Botulinum toxin is dangerously potent, but it can reduce inflammation caused by viper venom.
Fight fire with fire? Try to combat the venom with toxins. Botulinum toxin – probably the deadliest chemical compound ever known in nature – can help suppress the most destructive effects of snake venom.
Preliminary results, published on February 1 Toxiconsuggest the powerful neurotoxin could be an effective treatment to mitigate catastrophic muscle damage This can result from numerous bites from venomous snakes, possibly reducing the body’s inflammatory response to the venom.
Snake bites are a major global health problem, accounting for more than 100,000 dead annually. Of the millions of people bitten each year, many more are left with permanent disabilities, such as loss of limbs, due to the rapid swelling, inflammation and tissue death caused by the venom of many snakes.
Wounds from snake bites themselves can be treated with vacuums or high concentrations of oxygen. But there is a “critical need for intellectual and financial investment” in more effective and faster treatments, says David Williams, a herpetologist at the World Health Organization based in Melbourne, Australia, who was not involved in the research. And because venoms vary by species and region, and antivenoms don’t work universally on all snake species, developing broadly effective treatments is particularly helpful.
A potential treatment for the bites of many species could come from a somewhat counterintuitive source: botulinum toxin, produced by the Clostridium botulinum bacterium. There is evidence that the neurotoxin, perhaps best known for its use in pain management and flattening wrinkles under the brand name Botox, could facilitate wound healing in general by suppressing inflammation.
Pin Lan, a medical toxicologist at Lishui Central Hospital in China, and colleagues put the idea to the test. The researchers used the venom of a Chinese moccasin (Pointed Deinagkistrodon), a species of Asian viper whose bite, like that of many vipers, can cause significant muscle damage.
In the laboratory, the team separated 22 rabbits into three groups. One received venom injections in the hind legs, another received both venom and a toxin injection and the control group received saline injections. Twenty-four hours after the rabbits were injected, the animals were euthanized and researchers took muscle samples from the venom and saline injection sites. Next, they analyzed how the effects of the venom – muscle damage, presence of proteins and characteristics of the rabbits’ immune cells – differed between treatments. This gave researchers insight into how the body’s rapid flood of chemical and cellular immune responses to injury, or “inflammatory cascade,” was influenced by venom and toxin treatments.
Compared to venom-only injections, the addition of botulinum toxin alleviated some of the harmful effects of the venom. Instead of the thigh muscle swelling to more than 30 percent of its original circumference, rabbits that also received the toxin had virtually no swelling. Rabbits treated with the toxin also had less muscle death.
“These findings suggest potentially significant implications for future snakebite treatments,” says Ornella Rossetto, a neurobiologist at the University of Padua in Italy, who was not involved in the research. “Traditional antivenoms neutralize circulating toxins, but do not reverse local inflammatory cascades or prevent the occurrence of widespread muscle damage. [tissue death].”
Lan’s team also found that botulinum toxin changed the types of macrophages – large immune cells – detected at the injection site compared to rabbits given venom alone. The botulinum toxin rabbits had fewer M1 macrophages, which are the versions of the cell that respond and fight toxins by producing inflammation. And they had more M2 macrophages, which focus on tissue repair. Each form of macrophage can transform into another. The researchers hypothesize that the toxin could deactivate the inflammatory mode of macrophages, thereby pushing them toward their anti-inflammatory form.
Rossetto and Williams say more research is needed before testing on humans. But maybe one day Botox will join antivenom in toxic treatment tag team.
