AIM： To investigate the effect of selective Cyclooxygenase-2 （COX-2） inhibitor 4-[5-（4-Chloro-phenyl）-3- （trifluoromethyl）- 1H-pyrazol- 1-yl] benzenesulfonamide （SC-236）, on the cholecystokinin （CCK）-octape...AIM： To investigate the effect of selective Cyclooxygenase-2 （COX-2） inhibitor 4-[5-（4-Chloro-phenyl）-3- （trifluoromethyl）- 1H-pyrazol- 1-yl] benzenesulfonamide （SC-236）, on the cholecystokinin （CCK）-octapeptideinduced 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-KB 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.展开更多
基金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
文摘AIM： To investigate the effect of selective Cyclooxygenase-2 （COX-2） inhibitor 4-[5-（4-Chloro-phenyl）-3- （trifluoromethyl）- 1H-pyrazol- 1-yl] benzenesulfonamide （SC-236）, on the cholecystokinin （CCK）-octapeptideinduced 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-KB 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.
