title: Metformin improves skin flap survival through nitric oxide system.
abstract: BACKGROUND
  Metformin has shown cardioprotective effects in experimental models of ischemia reperfusion, which is partially mediated through nitric oxide (NO) synthesis. We investigated the effects of metformin pretreatment in a rat model of random-pattern skin flap, and the probable role of NO system.
  
  
  METHODS
  In the first experiment, the rats received increasing doses of metformin (150, 200, and 300 mg/kg), 4 h before the procedure. Dorsal skin flaps with caudal pedicles were elevated at the midline and flap survival was measured 7 d after surgery. Pathologic review of the skin flap specimen was performed in a subset of animals. In the second experiment, for evaluation of the role of NO, an NO synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME) was administered with and without the effective dose of metformin. In the next experiment, subtherapeutic dose of NO precursor, L-Arginine, was administered with and without subeffective dose of metformin.
  
  
  RESULTS
  Metformin pretreatment at doses of 200 and 300 mg/kg significantly increased skin flap survival rate. However, administration of L-NAME abolished the protective effects of metformin. On the other hand, subtherapeutic dose of L-arginine augmented the effects of low-dose metformin and significantly increased skin flap survival. Skin flaps from those rats that received 300 mg/kg metformin pretreatment and those treated with subtherapeutic doses of L-arginine and metformin showed increased vasodilation compared with control group.
  
  
  CONCLUSIONS
  Metformin pretreatment can improve skin flap survival through an NO dependent pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shayandokht
authors.initials: S
authors.lastname: Taleb
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Peiman
authors.initials: P
authors.lastname: Moghaddas
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahimi Balaei
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Taleb
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sina
authors.initials: S
authors.lastname: Rahimpour
authors.affiliation: Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ata
authors.initials: A
authors.lastname: Abbasi
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Ejtemaei-Mehr
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpour@yahoo.com.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D019651:Plastic Surgery Procedures / Q000379:methods; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control*; D012867:Skin / Q000098:blood supply / Q000473:pathology; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology
chemical_list: D007004:Hypoglycemic Agents; D009569:Nitric Oxide; D008687:Metformin
keywords: Metformin; Nitric oxide; Preconditioning; Skin flap