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High-dose antithrombin III prevents heat stroke by attenuating systemic inflammation in rats

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Abstract

Objective

Systemic inflammatory mediators, including the high mobility group box 1 (HMGB1) protein, play important roles in the development of various inflammatory conditions. Although anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, their anti-inflammatory mechanism of action is not well understood. Nevertheless, as heat stroke is a severe inflammatory response disease, we hypothesized that AT III would inhibit inflammation and prevent heat stress-induced acute heat stroke.

Methods

Male Wistar rats received a bolus injection of saline or 250 U of AT III per kg of body weight into the tail vein, followed by heat stress (exposure to 42°C for 30 min). Levels of cytokines (interleukin-1 β, interleukin-6, and TNF-α), NOx, and HMGB1 were measured in serum and tissue at regular intervals for 6 h after the heat stress induction.

Results

Levels of cytokines, NOx, and HMGB1 in serum decreased over time in AT III-treated rats. AT III pretreatment also reduced NOx levels during heat stress-induced inflammation. As a result, AT III pretreatment improved survival in a rat model of heat stress-induced acute inflammation.

Conclusions

Our data suggest that AT III pretreatment inhibited the secretion of cytokines, NOx, and HMGB1, and prevented heat stress-induced acute inflammation.

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Acknowledgments

The authors wish to thank Hiroaki Kawazato and Aiko Yasuda for helpful advice on hematoxylin and eosin staining.

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Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, 879-5593, Yufu City, Oita, Japan

    Satoshi Hagiwara, Hideo Iwasaka, Chihiro Shingu, Shigekiyo Matsumoto & Takayuki Noguchi

  2. Department of Molecular Pathology, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, 879-5593, Yufu City, Oita, Japan

    Tomohisa Uchida

Authors
  1. Satoshi Hagiwara
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  2. Hideo Iwasaka
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  3. Chihiro Shingu
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  4. Shigekiyo Matsumoto
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  5. Tomohisa Uchida
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  6. Takayuki Noguchi
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Corresponding author

Correspondence to Satoshi Hagiwara.

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Responsible Editor: L. Li.

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Hagiwara, S., Iwasaka, H., Shingu, C. et al. High-dose antithrombin III prevents heat stroke by attenuating systemic inflammation in rats. Inflamm. Res. 59, 511–518 (2010). https://doi.org/10.1007/s00011-009-0155-y

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  • DOI: https://doi.org/10.1007/s00011-009-0155-y

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