Flavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone
| Autor: | Sonia Messina, Maria Grazia De Pasquale, Giuseppe Vita, Gian Luca Vita, Francesca Polito, Antonino Naro, Domenica Altavilla, Anna Mazzeo, Emanuele Rizzuto, Francesco Squadrito, Natasha Irrera, M'hammed Aguennouz, Antonio Musarò, Alba Migliorato, Massimo Russo, Alessandra Bitto |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Flavocoxid Necrosis Duchenne muscular dystrophy Anti-Inflammatory Agents Electrophoretic Mobility Shift Assay medicine.disease_cause Catechin Muscular Dystrophies Mice muscle degeneration mdx nfkb anti-inflammation anti-oxidante flavoxid oxidative stress Creatine Kinase limbrel® Immunohistochemistry Drug Combinations Neurology Methylprednisolone Cytokines Tumor necrosis factor alpha mdx mice medicine.symptom flavocoxid Signal Transduction medicine.drug medicine.medical_specialty nf-kappa b duchenne muscular dystrophy limbrel (r) medical food methylprednisolone nf-κb Developmental Neuroscience In vivo Internal medicine medicine Animals Muscle Skeletal Peroxidase Arachidonate 5-Lipoxygenase business.industry DNA Hydrogen Peroxide medicine.disease Mice Inbred C57BL Endocrinology Prostaglandin-Endoperoxide Synthases Mice Inbred mdx business Ex vivo Oxidative stress |
| Popis: | Muscle degeneration in dystrophic muscle is exacerbated by the endogenous inflammatory response and increased oxidative stress. A key role is played by nuclear factor(NF)-kappaB. We showed that NF-kappaB inhibition through compounds with also antioxidant properties has beneficial effects in mdx mice, the murine model of Duchenne muscular dystrophy (DMD), but these drugs are not available for clinical studies. We evaluated whether flavocoxid, a mixed flavonoid extract with anti-inflammatory, antioxidant and NF-kappaB inhibiting properties, has beneficial effects in mdx mice in comparison with methylprednisolone, the gold standard treatment for DMD patients. Five-week-old mdx mice were treated for 5 weeks with flavocoxid, methylprednisolone or vehicle. The evaluation of in vivo and ex vivo functional properties and morphological parameters was performed. Serum samples were assayed for oxidative stress markers, creatine-kinase (CK) and leukotriene B-4. Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), tumor necrosis factor-alpha, p-38, JNK1 expression was evaluated in muscle by western blot analysis. NF-kappaB binding activity was investigated by electrophoresis mobility shift assay. The administration of flavocoxid: (1) ameliorated functional properties in vivo and ex vivo; (2) reduced CK; (3) reduced the expression of oxidative stress markers and of inflammatory mediators; (4) inhibited NF-kappaB and mitogen-activated protein kinases (MAPKs) signal pathways; (5) reduced muscle necrosis and enhanced regeneration. Our results highlight the detrimental effects of oxidative stress and NF-kappaB, MAPKs and COX/5-LOX pathways in the dystrophic process and show that flavocoxid is more effective in mdx mice than methylprednisolone. |
| Databáze: | OpenAIRE |
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