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Antioxidant Inhibits HMGB1 Expression and Reduces Pancreas Injury in Rats with Severe Acute Pancreatitis

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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-κB activation, tumor necrosis factor-α 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-α 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-κB activity, tumor necrosis factor-α, 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-κB to blockade tumor necrosis factor-α, thereby indirectly suppressing the high-mobility group box protein-1 and reducing pancreatic tissue damage in rats with severe acute pancreatitis.

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Authors and Affiliations

  1. Department of General Surgery, Shaoxing Second Hospital, 123 Yan’an Road, 312000, Shaoxing, Zhejiang province, China

    Zhong Wei Zhang

  2. Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical College, 325000, Wenzhou, Zhejiang province, China

    Qi Yu Zhang, Meng Tao Zhou, Na **n Liu & Ye Fan Zhu

  3. Department of Animal Research Center, Wenzhou Medical College, 325000, Wenzhou, Zhejiang province, China

    Tong Ke Chen

  4. Department of Pathology, The First Affiliated Hospital of Wenzhou Medical College, 325000, Wenzhou, Zhejiang province, China

    Liang Wu

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  1. Zhong Wei Zhang
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  4. Na **n Liu
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Correspondence to Zhong Wei Zhang.

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Zhang, Z.W., Zhang, Q.Y., Zhou, M.T. et al. Antioxidant Inhibits HMGB1 Expression and Reduces Pancreas Injury in Rats with Severe Acute Pancreatitis. Dig Dis Sci 55, 2529–2536 (2010). https://doi.org/10.1007/s10620-009-1073-0

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  • DOI: https://doi.org/10.1007/s10620-009-1073-0

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