title: Thrombolytic effects in vivo of nattokinase in a carrageenan-induced rat model of thrombosis.
abstract: OBJECTIVE
  Nattokinase is a serine protease produced by Bacillus subtilis during the fermentation of the soybean product natto. The fibrinolytic activity and thrombolytic effects of nattokinase have been observed in vitro, but the effect in vivo has still to be researched. The objective of this study was to demonstrate the activity of nattokinase in vivo.
  
  
  METHODS
  To establish a rat model of thrombosis, κ-carrageenan was injected subcutaneously into the toes of Sprague-Dawley (SD) rats. Histological examination confirmed thrombosis. The rats were then treated with varying doses of nattokinase and the resulting thrombolysis was histologically assessed. ELISA was used to determine the levels of the fibrin/fibrinogen degradation products (FDPs) and D-dimer, which are sensitive indices of fibrinolytic activity. Vermis kinase, a known thrombolytic agent, was used as a positive control.
  
  
  RESULTS
  Biopsy results revealed partial thrombolysis in the tail vessels of the rats treated with nattokinase or vermis kinase. FDP and D-dimer levels were higher in rats treated with high-dose nattokinase than in those treated with saline. No difference in FDP or D-dimer levels was observed between rats treated with high-dose nattokinase and those treated with vermis kinase.
  
  
  CONCLUSIONS
  Both the histological and physiological evidence from this study indicate that nattokinase exerts thrombolytic effects in vivo.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Du
authors.forename: Xiulin
authors.initials: X
authors.lastname: Yang
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Dong-Hong
authors.initials: DH
authors.lastname: Lin
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D010450:Endopeptidases / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013381:Subtilisins / Q000494:pharmacology / Q000627:therapeutic use*; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; C036309:fibrin fragment D; D002351:Carrageenan; D010450:Endopeptidases; D013381:Subtilisins; C083421:lumbrokinase; C053771:nattokinase