Abstract
A novel proteinase fraction, SPP-501, was purified from the earthworm, Eisenia andrei, and its antithrombotic effects compared with those of urokinase and t-PA (tissue type-plasminogen activator) in a thrombosis model, induced by the insertion of a stainless wire coil into the inferior vena cava. SPP-501, urokinase and t-PA were administrated once a day for 14 days. On the oral administration of SPP-501, as well as urokinase and t-PA, the thrombus weight was dramatically decreased. The euglobulin lysis time (ELT) was also shortened by SPP-501, but urokinase and t-PA failed to dissolve the euglobulin clot. Conversely, urokinase and t-PA produced detectable fibrinogen/fibrin degradation products (FDP), but SPP-501 did not. Thrombin induced platelet aggregation was desensitized in the SPP-501 treatment groups. With a high dose of SPP-501 (45 mg/kg), the APTT (activated partial thromboplastin time) was prolonged. These results suggest that SPP-501 shows both antithrombotic and fibrinolytic activities when orally administered.
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References
Becker, R. C., Seminars in thrombosis, thrombolysis and vascular biology. 4. Fibrinolysis.Cardiology, 79, 188–210 (1991).
Chang, C. S., Lee, C. K., Shin, J. S., Cho, I. H., and Suh, J. J., Fibrinolytic and anticoagulant effects of earthworm,Lumbricus rubellus, extracts.Yakhak Hoeji, 39, 666–670 (1995).
Cho, I. H., Choi, E. S., Lim, H. G., and Lee, H. H., Purification and characterization of six fibrinolytic serine-proteases from earthwormLumbricus rubellus.J. Biochem. Mol. Biol., 37, 199–205 (2004).
Cho, I. H., Lee, C. K., Lim, H. G., and Lee, H. H., Pharmaceutical characteristics of koreanLumbricus rubellus lumbrokinase.Korean J. Biotechnol. Bioeng., 19, 274–283 (2004).
Copley A. L., Niewiarowski, S., and Marechal, J., A micromethod of euglobulin fibrinolysis in plasma of human subjects and small laboratory animals.J. Lab. Clin. Med., 53, 468–473 (1959).
Fan, Q., Wu, C., Li, L., Fan, R., Wu, C., Hou, Q., and He, R., Some features of intestinal absorption of intact fibrinolytic enzyme III-1 fromLumbricus rubellus.Biochim. Biophys. Acta., 1526, 286–292 (2001).
Hahn, B. S., Jo, Y. Y., Yang, K. Y., Wu, S. J., Pyo, M. K., Yun-Choi, H. S., and Kim, Y. S., Evaluation of thein vivo antithrombotic, anticoagulant and fibrinolitic activities ofLumbricus rubellus earthworm powder.Arch. Pharm. Res., 20, 1–23 (1997).
Hrzenjak, T., Popovic, M., Bozic, T., Grdisa, M., Kobrehel, D., and Tiska-Rudman, L., Fibrinolytic and anticoagulative activities from the earthwormEisenia foetida.Comp. Biochem. Physiol., 119, 825–832 (1998).
Hwang, C. M., Kim, D. I., Kim, J. E., Huh, S. H., Min, B. G., Park, J. H., Han, J. S., Lee, B. B., Kim, Y. I., Ryu, E. S., and Kim, J. W.,In vivo evaluation of lumbrokinase, a fibrinolytic enzyme extracted fromLumbricus rubellus, in a prosthetic vascular graft.J. Cardiovasc. Surg., 43, 891–894 (2002).
Jin, L., Jin, H., Zhang, G., and Xu, G., Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase.Clin. Hemorheol. Microcirc., 23, 213–218 (2000).
Kim, Y. S., Pyo, M. K., Park, K. M., Hahn, B. S., Yang, K. Y., and Yun-Choi, H. S., Dose dependency of earthworm powder on antithrombotic and fibrinolitic effects.Arch. Pharm. Res., 21,374–377(1998).
Kumada, T., Ishihara, M., Ogawa, H., Abiko, Y., Experimental model of venous thrombosis in rats and effect of some agents.Thrombosis Res., 18,189–203 (1980).
Mihara, H., Sumi, H., Akazawa, K., Yoneds, T., Mizumodo, H., and Maruyama, M., A novel fibrinolytic enzyme extracted from the earthwormLumbricus rubellus.Jap. J. Physiol., 41, 461–472(1991).
Nakajima, N., Mihara, H., and Sumi, H., Characterization of potent fibrinolytic enzymes in earthworm:Lumbricus rubellus.Biotech. Biochem., 57, 1726–1730 (1993).
Park, Y. D., Ryu, E. S., Kim, H. J., Jeong, J. S., Kim, J. H., Jeon, S.M., Jo, Y. H., Kim, W. K., and Min, B. G., Characterization of antithrombotic activity of Lumbrikinase-immobilized polyurethane valves in the total artificial heart.Artif. Organs, 23, 210–214(1999).
Radomski, M. and Moncada, S., An improved method for washing of human platelets with prostacyclin.Thromb. Res., 30, 383–389 (1983).
Robbins, K. C. and Summaria, L., Plasminogen and plasmin.Methods Enzymol., 45, 257–273 (1976).
Ryu, G. H., Park, S. Y., Han, D. K., Kim, Y. H., and Min, B. G., Antithrombotic Activity of a Lumbrikinase immobilized polyurethane surface.ASAIO J., 39, M314-M318 (1993)
Ryu, G. H., Park, S. Y., Kim, M.R., Han, D. K., Kim, Y. H., and Min, B. G., Antithrombogenicity of Lumbrikinase-immobilized Polyurethane.J. Biomedi. Mater. Res., 28, 1069–1077 (1994).
Ryu, G. H., Han, D. K., Park, S. Y., Kim, M. R., Kim, Y. H., and Min, B. G., Surface characteristics and properties of Lumbrikinase-immobilized polyurethane.J. Biomedi. Mater. Res., 29, 403–409 (1995).
Sawdey, M. S. and Loskutoff, D. J., Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta.J. Clin. Invest., 88, 1346–1353 (1991).
Sumi, H., Sasaki, K., Toki, N., and Robbins, K. C., Oral administration of urokinase.Thromb. Res., 20, 711–714 (1980).
Sumi, H., Hamada, H., Nakanishi, K., and Hiratani, H., Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.Acta Haematol., 84, 139–143 (1990).
Vassalli, J. D., Sappino, A. P., and Belin, D., The plasminogen activator/plasmin system.J. Clin. Invest., 88, 1067–1072 (1991).
Wu, C., Li, L., Zhao, J., Fan, Q., Tian, W. X. and He, R. Q., Effect of α2-M on earthworm fibrinolytic enzyme III-1 fromLumbricus rubellus.Int. J. Biol. Macromol., 31, 71–77 (2002).
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Lee, C.K., Shin, J.S., Kim, B.S. et al. Antithrombotic effects by oral administration of novel proteinase fraction from earthworm eisenia andrei on venous thrombosis model in rats. Arch Pharm Res 30, 475–480 (2007). https://doi.org/10.1007/BF02980222
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DOI: https://doi.org/10.1007/BF02980222