Botox could be used to fight snakebite

Fighting fire with fire? Try fighting venom with toxins. Botulinum toxin — possibly the deadliest chemical compound yet known in nature — may help suppress the most destructive effects of snake venom. 

The preliminary findings, published in the Feb. 1 Toxicon, suggest that the potent neurotoxin could be an effective treatment to blunt the catastrophic muscle damage that can result from many venomous snakes’ bites, possibly by turning down the dial on the body’s inflammatory response to the venom.

Snakebite is a major global health challenge, accounting for over 100,000 deaths annually. Many more among the millions bitten every year are left with permanent disabilities, such as the loss of limbs, due to the rapid swelling, inflammation and tissue death caused by many snakes’ venoms.

The snakebite wounds themselves can be treated with vacuums or high concentrations of oxygen. But there is a “critical need for intellectual and fiscal investment” in more effective and timely treatments, says David Williams, a herpetologist with the World Health Organization based in Melbourne, Australia, who was not involved with the research. And since venoms vary between species and regions, and antivenoms don’t work across snake species universally, developing treatments that are broadly effective is particularly valuable.

One potential treatment against many species’ bites may come from a somewhat counterintuitive source: botulinum toxin, produced by the Clostridium botulinum bacterium. There’s some evidence that the neurotoxin, perhaps best known for its use in pain management and flattening wrinkles under the brand name Botox, might aid wound healing in general by stifling inflammation. 

Pin Lan, a medical toxicologist at Lishui Central Hospital in China, and colleagues put the idea to the test. The researchers used venom from a Chinese moccasin (Deinagkistrodon acutus), an Asian viper species whose bite — like that of many vipers — can cause substantial muscle damage.

In the lab, the team separated 22 rabbits into three groups. One received venom injections in their hind legs, another got both venom and a toxin injection and the control group received saline injections. Twenty-four hours after injecting the rabbits, the animals were euthanized and the researchers took muscle samples from the venom and saline injection sites. Then, they analyzed how the venom’s effects — muscle damage, the presence of proteins and features of the rabbits’ immune cells — differed between treatments. This gave researchers insights into how the body’s rapid flood of chemical and cellular immune responses to injury, or “inflammatory cascade,” was influenced by the venom and toxin treatments.

Compared with the venom-only injections, adding botulinum toxin mitigated some of the venom’s damaging effects. Instead of the thigh muscle swelling to over 30 percent larger than its original circumference, the rabbits that also got the toxin barely had any swelling. Rabbits treated with toxin also had less muscle death.

“These findings suggest potentially significant implications for future snakebite therapies,” says Ornella Rossetto, a neurobiologist at the University of Padua in Italy who was not involved in the research. “Traditional antivenom neutralizes circulating toxins but does not reverse local inflammatory cascades or prevent extensive muscle [tissue death].”

Lan’s team also found that the botulinum toxin changed the types of macrophages — large immune cells — detected at the injection site compared with the rabbits given only venom. The botulinum toxin rabbits had fewer M1 macrophages, which are the versions of the cell that react to and fight the toxins by producing inflammation. And they had more M2 macrophages, which focus on repairing tissues. Each form of macrophage can transform into the other. The researchers hypothesize the toxin may be toggling off macrophages’ inflammatory setting, pushing them into their anti-inflammatory form.

Both Rossetto and Williams say more research is needed before testing in humans. But perhaps one day Botox will join antivenom in a toxic treatment tag team.