Evaluation of three Brazilian antivenom ability to antagonize myonecrosis and hemorrhage induced by Bothrops snake venoms in a mouse model.
Despite preventing death after snakebites, there is little evidence that polyvalent antivenoms (PAVs) protect against myotoxicity and local damages. We evaluated antibothropic Brazilian PAVs from three manufacturers against the myotoxicity and hemorrhagic activity of Bothrops jararacussu and B. jararaca venoms, respectively, by using two protocols: preincubation of PAVs with venom, and i.v. pretreatment with PAVs, prior to the venom inoculation. In this investigation, we used doses of PAVs ranging from 0.4 to 4.0mL/mg of venom equivalent up to 10 times the amount recommended by the producers for the clinical practice in Brazil. In our preincubation protocol in vivo, PAVs antagonized myotoxicity of B. jararacussu venom by 40-95%, while our pretreatment protocol antagonized myotoxic activity by 0-60%. Preincubation of antivenoms with B. jararaca venom antagonized its hemorrhagic activity by 70-95%, while pretreatment antagonized hemorrhagic activity by 10-50%. Although all PAVs demonstrated partial antagonism against both venoms, the magnitude of these effects varied greatly among the manufactures. The results suggest that the current clinical doses of these PAVs may have negligible antimyotoxic effect.
da Silva
Noelson M V
NM
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro--UFRJ, CEP 21941-590, Rio de Janeiro, RJ, Brazil.
Arruda
Emerson Z
EZ
Murakami
Yugo L B
YL
Moraes
Raphael A M
RA
El-Kik
Camila Z
CZ
Tomaz
Marcelo A
MA
Fernandes
Fabrício F A
FF
Oliveira
Clayton Z
CZ
Soares
Andreimar M
AM
Giglio
Jose R
JR
Melo
Paulo A
PA
D000818:Animals; D000997:Antivenins / Q000627:therapeutic use*; D017837:Bothrops / Q000502:physiology*; D001938:Brazil; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors* / Q000201:enzymology / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006470:Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control*; D066298:In Vitro Techniques; D051379:Mice; D009135:Muscular Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009336:Necrosis; D010447:Peptide Hydrolases / Q000633:toxicity; D010740:Phospholipases / Q000037:antagonists & inhibitors / Q000633:toxicity; D011480:Protease Inhibitors / Q000494:pharmacology
D000997:Antivenins; D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D010740:Phospholipases; D010447:Peptide Hydrolases