The Putantan Institute uses a citrus molecule against snakebite

SÃO CARLOS, SP (FOLHAPRESS) – Researchers from the Butantan Institute have been able to use a molecule found in the peel of citrus fruits to counteract most of the effects of the jarac toxin (Pothrops jaraca). A modified version of the substance was able to protect mice from death often caused by reptile venom.

The idea is that succinyl rutin, as the molecule is known, will be used in the future as an adjunct (adjuvant) to an antivenom, which should remain the standard treatment for snakebites.

Serum is produced from the venom of each species of snake and corresponds to a mixture of antibodies capable of neutralizing it. The problem is that some of the effects of the poisoning continue to occur even when the serum is applied, and it is not always easy to reach them. Because of this, the auxiliary material will be welcome.

“We still need to take a lot of details into account before considering a clinical trial. [em seres humanos]even because it is not easy to control the circumstances in which a person is bitten,” said Folha, director of the Pathophysiology Laboratory in Butantan, Marcelo Santoro, who is responsible for coordinating the study. “But we have an interesting path to explore in the future.”

The research findings were recently published in Frontiers in Pharmacology by a team that includes Santoro, doctoral student Ana Teresa Azevedo Sacchito and other colleagues.

According to the Butantan researcher, a major advance in the work was to show that it was possible to chemically modify rutin, whose anti-venom potential was already known, so that it became water-soluble and, therefore, could be administered into the patient’s veins (or, in the case of lab mice) , enhance its work.

Snakes of the genus Pothrops, to which the Jaracas and Euthos belong, are the most vulnerable to human casualties on the American continent. Its poison is a powerful mixture of enzymes (molecules capable of accelerating biochemical reactions and “cutting” other substances). The venom has many effects on the circulation and blood clotting of people and animals that are bitten.

Among the consequences of the bite are severe swelling, bleeding from the nose and gums, vomiting of blood, low platelet count (which makes clotting difficult), low blood pressure and tachycardia. In the most severe cases, there is kidney failure, brain hemorrhage, and death.

Based on previous studies, rutin was already known to have anti-inflammatory and anti-bleeding effects that could be beneficial in situations such as a snake bite.

Moreover, obtaining the molecule is relatively simple and inexpensive. But it was still necessary to take into account possible changes in its effectiveness when ingested, since passing through the digestive tract can change its properties. Therefore, Butantan’s team focused its efforts on creating a different type of molecule that is water-soluble, and therefore injectable.

“We used a very simple method, that works on a lab scale, and we will need to adapt it for production on a larger scale,” Santoro says.

The result, succinyl rutin, was given to a group of mice that also received varying doses of the toxin, between medium and high. As a control, the other rodents received only jaraka toxin.

In the lab, none of the animals that received the lowest dose of the poison died, but two-thirds of those that received the higher dose died 48 hours later—in the case of those that didn’t benefit from the effect of succinylrutin. On the other hand, among the mice that received the modified molecule, there were no deaths.

The analyzes also showed that disorders that normally affect blood clotting were partially stopped by succinylrutin, which also helped prevent local bleeding.

Despite the success of the intravenous method, Santoro says researchers are not ruling out considering another oral formula, as long as it maintains similar efficacy to the water-soluble formula.

This is because taking a single pill would be more practical and faster in situations where hospital resources have little access, which is relatively rare in rural areas where accidents with snakes can occur. According to the specialist, there is a good chance that the molecule will be useful against bites from different species of the genus Pothrops.

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