Comparison of the in vitro neuromuscular activity of venom from three Australian snakes (Hoplocephalus stephensi, Austrelaps superbus and Notechis scutatus): … (original) (raw)
Toxicon, 2004
We examined the neurotoxicity of the following sea snake venoms: Enhydrina schistosa (geographical variants from Weipa and Malaysia), Lapemis curtus (Weipa and Malaysia), Laticauda colubrina, Aipysurus laevis, Aipysurus fuscus and Aipysurus foliosquamatus. Venom from a terrestrial snake, Notechis scutatus (tiger snake), was used as a reference. All venoms (1 and 3 mg/ml) abolished indirect twitches of the chick biventer cervicis muscle and significantly inhibited responses to ACh (1 mM) and CCh (20 mM), but not KCl (40 mM), indicating the presence of post-synaptic toxins. Prior administration (10 min) of CSL sea snake antivenom (1 unit/ml) attenuated the twitch blockade produced by N. scutatus venom and all sea snake venoms (1 mg/ml). Prior administration (10 min) of CSL tiger snake antivenom (1 unit/ml) attenuated the twitch blockade of all venoms except those produced by E. schistosa (Malaysia and Weipa) and A. foliosquamatus. Administration of CSL sea snake antivenom (1 unit/ml) at t 90 (i.e. time at which 90% inhibition of initial twitch height occurred) reversed the inhibition of twitches (20 -50%) produced by the sea snake venoms (1 mg/ml) but not by N. scutatus venom (1 mg/ml). CSL tiger snake antivenom (1 unit/ml) administered at t 90 produced only minor reversal (i.e. 15 -25%) of the twitch blockade caused by L. curtus (Weipa), A. foliosquamatus, L. colubrina and A. laevis venoms (1 mg/ml). Differences in the rate of reversal of the neurotoxicity produced by the two geographical variants of E. schistosa venom, after addition of CSL sea snake antivenom, indicate possible differences in venom components. This study shows that sea snake venoms contain potent post-synaptic activity that, despite the significant genetic distances between the lineages, can be neutralised with CSL sea snake antivenom. However, the effects of CSL tiger snake antivenom are more variable. q
Basic & Clinical Pharmacology & Toxicology, 2013
Research into Australian elapid venoms has mainly focused on the seven genera of greatest clinical significance: Acanthophis, Hoplocephalus, Notechis, Oxyuranus, Pseudechis, Pseudonaja and Tropidechis. However, even small species represent a potential for causing severe clinical envenoming. Further, owing to taxonomic distinctiveness, these species are a potential source of novel toxins for use in drug design and development. This is the first study to characterize the venoms of Cryptophis boschmai, Denisonia devisi, Echiopsis curta, Hemiaspis signata and Vermicella annulata. MALDI analysis of each venom, over the range of 4-40 kDa, indicated components in the weight range for three finger toxins (6-8 kDa) and phospholipase A 2 (PLA 2 ; 12-14 kDA). Interestingly, C. boschmai venom was the only venom, which contained components > 25 kDa. All venoms (10 lg/ml) demonstrated in vitro neurotoxicity in the chick biventer cervicis nerve-muscle preparation, with a relative rank order of: H. signata ! D. devisi ! V. annulata = E. curta > C. boschmai. CSL polyvalent antivenom neutralized the inhibitory effects of C. boschmai venom but only delayed the inhibitory effect of the other venoms. All venoms displayed PLA 2 activity but over a wide range (i.e. 1-621 lmol/min./mg). The venoms of C. boschmai (60 lg/kg, i.v.), D. devisi (60 lg/kg, i.v.) and H. signata (60 lg/kg, i.v.) produced hypotensive effects in vivo in an anaesthetized rat preparation. H. signata displayed moderate pro-coagulant activity while the other venoms were weakly pro-coagulant. This study demonstrated that these understudied Australian elapids have varying pharmacological activity, with notable in vitro neurotoxicity for four of the venoms, and may produce mild to moderate effects following systemic envenoming.
Basic & clinical …, 2007
Australia has a tremendous diversity of elapid snakes, including many unique smaller sized species of this venomous snake family. However, little if anything is known about the majority of the venoms of these lesser studied snakes. In the current study, the venoms of Suta suta (curl snake) and Suta punctata (spotted-curl snake) were examined for in vitro activity using a skeletal muscle preparation (i.e. chick biventer cervicis nerve-muscle preparation). Both venoms caused concentration-dependent (3-10 µ g/ml) inhibition of nerve-mediated twitches, and inhibited responses to exogenous acetylcholine and carbachol, indicating the presence of postsynaptic neurotoxins. These effects were prevented by prior addition of CSL Ltd. polyvalent snake antivenom (5 units/ml) but only partially reversed by the addition of antivenom (5 units/ml) at the t 90 time-point (i.e. time at which twitches were inhibited by 90%). Suta punctata venom (10 µ g/ml) was also myotoxic as indicated by the inhibition of direct twitches of the chick biventer cervicis nerve-muscle preparation. This effect was not reversed by antivenom (5 units/ml). This study highlights the danger of underestimating the potential severe clinical effects posed by these small but highly venomous snakes.
Anaesthesia and Intensive Care, 1989
The haemodynanic effects of Brown Snake (Pseudonaja) species (textilis, nuchalis, affinis) were investigated in anaesthetised, mechanically ventilated dogs. Blood pressure decreased to minimal levelsfive minutes after intravenous envenomation. Hypotension was accompanied by significant decrements in cardiac output and stroke volume and a rise in peripheral vascular resistance. Heart rate increased transiently during 0.5-2.0 minutes after envenomation but had declined below resting levels five minutes after envenomation. No statistically significant change was recorded in central venous pressure. Depression of myocardial con tractility is postulated as the mechanism of venom induced hypotension.
Effectiveness of snake antivenom: species and regional venom variation and its clinical impact
Toxin …, 2003
The ubiquity of venom variation in snakes poses special problems for the manufacture of antivenom and has undermined the commercial attractiveness of this class of therapeutic agent. In particular, it has been amply documented that both interspecific and intraspecific variation in venom composition can affect the neutralisation capacity of antivenoms. This may be exacerbated by the selective use of tests of venom toxicity
The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t 90 , time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation.