Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes
| Autor: | Julien Slagboom, Nicholas R. Casewell, Govert W. Somsen, Zhengjin Jiang, Freek J. Vonk, Yumei Zhao, Jeroen Kool, Laura-Oana Albulescu, Kristina B.M. Still, Chunfang Xie |
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| Přispěvatelé: | AIMMS, BioAnalytical Chemistry, Chemistry and Pharmaceutical Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
coagulopathic toxicity Medicine (miscellaneous) Venom Pharmacology varespladib medicine.disease_cause Nanofractionation complex mixtures General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Oxyuranus scutellatus chemistry.chemical_compound 0302 clinical medicine Phospholipase A2 Neutralization Coagulopathic toxicity medicine Varespladib lcsh:QH301-705.5 nanofractionation Echis ocellatus biology Chemistry Toxin PLA activity neutralization biology.organism_classification 030104 developmental biology Echis carinatus lcsh:Biology (General) Snake venom biology.protein lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery PLA2 activity |
| Zdroj: | Biomedicines Volume 8 Issue 6 Biomedicines, Vol 8, Iss 165, p 165 (2020) Xie, C, Albulescu, L O, Still, K B M, Slagboom, J, Zhao, Y, Jiang, Z, Somsen, G W, Vonk, F J, Casewell, N R & Kool, J 2020, ' Varespladib inhibits the phospholipase A 2 and coagulopathic activities of venom components from hemotoxic snakes ', Biomedicines, vol. 8, no. 6, 165, pp. 1-17 . https://doi.org/10.3390/biomedicines8060165 Biomedicines, 8(6):165, 1-17. MDPI AG |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines8060165 |
| Popis: | Phospholipase A2 (PLA2) enzymes are important toxins found in many snake venoms, and they can exhibit a variety of toxic activities including causing hemolysis and/or anticoagulation. In this study, the inhibiting effects of the small molecule PLA2 inhibitor varespladib on snake venom PLA2s was investigated by nanofractionation analytics, which combined chromatography, mass spectrometry (MS), and bioassays. The venoms of the medically important snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus, Echis ocellatus, and Oxyuranus scutellatus were separated by liquid chromatography (LC) followed by nanofractionation and interrogation of the fractions by a coagulation assay and a PLA2 assay. Next, we assessed the ability of varespladib to inhibit the activity of enzymatic PLA2s and the coagulopathic toxicities induced by fractionated snake venom toxins, and identified these bioactive venom toxins and those inhibited by varespladib by using parallel recorded LC-MS data and proteomics analysis. We demonstrated here that varespladib was not only capable of inhibiting the PLA2 activities of hemotoxic snake venoms, but can also effectively neutralize the coagulopathic toxicities (most profoundly anticoagulation) induced by venom toxins. While varespladib effectively inhibited PLA2 toxins responsible for anticoagulant effects, we also found some evidence that this inhibitory molecule can partially abrogate procoagulant venom effects caused by different toxin families. These findings further emphasize the potential clinical utility of varespladib in mitigating the toxic effects of certain snakebites. |
| Databáze: | OpenAIRE |
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