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. 2022 May 16:14:11795735221092524.
doi: 10.1177/11795735221092524. eCollection 2022.

Edaravone Inhibits the Production of Reactive Oxygen Species in Phagocytosis- and PKC-Stimulated Granulocytes from Multiple Sclerosis Patients Edaravone Modulate Oxidative Stress in Multiple Sclerosis

Pedro Henrique Villar-Delfino  1 , Nathália Augusta Oliveira Gomes  1 , Paulo Pereira Christo  1 , José Augusto Nogueira-Machado  1 , Caroline Maria Oliveira Volpe  1
Affiliations

Edaravone Inhibits the Production of Reactive Oxygen Species in Phagocytosis- and PKC-Stimulated Granulocytes from Multiple Sclerosis Patients Edaravone Modulate Oxidative Stress in Multiple Sclerosis

Pedro Henrique Villar-Delfino et al. J Cent Nerv Syst Dis. .

Abstract

Background: Oxidative stress is associated with the pathogenesis of MS. Edaravone (EDV) has been proposed as a therapeutic resource for central nervous system diseases, and it was effective in reducing oxidative stress. However, the antioxidant mechanisms of EDV are poorly studied.

Objective: This study aimed to evaluate the effects of EDV on resting, phagocytosis, and PKC-activated granulocytes derived from MS patients and a healthy control group.

Methods: The effects of EDV on ROS production in phagocytosis (ROS production in the presence of opsonized particles) and PKC-stimulated granulocytes were evaluated in a luminol-dependent chemiluminescence method. Calphostin C was used in some experiments to compare with those of EDV.

Results: EDV inhibited ROS production in phagocytosis of opsonized particles and PKC-stimulated granulocytes from MS patients and healthy control group. In the presence of calphostin C, the inhibition of ROS production was similar to that observed with EDV.

Conclusion: These findings suggest the involvement of EDV on the ROS-PKC-NOX signaling pathways modulating oxidative stress in MS. EDV represents a promising treatment option to control oxidative innate immune response for MS.

Keywords: edaravone; innate immunity; multiple sclerosis; phagocytosis; protein kinase C; reactive oxygen species.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Dose response curve of Edaravone. Values expressed in mean ± standard deviation. n = 3 for each concentration. EDV: Edaravone; G: granulocytes; PBS: phosphate buffered saline; RLU/min: Relative Light Units/minute.
Figure 2.
Figure 2.
EDV-induced down-regulation on ROS generation in resting (A), phagocytosis-stimulated cells (B), and PDB-stimulated granulocytes (C) from healthy control group and Multiple Sclerosis patients. Typical curves obtained in kinetic studies of 5 experimental protocols for each group. EDV: Edaravone; G: granulocytes; PDB: Phorbol Dibutyrate; ZC3b: Zymosan recovered using C3b fragments (opsonized particles).
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