title: Saralasin, a nonspecific angiotensin II receptor antagonist, attenuates oxidative stress and tissue injury in cerulein-induced acute pancreatitis.
abstract: BACKGROUND
  Free radical-mediated pancreatic injury is believed to play a key role in the pathogenesis of acute pancreatitis. Most of these studies have focused on the effects of antioxidant enzymes and free radical scavengers on improving the pancreatic injury. Recent findings showed that cerulein-induced acute pancreatitis was associated with an upregulation of a local pancreatic renin-angiotensin system in the pancreas. In the current study we hypothesized that inhibition of this renin-angiotensin system by saralasin, a nonspecific antagonist for angiotensin II receptor, could attenuate the severity of cerulein-induced pancreatitis.
  
  
  METHODS
  The effects of saralasin on oxidative stress and tissue injury in cerulein-induced pancreatitis were assessed by histopathologic analysis and on the basis of biochemical changes of plasma alpha-amylase level, pancreatic glutathione status, oxidative modification of protein, and lipid peroxidation.
  
  
  RESULTS
  Data from the biochemical analysis showed that intravenous injections of saralasin at doses of 10 microg/kg to 50 microg/kg 30 minutes before the induction of acute pancreatitis significantly reduced pancreatic injury, as indicated by a decrease in plasma alpha-amylase activity in comparison with the cerulein-treated control. The effect of saralasin was further manifested by significant suppressions of glutathione depletion, oxidative modification of proteins, and lipid peroxidation in cerulein-treated rat pancreas. Histopathologic examination findings were in agreement with the biochemical data.
  
  
  CONCLUSIONS
  These data suggest that prophylactic administration of saralasin can ameliorate the oxidative stress and tissue injury in cerulein-induced pancreatitis. Such a protective effect may provide new insight into the potential value of angiotensin II receptor antagonists in the clinical therapy for acute pancreatitis.
authors.affiliation: Department of Physiology and School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Siu Po
authors.initials: SP
authors.lastname: Ip
authors.forename: Siu Wai
authors.initials: SW
authors.lastname: Tsang
authors.forename: Tung Po
authors.initials: TP
authors.lastname: Wong
authors.forename: Chun Tao
authors.initials: CT
authors.lastname: Che
authors.forename: Po Sing
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000208:Acute Disease; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002108:Ceruletide; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012504:Saralasin / Q000627:therapeutic use*; D000516:alpha-Amylases / Q000097:blood
chemical_list: D057911:Angiotensin Receptor Antagonists; D002108:Ceruletide; D000516:alpha-Amylases; D005978:Glutathione; D012504:Saralasin