title: Effect of diazepam on severity of acute pancreatitis: possible involvement of peripheral benzodiazepine receptors.
abstract: 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  μ g), 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.
authors: Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 8146-73461, Iran.
authors: Alireza
authors: A
authors: Abed
authors: Mohsen
authors: M
authors: Minaiyan
authors: Azadeh
authors: A
authors: Safaei
authors: Diana
authors: D
authors: Taheri
references: Arch Toxicol Suppl. 1995;17:261-87
references: 7786163
references: Eur J Pharmacol. 2006 Nov 7;549(1-3):149-56
references: 16979620
references: Crit Care Med. 1999 Apr;27(4):749-55
references: 10321665
references: Cancer Res. 2002 Mar 1;62(5):1388-93
references: 11888910
references: Int J Prev Med. 2012 May;3(5):351-7
references: 22708031
references: Life Sci. 1988;43(25):2159-67
references: 2905410
references: Eur J Pharmacol. 2003 Oct 8;478(2-3):97-104
references: 14575793
references: Life Sci. 2006 May 22;78(26):3027-34
references: 16438989
references: Am J Gastroenterol. 1982 Jun;77(6):392-6
references: 7046428
references: Neurochem Int. 2002 May;40(6):475-86
references: 11850104
references: Ann N Y Acad Sci. 2003 Dec;1010:66-9
references: 15033695
references: J Invest Dermatol. 1982 Mar;78(3):206-9
references: 6276474
references: Pancreas. 2013 Jan;42(1):123-9
references: 22850623
references: Exp Cell Res. 1998 Jun 15;241(2):426-34
references: 9637784
references: Trends Pharmacol Sci. 2006 Aug;27(8):402-9
references: 16822554
references: Dig Dis Sci. 1997 Aug;42(8):1783-8
references: 9286248
references: Rev Gastroenterol Peru. 2012 Jul-Sep;32(3):241-50
references: 23128943
references: Neuroscience. 2008 Apr 22;153(1):338-48
references: 18367337
references: J Chin Med Assoc. 2004 Sep;67(9):442-6
references: 15617304
references: Eur J Pharmacol. 2000 Nov 17;408(2):199-211
references: 11080527
references: Am J Gastroenterol. 2012 Aug;107(8):1146-50
references: 22858994
references: Immunopharmacol Immunotoxicol. 2001 May;23(2):253-65
references: 11417852
references: Gastroenterology. 1998 Feb;114(2):372-81
references: 9453499
references: ISRN Gastroenterol. 2012;2012:141548
references: 23008778
references: Eur J Pharmacol. 2008 Sep 4;591(1-3):284-92
references: 18593574
references: Am J Gastroenterol. 1999 Jan;94(1):213-8
references: 9934758
references: Nutr Clin Pract. 2004 Feb;19(1):5-15
references: 16215091