High-dose antithrombin III prevents heat stroke by attenuating systemic inflammation in rats
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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.
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.
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.
Our data suggest that AT III pretreatment inhibited the secretion of cytokines, NOx, and HMGB1, and prevented heat stress-induced acute inflammation.
KeywordsInflammation Cytokine Nitric oxide Anticoagulant Heat stress
The authors wish to thank Hiroaki Kawazato and Aiko Yasuda for helpful advice on hematoxylin and eosin staining.
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