18 February 2020

Crotoxin in nanodoses

Venom of the Brazilian rattlesnake learned to use for the treatment of chronic pain


Scientists have been studying crotoxin, a component of the venom of one of the South American rattlesnakes, for more than a hundred years. This substance has analgesic, anti-inflammatory and antitumor properties, but its high toxicity has so far prevented its use in medicine. The new method allows to reduce the toxic effect of the substance and at the same time enhance its therapeutic effect.

Crotoxin is included in the venom of the terrible rattlesnake (Crotalus durissus terrificus), a subspecies of snakes common in southern Brazil, southern Peru, as well as in Bolivia, Paraguay, Uruguay and northern Argentina.


The venom of this snake contains a number of components of different actions, as a result of its bite leads to internal bleeding, pain throughout the body, hypotension, visual impairment or complete blindness, auditory disorders, paralysis of peripheral muscles, especially the neck, which becomes so weak that it seems broken, and eventually to life-threatening respiratory paralysis muscles. Crotoxin is a neurotoxic component of poison, experiments show that its paralyzing effect is stronger than that of botulinum toxin (botox).

In a new study conducted by scientists from the Butantan Institute in Sao Paulo, crotoxin was proposed to be encapsulated in nanostructured silicon dioxide SBA-15 - a material originally developed for use in vaccines. "People who do not respond well to vaccines usually have macrophages that break down the antigen very quickly, so their lymphocytes do not have time to produce antibodies," says the first author of the article, Osvaldo Augusto Sant'Anna. "Studies have shown that nanostructured silicon dioxide slows down the action of macrophages."

During the experiments with SBA-15, scientists tried to apply it with various toxins – for example, with diphtheria or tetanus bacillus toxins to improve the corresponding vaccines. They found that the administration of toxins to horses in this form reduces the adverse effects of diphtheria toxin. Based on these observations, they decided to use SBA-15 to mitigate the properties of crotoxin.

An article published by the journal Toxins (Sant'Anna et al., Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice) reports an experiment on the use of a new form of crotoxin in neuropathic pain – a chronic condition in which pain is not caused by physical trauma, and the pathological excitation of neurons responsible for the transmission of pain. Treatment of neuropathic pain is difficult, since conventional painkillers are ineffective in this case.

In an experiment on mice, it was found that the safe dose of crotoxin, if administered together with SBA-15, increases by 35%. Next, the analgesic effect of the drug was tested on mice in which a condition similar to neuropathic pain was caused by damage to the sciatic nerve. The effect of the drug lasted longer when crotoxin was administered together with SBA-15. Researchers are currently investigating whether a combination of crotoxin with SBA-15 can be used to treat multiple sclerosis. They have already reported positive results, which will be detailed in a forthcoming article.

Scientists recognize that for the widespread use of crotoxin in treatment, it is necessary to learn how to synthesize this substance, and this is not an easy task. "Crotoxin is a large molecule with a complex structure that is difficult to reproduce in the laboratory," says Gisele Picolo, head of the laboratory. So far, crotoxin isolated from snake venom is used in research.

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