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Comparative anti-thrombotic activity and haemorrhagic adverse effect of nattokinase and tissue-type plasminogen activator

Food Science and Biotechnology 2019년 28권 5호 p.1535 ~ 1542
 ( Guo Haiyu ) - Chungbuk National University College of Veterinary Medicine

 ( Ban Young-Hwan ) - Chungbuk National University College of Veterinary Medicine
 ( Cha Ye-Seul ) - Chungbuk National University College of Veterinary Medicine
 ( An Eun-Suk ) - Chungbuk National University College of Veterinary Medicine
 ( Choi Ji-Eun ) - Chungbuk National University College of Veterinary Medicine
 ( Seo Da-Woom ) - Chungbuk National University College of Veterinary Medicine
 ( Park Dong-Sun ) - Korea National University of Education Department of Biology Education
 ( Choi Ehn-Kyoung ) - Chungbuk National University College of Veterinary Medicine
 ( Kim Yun-Bae ) - Chungbuk National University College of Veterinary Medicine

Abstract


Anti-thrombotic activity and safety of nattokinase, an enzyme produced by Bacillus subtilis during soybean fermentation, were investigated in comparison with tissue-type plasminogen activator (t-PA). Carotid arterial thrombosis was produced with a FeCl3-soaked paper, followed by intravenous injection of nattokinase or t-PA. Nattokinase and t-PA delayed thrombus formation, near-fully (>?90%) inhibiting at 75 and 8.5 mg/kg, respectively. As adverse effects, t-PA induced petechial haemorrhage at 10 mg/kg in the lungs and thymus, and extensive bleeding at 20 mg/kg. Nattokinase also caused pulmonary haemorrhage from 300 mg/kg. Collectively, the standard safety margins (SSMs) for t-PA and nattokinase were calculated to be 1.2 and 4.0, respectively. Combinational treatment with dexamethasone (2 mg/kg) increased the efficacy and safety of t-PA and nattokinase, widening their SSMs to 2.4 and 8.0, respectively. The results indicate that nattokinase delayed thrombus formation and dissolved thrombi, and that nattokinase could be a good candidate anti-thrombotic agent with relatively-low haemorrhagic risk.

키워드

Nattokinase; Tissue-type plasminogen activator; Dexamethasone; Thrombosis; Haemorrhage
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