Advances in the characterization of the Mapanare venom Bothriopsis Medusa: hemostatic alterations and antigenic recognition by a venezuelan antivenom

Avances en la caracterización del veneno de la Mapanare Bothriopsis Medusa: alteraciones hemostáticas y reconocimiento antigénico por un antiveneno venezolano

  • Carmen Teresa Duque-Zerpa Universidad Central de Venezuela
  • Katherine Grillet Universidad Central de Venezuela
  • María Eugenia Pineda Universidad Central de Venezuela
Keywords: Bothriopsis medusa, mapanare, hemostatic alterations, antivenom

Abstract

Bothriopsis medusa, commonly known as "viejita" or "mapanare" is a venom species endemic to Venezuela. This is distributed in the States of Aragua, Carabobo, Miranda, Vargas and Capital District. This important geographic location, its cryptic coloration, small size and semi-aerial habits, could give it some relevance in the incidence of ophidian accidents. Like all mapanare, it is considered that it could induce an accident characterized by edema, necrosis, hemorrhages and/or coagulopathies, however the experimental and clinical information on this species is scarce. This study partially characterized the venom from B. medusa, evaluating its eletrophoretic and chromatographic profiles by molecular exclusion, its hemorrhagic, fibrinogenolytic, coagulant and anticoagulant activities. In addition to its antigenic recognition by a Venezuelan antivenom, using immuno-precipitation assays. The results obtained showed an electrophoretic profile constituted by proteins of ~19 to 130 kDa, although clearly distributed in three groups (~19-27, 55-68 and 100-130 kDa). The fractionation presented five fractions, however only the first three showed important levels of proteins. The venom induced hemorrhagic and fibrinogenolytic activities, but not anticoagulant or procoagulant in vitro. The immuno-precipitation assays showed venom-antivenom recognition bands. In conclusion, the venom of B. medusa presented toxinological characteristics that showed important variations with respect to those exhibited by other groups of mapanares in Venezuela, as those belonging to the Bothrops genus, which were essentially related to the absence of a procoagulant effect which determines the diagnosis and treatment in case of ophidian envenomation in the Country. Additionally, the venom shares antigens or, failing that, common epithets, with those used in the production of the antivenom evaluated. This study presented new evidences about the toxinological potential of the venom of B. medusa, which can contribute to broaden the knowledge about the envenomation from “mapanares” in the Country and improve the clinical management of these accidents.

Downloads

Download data is not yet available.

Author Biographies

Carmen Teresa Duque-Zerpa, Universidad Central de Venezuela

Servicio de Análisis Toxicológico (SATOX), Facultad de Farmacia, Universidad Central de Venezuela

Katherine Grillet, Universidad Central de Venezuela

Escuela de Bioanálisis. Facultad de Medicina. Universidad Central de Venezuela

María Eugenia Pineda, Universidad Central de Venezuela

Unidad de Biotecnología, Facultad de Farmacia, Universidad Central de Venezuela

References

AZAÑERO, M.; ESCOBAR, E.; YARLEQUÉ, A. Purificación de una enzima proteolítica del veneno de Bothrops brazili y estudio de su actividad sobre fibrinógeno. Rev. Peru Biol. 7: 55-66. 2000.

CARONE, S.; MENALDO, D.; SARTIM, M.; BERNARDES, C.; CAETANO, R.; DA SILVA, R.; CABRAL, H.; BARRAVIERA, B.; FERREIRA, R.; SAMPAIO, S. BjSP, a novel serine protease from Bothrops jararaca snake venom that degrades fibrinogen without forming fibrin clots. Toxicol. Appl. Pharmacol. 357: 50-61. 2018.

CARRASCO, P.; MATTONI, C.; LEYNAUD, G.; SCROCCHI, G. Morphology, phylogeny and taxonomy of South American bothropoid pitvipers (Serpentes, Viperidae). Zool. Scripta 41: 109–124. 2012.

DE SOUSA, L.; BASTOURI-CARRASCO, J.; MATOS, M., BORGES, A.; BÓNOLI, S.; VÁSQUEZ-SUÁREZ, A.; GUERRERO, B.; RODRÍGUEZ-ACOSTA, A. Epidemiología del ofidismo en Venezuela (1996-2004). Invest. Clin. 54(2): 123-137. 2013.

DEBONO, J., COCHRAN, C.; KURUPPU, S.; NOUWENS, A.; RAJAPAKSE, N.W.; KAWASAKI, M.; WOOD, K.; DOBSON, J.; BAUMANN, K.; JOUIAEI, M.; JACKSON, T.; KOLUDAROV, I.; LOW, D.; ALI, S.; SMITH, I.; BARNES, A. FRY, B. Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms. Toxins. 8 (210): 2-19. 2016.

DUQUE-ZERPA, C.T.; FERNÁNDEZ, I.; VARGAS, A.; LÓPEZ-JOHNSTHON, J.C.; SCANNONE-TEMPONE, H. Caracterización toxinológica del veneno de Bothrops atrox de Puerto Ayacucho, Edo. Amazonas (Venezuela) y su neutralización por un antiveneno venezolano. Rev. Científ. FCV- LUZ. XXIV (4): 355-362. 2014.

DUQUE-ZERPA, C.T.; VARGAS, A. Caracterización toxinológica del veneno de la serpiente Bothrops colombiensis de Paracotos, Estado Miranda, Venezuela. Rev. Científ. FCV- LUZ. XXV (3): 239-247. 2015.

FUENTES, O., RODRÍGUEZ-ACOSTA, A. Sobre los géneros Bothriechis., Bothriopsis, Bothrops y Porthidium (Serpentes:Crotalidae) existentes en Venezuela. Claves para su identificación de interés biomédico. Acta Biol. Venez. 17(3): 31-38. 1997.

GAY, C.; LEIVA, L.; TEIBLER, P; ACOSTA DE P, O. Proteolitic, edematogenic and miotoxic activities of a hemorrhagic metalloproteinase isolated from Bothrops alternatus venom. Toxicon. 46: 546-554. 2005.

GIRÓN, M.E.; PADRÓN, V.; RAMOS, M.I.; SÁNCHEZ, E.; GUERRERO, B.; GARCÍA, A.; UZCÁTEGUI, N.; NAVARRETE. L.F.; RODRÍGUEZ-ACOSTA, A. Intraspecies geographical variability in the South American tigra mariposa (Bothrops venezuelensis Sandner 1952) snake venom activities. Toxicon. 144: 23-33. 2018.

GIRÓN, M.E.; RAMOS, M.I.; CEDEÑO, L.; CARRASQUEL, A.; SÁNCHEZ, E.; NAVARRETE, L.F.; RODRÍGUEZ-ACOSTA, A. Exploring the biochemical, haemostatic and toxinological aspects of mapanare dry-tail (Porthidium lansbergii rozei) snake´s venom causing human accidents in Eastern Venezuela. Invest. Clin. 59(3): 260-277. 2018.

GIRÓN, M.E.; SALAZAR, A.; AGUILAR, I.; PÉREZ, J.; SÁNCHEZ, E.; AROCHA-PINANGO, C.; RODRÍGUEZ-ACOSTA, A.; GUERRERO, B. Hemorrhagic, coagulant and fibrino(geno)litic activities of crude venom and fractions from mapanare (Bothrops colombiensis) snakes. Comp. Bioch. Phys. Part C. 147: 113-121. 2008.

HIGUCHI, D.A.; BARBOSA, C.M.; BINCOLETTO, C.; CHAGAS, J.R.; MAGALHAES, A; RICHARDSON, M.; SANCHEZ, E.F.; PESQUERO, J.B.; ARAUJO, R.C.; PESQUERO, J.L. Purification and partial characterization of two phospholipases A from Bothrops leucurus (white-tailed-jararaca) snake venom. Biochimie 89: 319-328. 2007.

HUATUCO, S.; ESCOBAR, E.; YARLEQUÉ, A. Aislamiento y caracterización parcial de una miotoxina del veneno de la serpiente Bothrops atrox (Ophidia: Viperidae). Rev. Peru Biol. 11(1): 79-86. 2004.

INSTITUTO CLODOMIRO PICADO. Técnicas para determinación de actividades tóxicas de venenos y su neutralización por antivenenos. Manual de Procedimientos. Publicaciones de la Universidad de Costa Rica, Facultad de Microbiología. Pp 2-18. 1998.

KANG, T.; GEORGIEVA, D.; GENOV, N.; MURAKAMI, M.T.; SINHA, M.; KUMAR, R.P.; KAUR, P.; KUMAR, S.; DEY, S.; SHARMA, S.; VRIELINK, A.; BETZEL, C.; TAKEDA, S.; ARNI, R.K.; SINGH, T.P.; KINI, R.M. Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis. FEBS J. 278 (23): 4544-4576. 2011.

KINI, R. Anticoagulant proteins from snake venoms: structure, function and mechanism. Biochem. J. 397: 377-387. 2006

KUCH, U.; MEBS, D.; GUTIERREZ, J.M.; FREIRE, A. Biochemical and biological characterization of ecuadorian pitviper venoms (genera Bothriechis, Bothriopsis, Bothrops and Lachesis). Toxicon. 34 (6): 714-717. 1996.

LAEMMLI, U. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227:680- 685. 1970.

LEÓN, G.; SÁNCHEZ, L.; HERNÁNDEZ, A.; VILLALTA, M.; HERRERA, M. SEGURA, A.; ESTRADA, R.; GUTIÉRREZ, J.M. Immune Response Towards Snake Venoms. Inflam. Allergy Drug Targets. 10 (5): 1-18. 2011.

LOMONTE, B. Manual de métodos Inmunológicos. Universidad de Costa Rica. En línea http://www.icp.ucr.ac.cr/~blomonte/. 30/01/2019.

LÓPEZ-JOHNSTON, J.C. Los venenos de las serpientes. En: Guía de las serpientes de Venezuela. Biología, venenos, conservación y listado de especies. Navarrete, L.F.; López-Johnston, J.C.; Blanco, A. (Eds.). 1a. Ed. Caracas. Pp 21-47. 2009.

NATERA, M.; ESQUEDA, L.F.; CASTELAÍN, M. Bothrops medusa (Sternfeld, 1920). En: Atlas serpientes de Venenzuela: Una visión actual de su diversidad. Natera, M.; Diaz, M. (Eds.). 1a. Ed. Editorial Santiago de Chile. Chile. Pp. 248-249. 2015.

PORTO, B.; TELLI, C.; DUTRA, T.; ALVES, L.; BOZZA, M.; FIN, C.; THIESEN, F.; RENNER, R. Biochemical and biological characterization of the venoms of Bothriopsis bilineata and Bothriopsis taeniata (Serpentes: Viperidae). Toxicon. 50: 270-277. 2007.

REY-SUÁREZ, P.; NÚÑEZ, V.; GUTIÉRREZ, J.; LOMONTE, B. Proteomic and biological characterization of the venom of the redtail coral snake, Micrurus mipartitus (Elapidae), from Colombia and Costa Rica. J. Proteomic.75: 655-667. 2011.

RIVAS, G.; MOLINA, C.; UGUETO, G.; BARROS, T.; BARRIO-AMORÓS, C.; KOK, P. Reptiles of Venezuela: an updated and commented checklist. Reptiles of Venezuela: an up dated and commented checklist. 2012. ZOOTAXA. Magnolia Press. Anckland, Nueva Zelanda. On line: http://www.aca- demia.edu/1459595/ Reptiles_of_Venezuela_an_up_dat-ed_and_commented_checklist.30/01/2019.

RODRÍGUEZ-ACOSTA, A. ¿Qué hacer frente a un accidente ofídico? Un manual para el diagnóstico y tratamiento de las mordeduras ocasionadas por serpientes venenosas en Venezuela. Botica. 33: 1-21. 2015.

RODRÍGUEZ-ACOSTA, A.; SALAZAR, A.M.; SALAZAR, E.; SÁNCHEZ, E.; GIRÓN, M.E.; AGUILAR, I.; VIVAS, J; GUERRERO, B. Sistema fibrinolítico: Métodos de estudio y hallazgos en venenos de serpientes de los géneros Bothrops, Crotalus, Micrurus en Venezuela. Saber-UDO. Venezuela. 28 (4): 666-705. 2016.

RODRÍGUEZ-ACOSTA, A.; SÁNCHEZ, E.; MÁRQUEZ, A.; CARVAJAL, C.; SALAZAR, A.M.; GIRÓN, M.E.; AMALID- ESTRELLA, A.; GIL, A.; GUERRERO, B. Hemostatic properties of Venezuelan Bothrops snake venoms with special reference to Bothrops isabelae venom. Toxicon. 56 (6): 926-935. 2010.

RODRIGUES, C.; TEIXEIRA-FERREIRA, A.; VARGAS, F.; GUERRA-DUARTE, C.; COSTAL-OLIVEIRA, F.; STRANS-KY, S.; LOPES, L.; DUTRA, A.; YARLEQUÉ, A.; BONILLA, C.; SANCHEZ, E.; PERALES, J.; CHÁVEZ-OLÓRTEGUI, C. Proteomic profile, biological activities and antigenic analysis of the venom from Bothriopsis bilineata smaragdina (“loro machaco”), a pitviper snake from Peru. J. Proteomics. 15 (187): 171-181. 2018.

RODRÍGUEZ-ACOSTA, A.; UZCATEGUI, W.; AZUAJE, R.; AGUILAR, I.; GIRÓN, M.E. Análisis clínico y epidemiológico de los accidentes por mordeduras de serpientes del género Bothrops en Venezuela. Rev. Cub. Med. Trop. 52 (2): 90- 94. 2000.

SAJEVIC, T.; LEONARDI, A.; KRIŽAJ, I. Haemostatically active proteins in snake venoms. Toxicon. 57: 627–645. 2011.

SARAVIA, P.; ROJAS, E.; ARCE, V.; GUEVARA, C.; LÓPEZ, J.C.; CHAVES, E.; VELÁSQUEZ, R.; ROJAS, G.; GUTIÉRREZ, J.M. Geographic and ontogenic variability in the venom of the neotropical rattlesnake Crotalus durissus: Patho-physiological and therapeutic implications. Rev. Biol. Trop. 50 (1): 337-346, 2002.

SÁNCHEZ, E.; GIRÓN, M.E.; GUERRERO, B.; UZCÁTEGUI, N.; RODRÍGUEZ-ACOSTA, A. Caracterización bioquímica y biológica del veneno de la serpiente Neotropical Macagua (Bothrops colombiensis) de la región de Barlovento, estado Miranda, Venezuela. Rev. Cub. Med. Trop. 67 (2):213-230. 2015.

SCHRAMER, T.; KALKI, Y.; WYLIE, D. The first documented prey items for Bothrops medusa (Sternfeld, 1920). Primeras presas documentadas para Bothrops medusa (Sternfeld, 1920). Rev. Lat. Herp. 2(1): 48-50. 2019.

TORREZ, P.; DUARTE, M.; FRANÇA, F.; FIGUEIREDO, L.; ABATI, P.; CAMPOS, L.; PEREIRA, P.; QUIROGA, M.; MASCHERETTI, M.; BOULOS, M. First report of an accident with the speckled forest pit viper (Bothriopsis taeniata) in Brazil. Rev. Soc. Bras. Med. Trop. 42 (3): 342-344. 2009.

TORRES-HUACO, F.; MARUÑAK, S.; TEIBLER, P.; BUSTILLO, S.; ACOSTA DE P, O.; LEIVA, L.C.; PONCE-SOTO, L.A.; MARANGONI, S. Local and systemic effects of BtaMP-1, a new weakly hemorrhagic Snake Venom Metalloproteinase purified from Bothriopsis taeniata Snake Venom. Int. J. Biol. Macromol. 5 (141):1044-1054. 2019.

VERHEIJ, H.M.; BOFFA, M.C.; ROTHEN, C.; BRYCKAERT, M.C.; VERGER, R.; DE HAAS, G.H. Corre1ation of enzymatic activity and anticoagulant properties of phospholipase A . Eur. J. Biochem. 112: 25-32 1980.
Published
2019-08-18
How to Cite
1.
Duque-Zerpa CT, Grillet K, Pineda ME. Advances in the characterization of the Mapanare venom Bothriopsis Medusa: hemostatic alterations and antigenic recognition by a venezuelan antivenom: Avances en la caracterización del veneno de la Mapanare Bothriopsis Medusa: alteraciones hemostáticas y reconocimiento antigénico por un antiveneno venezolano. Rev. Cient. FCV-LUZ [Internet]. 2019Aug.18 [cited 2024Nov.24];29(4):291-9. Available from: https://produccioncientificaluz.org/index.php/cientifica/article/view/36552