HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients

Oxylipins play a critical role in regulating the onset and resolution phase of inflammation. Despite inflammation is a pathological hallmark in amyotrophic lateral sclerosis (ALS), the plasma oxylipin profile of ALS patients has not been assessed yet. Herein, we develop an oxylipin profile-targeted...

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Main Authors: Mauricio Mastrogiovanni, Andrés Trostchansky, Hugo Naya, Raúl Dominguez, Carla Marco, Mònica Povedano, Rubèn López-Vales, Homero Rubbo
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/3/674
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author Mauricio Mastrogiovanni
Andrés Trostchansky
Hugo Naya
Raúl Dominguez
Carla Marco
Mònica Povedano
Rubèn López-Vales
Homero Rubbo
author_facet Mauricio Mastrogiovanni
Andrés Trostchansky
Hugo Naya
Raúl Dominguez
Carla Marco
Mònica Povedano
Rubèn López-Vales
Homero Rubbo
author_sort Mauricio Mastrogiovanni
collection DOAJ
description Oxylipins play a critical role in regulating the onset and resolution phase of inflammation. Despite inflammation is a pathological hallmark in amyotrophic lateral sclerosis (ALS), the plasma oxylipin profile of ALS patients has not been assessed yet. Herein, we develop an oxylipin profile-targeted analysis of plasma from 74 ALS patients and controls. We found a significant decrease in linoleic acid-derived oxylipins in ALS patients, including 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE. These derivatives have been reported as important regulators of inflammation on different cell systems. In addition, some 5-lipoxygenase metabolites, such as 5-hydroxy- eicosatetraenoic acid also showed a significant decrease in ALS plasma samples. Isoprostanes of the F2α family were detected only in ALS patients but not in control samples, while the hydroxylated metabolite 11-HETE significantly decreased. Despite our effort to analyze specialized pro-resolving mediators, they were not detected in plasma samples. However, we found the levels of 14-hydroxy-docosahexaenoic acid, a marker pathway of the Maresin biosynthesis, were also reduced in ALS patients, suggesting a defective activation in the resolution programs of inflammation in ALS. We further analyze oxylipin concentration levels in plasma from ALS patients to detect correlations between these metabolites and some clinical parameters. Interestingly, we found that plasmatic levels of 13-HODE and 9-HODE positively correlate with disease duration, expressed as days since onset. In summary, we developed a method to analyze “(oxy)lipidomics” in ALS human plasma and found new profiles of metabolites and novel lipid derivatives with unknown biological activities as potential footprints of disease onset.
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spelling doaj.art-fabe257cb7fb4090ba67a46f9f829ada2023-11-30T20:52:48ZengMDPI AGBiomedicines2227-90592022-03-0110367410.3390/biomedicines10030674HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis PatientsMauricio Mastrogiovanni0Andrés Trostchansky1Hugo Naya2Raúl Dominguez3Carla Marco4Mònica Povedano5Rubèn López-Vales6Homero Rubbo7Departamento de Bioquímica, Facultad de Medicina and Centro de Investigaciones Biomédicas, Universidad de la República, Montevideo 11800, UruguayDepartamento de Bioquímica, Facultad de Medicina and Centro de Investigaciones Biomédicas, Universidad de la República, Montevideo 11800, UruguayUnidad de Bioinformática, Institut Pasteur-Montevideo, Montevideo 11400, UruguayInstituto de Investigación Biomédica de Bellvitge, 08907 Hospitalet del Llobregat, SpainInstituto de Investigación Biomédica de Bellvitge, 08907 Hospitalet del Llobregat, SpainInstituto de Investigación Biomédica de Bellvitge, 08907 Hospitalet del Llobregat, SpainInstitute of Neurosciences, Universitat Autònoma de Barcelona, 08193 Barcelona, SpainDepartamento de Bioquímica, Facultad de Medicina and Centro de Investigaciones Biomédicas, Universidad de la República, Montevideo 11800, UruguayOxylipins play a critical role in regulating the onset and resolution phase of inflammation. Despite inflammation is a pathological hallmark in amyotrophic lateral sclerosis (ALS), the plasma oxylipin profile of ALS patients has not been assessed yet. Herein, we develop an oxylipin profile-targeted analysis of plasma from 74 ALS patients and controls. We found a significant decrease in linoleic acid-derived oxylipins in ALS patients, including 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE. These derivatives have been reported as important regulators of inflammation on different cell systems. In addition, some 5-lipoxygenase metabolites, such as 5-hydroxy- eicosatetraenoic acid also showed a significant decrease in ALS plasma samples. Isoprostanes of the F2α family were detected only in ALS patients but not in control samples, while the hydroxylated metabolite 11-HETE significantly decreased. Despite our effort to analyze specialized pro-resolving mediators, they were not detected in plasma samples. However, we found the levels of 14-hydroxy-docosahexaenoic acid, a marker pathway of the Maresin biosynthesis, were also reduced in ALS patients, suggesting a defective activation in the resolution programs of inflammation in ALS. We further analyze oxylipin concentration levels in plasma from ALS patients to detect correlations between these metabolites and some clinical parameters. Interestingly, we found that plasmatic levels of 13-HODE and 9-HODE positively correlate with disease duration, expressed as days since onset. In summary, we developed a method to analyze “(oxy)lipidomics” in ALS human plasma and found new profiles of metabolites and novel lipid derivatives with unknown biological activities as potential footprints of disease onset.https://www.mdpi.com/2227-9059/10/3/674amyotrophic lateral sclerosislipidomicsoxylipinspecialized pro-resolving mediatorsmass spectrometry
spellingShingle Mauricio Mastrogiovanni
Andrés Trostchansky
Hugo Naya
Raúl Dominguez
Carla Marco
Mònica Povedano
Rubèn López-Vales
Homero Rubbo
HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients
Biomedicines
amyotrophic lateral sclerosis
lipidomics
oxylipin
specialized pro-resolving mediators
mass spectrometry
title HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients
title_full HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients
title_fullStr HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients
title_full_unstemmed HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients
title_short HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients
title_sort hplc ms ms oxylipin analysis of plasma from amyotrophic lateral sclerosis patients
topic amyotrophic lateral sclerosis
lipidomics
oxylipin
specialized pro-resolving mediators
mass spectrometry
url https://www.mdpi.com/2227-9059/10/3/674
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