Potential applications of lipid peroxidation products – F4-neuroprostanes, F3-neuroprostanesn-6 DPA, F2-dihomo-isoprostanes and F2-isoprostanes ‐ in the evaluation of the allograft function in renal transplantation

Abstract

F-neuroprostanes, F-neuroprostanes, and F-dihomo-isoprostanes, metabolites of non-enzymatic lipid peroxidation of polyunsaturated fatty acids [docosahexaenoic acid, n-6 docosapentanoic acid, and adrenic acid respectively], have become important biomarkers for oxidative stress in several diseases like epilepsy and alzheimer. These biomarkers and the 15-F-isoprostane (also known as 8-iso-PGF) a F-isoprostane isomer measured as reference oxidative marker at systemic level, were analyzed by UHPLC-QqQ-MS/MS in the urine of 60 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca, at six different times during the first six months after renal transplantation, and were compared with a control group of 60 healthy subjects from the same hospital. A total of 11 metabolites were analyzed and different patterns were observed. A tendency to decrease was observed in three metabolites (4-epi-4-F- NeuroP, ent-7(RS)-7-F-dihomo-IsoP, and ent-7(S)-7-F-dihomo-IsoP) and in our reference oxidative marker (15-F-IsoP) when kidney function improved and the excretion of urine proteins decreased. These results suggest that these three biomarkers of oxidative stress could be useful to assess renal function in the postransplant phase. Unfortunately, little is known about this kind of biomarker in this cohort of patients, so further investigation would be required in the clinical field to clarify the relationship between oxidative stress and the graft function, as well as the usefulness of these biomarkers as rejection markers.

Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers

“…The present work describes a reliable and sensitive UPLC-MS/MS method for the simultaneous determination of 17 analytes (F 2 -IsoPs, prostaglandins, F 4 -NeuroPs, F 2 -dihomo-IsoPs, dihomo-IsoFs) and 4 total parameters (IsoP, NeuroP, IsoF, NeuroF) in urine samples. Of note, most of these analytes have not been measured in previous works found in literature [38,42], and the lack of validated liquid chromatographic methods to determine these new set of lipid peroxidation biomarkers in urine human samples adds relevance to this new method. The described UPLC-MS/MS method can be considered a simple alternative to previously published methods, which employ chemical derivatization and gas chromatography.…”

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

“…Isoprostanoids, the metabolites of non-enzymatic lipid peroxidation of polyunsaturated fatty acid (PUFA), are measured to assess in vivo oxidative stress status [1,2]. Among all the metabolites from PUFAs, 15-F 2t -isoprostane (15-F 2t -IsoP) derived from arachidonic acid (AA) has been largely studied in medical research [3][4][5]. Also, 15-F 2t -IsoP (also referred to as 8-iso-PGF 2α ) has been identified to be the most abundant F 2 -IsoP isomer in the free radical-induced AA oxidation [6] and elevated levels are closely related for example, to inflammation and cardiovascular diseases.…”

“…In this regard, it was shown that NeuroPs and not IsoPs are the critical metabolites for neuronal damage. Among all the F 4 -NeuroP molecules, only a handful of the isomers are characterized in neuro-pathological conditions and so far, 4-F 4t -NeuroPs and 10-F 4t NeuroPs are considered to be the most represented [8,[15][16][17][18][19][20][21][22][23][24][25].…”

Moving forward with isoprostanes, neuroprostanes and phytoprostanes: where are we now?

“…Recently, F 3t -NeuroP n-6 a metabolite of DPA and F 2t -dihomo-IsoPs were found useful to assess renal function after kidney transplantation [110,111]. The authors noted that these three metabolites namely, 4-epi-4-F 3t -NeuroP n-6 DPA , ent-7(RS)-7-F 2t -dihomo-IsoP and ent-7(S)-7-F 2t -dihomo-IsoP tended to decrease when kidney function improved and the excretion of urine proteins decreased.…”