The tail and sting of a South African burrowing scorpion (Scorpionidae: Opistophthalmus sp.) © Jan A. Neethling 2012
Scorpions have been around for more than 420 million years. Originally aquatic, they were some of the first creatures to venture onto land and have since taken up a completely terrestrial lifestyle. They occur on every continent except Antarctica, and are most prevalent in arid regions, though many species do occur in the tropics. They are amongst the most recognizable arachnids and are characterized by an elongate body, pincer-like grasping appendages (called pedipalps), four pairs of walking legs and a tail that terminates in a sting (telson). Scorpions are predatory arachnids that either actively hunt, or use ambush tactics to capture prey by grasping them with their pincers and then using their sting to envenom the prey, thus subduing it. There are currently more than 2400 described scorpion species worldwide, and it is estimated that their biodiversity could be as large as 7000 species. Of those, only about 50 species pose any significant health risks to humans.
Scorpion venom is a complex cocktail containing multiple toxins and other compounds that is not only unique to each scorpion species, but the venom of individuals within a species can vary with specimen age, health, sex and region of origin. As such it is believed that, worldwide, scorpion venom is comprised of around 100 000 unique bio-active molecules. Of particular note are the varying concentrations of neurotoxins that destroy or impair the functioning of the central and/or peripheral nervous system, cardiotoxins that inhibit heart muscle contraction, nephrotoxins that inhibit or damage tissues of the kidneys, hemolytic toxins that target and destroy blood cells, and various enzymes and other bio-active molecules that interfere with intracellular processes and neurobehavioral functions, such as phosphodiesterases, cause inflammation, such as histamine, or pain, such as serotonin. Due to the complex nature of scorpion envenomation, most mild stings are only treated symptomatically, though some of the most dangerous stings can result in multisystem organ failure and death if immediate medical intervention is not applied. Symptoms at the sting site can include immediate and intense pain, tingling, swelling or numbness around the site and will manifest within the first couple of minutes. More potent stings can furthermore result in breathing difficulties, muscle cramps and spasms, excessive salivation, sweating, nausea, vomiting, high blood pressure and an accelerated or irregular heartbeat. In rare cases the victim can also experience anaphylactic shock.
Yearly there are an estimated 1.2 million scorpion envenomations worldwide, with only 3250 (0.27%) resulting in death. Most of these occur in rural areas of tropical and subtropical countries, especially Sahelian Africa, South India, the Middle East, Mexico, and southern Latin America. Children and the elderly are the most susceptible to these venoms. Currently, Androctonus crassicauda, the Arabian fat-tailed scorpion, Buthus occitanus, the common yellow scorpion and Leiurus quinquestriatus, the deathstalker scorpion, are considered to be the deadliest scorpions on earth. In mice the LD50, shorthand for the amount of a substance needed to kill half of the test subjects, for all three of the scorpions was around 0.25 mg/kg. Meaning that only 17.5mg of venom is needed to kill the average person of around 70kg. Unfortunately it has been found that humans are even more susceptible to these venoms than mice.
Most South African scorpions are burrowers that use large pincers to crush their prey, and have thin tails with mild venom to help subdue the prey or deter predators. Like the rest of the world, our most venomous scorpions belong to the Buthidae family, or fat-tailed scorpions. These scorpions have weak, slender pincers and rely on their potent venom to quickly immobilize their prey. To this end their tails are usually large, strong and very flexible. In South Africa you can generally determine the relative potency of a scorpion’s venom by looking at the ratio between their tail’s thickness and the robustness of their pincers. If the specimen has a thin tail and robust pincers it will be only mildly venomous, while if the specimen has a thick tail and slender pincers the venom could be very potent.
As a general rule of thumb when trying to assess how venomous a scorpion’s venom could be, one has to look at the ratio between the robustness of scorpion’s pincers and the thickness of its tail. In mildly venomous scorpions, such as the burrowing scorpion (Opistophthalmus sp.) on the left, the pincers are robust while the tail is thin. In contrast, the highly venomous rough-tail scorpion (Parabuthus granulatus) on the right has thin pincers and a large, thick tail. Opistophthalmus sp. © Jan A. Neethling 2012, Parabuthus granulatus © Bernard Dupont 2012.
Dried and crushed scorpion bodies and tails, also known as Quan Xie, have been used in Chinese traditional medicine for over 2000 years, and is said to be effective in the treatment of a variety of ailments. Modern research focuses on the venom of scorpions. Since the toxins in scorpion venom exert their effects by interacting with a wide range of biological components including cellular receptors, membranes and ion channels, they serve as a rich source of bioactive compounds that are of interest to the pharmaceutical and biotech industries. With advancements in our ability to isolate, identify and synthesize components of scorpion venom it has become clear that many of them have novel properties that could be used to improve modern pharmaceuticals. So far, research has uncovered many unique uses for the compounds in the venom. These include:
Antibacterial and Antifungal Effects
Arguably one of the greatest medical breakthroughs of the 20th century, the discovery antibiotics not only led to the treatment of infectious disease, but also made modern medical procedures such as organ transplants and open-heart surgery possible. Unfortunately the widespread use of antibiotics has led to the emergence of multi-drug resistant bacteria (MRB’s) that are notoriously difficult to treat. Research into scorpion-derived anti-microbial peptides has shown that many scorpion species possess venom with anti-microbial components that are effective at combatting certain MRB’s. Stigmurin, a compound synthesized from the venom of Tityus stigmurus, has been shown to be effective not only against certain MRB’s, but also certain fungal infections, while displaying low toxicity towards healthy human tissue.
There are more than 200 viruses known to infect humans and only a few antiviral vaccines and drugs are commercially available to combat these, a situation that has been highlighted by the ongoing Covid-19 infectious disease caused by the SARS-CoV-2 virus. Venomous animals such as scorpions are considered by many researchers to be promising sources for the discovery of new antiviral agents. One such antiviral agent, Mucroporin-M1, derived from the venom of Lychas mucronatus, has been shown to demonstrate antiviral activity against three RNA viruses, namely measles (MeV), influenza (H5N1) and severe acute respiratory syndrome-related coronavirus (SARS-CoV).
Malaria, Sleeping Sickness and Leishmaniasis are diseases caused by parasitic organisms, and are particularly prevalent in developing countries. Many antiparasitic therapeutic agents are often toxic to the host as well, and as such there is a need to find and develop novel therapeutics that are safe for the host to take. Research has revealed that scorpion venom contains various components that have inhibitory effects on parasites. Scorpine, a purified toxin found in the venom of Pandinus imperator, was found to be effective against Plasmodium falciparum, the parasite responsible for causing malaria in humans. According to the Centers for Disease Control and Prevention (CDC) an estimated 627 000 people died due to malaria in 2020, making it the 5th leading cause of death from infectious diseases worldwide.
Chemotherapy, while effective and life-saving, utilizes many compounds with toxic side effects on humans. For that reason, there is a need to discover novel therapeutic substances that can either act directly on tumours, work synergistically with currently available therapeutics or function as carrier molecules to transport therapeutics to tumour locations. Chlorotoxin, purified from the venom of the deathstalker scorpion (Leiurus quinquestriatus), acts directly on the chloride channels of tumour cells and has been shown to be very effective at inhibiting the growth of glioma tumours. It has the added advantage of being able to penetrate deep into tumour tissue.
As research into scorpion- derived therapeutic substances has intensified, demand for crude scorpion venom has also risen. For this reason, scorpion venom is one of the most expensive substances on earth, with an estimated value of around R164 million per litre. This is not only due to the myriad of bio-active compounds present in the venom, but also to the fact that the venom has to be harvested by hand. A single scorpion only yields around two milligrams of venom at a time, and then requires multiple days of rest to reconstitute its lost reserve.
The above examples are only a few in a long list of possible uses for scorpion venom and as technology improves, so does our ability to study the bio-active molecules found within it. With around 100 000 of these molecules to study, the venom that so often hurts people, has the potential to greatly improve our access to effective drug treatments and thus greatly improve the health of those suffering under a range of ailments.
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