Pharmacologically Distinct CardiovascularActions of Box Jellyfish (Chironex fleckeri) Venom and a Tentacle-Only Extract in Rats

^{1Ramasamy, S}, ¹Isbister, G.K., ²Seymour, J.E. and ¹Hodgson, W.C. 

1 Monash Venom Group, Dept of Pharmacology, Monash University, Australia 3800, 2 Dept of Tropical Biology, James Cook University, Australia 4878.

The Australian box jellyfish (Chironex fleckeri) is arguably the most venomous animal in the world. Difficulties in obtaining pure venom samples have hindered the biochemical and pharmacological characterization of jellyfish venoms. Many previous studies have employed samples that contain an incomplete complement of clinically relevant toxin(s) and/or may be contaminated with tentacular material. However, a superior technique for the extraction of venom from the nematocysts has been developed. Using this method, a pure C. fleckeri venom sample and a tentacle-only extract (devoid of nematocysts) were examined in anaesthetised rats. Male Sprague-Dawley rats (250-300 g) were anaesthetised with pentobarbitone sodium (60-100 mg/kg, i.p. supplemented as required). Cannulas were inserted in the trachea (for respiratory support, if necessary), jugular vein (for administration of venom and drugs) and carotid artery (for mean arterial pressure (MAP) measurement). C. fleckeri venom (10 mg/kg, i.v.) produced a transient pressor response (23 ± 4 mmHg; p<0.05, one-way ANOVA; n=5) and cardiovascular collapse in two out of five anaesthetised rats. C. fleckeri tentacle-only extract (100 mg/kg, i.v.) produced a more prolonged hypertensive response (31 ± 3 mmHg; p<0.05, one-way ANOVA; n=4). Neither prazosin (50 mg/kg; i.v.) nor ketanserin (1 mg/kg; i.v.) had any effect on the venom-induced transient hypertensive response (35 ± 3 mmHg, n=4 and 25 ± 1 mmHg, n=4, respectively) observed in anaesthetised rats. In contrast, prazosin (50 mg/kg; i.v.) significantly attenuated the pressor response produced by C. fleckeri tentacle-only extract (100 mg/kg, i.v.; 16 ± 4 mmHg; p<0.05, one-way ANOVA; n=4). Vehicle (dH2O; i.v.) did not have any significant effect on the MAP of anaesthetised animals (2 ± 1 mmHg; n=4). We show, for the first time, the pharmacologically distinct cardiovascular actions of a C. fleckeri pure venom sample and those of a C. fleckeri tentacle-only extract. Although tentacular preparations may be potential sources for novel toxins, pure nematocyst extract must be used for all investigations focusing on envenoming and its treatment.

Correspondence to: sharmaine.ramasamy@med.monash.edu.au