title: Melatonin attenuates I/R-induced mitochondrial dysfunction in skeletal muscle.
abstract: BACKGROUND
  Our recent studies have shown that ischemia/reperfusion (I/R) produces significant necrosis and apoptosis in the cells of skeletal muscle. Our previous studies also demonstrated that melatonin provides significant protection against superoxide generation, endothelial dysfunction, and cell death in the skeletal muscle after I/R. Mitochondria are essential for cell survival, because of their roles as ATP producers as well as regulators of cell death. However, the efficacy of melatonin on I/R-induced mitochondrial dysfunction in the skeletal muscle in vivo has not been demonstrated in the literature.
  
  
  METHODS
  Vascular pedicle isolated rat gracilis muscle model was used. After 4 h of ischemia followed by 24 h of reperfusion, gracilis muscle was harvested, and mitochondrial as well as cytosolic fractions were isolated. Mitochondrial dysfunction was determined by the alteration of mitochondrial membrane potential and the release of the proapoptotic protein, cytochrome c. Three groups were designed; sham I/R, I/R-V (I/R with vehicle), and I/R-Mel (I/R with melatonin). Melatonin or vehicle was given intravenously 10 min prior to reperfusion and 10 min after reperfusion.
  
  
  RESULTS
  We found that the capability of uptake of fluorescent JC-1 dye in skeletal muscle cells was substantially improved in I/R-Mel group compared with I/R-V group. Melatonin significantly inhibited the outflow of cytochrome c from mitochondria to cytoplasm, which was demonstrated in the I/R-V group.
  
  
  CONCLUSIONS
  Melatonin significantly attenuates I/R-induced mitochondrial dysfunction, such as the depolarization of mitochondrial membrane potential and the release of the proapoptotic protein, cytochrome c, from the mitochondria.
authors.affiliation: Department of Surgery, Division of Plastic Surgery, University of Nevada School of Medicine, Las Vegas, Nevada 89102, USA. wwang@medicine.nevada.edu
authors.forename: Wei Z
authors.initials: WZ
authors.lastname: Wang
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Fang
authors.forename: Linda L
authors.initials: LL
authors.lastname: Stephenson
authors.forename: Xinlan
authors.initials: X
authors.lastname: Zhang
authors.forename: Kayvan T
authors.initials: KT
authors.lastname: Khiabani
authors.forename: William A
authors.initials: WA
authors.lastname: Zamboni
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001562:Benzimidazoles / Q000493:pharmacokinetics; D002232:Carbocyanines / Q000493:pharmacokinetics; D045304:Cytochromes c / Q000378:metabolism; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001562:Benzimidazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D013481:Superoxides; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D045304:Cytochromes c; D008550:Melatonin