Comparison of the neurotoxic and myotoxic effects of Brazilian Bothrops venoms and their neutralization by commercial antivenom.
The venoms of some Bothrops species produce neuromuscular blockade in avian and mammalian nerve-muscle preparations in vitro. In this study, we compared the neuromuscular activities (myotoxicity and neurotoxicity) of venoms from several Brazilian species of Bothrops (B. jararaca, B. jararacussu, B. moojeni, B. erythromelas and B. neuwiedi) in chick isolated biventer cervicis muscle preparations and examined their neutralization by commercial antivenom. All of the venoms (50-200 microg/ml, n = 3 - 7 each) induced long-lasting, concentration-dependent muscle contracture and twitch-tension blockade, and also inhibited the muscle responses to acetylcholine and KCl. Preincubation of the venoms (200 microg/ml) with bothropic antivenom (0.2 ml) for 30 min at 37 degrees C prevented the twitch-tension blockade to different extents, with the protection varying from 0.5% (B. neuwiedi) to 88% (B. moojeni). Complete protection against the neuromuscular action of B. neuwiedi venom was observed only with a mixture of bothropic and crotalic antivenoms. The venoms caused either high (B. jararacussu, B. neuwiedi and B. moojeni) or low (B. jararaca and B. erythromelas) creatine kinase release. Morphologically, myonecrosis was greatest with B. jararacussu venom (98-100% of fibers damaged) and least with B. jararaca venom (74% damage). The extent of neutralization by bothropic antivenom was B. jararaca (93%)>B. erythromelas (65.8%)>B. moojeni (30.7%)>B. neuwiedi (20%)>B. jararacussu (no neutralization). Despite this variation in neutralization, enzyme-linked immunosorbent assays indicated similar immunoreactivities for the venoms, although immunoblots revealed quantitative variations in the bands detected. These results show that Bothrops venoms produce varying degrees of neuromuscular blockade in chick nerve-muscle preparations. The variable protection by antivenom against neuromuscular activity indicates that the components responsible for the neuromuscular action may differ among the venoms.
Zamunér
Stella R
SR
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, P.O. Box 6111, 13083-970, Campinas, SP, Brazil.
da Cruz-Höfling
Maria Alice
MA
Corrado
Alexandre P
AP
Hyslop
Stephen
S
Rodrigues-Simioni
Léa
L
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D017837:Bothrops; D001938:Brazil; D002645:Chickens; D003402:Creatine Kinase / Q000378:metabolism; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D015151:Immunoblotting; D007928:Lethal Dose 50; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D009469:Neuromuscular Junction / Q000187:drug effects*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors
D000997:Antivenins; D003435:Crotalid Venoms; D011189:Potassium Chloride; D003402:Creatine Kinase; D000109:Acetylcholine