A global review of medically important scorpions and scorpionism

Micaiah Ward and co-workers at Florida State University recently published an extensive review of medically important scorpions, epidemiology and scorpionism. The number of medical important species is raised to 104 (Buthidae: 101, Hemiscorpiidae: 2, Scorpionidae: 1). Of these, 36 species are considered dangerous (causing class II and III symptoms).

It is important to understand that a list like this can not be perfect. The species identification in many sting cases can be missing or wrong. Taxonomy is changing, and a species may turn out to be a species complex with potentially different venom potency (e.g. The Buthus occitanus complex). We should be careful not to label all species not on this list as harmless. A dangerous species may never have stung a human or the sting case was never reported. Also, many stings are dry or a reduced amount of venom is used, causing minor/mild symptoms and by this camouflaging a dangerous species. The article discuss some of these conserns.

 The article also has information about the distribution of medically important species, venom composition and the use of scorpion venom in biomedical research.

Abstract:
Scorpions are an ancient and diverse venomous lineage, with over 2200 currently recognized species. Only a small fraction of scorpion species are considered harmful to humans, but the often life-threatening symptoms caused by a single sting are significant enough to recognize scorpionism as a global health problem. The continued discovery and classification of new species has led to a steady increase in the number of both harmful and harmless scorpion species. The purpose of this review is to update the global record of medically significant scorpion species, assigning each to a recognized sting class based on reported symptoms, and provide the major toxin classes identified in their venoms. We also aim to shed light on the harmless species that, although not a threat to human health, should still be considered medically relevant for their potential in therapeutic development. Included in our review is discussion of the many contributing factors that may cause error in epidemiological estimations and in the determination of medically significant scorpion species, and we provide suggestions for future scorpion research that will aid in overcoming these errors.

Reference:
Ward MJ, Ellsworth SA, Nystrom GS. A global accounting of medically significant scorpions: Epidemiology, major toxins, and comparative resources in harmless counterparts. Toxicon. 2018;151:137-55. [Subscription required for full text]

Thanks to Matt Simon for informing me about this article!

The history of scorpion antivenom in North America

Leslie Boyer has written a very interesting article on the history of scorpion antivenom. The paper's main focus is North America, but main globale events in the history of scorpion antivenom and treatment are also presented.

Abstract:
This paper was originally presented as the Elsevier Lecture in July, 2012 at the International Society on Toxinology/Venom Week combined meeting in Honolulu, Hawaii. In it, the author addresses the ancient history of venom and immunity, from the Silurian Era to the 1890s; the development of the first antivenoms; the impact of shifting political and economic pressures; the special case of Arizona; the relative stability of the 1960s through 1990s; the transition to regulatory compliance that took place at the time of the author’s own research; and concluding thoughts regarding the instability of apparent success.

Reference:
Boyer L. History of scorpion antivenom: One Arizonan's view. Toxicon. 2013;69:14-20. [Subscription required for full text]

Rhopalurus junceus venom in alternative cancer treatment

Rhopalurus junecus from Cuba. Photo: Rick West (C)

The venom from the Cuban scorpion Rhopalurus junceus (Herbst, 1800) (Buthidae) has been used in alternative cancer treatment for several years, but there have been few if any systematic, scientific studies of the venom and its effects on cancerous conditions. Di Lorenzo and co-workers now report of a patient case where the patient experienced an unexpected total pain relief and other positive effects after using the medicine "Escozul" (based on the venom of R. junceus).

It is important to stress that this is no proof that the venom of Rhopalurus contains superior anti-cancer components, but it is an indication that it is important that the venom of this species is subjected to more research to uncover the working components and also to get clinical evidence for its therapeutic effects (similar to what has been done with the venom of Leiurus quinquestriatus and other species).

Abstract:
During the management of cancer pain sometimes patients ask for alternative, unusual, non recognized approaches. Last year we followed a cancer patient treated with an active substance that is the venom of blue scorpions endemic to Cuba, called Rhopalurus junceus “Escozul” that experienced an unexpected total pain relief with a good recovery of muscle strength, vital energy and capacity to cope with daily activities such as meal, walking and interacting with relatives and caregivers. Researchers' working on the blue scorpion venom published preliminary data online referring of postulate antitumoral activity in human tumors in vivo and analgesic, anti-inflammatory and antiproliferative activities in experimental models in vitro and in vivo but unfortunately actual available clinical data are not results coming from recognized Randomized Controlled Trials supervised by appropriate IRB regulatory bodies but in a recent paper published on Toxicon in July 2011 Garcia-Gomez et al. describe the first general biochemical, molecular and functional characterization of the venom. What it is sure is this venom certainly warrant further investigation.

Reference:
Di Lorenzo L, Chiara P, Antonio C, Calogero F. Cancer pain managment with a venom of blue scorpion endemic in Cuba, called rhopalurus junceus "escozul". Open Cancer Journal. 2012;5(1):1-2. [Free full text]

Odontobuthus doriae venom as cancer medicine

Scorpions have been used in traditional medicine since ancient times, and in the last decade there have been a lot of research into scorpion venom to find potential agents to be used in medicine and treatment of serious diseases like cancer. Chlorotoxin from the venom of Leiurus quinquestriatus is one example of a very promising agent in the fight against serious brain cancer.

Jamil Zargan and co-workers have now showed that the venom of Odontobuthus doriae (Thorell, 1876) (Buthidae) induced apoptosis (programmed cell death) and inhibits DNA synthesis (inhibit cell growth and cell proliferation) in human neuroblastoma cells (Wikipedia on neuroblastoma). More investigations of the venom of this species are of course necessary, but the properties shown by the venom in this study will make it a valuable therapeutic agent in cancer research.

Abstract:
Scorpion and its organs have been used to cure epilepsy, rheumatism, and male impotency since medieval times. Scorpion venom which contains different compounds like enzyme and non-enzyme proteins, ions, free amino acids, and other organic inorganic substances have been reported to posses antiproliferative, cytotoxic, apoptogenic, and immunosuppressive properties. We for the first time report the apoptotic and antiproliferative effects of scorpion venom (Odontobuthus doriae) in human neuroblastoma cells. After exposure of cells to medium containing varying concentrations of venom (10, 25, 50, 100, and 200 lg/ml), cell viability decreased to 90.75, 75.53, 55.52, 37.85, and 14.30%, respectively, after 24 h. Cells expressed morphological changes like swelling, inhibition of neurite outgrowth, irregular shape, aggregation, rupture of membrane, and release of cytosolic contents after treatment with venom. Lactate dehydrogenase (LDH) level increased in 50 and 100 lg/ml as compared to control, but there was no significant increase in LDH level at a dose of 10 and 20 lg/ml. Two concentrations viz. 50 and 100 lg/ml were selected because of the profound effect of these concentrations on the cellular health and population. Treatment with these two concentrations induced reactive nitrogen intermediates and depolarization in mitochondria. While caspase-3 activity increased in a concentrationdependent manner, only 50 lg/ml was able to fragment DNA. It was interesting to note that at higher dose, i.e., 100 lg/ml, the cells were killed, supposedly by acute necrosis. DNA synthesis evidenced by bromodeoxyuridine (BrdU) incorporation was inhibited in a concentrationdependent manner. The cells without treatment incorporated BrdU with high affinity confirming their cancerous nature whereas very less incorporation was noticed in treated cells. Our results show apoptotic and antiproliferative potential of scorpion venom (O. doriae) in human neuroblastoma cells. These properties make scorpion venom a valuable therapeutic agent in cancer research.

Reference:
Zargan J, Sajad M, Umar S, Naime M, Ali S, Khan HA. Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells. Mol Cell Biochem. 2011 Feb;348(1-2):173-81. [Subscription required for fulltext]

Another Leiurus peptid may be important in fighting serious diseases

The venom of Leiurus quinquestriatus has been subjected to massive research in the last years. It has already been shown that a syntetic version the peptid Chlorotoxin (TM-601) binds to malignant brain tumor cells (gliomas) with high affinity and does not seem to bind to normal brain tissue. This ability has been promising in developing new treatment for this serious disease, and the first human trials have been conducted.

In a recent article in Journal of Biological Chemistry, an international research team describes a new peptid from Leiurus (GaTx1). This peptid controls the movement of ions and water out of cells by interacting with a crucial chlorid channel. This particular ability may be instrumental in developing treatment for the very serious disease cystic fibrosis, which affect more than 70 000 peoples worldwide.

A lot more research is of course neccessary before we know for sure that GaTx1 can be used in treating cystic fibrosis, but it is very interesting that what is belived to be the most venomous scorpion in the world also can save lives.

Read more about this story here:
Scorpion peptide may be key to secretory diseases

Original article:
Fuller, M.D., Thompson, C.H., Zhang, Z. R., Freeman, C.S., Schay, E., Szakacs, G., Bakos, E., Sarkadi, B., McMaster, D., French, R.J., Pohl, J., Kubanek, J. & McCarty, N. A. State-dependent inhibition of cystic fibrosis transmembrane conductance regulator chloride channels by a novel peptide toxin. Journal of Biological Chemistry. 2007. 282(52):37545-55 (Subscription required for fulltext).