%0 Journal Article
%T Effect of Diazepam on Severity of Acute Pancreatitis: Possible Involvement of Peripheral Benzodiazepine Receptors
%A Alireza Abed
%A Mohsen Minaiyan
%A Azadeh Safaei
%A Diana Taheri
%J ISRN Gastroenterology
%D 2013
%R 10.1155/2013/484128
%X Acute pancreatitis is a lethal inflammatory condition of pancreas with high mortality rate. There is a pressing need for research to explore active agents and novel mechanisms involving in the treatment of pancreatitis. Clinical studies have shown after the initial acinar cell injury plasma levels of pro-inflammatory cytokines are elevated in patients with acute pancreatitis and the degree of cytokine elevation correlates with disease severity. Diazepam may decrease interleukin release from macrophages, suppress neutrophil activities, and exhibit anti-inflammatory effects. So it is expected that in vivo pretreatment of acute pancreatitis with different doses of diazepam can attenuate its severity. Thus, we evaluated the effects of diazepam, intraperitoneally (5, 10, and 20£¿mg/kg i.p.), intracerebroventricularly (ICV 10£¿¦Ìg), and concurrently with flumazenil (1£¿mg/kg) on cerulein-induced acute pancreatitis in mice. Interestingly, the pretreatment with diazepam (5£¿mg/kg i.p.) reduced significantly the inflammatory response of acute pancreatitis by ameliorating pancreatic edema, amylase and lipase serum levels, myeloperoxidase activity, pancreatic TNF-alpha, and pathological alteration compared to control group. Diazepam i.c.v. was ineffective, suggesting that central benzodiazepine receptors have no significant role in this property. These results demonstrate that pretreatment with diazepam exhibits anti-inflammatory property in cerulein-induced acute pancreatitis possibly through peripheral benzodiazepine receptors. 1. Introduction Acute pancreatitis is a potentially lethal disorder which is characterized by pancreatic tissue inflammation and elevation in serum level of digestive enzymes without specific therapy [1]. The morbidity and mortality associated with pancreatitis are secondary to circulatory shock, cardiac insufficiency, respiratory distress, and hepatic failure [2]. The main causes of pancreatitis are alcohol beverages drinking and biliary tract disorders which are the most important etiologies of pancreatitis [3]. The early pathophysiology of the acute pancreatitis has not been well understood [4]. But some clinical studies have shown that after an initial acinar cell injury, proinflammatory cytokines such as interleukin-(IL-) 1, tumor necrosis factor, IL-6, and IL-8 are increased in the serum of patients with acute pancreatitis, and the degree of cytokine elevation correlates with disease severity [5]. Cytokines are responsible for both the local and the systemic inflammatory response and organ dysfunction in acute pancreatitis [6]. Also, a
%U http://www.hindawi.com/journals/isrn.gastroenterology/2013/484128/