title: Danaparoid sodium attenuates the increase in inflammatory cytokines and preserves organ function in endotoxemic rats.
abstract: BACKGROUND
  Anticoagulant therapy attracts much attention for the treatment of severe sepsis since recent studies have revealed that some anticoagulants have the ability to regulate the inflammatory response. The purpose of this study was to examine whether danaparoid sodium (DA) is effective for the treatment of organ dysfunction in sepsis.
  
  
  METHODS
  Sixty-four Wistar rats were intravenously injected with 5.0 mg/kg of lipopolysaccharide (LPS) and then divided into two groups: the DA group and the control group (n = 32 each). The DA group was injected intravenously with 400 U/kg of DA immediately after LPS injection, whereas the control group received saline. Blood samples were drawn at 1, 6, 12, and 24 hours after LPS injection, and organ damage markers and coagulation markers were measured. In the other series, 10 rats treated with LPS were divided into DA and control groups (n = 5 each). Blood samples were collected at 1, 3, and 6 hours after LPS injection and served for the cytokine measurements.
  
  
  RESULTS
  The elevation of the organ damage markers, such as alanine aminotransferase and lactate dehydrogenase, was significantly suppressed in the DA group. Coagulation markers, such as AT activity and fibrinogen levels, were maintained better in the DA group at 6 hours. The elevation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 was significantly suppressed in the DA group. On the other hand, there was no significant difference in anti-inflammatory cytokines such as IL-4 and IL-10.
  
  
  CONCLUSIONS
  DA preserves the organ dysfunction in LPS-challenged rats. Although the mechanism is not fully elucidated, not only the improvement of coagulation disorder but also the regulation of circulating levels of proinflammatory cytokines may play a role in the mechanism.
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University, Tokyo, Japan, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. toshiiba@cf6.so-net.ne.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Iba
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
mesh_terms: D000818:Animals; D002809:Chondroitin Sulfates / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D003871:Dermatan Sulfate / Q000494:pharmacology / Q000627:therapeutic use*; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced / Q000517:prevention & control; D006497:Heparan Sulfate / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D008070:Lipopolysaccharides / Q000633:toxicity; D009102:Multiple Organ Failure / Q000097:blood* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002809:Chondroitin Sulfates; D016207:Cytokines; D003871:Dermatan Sulfate; D006497:Heparan Sulfate; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C035838:danaparoid