Delayed oral LY333013 rescues mice from highly neurotoxic, lethal doses of Papuan Taipan (Oxyuranus scutellatus) venom
| Autor: | Philip E. Bickler, Bruno Lomonte, José María Gutiérrez, Stephen P. Samuel, Matthew R. Lewin, María Herrera, Tommaso C. Bulfone, David J. Williams, Wendy Bryan-Quirós |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Field antidote Indoles Envenoming Health Toxicology and Mutagenesis Antivenom Administration Oral lcsh:Medicine Venom Pharmacology Acetates Toxicology snakebite Oxyuranus scutellatus Mice 615.94 Venenos animales Oral administration Phospholipase A2 neurotoxicity Elapidae Snakebite Taipan biology Antivenins Communication Pharmacology and Pharmaceutical Sciences field antidote Keto Acids inhibitor neglected tropical disease 5.1 Pharmaceuticals Snake venom Administration Female Oral Inhibitor Phospholipase A2 Inhibitors Neurotoxins Neglected tropical disease 03 medical and health sciences medicine Neurotoxicity Animals taipan Envenomation Elapid Venoms PLA2 antivenom business.industry lcsh:R biology.organism_classification medicine.disease 030104 developmental biology envenoming phospholipase A2 Biochemistry and Cell Biology business |
| Zdroj: | Toxins, vo.10(10), pp. 1-7. Kérwá Universidad de Costa Rica instacron:UCR Toxins, Vol 10, Iss 10, p 380 (2018) Toxins, vol 10, iss 10 Toxins |
| Popis: | There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP) UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiología |
| Databáze: | OpenAIRE |
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