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.


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 °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]-1β, IL-6, and tumor necrosis factor [TNF]-α), 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.


CONCLUSIONS
Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke.
Hagiwara
Satoshi
S
Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan. saku@med.oita-u.ac.jp
Iwasaka
Hideo
H
Shingu
Chihiro
C
Matsumoto
Shigekiyo
S
Uchida
Tomohisa
T
Nishida
Taichi
T
Mizunaga
Shouichi
S
Saikawa
Tetsunori
T
Noguchi
Takayuki
T
D000208:Acute Disease; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D003871:Dermatan Sulfate / Q000494:pharmacology*; D004195:Disease Models, Animal; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D024243:HMGB1 Protein / Q000097:blood; D006359:Heat Exhaustion / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018883:Heat Stroke / Q000517:prevention & control*; D006497:Heparan Sulfate / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate
D000925:Anticoagulants; D000990:Antithrombin III; D002809:Chondroitin Sulfates; D016207:Cytokines; D003871:Dermatan Sulfate; D005338:Fibrin Fibrinogen Degradation Products; D024243:HMGB1 Protein; D006497:Heparan Sulfate; D009566:Nitrates; D009569:Nitric Oxide; D009573:Nitrites; D010447:Peptide Hydrolases; C104200:Hbp1 protein, rat; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C035838:danaparoid