Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab')2 and whole IgG antivenoms (original) (raw)
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Toxins, 2016
There is limited information on the cross-neutralisation of neurotoxic venoms with antivenoms. Cross-neutralisation of the in vitro neurotoxicity of four Asian and four Australian snake venoms, four post-synaptic neurotoxins (α-bungarotoxin, α-elapitoxin-Nk2a, α-elapitoxin-Ppr1 and α-scutoxin; 100 nM) and one pre-synaptic neurotoxin (taipoxin; 100 nM) was studied with five antivenoms: Thai cobra antivenom (TCAV), death adder antivenom (DAAV), Thai neuro polyvalent antivenom (TNPAV), Indian Polyvalent antivenom (IPAV) and Australian polyvalent antivenom (APAV). The chick biventer cervicis nerve-muscle preparation was used for this study. Antivenom was added to the organ bath 20 min prior to venom. Pre- and post-synaptic neurotoxicity of Bungarus caeruleus and Bungarus fasciatus venoms was neutralised by all antivenoms except TCAV, which did not neutralise pre-synaptic activity. Post-synaptic neurotoxicity of Ophiophagus hannah was neutralised by all antivenoms, and Naja kaouthia by a...
Biomedicines, 2020
The Chinese Cobra (Naja atra) is an elapid snake of major medical importance in southern China. We describe the in vitro neurotoxic, myotoxic, and cytotoxic effects of N. atra venom, as well as examining the efficacy of three Chinese monovalent antivenoms (N. atra antivenom, Gloydius brevicaudus antivenom and Deinagkistrodon acutus antivenom) and an Australian polyvalent snake antivenom. In the chick biventer cervicis nerve-muscle preparation, N. atra venom (1–10 µg/mL) abolished indirect twitches in a concentration-dependent manner, as well as abolishing contractile responses to exogenous acetylcholine chloride (ACh) and carbamylcholine chloride (CCh), indicative of post-synaptic neurotoxicity. Contractile responses to potassium chloride (KCl) were also significantly inhibited by venom indicating myotoxicity. The prior addition of Chinese N. atra antivenom (0.75 U/mL) or Australian polyvalent snake antivenom (3 U/mL), markedly attenuated the neurotoxic actions of venom (3 µg/mL) an...
Electrophysiological Study of Neuromuscular Blocking Action of Cobra Neurotoxin*
British Journal of Pharmacology and Chemotherapy, 1966
It is well established that the respiratory failure caused by cobra venom in dogs and rabbits is due to its peripheral curare-like action (Kellaway, Cherry & Williams, 1932; Lee & Peng, 1961; Vick, Ciuchta & Polley, 1965). Su (1960) has concluded that the neuromuscular blocking effect of the Formosan cobra (Naja naja atra) venom is mainly due to non-depolarizing curare-like action, but is complicated with a direct musculotropic effect, probably due to other components than its neurotoxin. Recently, Su, Chang & Lee (1966) have analysed this problem again with a purified neurotoxin isolated electrophoretically from this venom. In contrast to the crude venom, the purified neurotoxin blocks neuromuscular transmission by competing with acetylcholine (ACh), without affecting the release of ACh on nerve stimulation in the rat phrenic nerve-diaphragm preparation or causing contracture of the chick biventer cervicis or frog rectus abdominis muscle. These findings led them to conclude that cobra neurotoxin behaves just like d-tubocurarine, although the former agent acts much more slowly and less reversibly than the latter. On the other hand, Meldrum (1965a) isolated component(s) by electrophoresis from Indian cobra venom (Naja naja), which possessed most of the toxicity of the original venom and also depolarized the frog sartorius muscle. It was of interest therefore to study neurotoxin, the major toxic component of Formosan cobra venom, with electrophysiological techniques, in order to clarify the exact mechanism of action. The results so obtained are in good agreement with our previous conclusion that cobra neurotoxin acts quite similarly with d-tubocurarine and indicate that depolarization induced by Meldrum's neurotoxic fraction might be due to incomplete separation from other depolarizing component(s), such as cardiotoxin. METHODS Cobra neurotoxin This was prepared by either ammonium sulphate precipitation (70-95% saturation) or starch zone electrophoresis as described by Su, Chang & Lee (1966). For the convenience of comparison, the pattern of protein distribution on electrophoresis is shown in Fig. 1. As reported previously, the neurotoxin was located on Peak II while phospholipase A activity and the cardiotoxic component * This investigation was supported by the U.S. Army Medical Research and Development Command, Department of the Army under Research Grant No. DA-MD-49-193-64-G108.
PLOS ONE
Naja sumatrana and Naja kaouthia are medically important elapids species found in Southeast Asia. Snake bite envenoming caused by these species may lead to morbidity or mortality if not treated with the appropriate antivenom. In this study, the in vitro neurotoxic and myotoxic effects N. sumatrana and N. kaouthia venoms from Malaysian specimens were assessed and compared. In addition, the neutralizing capability of Cobra Antivenom (CAV), King Cobra Antivenom (KCAV) and Neuro Polyvalent Antivenom (NPAV) from Thailand were compared. Both venoms produced concentration-dependent neurotoxic and myotoxic effects in the chick biventer cervicis nerve-muscle preparation. Based on the time to cause 90% inhibition of twitches (i.e. t90) N. kaouthia venom displayed more potent neurotoxic and myotoxic effects than N. sumatrana venom. All three of the antivenoms significantly attenuated venom-induced twitch reduction of indirectly stimulated tissues when added prior to venom. When added after N. ...
Neuropharmacology, 2007
The inland taipan is the world's most venomous snake. However, little is known about the neuromuscular activity of the venom or paradoxin (PDX), a presynaptic neurotoxin from the venom. Venom (10 mg/ml) and PDX (65 nM) abolished indirect twitches of the chick biventer cervicis and mouse phrenic nerve diaphragm preparations. The time to 90% inhibition by PDX was significantly increased by replacing Ca 2þ (2.5 mM) in the physiological solution with Sr 2þ (10 mM). In the biventer cervicis muscle, venom (10 mg/ml), but not PDX (65 nM), significantly inhibited responses to ACh (1 mM) and carbachol (20 mM), but not KCl (40 mM). In the mouse diaphragm (low Ca 2þ ; room temperature), the inhibitory effect of PDX (6.5 nM) was delayed and a transient increase (746 AE 64%; n ¼ 5) of contractions observed. In intracellular recording experiments using the mouse hemidiaphragm, PDX (6.5e65 nM) significantly increased quantal content and miniature endplate potential frequency prior to blocking evoked release of acetylcholine. In extracellular recording experiments using the mouse triangularis sterni, PDX (2.2e65 nM) significantly inhibited the voltage-dependent K þ , but not Na þ , waveform. In patch clamp experiments using B82 mouse fibroblasts stably transfected with rKv 1.2, PDX (22 nM; n ¼ 3) had no significant effect on currents evoked by 10 mV step depolarisations from À60 to þ20 mV. PDX exhibits all the pharmacology associated with b-neurotoxins, and appears to be one of the most potent, if not the most potent b-neurotoxin yet discovered.
Toxins, 2014
Bungarus candidus and Bungarus fasciatus are two species of krait found in Southeast Asia. Envenoming by these snakes is often characterized by neurotoxicity and, without treatment, causes considerable morbidity and mortality. In this study, the in vitro neurotoxicity of each species, and the effectiveness of two monovalent antivenoms and a polyvalent antivenom, against the neurotoxic effects of the venoms, were examined in a skeletal muscle preparation. Both venoms caused concentration-dependent inhibition of indirect twitches, and attenuated responses to exogenous nicotinic receptor agonists, in the chick biventer preparation, with B. candidus venom being more potent than B. fasciatus venom. SDS-PAGE and western blot analysis indicated different profiles between the venoms. Despite these differences, most proteins bands were recognized by all three antivenoms. Antivenom, added prior to the venoms, attenuated the neurotoxic effect of the venoms. Interestingly, the respective monovalent antivenoms did not neutralize the effects of the venom from the other Bungarus species indicating a relative absence of cross-neutralization. Addition of a high concentration of polyvalent antivenom, at the t90 time point after addition of venom, partially reversed the neurotoxicity of B. fasciatus venom but not B. candidus venom. The monovalent antivenoms had no significant effect when added at the t90 time point. This study showed that B. candidus and B. fasciatus venoms display marked in vitro neurotoxicity in the chick biventer preparation and administration of antivenoms at high dose is necessary to prevent or reverse neurotoxicity