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Effects of Acetyl-L-Carnitine on Oxidative Stress in Amyotrophic Lateral Sclerosis Patients: Evaluation on Plasma Markers and Members of the Neurovascular Unit

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Title: Effects of Acetyl-L-Carnitine on Oxidative Stress in Amyotrophic Lateral Sclerosis Patients: Evaluation on Plasma Markers and Members of the Neurovascular Unit
Authors: Elena Grossini, Fabiola De Marchi, Sakthipriyan Venkatesan, Angelica Mele, Daniela Ferrante, Letizia Mazzini
Source: Antioxidants, Vol 12, Iss 10, p 1887 (2023)
Publisher Information: MDPI AG, 2023.
Publication Year: 2023
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: astrocytes, vascular endothelial cells, glutathione, mitochondria, nitric oxide, oxidants, Therapeutics. Pharmacology, RM1-950
More Details: Oxidative stress, the alteration of mitochondrial function, and the neurovascular unit (NVU), play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. We aimed to demonstrate the changes in the plasma redox system and nitric oxide (NO) in 32 new ALS-diagnosed patients in treatment with Acetyl-L-Carnitine (ALCAR) compared to healthy controls. We also evaluated the effects of plasma on human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. The analyses were performed at the baseline (T0), after three months (T1), and after six months (T2). In ALS patients at T0/T1, the plasma markers of lipid peroxidation, thiobarbituric acid reactive substances (TBARS) and 4-hydroxy nonenal (4-HNE) were higher, whereas the antioxidants, glutathione (GSH) and the glutathione peroxidase (GPx) activity were lower than in healthy controls. At T2, plasma TBARS and 4-HNE decreased, whereas plasma GSH and the GPx activity increased in ALS patients. As regards NO, the plasma levels were firmly lower at T0–T2 than those of healthy controls. Cell viability, and mitochondrial membrane potential in HUVEC/astrocytes treated with the plasma of ALS patients at T0–T2 were reduced, while the oxidant release increased. Those results, which confirmed the fundamental role of oxidative stress, mitochondrial function, and of the NVU in ALS pathogenesis, can have a double meaning, acting as disease markers at baseline and potential markers of drug effects in clinical practice and during clinical trials.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2076-3921
Relation: https://www.mdpi.com/2076-3921/12/10/1887; https://doaj.org/toc/2076-3921
DOI: 10.3390/antiox12101887
Access URL: https://doaj.org/article/8f9254f8c87b4fdda3d21cefb7b08677
Accession Number: edsdoj.8f9254f8c87b4fdda3d21cefb7b08677
Database: Directory of Open Access Journals
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  Data: Effects of Acetyl-L-Carnitine on Oxidative Stress in Amyotrophic Lateral Sclerosis Patients: Evaluation on Plasma Markers and Members of the Neurovascular Unit
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  Data: <searchLink fieldCode="AR" term="%22Elena+Grossini%22">Elena Grossini</searchLink><br /><searchLink fieldCode="AR" term="%22Fabiola+De+Marchi%22">Fabiola De Marchi</searchLink><br /><searchLink fieldCode="AR" term="%22Sakthipriyan+Venkatesan%22">Sakthipriyan Venkatesan</searchLink><br /><searchLink fieldCode="AR" term="%22Angelica+Mele%22">Angelica Mele</searchLink><br /><searchLink fieldCode="AR" term="%22Daniela+Ferrante%22">Daniela Ferrante</searchLink><br /><searchLink fieldCode="AR" term="%22Letizia+Mazzini%22">Letizia Mazzini</searchLink>
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  Data: Antioxidants, Vol 12, Iss 10, p 1887 (2023)
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  Data: MDPI AG, 2023.
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  Data: <searchLink fieldCode="DE" term="%22astrocytes%22">astrocytes</searchLink><br /><searchLink fieldCode="DE" term="%22vascular+endothelial+cells%22">vascular endothelial cells</searchLink><br /><searchLink fieldCode="DE" term="%22glutathione%22">glutathione</searchLink><br /><searchLink fieldCode="DE" term="%22mitochondria%22">mitochondria</searchLink><br /><searchLink fieldCode="DE" term="%22nitric+oxide%22">nitric oxide</searchLink><br /><searchLink fieldCode="DE" term="%22oxidants%22">oxidants</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%2E+Pharmacology%22">Therapeutics. Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22RM1-950%22">RM1-950</searchLink>
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  Data: Oxidative stress, the alteration of mitochondrial function, and the neurovascular unit (NVU), play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. We aimed to demonstrate the changes in the plasma redox system and nitric oxide (NO) in 32 new ALS-diagnosed patients in treatment with Acetyl-L-Carnitine (ALCAR) compared to healthy controls. We also evaluated the effects of plasma on human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. The analyses were performed at the baseline (T0), after three months (T1), and after six months (T2). In ALS patients at T0/T1, the plasma markers of lipid peroxidation, thiobarbituric acid reactive substances (TBARS) and 4-hydroxy nonenal (4-HNE) were higher, whereas the antioxidants, glutathione (GSH) and the glutathione peroxidase (GPx) activity were lower than in healthy controls. At T2, plasma TBARS and 4-HNE decreased, whereas plasma GSH and the GPx activity increased in ALS patients. As regards NO, the plasma levels were firmly lower at T0–T2 than those of healthy controls. Cell viability, and mitochondrial membrane potential in HUVEC/astrocytes treated with the plasma of ALS patients at T0–T2 were reduced, while the oxidant release increased. Those results, which confirmed the fundamental role of oxidative stress, mitochondrial function, and of the NVU in ALS pathogenesis, can have a double meaning, acting as disease markers at baseline and potential markers of drug effects in clinical practice and during clinical trials.
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        Value: 10.3390/antiox12101887
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        StartPage: 1887
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      – TitleFull: Effects of Acetyl-L-Carnitine on Oxidative Stress in Amyotrophic Lateral Sclerosis Patients: Evaluation on Plasma Markers and Members of the Neurovascular Unit
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