SPLENIC HISTOPATHOLOGICAL CHANGES IN MACROVIPERA LEBETINA OBTUSA ENVENOMATION. EVALUATION OF INHIBITOR EFFECTS
DOI:
https://doi.org/10.46991/PYSUB.2026.60.1.061Keywords:
snakebite envenomation, spleen, histopathology, marimastat, varespladibAbstract
This study aimed to evaluate splenic histopathological alterations induced by Macrovipera lebetina obtusa venom and to assess the protective effects of enzyme inhibitors. Experiments were conducted on mice under controlled conditions using venom alone and in combination with marimastat and varespladib. The results showed that venom exposure led to edema, vascular congestion, and moderate hemorrhagic foci, indicating significant microvascular damage. In contrast, marimastat effectively preserved splenic architecture and prevented hemorrhage, whereas varespladib provided only partial protection with mild hemorrhagic changes persisting. It should also be noted that lymphoid follicles remained relatively preserved across all groups, suggesting lower susceptibility of the immune component to acute injury. These findings indicate the dominant role of metalloproteinases in venom-induced vascular damage and highlight the potential of targeted inhibition strategies for improving snakebite treatment outcomes.
References
Snakebite Envenoming – a Strategy for Prevention and Control. World Health Organization (2019). Available from: https://www.who.int/publications/i/item/snakebite-envenoming
Target Product Profiles for Animal Plasma-derived Antivenoms: Antivenoms for Treatment of Snakebite Envenoming in Sub-Saharan Africa (1st ed.). Geneva, World Health Organization (2023). Available from: https://www.who.int/publications/i/item/9789240079229
Williams D.J., Faiz M.A., et al. Strategy for a Globally Coordinated Response to Snakebite Envenoming. PLoS Neglected Tropical Diseases 13 (2019), e0007059. https://doi.org/10.1371/journal.pntd.0007059
Brown N., Landon J. Antivenom: The Most Cost-effective Treatment in the World? Toxicon. 55 (2010), 1405–1407. https://doi.org/10.1016/j.toxicon.2010.02.012
de Silva H.A., Ryan N.M., de Silva H.J. Adverse Reactions to Snake Antivenom, and Their Prevention and Treatment. Br. J. Clin. Pharmacol. 81 (2016), 446–52. https://doi.org/10.1111/bcp.12739
Tasoulis T., Isbister G.K. A Review and Database of Snake Venom Proteomes. Toxins (Basel) 9 (2017), 290. https://doi.org/10.3390/toxins9090290
Escalante T., Shannon J.D., et al. Novel Insights Into Capillary Vessel Basement Membrane Damage by Snake Venom Hemorrhagic Metalloproteinases: A Biochemical and Immuno-histochemical Study. Arch. Biochem. Biophys. 455 (2) (2006), 144–153. https://doi.org/10.1016/j.abb.2006.09.018
Slagboom J., Kool J., et al. Haemotoxic Snake Venoms: Their Functional Activity, Impact on Snakebite Victims and Pharmaceutical Promise. Br. J. Haematol. 177 (2017), 947–959. https://doi.org/10.1111/bjh.14591
Ferraz C.R., Arrahman A., et al. Multifunctional Toxins in Snake Venoms and Therapeutic Implications: from Pain to Hemorrhage and Necrosis. Front. Ecol. Evol. 7 (2019), 218. https://doi.org/10.3389/fevo.2019.00218
Hall S.R., Rasmussen S.A., et al. Repurposed Drugs and Their Combinations Prevent Morbidity-inducing Dermonecrosis Caused by Diverse Cytotoxic Snake Venoms. Nat. Commun. 14 (1) (2023), 7812. https://doi.org/10.1038/s41467-023-43510-w
Siigur J., Aaspõllu A., Siigur E. Biochemistry and Pharmacology of Proteins and Peptides Purified from the Venoms of the Snakes Macrovipera lebetina Subspecies. Toxicon. 158 (2019), 16–32. https://doi.org/10.1016/j.toxicon.2018.11.294
Markland F.S.Jr., Swenson S. Snake Venom Metalloproteinases. Toxicon. 62 (2013), 3–18. https://doi.org/10.1016/j.toxicon.2012.09.004
Ayvazyan N., Ghukasyan G., et al. The Contribution of Phospholipase A2 and Metalloproteinases to the Synergistic Action of Viper Venom on the Bioenergetic Profile of Vero Cells. Toxins (Basel) 14 (2022), 724. https://doi.org/10.3390/toxins14110724
Gutierrez J.M., Rucavado A., et al. Hemorrhage Induced by Snake Venom Metalloproteinases: Biochemical and Biophysical Mechanisms Involved in Microvessel Damage. Toxicon. 45 (2005), 997–1011. https://doi.org/10.1016/j.toxicon.2005.02.029
Escalante T., Rucavado A., et al. Key Events in Microvascular Damage Induced by Snake Venom Hemorrhagic Metalloproteinases. J. Proteomics 74 (2011), 1781–1794. https://doi.org/10.1016/j.jprot.2011.03.026
Fox J.W., Gutierrez J.M. Snake Venom Metalloproteinases (1st ed.). Basel (Switzerland), MDPI (2017).
Fischer T., Senn N., Riedl R. Design and Structural Evolution of Matrix Metalloproteinase Inhibitors. Chemistry 25 (2019), 7960–7980.
https://doi.org/10.1002/chem.201805361
Lewin M., Samuel S., et al. Varespladib (LY315920) Appears to be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation. Toxins 8 (2016), 248. https://doi.org/10.3390/toxins8090248
Lewin M.R., Gutirrez J.M., et al. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins (Basel) 10 (10) (2018), 380. https://doi.org/10.3390/toxins10100380
Bronte V., Pittet M.J. The Spleen in Local and Systemic Regulation of Immunity. Immunity 39 (2013), 806–818. https://doi.org/10.1016/j.immuni.2013.10.010
Erratum in: Immunity 56 (2023), 1152. https://doi.org/10.1016/j.immuni.2023.04.004
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