Doxycycline's Effectiveness in Blocking Harmful Enzymes from Snake Venom

Greg Howard
16th May, 2024

Doxycycline's Effectiveness in Blocking Harmful Enzymes from Snake Venom

Image Source: Natural Science News, 2024

Key Findings

  • The study by the Naval Medical Research Unit San Antonio explored the potential of doxycycline, a common antibiotic, to inhibit venom enzymes from three snake species
  • Doxycycline significantly reduced the activity of two key venom enzymes, PLA2 and SVMP, in a dose-dependent manner
  • In mouse experiments, doxycycline decreased muscle damage and reduced lethality from snake venom, suggesting it could be an effective interim treatment for snakebites
Snakebites present a significant threat to military personnel in various theaters of operation. The venom from snakes like Agkistrodon piscivorus, Naja kaouthia, and Daboia russelii contains complex mixtures of toxins, including phospholipases A2 (PLA2) and snake venom metalloproteinases (SVMP), which cause severe tissue damage and can be lethal. Traditional treatments using antibody-based antivenoms have limitations, prompting the search for alternative therapies. A recent study by the Naval Medical Research Unit San Antonio explored the potential of doxycycline, a common antibiotic, as an inhibitor of these venom enzymes[1]. The study focused on the enzymatic activities of PLA2 and SVMP in the venoms of the three snake species. Using EnzChek Phospholipase A2 and Gelatinase Assay Kits, researchers measured the activities of these enzymes with and without doxycycline. The results showed that doxycycline significantly reduced the activity of both PLA2 and SVMP in a dose-dependent manner. Specifically, PLA2 activity was reduced to 1.5% to 44.0%, and SVMP activity was reduced to 4% to 62% when compared to venom-only controls (P < .0001). To further validate these findings, the researchers conducted experiments using a murine model with adult Bagg Albino (BALB/c) mice. They determined the median lethal dose (LD50) of the venoms and the effective dose (ED50) of doxycycline. The LD50 values were 20.29 mg/kg for A. piscivorus, 0.38 mg/kg for N. kaouthia, and 7.92 mg/kg for D. russelii. The ED50 of doxycycline was 20.82 mg/kg for A. piscivorus and 72.07 mg/kg for D. russelii. No ED50 could be calculated for N. kaouthia venom. Additionally, creatine kinase (CK) activity, an indicator of muscle damage, was significantly decreased in all three venoms treated with doxycycline (P < .0001). These findings build on earlier research that identified the major protein families in snake venoms and their toxic effects[2]. The study demonstrated that doxycycline effectively inhibits the enzymatic activities of PLA2 and SVMP, which are among the dominant protein families in snake venoms. This aligns with previous findings that small molecule inhibitors can neutralize venom toxins[3]. Specifically, the combination of varespladib and marimastat has shown promise in neutralizing coagulopathic toxins in viper venoms[3]. The current study adds doxycycline to the list of potential small molecule inhibitors for snakebite treatment. The study's results suggest that doxycycline could be used as an interim treatment for snakebites, providing protection from muscle damage and reducing lethality until higher levels of medical care are available. The doxycycline concentrations identified in the ED50 studies correspond to dosages of 1,456 to 5,061 mg for a 70 kg human. However, factors such as venom yield and snake species would affect the actual dosage needed. Further research into the safety of high-dose doxycycline and its effectiveness against various snake species is necessary to fully translate these findings into human treatment protocols. In conclusion, the study by the Naval Medical Research Unit San Antonio demonstrates the potential of doxycycline as a treatment for snakebites. By inhibiting the activities of PLA2 and SVMP, doxycycline could reduce muscle damage and lethality in snakebite victims. This research paves the way for new therapeutic approaches that could complement or even replace traditional antivenoms, particularly in situations where immediate medical care is not available.

MedicineBiochemAnimal Science

References

Main Study

1) Doxycycline-Mediated Inhibition of Snake Venom Phospholipase and Metalloproteinase.

Published 15th May, 2024

https://doi.org/10.1093/milmed/usae184

Related Studies

2) A Review and Database of Snake Venom Proteomes.

https://doi.org/10.3390/toxins9090290

3) Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins.

https://doi.org/10.3390/biomedicines8090297


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