Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 28, 2007; 13(16): 2298-2304
Published online Apr 28, 2007. doi: 10.3748/wjg.v13.i16.2298
Selective cyclooxygenase-2 inhibitor ameliorates cholecystokinin-octapeptide-induced acute pancreatitis in rats
Sang-Wan Seo, Won-Seok Jung, Tai-Guang Piao, Seung-Heon Hong, Ki-Jung Yun, Rae-Kil Park, Min-Kyo Shin, Ho-Joon Song, Sung-Joo Park
Sang-Wan Seo, Won-Seok Jung, Min-Kyo Shin, Ho-Joon Song, Sung-Joo Park, Tai-guang Piao, Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea
Sang-Wan Seo, Won-Seok Jung, Seung-Heon Hong, Department of oriental Pharmacy, College of Oriental Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea
Ki-Jung Yun, Department of Pathology, College of Medicine, Wonkwng University, Iksna, Jeonbuk, South Korea
Rae-Kil Park, Vestibulocochlear Research Center & Department of Microbiology, College of Medicine, Wonkwng University, Iksna, Jeonbuk, South Korea
Author contributions: All authors contributed equally to the work.
Supported by the Ministry of Science & Technology/Korea Science & Engineering Foundation through the Vestibuloco-chlear Research Center at Wonkwang University, No. R13-2002- 055-00000-0
Correspondence to: Sung-Joo Park, Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea. parksj08@wku.ac.kr
Telephone: +82-63-8506450 Fax: +82-63-8562283
Received: December 18, 2006
Revised: December 29, 2006
Accepted: February 15, 2007
Published online: April 28, 2007
Abstract

AIM: To investigate the effect of selective Cycloo-xygenase-2 (COX-2) inhibitor 4-[5-(4-Chloro-phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-236), on the cholecystokinin (CCK)-octapeptide-induced acute pancreatitis (AP) in rats.

METHODS: Wistar rat weighing 240 g to 260 g were divided into three groups. (1) Normal DMSO treated group, (2) SC-236 at 4 mg/kg treated group; SC-236 systemically administered via the intravenous (i.v.) catheter, followed by 75 μg/kg CCK octapeptide subcutaneously three times, after 1, 3 and 5 h. This whole procedure was repeated for 5 d. (3) Dimethyl sulfoxide (DMSO) treated group: an identical protocol was used in this group as in the SC-236 cohort (see 2. above). Repeated CCK octapeptide treatment resulted in a typical experimentally induced pancreatitis in the Wistar rats.

RESULTS: SC-236 improved the severity of CCK-octapeptide-induced AP as measured by laboratory criteria [the pancreatic weight/body weight (p.w/b.w) ratio, the level of serum amylase and lipase]. The SC-236 treated group showed minimal histologic evidence of pancreatitis and a significant reduction in myeloperoxidase activity. SC-236 also increased heat shock protein (HSP)-60 and HSP72 compared with the DMSO-treated group in the CCK-octapeptide-induced AP and also reduced the pancreatic levels of COX-2. Furthermore, SC-236 reduced proinflammatory cytokine synthesis and inhibited NF-κB activation compared with the DMSO-treated group in the CCK-octapeptide-induced AP.

CONCLUSION: Our results suggested that COX-2 plays pivotal role in the development of AP and COX-2 inhibitors may play a beneficial role in preventing AP.

Keywords: SC-236; Acute pancreatitis; Cholecystokinin octapeptide