title: Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab')2 and whole IgG antivenoms.
abstract: The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21°C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20min at 21°C, and antivenom added and temperature increased to 37°C, neutralization was achieved only when the toxin was incubated for 5 or 10min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab')2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization.
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: María
authors.initials: M
authors.lastname: Herrera
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Rita
authors.initials: R
authors.lastname: de Cássia de O Collaço
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Mauren
authors.initials: M
authors.lastname: Villalta
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Segura
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Mariángela
authors.initials: M
authors.lastname: Vargas
authors.affiliation: Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Wright
authors.affiliation: Charles Campbell Toxinology Centre, School of Medicine & Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea.
authors.forename: Owen K
authors.initials: OK
authors.lastname: Paiva
authors.affiliation: Charles Campbell Toxinology Centre, School of Medicine & Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea.
authors.forename: Teatulohi
authors.initials: T
authors.lastname: Matainaho
authors.affiliation: Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia; Charles Campbell Toxinology Centre, School of Medicine & Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Jensen
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Guillermo
authors.initials: G
authors.lastname: León
authors.affiliation: Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia; Charles Campbell Toxinology Centre, School of Medicine & Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea.
authors.forename: David J
authors.initials: DJ
authors.lastname: Williams
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Léa
authors.initials: L
authors.lastname: Rodrigues-Simioni
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica. Electronic address: jose.gutierrez@ucr.ac.cr.
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects; D004546:Elapid Venoms / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017815:Elapidae; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000494:pharmacology*; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009468:Neuromuscular Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D009469:Neuromuscular Junction / Q000187:drug effects*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010791:Phrenic Nerve / Q000187:drug effects; D013696:Temperature
chemical_list: D000997:Antivenins; D004546:Elapid Venoms; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D009498:Neurotoxins; C015523:taipoxin
keywords: Neuromuscular blocking activity; Neutralization; Phrenic nerve-diaphragm preparation; Snake antivenom; Taipan venom