Clinical cardiac alterations and hemostatic toxicities caused by scorpion (Tityus discrepans) venom and its purified fractions on zebrafish (Danio rerio) larvae.
Alteraciones clínicas cardiológicas y toxicidades hemostáticas causadas por el veneno del escorpión (Tityus discrepans) y sus fracciones purificadas en las larvas del pez cebra (Danio rerio).
Palabras clave:
cardiotoxicidad, Danio rerio, escorpión, pez cebra, Tityus discrepans, veneno
Resumen
El envenenamiento por el escorpión venezolano Tityus discrepans se caracteriza por alteraciones locales y sistémicas. El trabajo actual investigó los procesos hemostáticos in vivo, la disfunción cardíaca y la destrucción tisular desencadenada por las fracciones de toxinas 1 (3 kDa) y 2 (5 kDa) purificadas. Estas fracciones se obtuvieron mediante cromatografía C-18-HPLC. La toxicidad hemostática y cardiovascular en el pez cebra de ambas fracciones se evaluó mediante expresiones fenotípicas específicas y comportamiento de las larvas a los 5, 15, 30, 40 y 60 min post-tratamiento con veneno. Las fracciones 1 y 2 del veneno de Tityus discrepans produjeron coagulación intravascular diseminada (presencia de trombos) en la vena central de la larva, alteraciones de la frecuencia/ritmo cardíaco y eventos necróticos en más del 90% de todas las larvas bajo su acción. Los resultados han establecido las posibles toxicidades hemostáticas y cardiovasculares del veneno de Tityus discrepans, advirtiendo la posibilidad de lesiones cardiovasculares y tromboembolismo en humanos después del envenenamiento por picaduras de escorpiones.
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Rojas-Muñoz A, Rajadhyksha S, Gilmour D, van Bebber F, Antos C, Rodríguez- Esteban C, Nüsslein-Volhard C, Izpisúa- Belmonte JC. ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration. Develop Biol 2009; 327:177-190.
Ghilardi A, Diana A, Prosperi L, Del Giacco L. Expression pattern of the small muscle protein, X-linked (smpx) gene during zebrafish embryonic and larval developmental stages. Gene Exp Pat 2020; 36: 119110.
Chan J, Bayliss PE, Wood JM, Roberts TM. Dissection of angiogenic signalling in zebrafish using a chemical genetic approach. Cancer Cell 2002; 1: 257-267.
MacRae CA, Peterson RT. Zebrafish as tools for drug discovery. Nat Rev Drug Disc 2015; 14: 721-731.
Pichler FB, Laurenson S, Williams LC, Dodd A, Copp BR, Love DR. Chemical discovery and global gene expression analysis in zebrafish. Nat Biotech 2003; 21: 879-883.
Sand S, von Rosen D, Victorin K, Filipsson AF., Identification of a critical dose level for risk assessment: developments in benchmark dose analysis of continuous endpoints. Toxicol Sci 2006; 90: 241-251.
Damico L. Zebrafish: Methods for Assessing Drug Safety and Toxicity. Assessment of drug-induced cardiotoxicity in zebrafish, New Jersey, Ny, USA: John Wiley and Sons, Inc; 2012, p. 45–54.
Pifano F. Investigación y docencia en medicina tropical. Arch Venez Med Trop Parasitol Med 1961;4: 1-203.
Stoscheck CM. Quantitation of protein. Meth Enzymol 1990; 182: 50–68.
Spearman-Kärber, F. Alternative Methods of Analysis for Quantal Responses. In: Statistical Method in Biological Assay. London: Finney DJ, Charles Griffin & Co Ltd; 1978.
Blanco M, Rodríguez-Acosta A, Strauss M, Pulido-Méndez M, Rodríguez C, González L. Pancreas ultrastructural alterations in mice inoculated with Tityus discrepans (Buthidae) venom. Submic J Cytol Pathol 1999; 31, 51-56.
World Health Organization: Progress in the characterization of venoms and standardization of antivenoms. Geneva: WHO offset Publication 1981; 1-58.
Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680–685.
Zanotty Y, Álvarez M, Perdomo L, Sanchez EE, Girón ME, Suntravat M, Montero Y, Medina R, Navarrete LF, Rodríguez-Acosta Mutacytin-1, a new C-Type Lectin-Like protein from the Venezuelan cuaima (Lachesis muta muta Linnaeus, 1766) (Serpentes: Viperidae) snake venom inducing cardiotoxicity in developing zebrafish (Danio rerio) embryos. Zebrafish 2019; 16: 379–387.
De Roodt A. Veneno de escorpiones (alacranes) y envenenamiento. Acta Bioquím Clín Latinoamericana 2015; 49: 55-71.
Parrilla-Alvarez P, D´Suze G, Quiroga M, Rodriguez-Acosta A, Sevcik C. Effects of formalinization on the immuno-pharmacological characteristics of the venom of the Tityus Scorpions and cross-reactivity between these venoms. J Venom Anim Toxins 1999; 5: 110.
Barona J, Batista V, Zamudio F, Gómez- Lagunas F, Wanke E, Otero R, Possani LD. Proteomic analysis of the venom and characterization of toxins specific for Na+- and K+- channels from the Colombian scorpion Tityus pachyurus. Biochim Biophys Acta 2006; 7: 76-84.
Oukkache N, Chgoury F, Lalaoui M, Cano AA, Ghalim N. Comparison between two methods of scorpion venom milking in Morocco. J Venom Anim Toxins incl Trop Dis 2013; 19: 5.
Joya G, Salazar V, Rosales A, Sevcik C, Visbal G, Ferreira A, D’Suze G. Scorpion toxins modify phytopathogenic fungus physiology. a possible source of new fungicides. J Agric Food Chem 2011; 2011: 6327–6337.
Brazón P, D’Suze G, Errico M, Sevcik C, Arocha-Pinango C, Guerrero B. Discreplasminin, a plasmin inhibitor isolated from Tityus discrepans scorpion venom. Arch Toxicol 2009; 83: 669- 678.
Batista C, D´Suze G, Gomez F, Zamudio F, Sevcik C, Possani L. Proteomic analysisof Tityus discrepans scorpion venom and aminoacid sequence of noveltoxins. Proteomics 2006; 23: 3718–3727.
D’Suze G, Zamudio F, Gomez-Lagunas F, Possani, L. A novel Kþ channel blocking toxin from Tityus discrepans scorpion venom. FEBS Letters 1999; 456: 146-148.
Díaz P, D’Suze G, Salazar V, Sevcik C, Shannon J, Sherman E, Fox, J. Antibacterial activity of six novel peptides from Tityus discrepans scorpion venom. a fluorescent probe study of microbial membrane Naþ permeability changes. Toxicon 2009; 54: 802-817.
Isbister G, Bawaskar H. Scorpion Envenomation. New England J Med 2014; 5: 457-463.
Gwee MCE, Nirthanan S, Khoo HE, Gopalakrisshnakone P, Kini RM, Cheah L. Autonomic effects of some scorpion venoms and toxins. Clin Experim Pharm Physiol 2002; 29: 795-781.
Borges A, Tsushima RG, Backx PH. Antibodies against Tityus discrepans venom do not abolish the effect of Tityus serrulatus venom on the rat sodium and potassium channels. Toxicon 1999; 37: 867-881.
D´Suze G, Sevcik C, Corona M, Zamudio F, Batista C, Coronas F, Possani L. Ardiscretin a novel arthropod-selective toxin from Tityus discrepans scorpion venom. Toxicon 2004; 43: 263–272.
Brazon J, Guerrero B, D´Suze G, Sevcik C. Anticoagulant and factor Xa-like activities of Tityus discrepans scorpion venom. Acta Toxicol Argentina 2013; 1: 26-32.
Shan K, Bick RJ, Poindexter BJ, Nagueh SF, Shimoni S, Verani MS, Keng F, Reardon MJ, Letsou GV, Howell JF, Zoghbi WA. Altered adrenergic receptor density in myocardial hibernation in humans: A possible mechanism of depressed myocardial function. Circulation 2000; 102: 2599-2606.
Mazzei-de-Dàvila CA, Dàvila DF, Donis JH, de-Bellabarba GA, Vilarreal V, Barboza JS. Sympathetic nervous system activation, antivenin administration and cardiovascular manifestations of scorpion envenomation. Toxicon 2002; 40: 1339-1346.
Schwerte T, Prem C, Mairösl A, Pelster B. Development of the sympatho-vagal balance in the cardiovascular system in zebrafish (Danio rerio) characterized by power spectrum and classical signal analysis. J Exp Biol 2006; 209(Pt 6), 1093-1100.
Bagatto B, Burggren W. A three-dimensional functional assessment of heart and vessel development in the larva of the zebrafish (Danio rerio) Physiol Biochem Zool 2005; 79: 194–201.33.
Abdelilah S, Mountcastle-Shah E, Harvey M., Solnica-Krezel L., Schier AF, Stemple DL, Malicki J, Neuhauss SC, Zwartkruis F, Stainier DY, Rangini Z, Driever W. Mutations affecting neural survival in the zebrafish Danio rerio. Development 1996; 123: 217-227.
Frezza E, Amans TM, Martin J. Allosteric Inhibition of adenylyl cyclase type 5 by G- Protein: a molecular dynamics study. Bio- molecules 2020; 10: 1330.
Laudette M, Formoso K, Lezoualch F. GRKs and Epac1 interaction in cardiac re- modelling and heart fFailure. Cells 2021; 10: E154.
Parker T, Libourel PA, Hetheridge MJ, Cumming RI, Sutcliffe TP, Goonesinghe AC, Jonathan SB, Stewart FO, Yann Ch, Matthew JW. A multi-endpoint in vivo larval zebrafish (Danio rerio) model for the assessment of integrated cardiovascular function. J Pharmacol Toxicol Met 2011; 69: 30-38.
Schwerte T, Fritsche R. Understanding cardiovascular physiology in zebrafish and Xenopus larvae: the use of microtechniques. Comp Biochem Physiol Part A: Mol Integ Physiol 2003; 135: 131-145.
Gibbins JM. Platelet adhesion signalling and the regulation of thrombus formation. J Cell Sci 2004; 117: 3415-3425.
Teixeira AL, Fontoura BF, Freire-Maia L, Machado CR, Camargo ER, Teixeira MM. Evidence for a direct action of Tityus serrulatus scorpion venom on the cardiac muscle. Toxicon 2001; 39: 703-709.
Amaral CF, Lopes JA, Magalhães RA, de Rezende NA. Electrocardiographic, enzymatic and echocardiographic evidence of myocardial damage after Tityus serrulatus scorpion poisoning. Am J Cardiol 1991; 67: 655-657.
Freire-Maia L, Campos JA. Pathophysiology and treatment of scorpion poisoning. Natural Toxins, Characterization, Pharmacology and Therapeutics. In: Ownby CL, Odell GV. (Eds.), Proceedings of the 9 thWorld Congress on Animal, Plant and Microbial Toxins. Oxford UK; Pergamon Press Still Water, Oklahoma USA; 1989; 139-159.
Cupo P. Clinical update on scorpion envenoming. J Brazil Soc Trop Med 2015; 48: 642-649.
De Sousa L, Borges A, De Sousa-Insana E, Vásquez-Suárez A. Mortality caused by venomous animals in Venezuela (2000-2009): A new epidemiological pattern. Biomedica. 2021; 41: 29-40.
Raventos J, Torres R, Alvarez M, Girón ME, Perdomo L, Rodriguez-Acosta A. Aspectos bioquímicos y funcionales de la acción tóxica de proteasas del veneno de la serpiente tigra mariposa (Bothrops venezuelensis) sobre las estructuras anatómicas del pez cebra (Danio rerio). Saber UDO. 2018; 30:103-114.
Ghilardi A, Diana A, Prosperi L, Del Giacco L. Expression pattern of the small muscle protein, X-linked (smpx) gene during zebrafish embryonic and larval developmental stages. Gene Exp Pat 2020; 36: 119110.
Chan J, Bayliss PE, Wood JM, Roberts TM. Dissection of angiogenic signalling in zebrafish using a chemical genetic approach. Cancer Cell 2002; 1: 257-267.
MacRae CA, Peterson RT. Zebrafish as tools for drug discovery. Nat Rev Drug Disc 2015; 14: 721-731.
Pichler FB, Laurenson S, Williams LC, Dodd A, Copp BR, Love DR. Chemical discovery and global gene expression analysis in zebrafish. Nat Biotech 2003; 21: 879-883.
Sand S, von Rosen D, Victorin K, Filipsson AF., Identification of a critical dose level for risk assessment: developments in benchmark dose analysis of continuous endpoints. Toxicol Sci 2006; 90: 241-251.
Damico L. Zebrafish: Methods for Assessing Drug Safety and Toxicity. Assessment of drug-induced cardiotoxicity in zebrafish, New Jersey, Ny, USA: John Wiley and Sons, Inc; 2012, p. 45–54.
Pifano F. Investigación y docencia en medicina tropical. Arch Venez Med Trop Parasitol Med 1961;4: 1-203.
Stoscheck CM. Quantitation of protein. Meth Enzymol 1990; 182: 50–68.
Spearman-Kärber, F. Alternative Methods of Analysis for Quantal Responses. In: Statistical Method in Biological Assay. London: Finney DJ, Charles Griffin & Co Ltd; 1978.
Blanco M, Rodríguez-Acosta A, Strauss M, Pulido-Méndez M, Rodríguez C, González L. Pancreas ultrastructural alterations in mice inoculated with Tityus discrepans (Buthidae) venom. Submic J Cytol Pathol 1999; 31, 51-56.
World Health Organization: Progress in the characterization of venoms and standardization of antivenoms. Geneva: WHO offset Publication 1981; 1-58.
Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680–685.
Zanotty Y, Álvarez M, Perdomo L, Sanchez EE, Girón ME, Suntravat M, Montero Y, Medina R, Navarrete LF, Rodríguez-Acosta Mutacytin-1, a new C-Type Lectin-Like protein from the Venezuelan cuaima (Lachesis muta muta Linnaeus, 1766) (Serpentes: Viperidae) snake venom inducing cardiotoxicity in developing zebrafish (Danio rerio) embryos. Zebrafish 2019; 16: 379–387.
De Roodt A. Veneno de escorpiones (alacranes) y envenenamiento. Acta Bioquím Clín Latinoamericana 2015; 49: 55-71.
Parrilla-Alvarez P, D´Suze G, Quiroga M, Rodriguez-Acosta A, Sevcik C. Effects of formalinization on the immuno-pharmacological characteristics of the venom of the Tityus Scorpions and cross-reactivity between these venoms. J Venom Anim Toxins 1999; 5: 110.
Barona J, Batista V, Zamudio F, Gómez- Lagunas F, Wanke E, Otero R, Possani LD. Proteomic analysis of the venom and characterization of toxins specific for Na+- and K+- channels from the Colombian scorpion Tityus pachyurus. Biochim Biophys Acta 2006; 7: 76-84.
Oukkache N, Chgoury F, Lalaoui M, Cano AA, Ghalim N. Comparison between two methods of scorpion venom milking in Morocco. J Venom Anim Toxins incl Trop Dis 2013; 19: 5.
Joya G, Salazar V, Rosales A, Sevcik C, Visbal G, Ferreira A, D’Suze G. Scorpion toxins modify phytopathogenic fungus physiology. a possible source of new fungicides. J Agric Food Chem 2011; 2011: 6327–6337.
Brazón P, D’Suze G, Errico M, Sevcik C, Arocha-Pinango C, Guerrero B. Discreplasminin, a plasmin inhibitor isolated from Tityus discrepans scorpion venom. Arch Toxicol 2009; 83: 669- 678.
Batista C, D´Suze G, Gomez F, Zamudio F, Sevcik C, Possani L. Proteomic analysisof Tityus discrepans scorpion venom and aminoacid sequence of noveltoxins. Proteomics 2006; 23: 3718–3727.
D’Suze G, Zamudio F, Gomez-Lagunas F, Possani, L. A novel Kþ channel blocking toxin from Tityus discrepans scorpion venom. FEBS Letters 1999; 456: 146-148.
Díaz P, D’Suze G, Salazar V, Sevcik C, Shannon J, Sherman E, Fox, J. Antibacterial activity of six novel peptides from Tityus discrepans scorpion venom. a fluorescent probe study of microbial membrane Naþ permeability changes. Toxicon 2009; 54: 802-817.
Isbister G, Bawaskar H. Scorpion Envenomation. New England J Med 2014; 5: 457-463.
Gwee MCE, Nirthanan S, Khoo HE, Gopalakrisshnakone P, Kini RM, Cheah L. Autonomic effects of some scorpion venoms and toxins. Clin Experim Pharm Physiol 2002; 29: 795-781.
Borges A, Tsushima RG, Backx PH. Antibodies against Tityus discrepans venom do not abolish the effect of Tityus serrulatus venom on the rat sodium and potassium channels. Toxicon 1999; 37: 867-881.
D´Suze G, Sevcik C, Corona M, Zamudio F, Batista C, Coronas F, Possani L. Ardiscretin a novel arthropod-selective toxin from Tityus discrepans scorpion venom. Toxicon 2004; 43: 263–272.
Brazon J, Guerrero B, D´Suze G, Sevcik C. Anticoagulant and factor Xa-like activities of Tityus discrepans scorpion venom. Acta Toxicol Argentina 2013; 1: 26-32.
Shan K, Bick RJ, Poindexter BJ, Nagueh SF, Shimoni S, Verani MS, Keng F, Reardon MJ, Letsou GV, Howell JF, Zoghbi WA. Altered adrenergic receptor density in myocardial hibernation in humans: A possible mechanism of depressed myocardial function. Circulation 2000; 102: 2599-2606.
Mazzei-de-Dàvila CA, Dàvila DF, Donis JH, de-Bellabarba GA, Vilarreal V, Barboza JS. Sympathetic nervous system activation, antivenin administration and cardiovascular manifestations of scorpion envenomation. Toxicon 2002; 40: 1339-1346.
Schwerte T, Prem C, Mairösl A, Pelster B. Development of the sympatho-vagal balance in the cardiovascular system in zebrafish (Danio rerio) characterized by power spectrum and classical signal analysis. J Exp Biol 2006; 209(Pt 6), 1093-1100.
Bagatto B, Burggren W. A three-dimensional functional assessment of heart and vessel development in the larva of the zebrafish (Danio rerio) Physiol Biochem Zool 2005; 79: 194–201.33.
Abdelilah S, Mountcastle-Shah E, Harvey M., Solnica-Krezel L., Schier AF, Stemple DL, Malicki J, Neuhauss SC, Zwartkruis F, Stainier DY, Rangini Z, Driever W. Mutations affecting neural survival in the zebrafish Danio rerio. Development 1996; 123: 217-227.
Frezza E, Amans TM, Martin J. Allosteric Inhibition of adenylyl cyclase type 5 by G- Protein: a molecular dynamics study. Bio- molecules 2020; 10: 1330.
Laudette M, Formoso K, Lezoualch F. GRKs and Epac1 interaction in cardiac re- modelling and heart fFailure. Cells 2021; 10: E154.
Parker T, Libourel PA, Hetheridge MJ, Cumming RI, Sutcliffe TP, Goonesinghe AC, Jonathan SB, Stewart FO, Yann Ch, Matthew JW. A multi-endpoint in vivo larval zebrafish (Danio rerio) model for the assessment of integrated cardiovascular function. J Pharmacol Toxicol Met 2011; 69: 30-38.
Schwerte T, Fritsche R. Understanding cardiovascular physiology in zebrafish and Xenopus larvae: the use of microtechniques. Comp Biochem Physiol Part A: Mol Integ Physiol 2003; 135: 131-145.
Gibbins JM. Platelet adhesion signalling and the regulation of thrombus formation. J Cell Sci 2004; 117: 3415-3425.
Teixeira AL, Fontoura BF, Freire-Maia L, Machado CR, Camargo ER, Teixeira MM. Evidence for a direct action of Tityus serrulatus scorpion venom on the cardiac muscle. Toxicon 2001; 39: 703-709.
Amaral CF, Lopes JA, Magalhães RA, de Rezende NA. Electrocardiographic, enzymatic and echocardiographic evidence of myocardial damage after Tityus serrulatus scorpion poisoning. Am J Cardiol 1991; 67: 655-657.
Freire-Maia L, Campos JA. Pathophysiology and treatment of scorpion poisoning. Natural Toxins, Characterization, Pharmacology and Therapeutics. In: Ownby CL, Odell GV. (Eds.), Proceedings of the 9 thWorld Congress on Animal, Plant and Microbial Toxins. Oxford UK; Pergamon Press Still Water, Oklahoma USA; 1989; 139-159.
Cupo P. Clinical update on scorpion envenoming. J Brazil Soc Trop Med 2015; 48: 642-649.
De Sousa L, Borges A, De Sousa-Insana E, Vásquez-Suárez A. Mortality caused by venomous animals in Venezuela (2000-2009): A new epidemiological pattern. Biomedica. 2021; 41: 29-40.
Raventos J, Torres R, Alvarez M, Girón ME, Perdomo L, Rodriguez-Acosta A. Aspectos bioquímicos y funcionales de la acción tóxica de proteasas del veneno de la serpiente tigra mariposa (Bothrops venezuelensis) sobre las estructuras anatómicas del pez cebra (Danio rerio). Saber UDO. 2018; 30:103-114.
Publicado
2021-11-29
Cómo citar
Álvarez, A. M., Álvarez, M., Perdomo, L., & Rodríguez-Acosta, A. (2021). Clinical cardiac alterations and hemostatic toxicities caused by scorpion (Tityus discrepans) venom and its purified fractions on zebrafish (Danio rerio) larvae.: Alteraciones clínicas cardiológicas y toxicidades hemostáticas causadas por el veneno del escorpión (Tityus discrepans) y sus fracciones purificadas en las larvas del pez cebra (Danio rerio). Investigación Clínica, 62(4), 325-338. https://doi.org/10.22209/IC.v62n4a04
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