Found in fruit, rutin helps combat the effects of jararaca viper venom

January 08, 2019

Rutin, a bioflavonoid (plant pigment) found in certain vegetables and fruits, protects mice against snake venom by minimizing bleeding and inflammation, according to a study performed at the Butantan Institute, a research institution belonging to the government of São Paulo State in Brazil.

The research focused on methods to combat the effects of envenomation by the lancehead pit viper Bothrops jararaca, which is responsible for approximately 70% of snakebites in the state, and was conducted by Marcelo Larami Santoro, Ana Teresa Azevedo Sachetto and Jaqueline Gomes Rosa at Butantan Institute's Physiopathology Laboratory, with funding from São Paulo Research Foundation - FAPESP, Brazil's National Council for Scientific and Technological Development (CNPq) and the Brazilian Ministry of Education's Office for the Improvement of Higher Education Personnel (CAPES).

The results were published in the journal PLOS Neglected Tropical Diseases.

Rutin is found in apples, bell peppers, chili peppers, blackberries, buckwheat, cherries, citrus, figs, grapes (and wine), persimmons, raspberries and strawberries, as well as black tea and green tea.

In plants, rutin and other flavonoid pigments attract pollinator insects, filter ultraviolet rays and fix nitrogen. Flavonoids also have anti-oxidant properties and participate in defense mechanisms, helping prevent attacks by insects and microbes.

Rutin specifically is known to be a powerful anti-oxidant and anti-inflammatory agent.

Antivenom therapy counteracts the main effects of snakebite, but there is no known treatment for the most frequent secondary complications. Toxins present in B. jararaca's venom can trigger both bleeding and adverse clotting. The toxins also cause a hazardous imbalance in cellular reduction-oxidation (redox) reactions.

"The mechanisms underlying clinical complications in patients bitten by B. jararaca are poorly understood, and antivenom therapy has a limited capacity to treat the entire range of complications that may be caused by snakebites," Santoro said.

"For example, the snake's venom increases the activity of tissue factor, a protein that plays a key role in the clotting process and is present in tissue, blood platelets and monocytes."

Tissue factor is activated by tissue exposure in cuts or wounds to assist blood clotting and is the primary cellular initiator of clotting after blood vessel injury.

In the case of snake envenoming, tissue factor is activated even in the absence of a wound, forming clots that impair blood circulation and can become large enough to lead to embolisms, blocking a vein or artery and causing tissue necrosis.

The researchers, therefore, reasoned that inhibiting tissue factor activity and making it return to its original condition could be a way to treat thrombosis, a significant secondary complication of viper bite. "Envenomation doesn't necessarily augment tissue factor, but it does heighten tissue factor activity," Santoro said.

Oxidative stress

An enzyme called PDI controls tissue factor activity, and rutin is known to inhibit the action of PDI.

"Envenoming by B. jararaca causes clotting problems due to an increase in tissue factor activity. This activity is controlled by PDI, and we know that rutin can inhibit PDI. It occurred to us that rutin could be used to avoid tissue factor expression in cases of viper bite to reduce secondary complications such as adverse blood clotting," Santoro said.

To test their hypothesis, the researchers conducted experiments in vitro and in mice. In the former, they dissolved B. jararaca venom in a rutin solution and discovered that the rutin has a beneficial effect against oxidative stress, a biological condition involving an imbalance between the production of free radicals and the organism's ability to counteract their harmful effects. Oxidative stress is another secondary complication of envenomation by snakebite.

The in vivo experiments involved 72 mice divided into three time-based groups of 24, each of which were randomly allocated to four groups of six. A saline solution was administered to all four groups. The control group received only saline. The second, third and fourth groups received injections of B. jararaca venom, rutin alone, and venom plus rutin, respectively.

Three, six and 24 hours after the injections, the animals were euthanized for the collection of blood and tissue samples. The researchers analyzed these samples to investigate the effects of rutin on the physiopathological events triggered by the snake venom.

"Tissue factor activity increases in response to envenomation. In the group that received venom plus rutin, we found that rutin reduced clotting and thereby protected the organism from the venom's clotting action," Santoro said. "However, we were unable to identify the target of rutin or how it acted in the organism to control tissue factor activity."

He added that future studies will be necessary to understand how rutin works once the venom has triggered the cascade of physiological events concerned and to further investigate the therapeutic effects of administering rutin with antivenom.

"Our research suggests rutin has great potential as an ancillary drug to be taken with antivenom for the treatment of snakebite, especially in countries where antivenom is in short supply," Santoro said.
About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. For more information:

Fundação de Amparo à Pesquisa do Estado de São Paulo

Related Snake Articles from Brightsurf:

First evidence of snake-like venom glands found in amphibians
Caecilians are limbless amphibians that can be easily mistaken for snakes.

Snake venom evolved for prey not protection
It is estimated that every year, over 100,000 human deaths can be attributed to snakebite from the world's 700 venomous snake species -- all inflicted in self-defence when the snakes feel threatened by encroaching humans.

Vibes before it bites: 10 types of defensive behaviour for the false coral snake
The False Coral Snake (Oxyrhopus rhombifer) may be capable of recognising various threat levels and demonstrates ten different defensive behaviours, seven of which are registered for the first time for the species.

Warming mountaintops put snake at risk of extinction
Climate change is a key factor contributing to the likely extinction of the Greek meadow viper, a new study has found.

When frogs die off, snake diversity plummets
A new study in the journal Science, shows that the snake community become more homogenized and the number of species declined dramatically after chytrid fungus decimated frog populations in a remote forest in Panama.

Venom-producing snake organoids developed in the lab
A team of scientists from the group of Hans Clevers at the Hubrecht Institute, the Netherlands, has developed a mini-venom glands of various snake species.

Snake stem cells used to create venom-producing organoids
Organoids have become an important tool for studying many disease processes and testing potential drugs.

Snake-like proteins can wrangle DNA
Theoretical simulations at Rice University suggest structural maintenance of chromosome proteins coil not only around each other but also around the strands of DNA they help manipulate.

An ancient snake's cheekbone sheds light on evolution of modern snake skulls
New research from a collaboration between Argentinian and University of Alberta palaeontologists adds a new piece to the puzzle of snake evolution.

Tropical sea snake uses its head to 'breathe'
Humans use a snorkel and fish have gills. Now researchers have found a sea snake which uses a complex system of blood vessels in its head to draw in extra oxygen when it dives and swims underwater.

Read More: Snake News and Snake Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to