In vivo Evaluation Method of the Effect of Nattokinase on Carrageenan-Induced Tail Thrombosis in a Rat Model

Kamiya, Seitaro; Hagimori, Masayori; Ogasawara, Masayoshi; Arakawa, Masayuki

doi:10.1159/000321518

Cited by 43 publications

(47 citation statements)

References 51 publications

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“…This model has been extensively used to test the effect of several anti-thrombus and thrombolytic agents clinically (Yuan et al 2012;Yan et al 2009;Kamiya et al 2010;Simkhada et al 2012). Carrageenan is a linear sulphur containing polysaccharide, extracted from edible red seaweeds.…”

Section: Carrageenan-induced Thrombosis Modelmentioning

confidence: 99%

Methods available to assess therapeutic potential of fibrinolytic enzymes of microbial origin: a review

2018

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Fibrinolytic enzymes are agents administered for the treatment of myocardial infarctions, strokes, cardiac and respiratory failure. Although several microorganisms are known to produce these fibrinolytic enzymes, only a few of such enzymes, along with the age-old oral anticoagulants, have been employed in the clinical and therapeutic applications in humans. The use of these agents is associated with drawbacks such as allergic reactions and bleeding complications; therefore, it necessitates frequent monitoring of drug levels in the blood. Due to this, there is an impetus on the current effort to identify newer potential candidates from the novel microbial sources which show longer half-life, higher fibrin specificity, higher therapeutic index and lesser allergic reactions. Various methods are available for the preliminary evaluation of a potential drug candidate for the therapeutic use. Choosing the right combination of in vitro and in vivo methods would give crucial insight on the therapeutic potential of the chosen test compound. This article discusses various assay techniques, in vitro trails and in vivo models available, to help researchers in choosing right biological methods and its combinations to evaluate efficacy of potential drug candidate.

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Section: Carrageenan-induced Thrombosis Modelmentioning

confidence: 99%

Methods available to assess therapeutic potential of fibrinolytic enzymes of microbial origin: a review

2018

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“…Kamiya et al [10 ]suggested that thrombosis in the tail artery of rats could be used to evaluate the thrombolytic effect of nattokinase in vivo. Using this rat model, we aimed to determine whether nattokinase is thrombolytically active in vivo.…”

Section: Introductionmentioning

confidence: 99%

Thrombolytic Effects in vivo of Nattokinase in a Carrageenan-Induced Rat Model of Thrombosis

Yang

et al. 2014

Acta Haematol

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Background/Aims: 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.

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“…Among these enzymes, NK is assumed an interesting one. This considerable interest is due to the direct fibrinolytic activity of this enzyme, both in vitro and in vivo (Fujita et al 1995a;Kamiya et al 2010;Xu et al 2014). It not only degrades fibrin directly but also increases the release of tissue plasminogen activator from cells to degrade fibrin (Yatagai et al 2008).…”

Section: Fibrinolytic and Antithrombotic Activitymentioning

confidence: 99%

Nattokinase: production and application

Dabbagh

Negahdaripour

Berenjian

et al. 2014

Appl Microbiol Biotechnol

105

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Nattokinase (NK, also known as subtilisin NAT) (EC 3.4.21.62) is one of the most considerable extracellular enzymes produced by Bacillus subtilis natto. The main interest about this enzyme is due to its direct fibrinolytic activity. Being stable enough in the gastrointestinal tract makes this enzyme a useful agent for the oral thrombolytic therapy. Thus, NK is regarded as a valuable dietary supplement or nutraceutical. Proven safety and ease of mass production are other advantages of this enzyme. In addition to these valuable advantages, there are other applications attributed to NK including treatment of hypertension, Alzheimer's disease, and vitreoretinal disorders. This review tends to bring a brief description about this valuable enzyme and summarizes the various biotechnological approaches used in its production, recovery, and purification. Some of the most important applications of NK, as well as its future prospects, are also discussed.

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In vivo Evaluation Method of the Effect of Nattokinase on Carrageenan-Induced Tail Thrombosis in a Rat Model

Cited by 43 publications

References 51 publications

Methods available to assess therapeutic potential of fibrinolytic enzymes of microbial origin: a review

Methods available to assess therapeutic potential of fibrinolytic enzymes of microbial origin: a review

Thrombolytic Effects in vivo of Nattokinase in a Carrageenan-Induced Rat Model of Thrombosis

Nattokinase: production and application

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