Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab')2 and whole IgG antivenoms

Toxicol Lett. 2016 Jan 22:241:175-83. doi: 10.1016/j.toxlet.2015.11.020. Epub 2015 Nov 24.

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.

Keywords: Neuromuscular blocking activity; Neutralization; Phrenic nerve-diaphragm preparation; Snake antivenom; Taipan venom.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antivenins / pharmacology*
  • Diaphragm / drug effects
  • Elapid Venoms / antagonists & inhibitors*
  • Elapid Venoms / toxicity*
  • Elapidae*
  • Immunoglobulin Fab Fragments / pharmacology*
  • Immunoglobulin G / pharmacology*
  • In Vitro Techniques
  • Lethal Dose 50
  • Male
  • Mice
  • Muscle Contraction / drug effects
  • Neuromuscular Diseases / chemically induced*
  • Neuromuscular Diseases / prevention & control*
  • Neuromuscular Junction / drug effects*
  • Neurotoxins / antagonists & inhibitors*
  • Neurotoxins / toxicity*
  • Phrenic Nerve / drug effects
  • Temperature

Substances

  • Antivenins
  • Elapid Venoms
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Neurotoxins
  • taipoxin