Increased isoprostanoid levels in brain from murine model of Krabbe disease – Relevance of isoprostanes, dihomo-isoprostanes and neuroprostanes to disease severity

Abstract

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Circulating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome

“…Our findings show that 4-F 4t -NeuroP or 10-F 4t -NeuroP, previously reported to be relevant to neurological diseases [29][30][31], are specifically linked to RTT severity, natural history, and MECP2 mutation type.…”

“…Although lipid peroxidation cannot be considered as a universal surrogate for oxidative stress evaluation [34], consistent evidence indicates that the levels of lipid peroxidation products are valuable biomarkers in measuring oxidative stress status [29,35]. The amounts of 4-F 4t -NeuroP or 10-F 4t -NeuroP in brain tissue have been reported to be predictive of severity score in a murine model of Krabbe disease [31] and symptomatic Mecp2 stop/y mice [30]. Moreover, in the Mecp2−/y mouse model of RTT, significant inverse relationships between F 4 -NeuroPs and brain weight were reported, thus suggesting the involvement of DHA-derived peroxidation products in the pathogenesis of microcephaly [26], which is a key clinical feature of the RTT phenotype.…”

“…Isoprostanoids, a large family of compounds derived from non-enzymatic oxidation of polyunsaturated fatty acids (PUFAs) [27,28], have been shown to be pertinent to RTT pathological mechanisms [26,29,30]. Among the isoprostanoids, neuroprostanes (NeuroPs), metabolites produced by oxidative metabolism of docosahexaenoic acid (DHA) in the neural cells, have been reported to be relevant in RTT and other conditions of neurological disease [30][31][32]. Prior data strongly suggest that in vivo DHA oxidation follows preferential chemical rearrangements according to different brain diseases [30].…”

Semen Biochemical Components in Varicocele, Leukocytospermia, and Idiopathic Infertility

“…The fertile group was composed of 10 individuals (aged [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] which fathered at least one child in the last 3 years. The fertile subjects were not affected by infections and/or anatomical problems.…”

“…The NH 2 final eluate was derivatized to convert the carboxyl group of F 2 -IsoPs into pentafluorobenzyl ester and the hydroxyl group into trimethylsilyl ethers [26]. For 8-iso-PGF 2α , also referred as 15-F 2 t-IsoP, one of the most represented isomers of F 2 -IsoPs, the product ion at m/z 299, derived from the [M−181] − precursor ion (m/z 569), was detected and referred to the internal standard PGF 2α -d4 (m/z 573 → m/z 303) [27].…”