Antioxidant inhibits HMGB1 expression and reduces pancreas injury in rats with severe acute pancreatitis.

Abstract

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: Zhong Wei Zhang, Qi Yu Zhang, Meng Tao Zhou, Na Xin Liu, Tong Ke Chen, Ye Fan Zhu, Liang Wu
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 55 Issue 9 Pg. 2529-36 (Sep 2010) ISSN: 1573-2568 [Electronic] United States
• PMID: 19997973 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• HMGB1 Protein
• Hbp1 protein, rat
• NF-kappa B
• Pyrrolidines
• Thiocarbamates
• Tumor Necrosis Factor-alpha
• pyrrolidine dithiocarbamic acid
• Amylases

Topics

• Acute Disease
• Amylases (blood)
• Animals
• Antioxidants (pharmacology)
• Disease Models, Animal
• Down-Regulation
• HMGB1 Protein (metabolism)
• Male
• NF-kappa B (metabolism)
• Pancreas (drug effects, metabolism, pathology)
• Pancreatitis (drug therapy, metabolism, pathology)
• Pyrrolidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Severity of Illness Index
• Thiocarbamates (pharmacology)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)