title: Protective effect of pharmacologic preconditioning with pioglitazone on random-pattern skin flap in rat is mediated by nitric oxide system.
abstract: BACKGROUND
  Pioglitazone, a thiazolidinedione, is primarily used as an antidiabetic agent. In addition, recent reports have identified anti-ischemic and anti-inflammatory properties of pioglitazone through nitric oxide (NO) pathways.
  
  
  OBJECTIVE
  To determine the protective effects of pioglitazone on random-pattern skin flaps in a rat model.
  
  
  METHODS
  Forty-eight male Rats were randomly assigned to eight groups. Bipedicled dorsal skin flaps (2 × 8 cm) were elevated at the midline. In pharmacologic preconditioning groups, three different doses of pioglitazone (25, 40, 80, mg/kg; doses were selected according to our pilot study) gavaged 4 h before elevating flaps. Seven days after operation, the survival of skin flap was measured. For investigating the role of NO system, in other groups the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg) was administered alone or with an effective dose of pioglitazone. Finally, in another group, subeffective dose of nitric oxide precursor L-arginine (100 mg/kg) was coadministered with subeffective pioglitazone.
  
  
  RESULTS
  Significant increase in flap survival was seen with pioglitazone (40 mg/kg). This protective effect was abolished by systemic administration of L-NAME (10 mg/kg). Coadministration of subeffective doses of pioglitazone with subeffetcive L-arginine significantly improved flap survival.
  
  
  CONCLUSIONS
  Pharmacologic preconditioning with pioglitazone improves survival of random-pattern skin flaps in rats through NO dependent mechanisms.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Afraz
authors.forename: Ali
authors.initials: A
authors.lastname: Kamran
authors.forename: Kasra
authors.initials: K
authors.lastname: Moazzami
authors.forename: Behtash G
authors.initials: BG
authors.lastname: Nezami
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D062109:Dermatologic Surgical Procedures; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D012867:Skin / Q000378:metabolism; D013524:Surgical Flaps / Q000098:blood supply*; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone