Edaravone Attenuates Disease Severity of Experimental Auto-Immune Encephalomyelitis and Increases Gene Expression of Nrf2 and HO-1

0558833 - MBÚ 2023 RIV CZ eng J - Článek v odborném periodiku
Michaličková, D. - Kubra Ozturk, H. - Hroudová, J. - Lupták, M. - Kučera, T. - Hrnčíř, Tomáš - Kutinová Canová, N. - Šíma, M. - Slanař, O.
Edaravone Attenuates Disease Severity of Experimental Auto-Immune Encephalomyelitis and Increases Gene Expression of Nrf2 and HO-1.
Physiological Research. Roč. 71, č. 1 (2022), s. 147-157. ISSN 0862-8408. E-ISSN 1802-9973
Grant CEP: GA ČR(CZ) GA17-07332S; GA ČR(CZ) GA20-09732S
Institucionální podpora: RVO:61388971
Klíčová slova: multiple-sclerosis * active induction * model * neurodegeneration * Experimental autoimmune encephalomyelitis * Edaravone * Mitochondrial dysfunction * Nrf2/HO-1 pathway * Oxidative stress
Obor OECD: Physiology (including cytology)
Impakt faktor: 2.1, rok: 2022
Způsob publikování: Open access
https://www.biomed.cas.cz/physiolres/pdf/2022/71_147.pdf

The aim of this study was to evaluate therapeutic potential of edaravone in the murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) and to expand the knowledge of its mechanism of action. Edaravone (6 mg/kg/day) was administered intraperitoneally from the onset of clinical symptoms until the end of the experiment (28 days). Disease progression was assessed daily using severity scores. At the peak of the disease, histological analyses, markers of oxidative stress (OS) and parameters of mitochondria! function in the brains and spinal cords (SC) of mice were determined. Gene expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-'alpha was determined at the end of the experiment. Edaravone treatment ameliorated EAE severity and attenuated inflammation in the SC of the EAE mice, as verified by histological analysis. Moreover, edaravone treatment decreased OS, increased the gene expression of the Nrf2 and HO-1, increased the activity of the mitochondrial complex reduced the activity of the mitochondrial complex IV and preserved ATP production in the SC of the EAE mice. In conclusion, findings in this study provide additional evidence of edaravone potential for the treatment of multiple sclerosis and expand our knowledge of the mechanism of action of edaravone in the EAE model.
Trvalý link: https://hdl.handle.net/11104/0332492