The nitric oxide donor Molsidomine shows therapeutic benefit toward muscle repair after an acute impact injury, in rats.

Reeves, Christopher Nicolas (2016-12)

Thesis (MSc)--Stellenbosch University, 2016.

Thesis

ENGLISH ABSTRACT: Background: Muscle injuries are highly prevalent and arise from a multitude of situations. Trauma to the soft tissue is painful and debilitating and it requires extensive healing that often involves the formation of a fibrotic scar. Current treatments are merely management strategies, such as the RICE principle. Nitric oxide (NO) knock-out models show reduced skeletal muscle regeneration and excessive fibrosis (Filippin et al., 2011 a & b), suggesting therapeutic promise for NO. NO-donation has shown therapeutic promise in mouse models of muscular dystrophy, and therefore, may be beneficial for the treatment of acute muscle injuries. Objective: To clarify the role of treatment-derived NO on muscle trauma, using the NO-donating drug: Molsidomine (MOLS), which has been approved for use in humans. Methods: Using a crush injury model in rats, placebo (PLA) or MOLS treatments were administered immediately and one day after the injury. MPO, MyoD, myogenin, fibronectin and TGF-β1 protein content in the injured tissue homogenates was assessed with Western blots. Collagen deposition at 21 days after injury was assessed using a Masson’s trichrome stain. Results: With MOLS, there was significantly less collagen deposition (p < 0.05) 21 days after injury, which was supported by less TGF-β1 protein (p = 0.01) and less fibronectin protein (p < 0.005) compared to the PLA group at this time point. Additionally, MOLS tended to modulate the amount of MPO and, therefore, the inflammatory response by 33% 5 days after injury. Conclusion: MOLS treatment improves, and potentially hastens, tissue repair after an acute impact injury through the reduction of excessive fibrosis, as well as through enhanced clearance of inflammatory radicals from injured muscle.

AFRIKAANS OPSOMMING: Agtergrond: Spierbeserings is baie algemeen en ontstaan as gevolg van verskeie oorsake. Trauma aan sagteweefsel is pynlik en benadeel funksie, en dit benodig omvattende genesing wat soms met die vorming van fibrotiese letsels gepaard gaan. Tans word behandeling gerig op beheerstrategieë deur gebruik te maak van die “RICE” beginsel. Stikstofoksied (NO) geen-uitklopmodelle toon aan dat daar ‘n verlaging in skeletspierregenerasie is en oormatige fibrose ontstaan (Filippin et al., 2011 a & b), wat daarop dui dat daar ‘n terapeutiese voordeel vir NO kan wees. In spierdistrofie muismodelle hou NO-skenking terapeutiese voordele in en kan dus potensieel ook voordelig wees in die behandeling van akute spierbeserings. Doelwit: Om duidelikheid te kry oor die rol van behandelings-afgeleide NO in spiertrauma deur van die NO-skenkingsmiddel, Molsidomien (MOLS), wat goedgekeur is vir menslike inname, gebruik te maak. Metode: Deur van ‘n vergruisingsbesering-rotmodel gebruik te maak, is ‘n plasebo (PLA) of MOLS behandeling direk, asook na een dag na besering, toegepas. MPO, MyoD, miogenien, fibronektien en TGF-β1 proteïeninhoud in ‘n homogene oplossing van die beskadigde weefsel is deur Westerse blattering ondersoek. Kollageen neersetting teen 21 dae na besering is deur middel van Masson se trichroomkleuring ondersoek. Resultate: Behandeling met MOLS het betekenisvol minder kollageen neersetting tot gevolg gehad (p < 0.05) teen 21 dae na besering, watverder bevestig is deur minder TGF-β1 proteïen (p = 0.01) en fibronektien proteïen (p < 0.005) vergeleke met die PLA groep by dieselfde tydpunt. Boonop het MOLS ook geneig om die hoeveelheid MPO – en dus die inflammatoriese respons - met 33% verminder, teen vyf dae na besering. Gevolgtrekking: MOLS behandeling verbeter, en versnel moontlik, weefselherstel na ‘n akute impakbesering deur oormatige fibrose te verminder, en ook deur middel van verbeterde verwydering van inflammatoriese radikale uit die beseerde spierweefsel.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/100310
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