Stan Lee, creator of the mutant superheroes X-Men, wishes he could have come up with a mutant power as awesome as the cowfish. The only similar creature I know of is The Spleen, a member of Champion City’s crime fighting team Mystery Men, with the ability to fart at will and render evil-doers unconscious. But the ability to kill? That’s cowfish territory.
The cowfish, Lactoria cornuta, is a variety of boxfish and a cousin of the paralytic, poisonous pufferfish. They make their home in tropical and subtropical coral reefs in the ocean waters from East Africa to Japan, and feed on just about anything, from algae to small fish and crustaceans. What sets the cowfish apart from other reef denizens is their ability, when threatened or stressed, to discharge poison through their skin to incapacitate and kill predators and would-be muggers.
The poisonous component of this mucus secretion is pahutoxin*, a soap-like chemical with a long chain hydrophobic tail and a positively-charged quaternary ammonium head. This is the same general structure of commercial soaps and detergents (except those have negatively charged heads), and just like the soaps you have at home, pahutoxin forms micelles – aggregates, or balls, with the hydrophobic tails in the center and the hydrophilic, charged heads on the surface. For quite a few years, it was believed that it was this micellular action, and the resulting formation of pores and changes in membrane ion permeability by pahutoxin, that accounted for its mechanism of action as an ichthyotoxin (fancy word for a toxin that kills fish, or is made by a fish).
* In the literature, you’ll also see ‘ostracitoxin,’ but I prefer pahutoxin – I’m a Chuck Palahniuk fan, and have to catch myself from saying ‘palatoxin’ – which would be awesome though. There is a ‘palytoxin,’ but it’s not the same thing, as you’ll read later.
There were a few things wrong with this hypothesis. First, pahutoxin is lethal at concentrations approximately 30-times less than the critical micelle concentration (the concentrations at which micelles are formed). Second, cowfish are unaffected. This excludes pahutoxin from acting, as micelles, on biological membranes. In fact, under normal conditions, there is virtually zero pahutoxin found in membranes.
An alternate theory is that pahutoxin is working at the receptor level, and specifically at receptors not possessed by cowfish. Injection of pahutoxin into fish, however, results in no toxicity. The lethal action is thus at receptors present on the surface exposed to water, such as on gills. Experiments with radiolabeled pahutoxin showed high radioactivity in the gills of experimental fish, but not in those of cowfish, supporting the hypothesis. Additionally, pahutoxin is hemolytic, and induces the rupture of red blood cells, like the arrow poison diamphotoxin. Without red blood cells to exchange oxygen and carbon dioxide, fish die, and seeing how predatory fish are often gilly – I’m thinking of grouper in particular – they would be particularly susceptible to the effects of pahutoxin.
The good news in all of this, as long as you’re not a fish, is that cowfish, and other boxfish species, don’t appear to be poisonous to humans. In some parts of the Pacific they are considered a delicacy, and roasted over the fire like chestnuts. However, other websites reference human fatalities from eating cowfish, but they were poisoned with palytoxin, a completely different, large molecule poison, and one of the most toxic non-protein poisons known. I can guarantee you there will be a post on this one down the line.
Pahutoxin is a fun poison. It’s like defensive chemical warfare. It doesn’t poison predators by being eaten – which has to be the worst defense ever – nor does it have to get close enough to poke a fish with a venomous barb. Cowfish just ooze poison. It’s the thing of comic books, hence the comic strip. I learned a few things though, one is to never put a cowfish in an aquarium, unless you’re not attached to your other fish. And the other? I have zero artistic ability.
- Boylan, D. B., and P. J. Scheuer. “Pahutoxin: A Fish Poison.” Science 155.3758 (1967): 52-56.
- Thomson, D. A. “Ostracitoxin: An Ichthyotoxic Stress Secretion of the Boxfish, Ostracion Lentiginosus.” Science 146.3641 (1964): 244-45.
- Kalmanzon, Eliahu, Yocheved Rahamim, Yechezkel Barenholz, Shmuel Carmeli, and Eliahu Zlotkin. “Receptor-mediated Toxicity of Pahutoxin, a Marine Trunkfish Surfactant.” Toxicon 42.1 (2003): 63-71.
Am I completely wrong or does that stuff look like a cholinergic?
You are 100% correct. Pahutoxin could be hydrolyzed to choline – and we already know that fish have decent amounts of choline already – but I haven’t seen anything to suggest that it is part of its mechanism of action, so I left that part out. Great job picking that out! And thanks for reading!
i don’t think it is cholinergic compound, I am more thinking along the strong structural analogy with platelet-activating factor, which happens to be a potent instant-acting bronchial epithelium constrictor and pro-inflammatory trigger, involved in asthma. I presume the action on gill irritation could be similar. Since PAF receptor antagonists are known, it would be interesting to see if they can abolish the toxic effect of pahutoxin
Correct, resembling and can break down to choline, but not cholinergic. I think you hit the nail on the head with PAF, the structural similarities are striking.
Pahutoxin research had its heyday in the late 60’s, and PAFs didn’t hit the scene until the 70’s. A re-boot of pahutoxin research would make a cool project for a student – either in marine sciences, chemistry, immunology, or toxicology – but I know a little less than nothing about fish pharmacology. Thanks for the insight!
Thank you for that reference, Milkshake. Yes, pahutoxin does look like PAF (which also has that choline-like thing on one end).
Pingback: The Poisonous ABCs: From Aconitine to Zetekitoxin | Nature's Poisons
Hi Justin! I understand the the box fish actually dies from its own secretion of palytoxin in an aquarium setting, is that so? Is the palytoxin the same for the cowfish as the box fish? I live in Cape Coral FL, where we have red tide, a snack that box fish could feed on (except they are not indigenous). Can the fish that make palytoxin mediate in their digestive system the neurotoxins created by red tide? Is there a way that that interaction/nuetralization could be used to clean up the toxic red time?