title: Protective effects of edaravone on experimental chronic pancreatitis induced by dibutyltin dichloride in rats.
abstract: OBJECTIVE
  To investigate the effects of edaravone, a potent free radical scavenger, on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and pancreatic fibrosis.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly divided into four groups (n = 16 each): control, DBTC, DBTC + edaravone, and control + edaravone. Edaravone or normal saline at a daily dose of 6 mg/kg body weight was given intraperitoneally from day 5 to day 28 after DBTC administration. On days 14 and 28, the rats were evaluated morphologically and biochemically. The expression of cytokines in pancreas TGF-β, IL-6 and TNF<alpha> was detected using RT-PCR. The activation of nuclear factor (NF)-κB in pancreatic tissue was evaluated by immunostaining and western-blot for NF-κB p65. α-smooth muscle actin (α-SMA) expression was also evaluated by immunostaining and western-blot to investigate the activation of pancreatic stellate cells (PSCs).
  
  
  RESULTS
  Edaravone treatment improved the rats' body weight (p < 0.01) and feed intake levels (p < 0.05), improved the histological scores and alleviated the fibrosis of pancreas samples (p < 0.05), as well as markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). The expression of cytokines TGF-β, IL-6 and TNF<alpha> in pancreas of DBTC group was also down-regulated by edaravone after treatment. Edaravone inhibited the activation of NF-κB and PSCs and exhibited protective effects on pancreatic tissue damage in CP.
  
  
  CONCLUSIONS
  This antioxidant may be a promising therapeutic intervention for human CP.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, Jiangsu Province, China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Zhou
authors.lastname: Lin-Li
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhu
authors.lastname: Wen-Tang
authors.forename: Duan-Min
authors.initials: DM
authors.lastname: Hu
authors.forename: Yun
authors.initials: Y
authors.lastname: Dong
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Li
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000077553:Edaravone; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline; D008297:Male; D009947:Organotin Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D050500:Pancreatitis, Chronic / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000983:Antipyrine; D016207:Cytokines; D000077553:Edaravone; D006909:Hydroxyproline; D009947:Organotin Compounds; D051996:Transcription Factor RelA; C498862:Acta2 protein, rat; C020735:dibutyldichlorotin