Web edition: December 13, 2012
Print edition: January 26, 2013; Vol.183 #2 (p. 12)
A zinc compound sometimes taken to treat the common cold might have a second career as emergency treatment for anyone unlucky enough to get stung by an Australian box jellyfish, a new study finds. Researchers also find that venom from stings seems to poke holes in red blood cells, triggering the release of potassium that stops the heart when tested in mice.
Box jellyfish (Chironex fleckeri), which roam the seas off northern Australia, deliver some of the most potent venom found in nature. In the last decade, scientists have shown that the venom can create pores in cells, spilling their contents. But the fundamental aspects of the venom’s lethality have been poorly understood.
Australian researchers have proposed that the venom attacks heart muscle cells, which would explain why sting victims sometimes suffer cardiac arrest. But in the new study, published online December 12 in PLOS ONE, Angel Yanagihara and Ralph Shohet of the University of Hawaii in Honolulu report that reinforced pores form in red blood cells exposed to the box jellyfish’s venom.
“These are structurally sound rings of pores that are catastrophic for cells,” says Yanagihara, a biochemist. While the venom can damage any cell, she says, her lab experiments showed that red blood cells formed the pores within 20 minutes of exposure to the venom, triggering potassium discharge. That, she suggests, alters the delicate balance of electrolytes that govern the electrical signals that keep the heart beating. Too much potassium in the blood is fatal.
In tests in mice, animals given a dose of the venom had aberrant heartbeats within 90 seconds, and their hearts showed steadily deteriorating ability to contract afterward. That is consistent with potassium poisoning. But when the scientists treated eight mice with zinc gluconate after exposure to the venom, four survived more than 12 hours. Untreated mice exposed to the venom died within an average of 19 minutes. Mice receiving a standard box jellyfish antivenom died as fast as those getting no medication.
The zinc compound blocks assembly of the pores, stanching potassium discharge, tests in red blood cells show.
The findings offer a “plausible explanation” for the rapid death sometimes seen after box jellyfish stings, says Kenneth Winkel, director of the Australian Venom Research Unit at the University of Melbourne. But he says more work is needed to prove that blood cells, and not heart cells, are the main targets. And while he says the zinc findings create opportunities for further work on zinc as a treatment, Winkel sees zinc as a potential add-on to the standard antivenom, an antibody-based drug aimed at neutralizing the toxin.
Yanagihara cautions that the antivenom not only failed to protect mice in her tests but may have made matters worse. “The fast-acting agent in the venom would be far too quick for an antibody-based approach,” she concludes.
A November 2012 report from Australia’s Centre for Disease Control attributes 64 deaths off the country’s shores to box jellyfish since 1883, with many more injuries. Box jellyfish appear similar to true jellyfish but are in a different class called cubozoans. Winkel and Yanagihara say the actual number of fatal stings is unknown because some probably occur in remote areas and are not reported. Recent reports of stings in Thailand have led to concerns that the range of the Australian box jellyfish is widening. But Bastian Bentlage, a zoologist at the University of Maryland, says the animals have probably always inhabited the seas from northern Australia to Indonesia, Thailand and the Philippines. “I wonder if it’s just due to increased tourism that we hear about them now,” he says.
A.A. Yanagihara and R.V. Shohet. Cubozoan venom-induced cardiovascular collapse is caused by hyperkalemia and prevented by zinc gluconate in mice. PLOS ONE. Vol. 7, December 12, 2012, p. e51368. doi: 10.1371/journal.pone.0051368. [Go to]
Fact sheet on box jellyfish from the Australian Centre for Disease Control: [Go to]
S. Ramasamy et al. The in vivo cardiovascular effects of box jellyfish Chironex fleckeri venom in rats: efficacy of pre-treatment with antivenom, verapamil and magnesium sulphate. Toxicon. Vol. 43, May 2004, p. 685. doi.org/10.1016/j.toxicon.2004.02.024. [Go to]
B. Bentlage et al. Evolution of box jellyfish (Cnidaria: Cubozoa), a group of highly toxic invertebrates. Proceedings of the Royal Society B. Vol. 277, February 7, 2010, p. 493. doi: 10.1098/rspb.2009.1707 [Go to]