Danaparoid Sodium Attenuates the Effects of Heat Stress

Background. Heat stroke is a condition characterized by high body temperature that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such as danaparoid sodium (DA), inhibit various types of inflammation; however, the anti-inflammatory mechanism of action is not well understood. Given that heat stroke is a severe inflammatory response disease, we hypothesized that DA could inhibit inflammation from heat stress and prevent acute heat stroke. Materials and Methods. Male Wistar rats were given a bolus injection of saline or DA (50 U/kg body weight) into the tail vein just prior to heat stress (42 degrees C for 30 min). Markers of inflammation were then determined in serum and tissue samples. Results. In rats pretreated with DA, induction of cytokines (interleukin [IL]-1 beta, IL-6, and tumor necrosis factor [TNF]-alpha), nitric oxide (NO), and high mobility group box 1 (HMGB1) protein were reduced compared with saline-treated rats. Histologic changes observed in lung, liver, and small intestine tissue samples of saline-treated rats were attenuated in DA-treated rats. Moreover, DA pretreatment improved survival in our rat model of heat stress-induced acute inflammation. Conclusion. Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke. (C) 2011 Elsevier Inc. All rights reserved.