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NEUTRALIZATION ON VENOMS FROM FIVE BOTHROPS SPECIES, PROVIDED BY TWO THERAPEUTIC ANTIVENOMS USED IN ARGENTINA.
* 1, 2 , 1 , 3 , 4 , 5 , 6 , 7 , 1 , 1 , 8
1  Área Investigación y Desarrollo – Venenos, Instituto Nacional de Producción de Biológicos, ANLIS “Dr. Carlos G. Malbrán”, Ministerio de Salud y Desarrollo Social, Argentina.
2  Primera Cátedra de Toxicología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
3  Laboratorio de Cultivos Celulares, LabInPro – IQUIBA, Universidad Nacional del Nordeste, Corrientes, Argentina.
4  Laboratorio de Control, INPB-ANLIS “Dr. Carlos G. Malbrán”, Ministerio de Salud y Desarrollo Social, Argentina.
5  Departamento de Vacunas y Sueros, Instituto Nacional de Producción de Biológicos, ANLIS “Dr. Carlos G. Malbrán”, Ministerio de Salud y Desarrollo Social, Argentina.
6  Dirección Técnica, Instituto Nacional de Producción de Biológicos, ANLIS “Dr. Carlos G. Malbrán”, Ministerio de Salud y Desarrollo Social, Argentina.
7  Laboratorio de Toxinopatología, Centro de Patología Experimental y Aplicada, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
8  Director, Instituto Nacional de Producción de Biológicos, ANLIS “Dr. Carlos G. Malbrán”, Ministerio de Salud y Desarrollo Social, Argentina.
Academic Editor: R. Manjunatha Kini

Abstract:

We studied the neutralizing capacity of three anti-Bothropic AVs (antivenoms): 1) BIV, produced by immunizing horses with venoms of Bothrops alternatus [Ba] and B. diporus [Bd) and 2) TTV, produced by immunizing the both mentioned venoms) plus B. jararaca [Bja] and B. jararacussu [Bju] venoms. Their neutralizing capacity on lethality, hemorrhagic, coagulant (plasma), proteolytic and PLA2 activities of Ba, Bd, Bn, Bja and Bju venoms, were studied. In addition the toxicity of Bja and Bju venoms on myolblast C2C12 cells and their neutralization by AVs was assayed. In all the cases BIV and TTV neutralized all the activities of the venoms. Volumetrically the neutralizing doses (mg of V [venom] neutralized by ml of AV [antivenom]), TTV showed more potency. However, when the neutralizing potency was expressed as the mg of AV, the doses turn very close. The ED50s (expressed as mg of AV) for Ba V were= 2.0(1.9-2.2) for BIV and 2.2(2.1-2.3) for TTV. For Bd= 1.9(1.7-2.1) for BIV and 1.4(1.3 to 1.6) for TTV; Bn= 2.7(2.0-2.9 for BIV) and 1.9(1.7-2.1) for TTV; Bja=1.5 (1.5-1.6) for BIV and 1.4(1.4-1.5) for TTV; Bju=3.8(3.4-4.2) for BIV and 3.5(3.4-3.7) for TTV. The hemorrhage and myotoxicity in C2C12 was well equally neutralized (p < 0.05). PLA2 activity (radial hydrolysis of phospholipids and indirect hemolysis) and plasma coagulation were neutralized in all the cases and all the doses got close when were considered as the amount of AV protein required for neutralizations. Bjca and Bju venoms were well neutralized by the BIV, which does not include them in their immunogenic mixture while Bn V was well neutralized by both AVs. The results showed that the cross neutralization on this venoms is high. Differences in neutralization, considering the volume of AV required to neutralize, were strongly related with the amount of specific F(ab´)2 fragments in the AVs.

Keywords: Venom; Bothrops; Antivenom; Neutralization

 
 
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