Protective effects of edaravone on experimental chronic pancreatitis induced by dibutyltin dichloride in rats

Pancreatology. 2013 Mar-Apr;13(2):125-32. doi: 10.1016/j.pan.2013.01.007. Epub 2013 Feb 6.

Abstract

Background/aims: 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).

Result: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Chronic Disease
  • Cytokines / genetics
  • Cytokines / metabolism
  • Edaravone
  • Gene Expression Regulation / drug effects
  • Hydroxyproline
  • Male
  • Organotin Compounds / toxicity*
  • Oxidative Stress / drug effects
  • Pancreatitis, Chronic / chemically induced*
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism

Substances

  • Actins
  • Cytokines
  • Organotin Compounds
  • Transcription Factor RelA
  • smooth muscle actin, rat
  • dibutyldichlorotin
  • Hydroxyproline
  • Edaravone
  • Antipyrine