title: Melatonin restores muscle regeneration and enhances muscle function after crush injury in rats.
abstract: The goal of this study was to provide evidence that melatonin improves muscle healing following blunt skeletal muscle injury. For this purpose, we used 56 rats and induced an open muscle injury. After injury, all animals received either daily melatonin or vehicle solution intraperitoneally. Subsequent observations were performed at day 1, 4, 7, and 14 after injury. After assessment of fast twitch and tetanic muscle force, we analyzed leukocyte infiltration, satellite cell number, and cell apoptosis. We further quantified the expression of the melatonin receptor and the activation of extracellular-signal-regulated kinase (ERK). Chronic treatment with melatonin significantly increased the twitch and tetanic force of the injured muscle at day 4, 7, and 14. At day 1, melatonin significantly reduced the leukocyte infiltration and significantly increased the number of satellite cells when compared to the control group. Consistent with this observation, melatonin significantly reduced the number of apoptotic cells at day 4. Furthermore, phosphorylation of ERK reached maximal values in the melatonin group at day 1 after injury. Additionally, we detected the MT1a receptor in the injured muscle and showed a significant up-regulation of the MT1a mRNA in the melatonin group at day 4. These data support the hypothesis that melatonin supports muscle restoration after muscle injury, inhibits apoptosis via modulation of apoptosis-associated signaling pathways, increases the number of satellite cells, and reduces inflammation.
authors.affiliation: Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Stratos
authors.forename: Nils
authors.initials: N
authors.lastname: Richter
authors.forename: Robert
authors.initials: R
authors.lastname: Rotter
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Li
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zechner
authors.forename: Thomas
authors.initials: T
authors.lastname: Mittlmeier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000293:injuries* / Q000502:physiology; D009142:Musculoskeletal Physiological Phenomena / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044122:Receptor, Melatonin, MT1 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D032496:Satellite Cells, Skeletal Muscle / Q000737:chemistry / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D044122:Receptor, Melatonin, MT1; D051028:bcl-2-Associated X Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D002265:Carboxylic Ester Hydrolases; C019873:chloroacetate esterase; C505410:Casp3 protein, rat; D053148:Caspase 3; D008550:Melatonin