The in vitro effects of two chirodropid (Chironex fleckeri and Chiropsalmus sp.) venoms: efficacy of box jellyfish antivenom

Ramasamy, Sharmaine; Seymour, Jamie; Hodgson, Wayne Clarence

doi:10.1016/s0041-0101(03)00046-1

Cited by 37 publications

(16 citation statements)

References 27 publications

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“…Conversely, if intravenous injection of antivenom could be administered as soon as possible, and life saving measures such as cardiopulmonary resuscitation could be undertaken unceasingly (as required by the victim), the antivenom would show its beneficial effects earlier. However, this partially implies that the effects of the venom are reversible (including that venom already bound to cells can be neutralized), which may contradict the currently believed pore-forming mode of action [2,12,22]. Finally, in the light of the rapid onset of symptoms and the fact that experimentally only prophylactic doses of antivenom were effective, the window of opportunity for antivenom administration may indeed be too short [16,19].…”

Section: Discussionmentioning

confidence: 99%

“…It has thus been suggested that the current initial treatment for human envenomation (one to three vials, i.e., 20,000-60,000 units) may be insufficient [9-11]. Further complications regarding the use and effectiveness of the antivenom exist with only prophylactic administrations being able to counteract the venom effects, which suggests that the antivenom is also too slow to attenuate the effects of C. fleckeri venom in a clinically relevant setting [10,12]. …”

Section: Introductionmentioning

confidence: 99%

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Dose and time dependence of box jellyfish antivenom

Andreosso

Smout

Seymour

2014

J Venom Anim Toxins incl Trop Dis

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BackgroundThe effectiveness of the currently available box jellyfish (Chironex fleckeri) antivenom has been subject of debate for many years. To assess whether the box jellyfish antivenom has the ability to attenuate venom-induced damage at cellular level, the present study analyzed the dose and time dependence of the antivenom in a cell-based assay.MethodsDifferent doses of antivenom were added to venom and subsequently administered to cells and the cell index was measured using xCelligence Technology (ACEA Biosciences). Similarly, antivenom and venom were incubated over different time periods and cell survival measured as stated above. For both experiments, the cell index was plotted as a measure of cell survival against the dose or incubation time and significance was determined with the use of a one-way ANOVA with a LSD post hoc test.ResultsIncreasing concentrations of antivenom significantly augmented cell survival, with a concentration of approximately five times the currently recommended dose for human envenomation, causing the first significant increase in cell survival compared venom alone. Further, cell survival improved with increasing incubation time of venom and antivenom prior to addition to the cells, indicating that box jellyfish antivenom requires approximately 70 minutes to neutralize C. fleckeri venom.ConclusionThe presented results suggest that the currently recommended dose of antivenom requires adjustment, and more importantly, a human trial to test the effects of higher concentrations is also necessary. Further, antivenom has delayed neutralizing effects (i.e. after 70 minutes) which underlines the eminence of immediate and prolonged cardiopulmonary resuscitation in victims suffering from a C. fleckeri venom-induced cardiovascular collapse.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dose and time dependence of box jellyfish antivenom

Andreosso

Smout

Seymour

2014

J Venom Anim Toxins incl Trop Dis

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“…However, our current understandings of the cardiovascular toxicity of jellyfish venom are very limited, and the underlying mechanism of cardiovascular abnormalities following jellyfish envenomation is still unclear [4,6]. The study on the cardiovascular toxicity of jellyfish venom is mainly hindered by the following reasons: (1) jellyfish venoms are fragile, thermolabile and liable to adhesion, which greatly hampers the identification and isolation of individual components [7,8]; and (2) the collection of venom samples is difficult, due to the small amount of the venoms in nematocysts [6]. To solve the problem, we have previously compared nematocyst venom with tentacle extract (TE, devoid of nematocyst) from the jellyfish, Cyanea capillata .…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Studies of Tentacle Extract from the Jellyfish Cyanea capillata in Isolated Rat Aorta

et al. 2013

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Our previous studies demonstrated that tentacle extract (TE) from the jellyfish, Cyanea capillata, could cause a dose-dependent increase of systolic blood pressure, which seemed to be the result of direct constriction of vascular smooth muscle (VSM). The aim of this study is to investigate whether TE could induce vasoconstriction in vitro and to explore its potential mechanism. Using isolated aorta rings, a direct contractile response of TE was verified, which showed that TE could induce concentration-dependent contractile responses in both endothelium-intact and -denuded aortas. Interestingly, the amplitude of contraction in the endothelium-denuded aorta was much stronger than that in the endothelium-intact one, implying that TE might also bring a weak functional relaxation in addition to vasoconstriction. Further drug intervention experiments indicated that the functional vasodilation might be mediated by nitric oxide, and that TE-induced vasoconstriction could be attributed to calcium influx via voltage-operated calcium channels (VOCCs) from the extracellular space, as well as sarcoplasmic reticulum (SR) Ca2+ release via the inositol 1,4,5-trisphosphate receptor (IP3R), leading to an increase in [Ca2+]c, instead of activation of the PLC/DAG/PKC pathway or the sympathetic nerve system.

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“…Box jellyfish antivenom has been shown to significantly neutralize the neurotoxic effects in vitro when given before envenomation (p Ͻ 0.05), with no significant neutralization after 1 h (p Ͻ 0.05), suggesting there may be clinical efficacy if applied quickly after an incident with C. fleckeri (48).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, faster and more refined techniques for venom extraction have been developed, and will hopefully lead to the development of additional antivenoms (48,60,61).…”

Section: Introductionmentioning

confidence: 99%