Mysore University scientists crack riddle of flesh-destroying viper venom

They say it is the body's own defence that plays a key role in damaging the flesh when a saw-scaled viper bites

Scientists from Mysore University say that the body's own defence plays a central role in damaging the flesh when a venomous saw-scaled viper bites humans.

The saw-scaled viper, formally called Echis carinatus, is among the poisonous snakes found in most parts of India.

The bites from the snake result in widespread tissue death around the wound and scientists had long assumed certain venom toxins were responsible. However, the exact mechanism was unknown.

They found that webs of DNA released by white blood cells called neutrophils to ensnare invading microbes actually block nearby blood vessels trapping damaging venom at the wound and starving cells of oxygen, according to the independent Science Media Centre.

But the researchers may have also discovered a way to counteract the damage. In experiments on mice, they discovered that injecting an enzyme that cuts through the DNA webs called DNase1 can prevent local tissue destruction.

"According to the World Health Organisation, more than 4 lakh people are subjected to amputations due to snake bites every year. Echis species are considered the major contributor for this terrifying debilitation in Africa and in Asia," said study leader Dr Kempaiah Kemparaju, a professor in the department of biochemistry. The study was published in the April issue of Nature Communications.

"All these years it was a challenge for toxinologists to understand the molecular mechanism of tissue destruction. That is why we have no treatment, but our study is now providing the lead."

The researchers injected viper venom into two groups of mice - one with low-levels of neutrophils and another with normal levels. Low neutrophil mice were eight times less likely to develop local tissue damage, but they all diedcompared to just half of normal mice. Injecting DNase1 at the same time as venom in the normal mice was found to prevent local tissue damage, but caused them to die much faster, it said.

Kemparaju says the results suggest that whilethe neutrophils' DNA webs, known as neutrophil extracellular traps (NETs), concentrate damaging venom at the wound sitethey also reduce the amount that spreads to vital organs where its effects are more lethal.

Critically though, the team demonstrated that injecting DNase1 an hour or two after mice were injected with venom prevented tissue damage without reducing the rodent's odds of survival.

Why this approach works was not revealed by the current study, but Nicholas Casewell, an expert in E. carinatus venom from the Liverpool School of Tropical Medicine, says the discovery is a major breakthrough.

"Much more research will be required to ensure that DNases can be given safely to people," he said. "Nonetheless, it's an important step forward in the development of new treatments that can protect against the horrific destructive effects of certain snake venoms."

Further research should investigate whether DNase is effective against other snake venoms that cause local damage, he added.

The study also investigated whether the same process occurred with cobra venom, but found DNase occurring naturally in the venom prevented build-up of NETs. However, Dr Joseph K Joseph, who helped draft the National Snakebite Management protocol, says he has encountered local tissue damage following cobra bites suggesting various processes may be at play.

But he says the paper still represents a major advance towards treating snake bite-induced tissue damage. "The problem is not taken seriously because it's not life threatening, but it can result in terrible disability," he added. "Unfortunately most of these things remain on the lab bench and never come to the bedside."