New broad-spectrum therapy for different types of hemorrhagic snake bites
Taiwan is situated in subtropical region. In less populated areas, we may encounter snakes of Viperidae (vipers), such as Chinese green tree viper or brown spotted pit viper, which are poisonous snakes with triangle heads. If bitten, the most effective treatment is injection of anti-venom serum. However, the high specificity results each antiserum can only rescue snake bite of particular viper. In other words, as there are many kinds of poisonous snakes in Taiwan, we need anti-venom serum for each kind of snake, if we are bitten. This could be a problem in remote areas, because the nearby hospitals or clinics may not be able to provide sufficient types of antiserum, once the accident happens and patient’s life is in danger. A team led by Professor Hsin-Hou Chang and Professor Der-Shan Sun, of the Department of Molecular Biology and Human Genetics, Tzu Chi University, discovered that the solution may be derived from endogenously expressed soluble P-selectin in our body.
Using the mouse model, Professor Chang and Professor Sun found that native soluble P-selectin protein appeared in the blood of mice challenged with hemorrhagic snake venom from vipers. Moreover, the elicitation levels of circulating soluble P-selectin protein were associated with the severity of disease progression. Therefore, a hypothesis was postulated by the research team that the rise of circulating P-selectin is a self-rescue physiological response. According to this hypothesis, the research team treated genetically engineered soluble P-selectin to experimental mice. Intriguingly, they found that P-selectin treated mice became resistant to a variety of viper venoms, and the mortality rate decreased significantly after venom challenges. This indicates that P-selectin protein is an endogenous protein having broad-spectrum anti-venom effects.
Because some components of the snake venom causes bleeding and tissue hypoxia, the research team further used anthrax toxin to simulate the effects in a mouse model. They found that the application of P-selectin was also able to inhibit hemorrhage and hypoxia caused by anthrax toxin, and significantly reduced the mortality of mice. These results inspired the interest of another research team of associate professors Shun-Ping Huang, who also affiliates in the same department (Department of Molecular Biology and Human Genetics, Tzu Chi University), in application of P-selectin in “soluble P-selectin promotes retinal ganglion cell survival through activation of Nrf2 signaling after ischemia injury”-related project.
Taken together, we realize that increasing the soluble P-selectin protein in the blood is a self-rescue response against bleeding and hypoxia. In the future, as long as the soluble P-selectin protein is prepared in a remote area, it can be widely used to cope with a variety of snake bites. In addition, because bleeding and hypoxia involve a wide range of fields, including cerebral stroke, and myocardial infarction, both Professor Chang and Professor Sun are actively expanding their studies of soluble P-selectin related to snake venom and infectious diseases as well as the treatment of organ bleeding and hypoxic diseases. The research on P-selectin protein and snake venom and anthrax toxin was published in the internationally renowned journals Scientific Reports and Virulence in 2016 and 2017.
Paper link: P-selectin protein and snake venom: https://www.nature.com/articles/srep35868
P-selectin protein and anthrax toxin: https://www.tandfonline.com/doi/full/10.1080/21505594.2017.1282027