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A cell-based assay for screening of antidotes to, and antivenom against Chironex fleckeri (box jellyfish) venom

Konstantakopoulos, N, Isbister, GK, Seymour, JE and Hodgson, WC (2009). A cell-based assay for screening of antidotes to, and antivenom against Chironex fleckeri (box jellyfish) venom. Journal of Pharmacological and Toxicological Methods,59(3):166-170.

Document type: Journal Article
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Title A cell-based assay for screening of antidotes to, and antivenom against Chironex fleckeri (box jellyfish) venom
Author Konstantakopoulos, N
Isbister, GK
Seymour, JE
Hodgson, WC
Journal Name Journal of Pharmacological and Toxicological Methods
Publication Date 2009
Volume Number 59
Issue Number 3
ISSN 1873-488X   (check CDU catalogue open catalogue search in new window)
Start Page 166
End Page 170
Total Pages 5
Place of Publication US
Publisher Elsevier Inc.
HERDC Category C1 - Journal Article (DEST)
Abstract Introduction: Chironex fleckeri is a large box jellyfish that has been labelled the ‘most venomous animal’ in the world. We have recently shown that the primary effect of C. fleckeri venom in vivo is cardiovascular collapse. This study utilised a cell-based assay to examine the effects of C. fleckeri venom on the proliferation of a rat aortic smooth muscle cell line. In addition, the ability of CSL box jellyfish antivenom and/or various potential treatment strategies to neutralise the effects of the venom was examined. Methods: A7r5 cells were cultured in media containing venom. The effect of CSL box jellyfish antivenom (5 U/mL), CSL polyvalent snake antivenom (5 U/mL), lanthanum (5 µM), MgSO4 (50 mM), verapamil (5 µM) or felodipine (5 µM) was examined. Cell viability was determined using a Cell titer 96 AQueous One Solution cell proliferation assay. Results: Incubation of A7r5 cells with serially diluted venom (2–0.004 µg/mL) caused a concentration-dependent inhibition of cell proliferation with an IC50 value of 0.056 µg/mL. This response was not affected by the absence of calcium or the presence of lanthanum in the media. Box jellyfish antivenom (5 U/mL) prevented the inhibition of cell proliferation caused by the venom. Verapamil (5 µM) had no significant effect on the inhibition. In contrast, felodipine (5 µM) or MgSO4 (50 mM) potentiated the effects of the venom and partially negated the protective effect of the antivenom. Discussion: This study displayed the ability to utilise a cell-based assay to determine the effects of C. fleckeri venom on vascular cell viability. It showed that CSL box jellyfish can neutralise the effects of the venom but only if added prior to the venom. In addition, potential adjunct therapies verapamil, felodipine and MgSO4 were found to be ineffective, with felodipine and MgSO4 potentiating the detrimental effects of the venom.
DOI http://dx.doi.org/10.1016/j.vascn.2009.02.003   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
 
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