BACKGROUND: Pathogenesis of severe acute pancreatitis is still unclear, which leads to a lack of proper treatment in severe acute pancreatitis therapeutic strategy. OBJECTIVE: To investigate the effect of treatment with antioxidant pyrrolidine dithiocarbamate on pancreas injury in rats with severe acute pancreatitis and its possible mechanism. METHODS: A total of 144 male Sprague-Dawley rats were randomly allocated into a sham operation group (n=48), a severe acute pancreatitis group (n=48), and a pyrrolidine dithiocarbamate-treated group (n=48). All the rats were killed at 1, 3, 6, 12, 24, and 48 h after operation. The pancreas histopathologies were observed and serum amylase levels were tested. Meanwhile, the nuclear factor-kappaB activation, tumor necrosis factor-alpha levels and high-mobility group box protein-1 expression levels in pancreatic tissue were studied. RESULTS: Animals receiving pyrrolidine dithiocarbamate had significantly improved pancreas histopathology and lower serum amylase levels (p<0.05). In the severe acute pancreatitis group, pancreas tumor necrosis factor-alpha levels reached a peak at 6 h after operation and afterwards rapidly declined to normal levels. However, high-mobility group box protein-1 levels in pancreatic tissue increased remarkably at the 12th hour, reached a peak at 24 h, and maintained up to 48 h post-severe acute pancreatitis. Compared to the severe acute pancreatitis group, the pancreas nuclear factor-kappaB activity, tumor necrosis factor-alpha, high-mobility group box protein-1 levels in the pyrrolidine dithiocarbamate-treated group all remarkably decreased (p<0.05). CONCLUSIONS: High-mobility group box protein-1 seems to act as a late cytokine mediator in the pathogenesis of severe acute pancreatitis. Pyrrolidine dithiocarbamate might inhibit the activation of nuclear factor-kappaB to blockade tumor necrosis factor-alpha, thereby indirectly suppressing the high-mobility group box protein-1 and reducing pancreatic tissue damage in rats with severe acute pancreatitis.
BACKGROUND: Pathogenesis of severe acute pancreatitis is still unclear, which leads to a lack of proper treatment in severe acute pancreatitis therapeutic strategy. OBJECTIVE: To investigate the effect of treatment with antioxidant pyrrolidine dithiocarbamate on pancreas injury in rats with severe acute pancreatitis and its possible mechanism. METHODS: A total of 144 male Sprague-Dawley rats were randomly allocated into a sham operation group (n=48), a severe acute pancreatitis group (n=48), and a pyrrolidine dithiocarbamate-treated group (n=48). All the rats were killed at 1, 3, 6, 12, 24, and 48 h after operation. The pancreas histopathologies were observed and serum amylase levels were tested. Meanwhile, the nuclear factor-kappaB activation, tumor necrosis factor-alpha levels and high-mobility group box protein-1 expression levels in pancreatic tissue were studied. RESULTS: Animals receiving pyrrolidine dithiocarbamate had significantly improved pancreas histopathology and lower serum amylase levels (p<0.05). In the severe acute pancreatitis group, pancreas tumor necrosis factor-alpha levels reached a peak at 6 h after operation and afterwards rapidly declined to normal levels. However, high-mobility group box protein-1 levels in pancreatic tissue increased remarkably at the 12th hour, reached a peak at 24 h, and maintained up to 48 h post-severe acute pancreatitis. Compared to the severe acute pancreatitis group, the pancreas nuclear factor-kappaB activity, tumor necrosis factor-alpha, high-mobility group box protein-1 levels in the pyrrolidine dithiocarbamate-treated group all remarkably decreased (p<0.05). CONCLUSIONS: High-mobility group box protein-1 seems to act as a late cytokine mediator in the pathogenesis of severe acute pancreatitis. Pyrrolidine dithiocarbamate might inhibit the activation of nuclear factor-kappaB to blockade tumor necrosis factor-alpha, thereby indirectly suppressing the high-mobility group box protein-1 and reducing pancreatic tissue damage in rats with severe acute pancreatitis.
Authors: Raquel Laveda; Juan Martinez; Carlos Munoz; Juan-Carlos Penalva; Jesus Saez; German Belda; Salvador Navarro; Faust Feu; Anton Mas; Jose-Ma Palazon; Jose Sanchez-Paya; Jose Such; Miguel Perez-Mateo Journal: World J Gastroenterol Date: 2005-09-14 Impact factor: 5.742
Authors: Carmen Fiuza; Michael Bustin; Shefali Talwar; Margaret Tropea; Eric Gerstenberger; James H Shelhamer; Anthony F Suffredini Journal: Blood Date: 2002-11-27 Impact factor: 22.113