Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem

Propentofylline (PROP) is a methylated xanthine compound that diminishes the activation of microglial cells and astrocytes, which are neuronal cells strongly associated with many neurodegenerative diseases. Based on previously observed remyelination and neuroprotective effects, PROP has also been pr...

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Main Authors: Deborah E. M. Baliellas, Marcelo P. Barros, Cristina V. Vardaris, Maísa Guariroba, Sandra C. Poppe, Maria F. Martins, Álvaro A. F. Pereira, Eduardo F. Bondan
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/6/1652
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author Deborah E. M. Baliellas
Marcelo P. Barros
Cristina V. Vardaris
Maísa Guariroba
Sandra C. Poppe
Maria F. Martins
Álvaro A. F. Pereira
Eduardo F. Bondan
author_facet Deborah E. M. Baliellas
Marcelo P. Barros
Cristina V. Vardaris
Maísa Guariroba
Sandra C. Poppe
Maria F. Martins
Álvaro A. F. Pereira
Eduardo F. Bondan
author_sort Deborah E. M. Baliellas
collection DOAJ
description Propentofylline (PROP) is a methylated xanthine compound that diminishes the activation of microglial cells and astrocytes, which are neuronal cells strongly associated with many neurodegenerative diseases. Based on previously observed remyelination and neuroprotective effects, PROP has also been proposed to increment antioxidant defenses and to prevent oxidative damage in neural tissues. Since most neurodegenerative processes have free radicals as molecular pathological agents, the aim of this study was to evaluate the antioxidant effects of 12.5 mg·kg<sup>−1</sup>·day<sup>−1</sup> PROP in plasma and the brainstem of Wistar rats exposed to the gliotoxic agent 0.1% ethidium bromide (EB) for 7–31 days. The bulk of the data here demonstrates that, after 7 days of EB treatment, TBARS levels were 2-fold higher in the rat CNS than in control, reaching a maximum of 2.4-fold within 15 days. After 31 days of EB treatment, lipoperoxidation in CNS was still 65% higher than that in the control. Clearly, PROP treatment limited the progression of lipoperoxidation in EB-oxidized CNS: it was, for example, 76% lower than in the EB-treated group after 15 days. Most of these effects were associated with PROP-induced activity of glutathione reductase in the brainstem: the EB + PROP group showed 59% higher GR activity than that of the EB or control groups within 7 days. In summary, aligning with previous studies from our group and with literature about MTXs, we observed that propentofylline (PROP) improved the thiol-based antioxidant defenses in the rat brainstem by the induction of the enzymatic activity of glutathione reductase (GR), which diminished lipid oxidation progression and rebalanced the redox status in the CNS.
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spelling doaj.art-939c9292daa748ad837c42cd98d6dabb2023-11-18T09:26:19ZengMDPI AGBiomedicines2227-90592023-06-01116165210.3390/biomedicines11061652Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat BrainstemDeborah E. M. Baliellas0Marcelo P. Barros1Cristina V. Vardaris2Maísa Guariroba3Sandra C. Poppe4Maria F. Martins5Álvaro A. F. Pereira6Eduardo F. Bondan7Department of Veterinary Medicine, Cruzeiro do Sul University, São Paulo 08060070, BrazilInterdisciplinary Programs in Health Sciences, Institute of Physical Activity and Sport Sciences (ICAFE), Cruzeiro do Sul University, São Paulo 01506000, BrazilInterdisciplinary Programs in Health Sciences, Institute of Physical Activity and Sport Sciences (ICAFE), Cruzeiro do Sul University, São Paulo 01506000, BrazilDepartment of Veterinary Medicine, Cruzeiro do Sul University, São Paulo 08060070, BrazilDepartment of Veterinary Medicine, Cruzeiro do Sul University, São Paulo 08060070, BrazilDepartment of Veterinary Medicine, Cruzeiro do Sul University, São Paulo 08060070, BrazilDepartment of Veterinary Medicine, Cruzeiro do Sul University, São Paulo 08060070, BrazilGraduate Program in Environmental and Experimental Pathology, University Paulista (UNIP), São Paulo 04057000, BrazilPropentofylline (PROP) is a methylated xanthine compound that diminishes the activation of microglial cells and astrocytes, which are neuronal cells strongly associated with many neurodegenerative diseases. Based on previously observed remyelination and neuroprotective effects, PROP has also been proposed to increment antioxidant defenses and to prevent oxidative damage in neural tissues. Since most neurodegenerative processes have free radicals as molecular pathological agents, the aim of this study was to evaluate the antioxidant effects of 12.5 mg·kg<sup>−1</sup>·day<sup>−1</sup> PROP in plasma and the brainstem of Wistar rats exposed to the gliotoxic agent 0.1% ethidium bromide (EB) for 7–31 days. The bulk of the data here demonstrates that, after 7 days of EB treatment, TBARS levels were 2-fold higher in the rat CNS than in control, reaching a maximum of 2.4-fold within 15 days. After 31 days of EB treatment, lipoperoxidation in CNS was still 65% higher than that in the control. Clearly, PROP treatment limited the progression of lipoperoxidation in EB-oxidized CNS: it was, for example, 76% lower than in the EB-treated group after 15 days. Most of these effects were associated with PROP-induced activity of glutathione reductase in the brainstem: the EB + PROP group showed 59% higher GR activity than that of the EB or control groups within 7 days. In summary, aligning with previous studies from our group and with literature about MTXs, we observed that propentofylline (PROP) improved the thiol-based antioxidant defenses in the rat brainstem by the induction of the enzymatic activity of glutathione reductase (GR), which diminished lipid oxidation progression and rebalanced the redox status in the CNS.https://www.mdpi.com/2227-9059/11/6/1652astrocyteglial cellsxanthineoxidative stressfree radicalsneurodegenerative
spellingShingle Deborah E. M. Baliellas
Marcelo P. Barros
Cristina V. Vardaris
Maísa Guariroba
Sandra C. Poppe
Maria F. Martins
Álvaro A. F. Pereira
Eduardo F. Bondan
Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem
Biomedicines
astrocyte
glial cells
xanthine
oxidative stress
free radicals
neurodegenerative
title Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem
title_full Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem
title_fullStr Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem
title_full_unstemmed Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem
title_short Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem
title_sort propentofylline improves thiol based antioxidant defenses and limits lipid peroxidation following gliotoxic injury in the rat brainstem
topic astrocyte
glial cells
xanthine
oxidative stress
free radicals
neurodegenerative
url https://www.mdpi.com/2227-9059/11/6/1652
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