title: Edaravone ameliorates diabetes-induced dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the rat.
abstract: BACKGROUND
  Diabetes mellitus (DM) represents a major risk factor for erectile dysfunction (ED). Although the etiology of diabetes-induced ED is multifactorial and still unknown, reactive oxygen species are thought to be one of the key factors.
  
  
  OBJECTIVE
  The aim of this article is to investigate whether administration of edaravone, a free radical scavenger, could prevent type 1 diabetes-induced dysfunction of nitric oxide (NO)-induced relaxation in corpus cavernosum smooth muscle in the rat.
  
  
  METHODS
  Six-week-old male Wistar rats were randomly divided into three groups. One group was treated with citrate-phosphate buffer plus normal saline (group Cont), whereas in the other two groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally [i.p.]). Subsequently, the diabetic rats were treated for 4 weeks either with edaravone (10 mg/kg/day, i.p.; group DM + E) or with normal saline (group DM).
  
  
  METHODS
  Serum glucose and malondialdehyde levels as well as penile cyclic guanosine monophosphate (cGMP) concentrations were determined, and penile function was estimated by organ bath studies with norepinephrine-mediated contractions and acetylcholine-mediated relaxations. The participation mRNA levels of muscarinic M(3) receptors, neuronal nitrous oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS), and participation protein levels of nNOS, eNOS, phosphorylated nNOS, and phosphorylated eNOS were investigated by quantitative real-time polymerase chain reaction (PCR) and immunoblot analysis, respectively.
  
  
  RESULTS
  Treatment with edaravone prevented partially but significantly the decreased body and penile weight induced by diabetes. Treatment with edaravone significantly improved the increased diabetes-induced malondialdehyde levels, the decreased penile cGMP concentrations, the increased diabetes-induced norepinephrine-mediated contractions, and the decreased acetylcholine-mediated relaxation. Although there were no significant differences in expression levels of mRNAs in nNOS, diabetes-induced upregulation of muscarinic M(3) receptor and iNOS mRNAs as well as diabetes-induced downregulations of eNOS, phosphorylated nNOS, and phosphorylated eNOS were significantly prevented by edaravone.
  
  
  CONCLUSIONS
  Edaravone decreases the oxidative insult in the penile corpus cavernosum by ameliorating the NO-NOS system and thus preventing partially the developing ED in DM in the rat.
authors.affiliation: Division of Molecular Pharmacology, Tottori University School of Medicine, Yonago, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Ohmasa
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Panagiota
authors.initials: P
authors.lastname: Tsounapi
authors.forename: Fotios
authors.initials: F
authors.lastname: Dimitriadis
authors.forename: Seiya
authors.initials: S
authors.lastname: Inoue
authors.forename: Kohei
authors.initials: K
authors.lastname: Shomori
authors.forename: Shogo
authors.initials: S
authors.lastname: Shimizu
authors.forename: Yukako
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Keisuke
authors.initials: K
authors.lastname: Satoh
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018783:Impotence, Vasculogenic / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D010413:Penis / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D008315:Malondialdehyde; D006152:Cyclic GMP; D000077553:Edaravone; D000983:Antipyrine