title: The soy isoflavone genistein blunts nuclear factor kappa-B, MAPKs and TNF-α activation and ameliorates muscle function and morphology in mdx mice.
abstract: Several lines of evidence suggest a detrimental role of the nuclear factor-κB (NF-κB) activation in the dystrophic process. We showed in previous studies that its inhibition through drugs with antioxidant properties, have beneficial effects in mdx mice. We tested whether genistein, a well-known isoflavone, inhibitor of NF-κB, MAPK and TNF-α and readily available for clinical use, could have a beneficial effect in mdx mice in comparison with methylprednisolone, the gold standard treatment for DMD patients. Five-week old mdx mice received for five weeks: genistein (daily or 3-times/week), methylprednisolone or vehicle. Genistein treatment: (1) increased forelimb strength and strength normalized to weight; (2) reduced serum creatine-kinase levels; (3) reduced markers of oxidative stress; (4) reduced muscle necrosis and enhanced regeneration. The positive results were more evident with the daily administration of genistein and were comparable to the effect of corticosteroids. Our data support the novel hypothesis that, as other more specific therapeutic approaches are still under development, this soy-derived compound is a promising option to be further investigated in dystrophic process.
authors.affiliation: Department of Neuroscience, Psychiatry and Anaesthesiology, University of Messina, Italy. messinasonia@libero.it
authors.forename: Sonia
authors.initials: S
authors.lastname: Messina
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: M'hammed
authors.initials: M
authors.lastname: Aguennouz
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Vita
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Alba
authors.initials: A
authors.lastname: Migliorato
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vita
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D019833:Genistein / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D005938:Glucocorticoids; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019833:Genistein; D020929:Mitogen-Activated Protein Kinase Kinases; D003402:Creatine Kinase; D008775:Methylprednisolone