Neuroprotective Effects of Telmisartan and Nifedipine Against Cuprizone-Induced Demyelination and Behavioral Dysfunction in Mice: Roles of NF-κB and Nrf2
Autor: | Amira E. Abd El Aziz, Rabab H. Sayed, Nada A Sallam, Nesrine S. El Sayed |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
biology business.industry Immunology Pharmacology Malondialdehyde medicine.disease_cause Neuroprotection Myelin basic protein 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Nifedipine chemistry Neurotrophic factors Apoptosis 030220 oncology & carcinogenesis biology.protein Immunology and Allergy Medicine Telmisartan business Oxidative stress medicine.drug |
Zdroj: | Inflammation. 44:1629-1642 |
ISSN: | 1573-2576 0360-3997 |
Popis: | Multiple sclerosis is a chronic inflammatory neurodegenerative disease of the central nervous system which injures the myelin sheath. Telmisartan and nifedipine are antihypertensive drugs that recently showed neuroprotective properties against neurodegenerative diseases. This study evaluated the neuroprotective effect of telmisartan or nifedipine in cuprizone-induced demyelination in mice by examining the underlying mechanisms. C57BL/6 mice received a diet containing 0.7% (w/w) cuprizone for 7 days followed by 3 weeks on a 0.2% cuprizone diet. Telmisartan (5 mg/kg/day, p.o.) or nifedipine (5 mg/kg/day, p.o.) was administered for 3 weeks starting from the second week. Telmisartan or nifedipine improved locomotor activity and enhanced motor coordination as demonstrated by open field, rotarod, and grip strength tests. Furthermore, telmisartan or nifedipine restored myelin basic protein mRNA and protein expression and increased luxol fast blue-staining intensity. Telmisartan or nifedipine attenuated cuprizone-induced oxidative stress and apoptosis by decreasing brain malondialdehyde and caspase-3 along with restoring reduced glutathione and brain-derived neurotrophic factor levels. Telmisartan or nifedipine exerted an anti-inflammatory effect by reducing the expression of nuclear factor kappa B (NF-κB p65) as well as pro-inflammatory cytokines and elevating the expression of IκB-α. In parallel, telmisartan or nifedipine upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the levels of heme oxygenase-1 and NADPH quinone oxidoreductase 1 enzymes. In conclusion, the current study provides evidence for the protective effect of telmisartan and nifedipine in cuprizone-induced demyelination and behavioral dysfunction in mice possibly by modulating NF-κB and Nrf2 signaling pathways. |
Databáze: | OpenAIRE |
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