gas chromatography/negative-ion chemical ionization tandem mass spectrometry (GC/NICI-MS/MS) using chemically synthesized 4-F-NeuroP and 10-F-NeuroP standards and in oxidized DHA liposome. Both 4-F-NeuroP and 10-F-NeuroP were detectable in all plasma samples from MS (n = 16), DS (n = 16), ASD (n = 9) and RTT (n = 20) patients. While plasma 10-F-NeuroP content was significantly higher in patients of all diseases as compared to age and gender matched healthy control subjects (n = 61), 4-F-NeuroP levels were significantly higher in MS and RTT as compared to healthy controls. Significant positive relationships were observed between relative disease severity and 4-F-NeuroP levels (r = 0.469, P <0.0001), and 10-F-NeuroP levels (r = 0.757, P < 0.0001). The study showed that the plasma amount ratio of 10-F-NeuroP to 4-F-NeuroP and the plasma amount as individual isomer can be used to discriminate between different brain diseases. Overall, by comparing the different types of disease, our plasma data indicates that 4-F-NeuroP and 10-F -NeuroP: i) are biologically synthesized in vivo and circulated, ii) are related to clinical severity of neurological diseases, iii) are useful to identify shared pathogenetic pathways in distinct brain diseases, and iv) appears to be distinctive for different neurological conditions, thus representing potentially new biological disease markers. Our data strongly suggest that in vivo DHA oxidation follows preferential chemical rearrangements according to different brain diseases.

Effect of Dietaryn‐3Source on Rabbit Male Reproduction

“…After thawing, the plasma and seminal samples were treated with a volume of acidified water (pH 3) and spiked with a tetradeuterated derivative of prostaglandin F 2α (PGF 2α -d 4 ; 500 pg), as internal standard. Subsequently, solid phase extraction procedures were carried out according to a previously reported methodology [29]. Briefly, each sample (plasma or seminal plasma) was applied to an octadecylsilane (C 18 ) cartridge and the eluate was transferred to an aminopropyl (NH 2 ) cartridge to collect isoprostanes.…”

“…Oxidative Medicine and Cellular Longevity reported[29]. The derivatised F 2 -IsoPs and PGF 2α -d 4 were analysed by GC/NICI-MS/MS.…”

Cytosolic phospholipase A 2 and F 2 isoprostanes are involved in semen quality and human infertility—A study on leucocytospermia, varicocele and idiopathic infertility

“…Gas chromatography/negative-ion chemical ionisation tandem mass spectrometry (GC/NICI-MS/MS) was used to evaluate the total (free plus esterified) F 2 -IsoPs amount as previously reported in Signorini et al (2018). Each seminal plasma sample was applied to an octadecylsilane (C 18 ) cartridge, and the obtained eluate was transferred to an aminopropyl (NH 2 ) cartridge to complete isoprostane extraction.…”

Isoprostanoids in Clinical and Experimental Neurological Disease Models

“…Through interaction of radical species, such as radical oxygen species (ROS), PUFAs undergo a series of non-enzymatic lipid peroxidation and generate specialized lipid mediators such as F 2 -isoprostanes (F 2 -IsoPs), F 2 -dihomo-isoprostanes (F 2 -dihomo-IsoPs), and F 4 -neuroprostanes (F 4 -NeuroPs) from AA, AdA, and DHA, respectively. Among all the isoprostanoids identified so far, the chemical structures related closest to neurological diseases [ 25 , 26 , 27 , 28 ] are reported in Figure 2 .…”