Researchers from the Butantan Institute were able to use a molecule present in the peel of citrus fruits to deal with most of the effects of the jararaca venom (Bothrops jararaca). A modified version of the substance was able to protect mice from the death often caused by the reptile’s venom.
The idea is that succinyl rutin, as the molecule is known, will be used in the future as an adjuvant (auxiliary) to antivenom, which should continue to be the standard treatment for snakebites.
The serum is produced from the venom of each snake species and corresponds to a cocktail of antibodies capable of neutralizing it. The problem is that some effects of poisoning continue to occur even when the serum is applied, and access to it is not always easy. Because of this, the adjuvant substance would be welcome.
“We still need to take a lot of details into consideration before thinking about a clinical trial. [em seres humanos]not least because it is not easy to control the circumstances in which a person is bitten”, he told Sheet the director of the Pathophysiology Laboratory at Butantan, Marcelo Santoro, responsible for coordinating the study. “But we have an interesting path to explore going forward.”
The research results were recently published in the journal Frontiers in Pharmacology by a team that includes Santoro, his doctoral student Ana Teresa Azevedo Sachetto and other colleagues.
According to the Butantan researcher, the main advance of the work was to show that it was possible to chemically modify rutin, whose antivenom potential was already known, so that it became soluble in water and, therefore, could be administered into the patient’s veins (or, in the case of laboratory mice), enhancing its action.
The snakes of the genus Bothrops, to which the jararacas and urutus belong, are the most involved in accidents with human victims in the American continent. Its venom is a potent cocktail of enzymes (molecules capable of accelerating biochemical reactions and “cutting” other substances). The venom produces several effects on the circulation and blood clotting of people and animals bitten.
Among the consequences of the bite are severe swelling, bleeding in the nose and gums, vomiting with blood, a drop in the presence of platelets (which makes clotting difficult), low blood pressure and tachycardia. In the most severe cases, there is kidney failure, bleeding in the brain and death.
Based on previous studies, it was already known that rutin has anti-inflammatory and anti-hemorrhagic effects that could prove valuable in situations such as a pit viper bite.
Furthermore, obtaining the molecule is relatively simple and inexpensive. But it was still necessary to take into account possible changes in its effectiveness when it is ingested, since passing through the digestive system could modify its properties. The Butantan team, therefore, focused its efforts on creating a variant of the molecule that was soluble in water and, therefore, injectable.
“We used a very simple method, which works on a laboratory scale and would need to be adapted for production on a larger scale”, says Santoro.
The result, succinyl rutin, was administered to a group of mice that also received varying doses of the venom, between medium and high. As a control, other rodents received only jararaca venom.
In the laboratory, none of the animals that received the lowest dose of the venom died, but two-thirds of those that received the high dose died after 48 hours – in the case of those that did not benefit from the action of succinyl rutin. On the other hand, among the mice that received the modified molecule, there were no deaths.
The analyzes also showed that the disorders that normally affect blood clotting were partially stopped by succinyl rutin, which also helped to prevent localized bleeding.
Despite the success of the intravenous approach, Santoro says that the researchers do not rule out thinking about another oral formulation, as long as it maintains similar efficacy to the water-soluble form.
This is because the ingestion of a single pill would be more practical and faster in situations with little access to hospital resources, relatively rare in rural areas where accidents with snakes can happen. According to the specialist, there is a good chance that the molecule will be useful against bites from different species of the genus. Bothrops.
