Propiedades anticoagulantes de una fracción polisacárida de alto peso molecular (1000RS) del ascidian Microcosmus exasperatus

Diana C. Restrepo-Espinosa, Juliana María Motta, Felipe Castro O. de B. Teixeira, Yony Román, Jhonny Colorado-Ríos, Mauro S. G. Pavão, Alejandro Martínez

Resumen


Objetivos: El efecto anticoagulante y la citotoxicidad de una fracción de polisacáridos de alto peso molecular (1000RS), obtenida de la túnica de la ascidia Microcosmus exasperatus, fueron evaluados.

Métodos: La actividad anticoagulante de 1000RS fue evaluada mediante los ensayos de tiempo de tromboplastina parcial activado (TTPa), tiempo de trombina (TT), tiempo de protrombina (TP), anti factor Xa y anticoagulante lúpico (dRVVT). La citotoxicidad sobre las células hematopoyéticas murinas fue evaluada usando el método del MTT.

Resultados: Esta fracción rica en galactosa mostró ser un anticoagulante potencial debido a su efecto inhibidor de la vía intrínseca de la coagulación. Así mismo, las dosis anticoagulantes de esta fracción no afectan la viabilidad celular, lo cual ratifica su potencial como agente terapéutico.

Conclusión: El efecto anticoagulante in vitro de 1000RS ocurre a dosis inocuas, sin embargo, éste debe ser evaluado en modelos in vivo, así como su citotoxicidad sobre células humanas normales.


Palabras clave


Anticoagulantes; ascidia; Microcosmus exasperatus; polisacáridos

Citas


Paulo Mourão. Perspective on the Use of Sulfated Polysaccharides from Marine Organisms as a Source of New Antithrombotic Drugs. Mar Drugs 2015;13(5):2770-84.

Yang J, Du Y, Huang R, Wan Y, Wen Y. The structure–anticoagulant activity relationships of sulfated lacquer polysaccharide. Int J Biol Macromol 2005;36(1):9-15.

Cassinelli G, Naggi A. Old and new applications of non-anticoagulant heparin. Int J Cardiol 2016;212:S14–S21.

Ling L, Camilleri ET, Helledie T, Samsonraj RM, Titmarsh DM, Chua RJ, et al. Effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells. Gene 2016;576(1 Pt 2):292.

Page C. Heparin and Related Drugs: Beyond Anticoagulant Activity. Int Sch Res Not 2013;2013:e910743.

Zhang Z, Till S, Jiang C, Knappe S, Reutterer S, Scheiflinger F, et al. Structure-activity relationship of the pro- and anticoagulant effects of Fucus vesiculosus fucoidan. Thromb Haemost 2014;111(3):429-37.

Kozlowski EO, Lima PC, Vicente CP, Lotufo T, Bao X, Sugahara K, et al. Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [→4IdoA(2-Sulfate)β-1→3GalNAc(4-Sulfate)β-1→] motifs in dermatan sulfate on heparin cofactor II activity. BMC Biochem 2011;12:29.

Lee D-H, Hong J-H. Immune-Enhancing Effects of Polysaccharides Isolated from Ascidian (Halocynthia roretzi) Tunic. ResearchGate 2015;44(5):673-80.

Núñez-Pons L, Carbone M, Vázquez J, Rodríguez J, Nieto RM, Varela MM, et al. Natural Products from Antarctic Colonial Ascidians of the Genera Aplidium and Synoicum: Variability and Defensive Role. Mar Drugs 2012;10(8):1741-64.

Sarhadizadeh N, Afkhami M, Ehsanpour M. Evaluation of antibacterial, antifungal and cytotoxic agents of Ascidian Phallusia nigra (Savigny, 1816) from Persian Gulf. Eur J Exp Biol 2014;4(1):250–253.

Pereira MS, Melo FR, Mourao PAS. Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans? Glycobiology 2002;12(10):573-80.

Santos JA, Mulloy B, Mourao PAS. Structural diversity among sulfated alpha-L-galactans from ascidians (tunicates). Studies on the species Ciona intestinalis and Herdmania monus. Eur J Biochem 1992;204(2):669-77.

Pomin VH. Phylogeny, structure, function, biosynthesis and evolution of sulfated galactose-containing glycans. Int J Biol Macromol 2016;84:372-9.

Gomes AM, Kozlowski EO, Pomin VH, de Barros CM, Zaganeli JL, Pavão MSG. Unique extracellular matrix heparan sulfate from the bivalve Nodipecten nodosus (Linnaeus, 1758) safely inhibits arterial thrombosis after photochemically induced endothelial lesion. J Biol Chem 2010;285(10):7312-23.

do Nascimento GE, Corso CR, de Paula Werner MF, Baggio CH, Iacomini M, Cordeiro LMC. Structure of an arabinogalactan from the edible tropical fruit tamarillo (Solanum

betaceum) and its antinociceptive activity. Carbohydr Polym 2015;116:300-6.

Stockert JC, Blázquez-Castro A, Cañete M, Horobin RW, Villanueva Á. MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets. Acta Histochem 2012;114(8):785-96.

Riss TL, Moravec RA, Niles AL, Benink HA, Worzella TJ, Minor L. Cell Viability Assays [Internet]. Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2015.

Pomin VH, Mourão PA de S. Structure versus anticoagulant and antithrombotic actions of marine sulfated polysaccharides. Rev Bras Farmacogn 2012;22(4):921-8.

Gailani D, Renné T. Intrinsic Pathway of Coagulation and Arterial Thrombosis. Arterioscler Thromb Vasc Biol 2007;27(12):2507-13.

Björk I, Lindahl U. Mechanism of the anticoagulant action of heparin. Mol Cell Biochem 1982;48(3):161-82.

Faham S, Hileman R, Fromm J, Lindhardt R, Rees D. Heparin structure and interactions with basic fibroblast growth factor. Science 1996;271(5252):1116-20.

Vasconcelos AFD, Dekker RFH, Barbosa AM, Carbonero ER, Silveira JLM, Glauser B, et al. Sulfonation and anticoagulant activity of fungal exocellular β-(1→6)-d-glucan (lasiodiplodan). Carbohydr Polym 2013;92(2):1908-14.

Hood JL, Eby CS. Evaluation of a Prolonged Prothrombin Time. Clin Chem 2008;54(4):765-8.

Hirsh J, Anand SS, Halperin JL, Fuster V. Mechanism of Action and Pharmacology of Unfractionated Heparin. Arterioscler Thromb Vasc Biol 2001;21(7):1094-6.

Newall F. Anti-factor Xa (anti-Xa) assay. Methods Mol Biol 2013;992:265-72.

Cabral K, Ansell J. The role of factor Xa inhibitors in venous thromboembolism treatment. - PubMed - NCBI. Vasc Health Risk Manag 2015;11:117-23.

Jacquot C, Wool GD, Kogan SC. Dilute Russell Viper Venom Time Interpretation and Clinical Correlation: A Two-Year Retrospective Institutional Review. Blood 2016 [cited 2017 mar 26];128. Available from: http://www.bloodjournal.org/content/128/22/2609?sso-checked=true

Moore GW, Rangarajan S, Savidge GF. The Activated Seven Lupus Anticoagulant Assay Detects Clinically Significant Antibodies. Clin Appl Thromb 2008;14(3):332-7.

Radhakrishnan K. The dilute Russell’s viper venom time. Methods Mol Biol 2013;992:341-8.

Jayakumar R, Nwe N, Tokura S, Tamura H. Sulfated chitin and chitosan as novel biomaterials. Int J Biol Macromol 2007;40(3):175-81.

Schoen P, Lindhout T, Hemker H. Ratios of anti-factor Xa to antithrombin activities of heparins as determined in recalcified human plasma. - PubMed - NCBI. Br J Haematol 1992;81:255-62.

Bhakuni T, Ali MF, Ahmad I, Bano S, Ansari S, Jairajpuri MA. Role of heparin and non heparin binding serpins in coagulation and angiogenesis: A complex interplay. Arch Biochem Biophys 2016;604:128-42.

Law RH, Zhang Q, McGowan S, Buckle AM, Silverman GA, Wong W, et al. An overview of the serpin superfamily. Genome Biol 2006;7(5):216.


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