Delayed oral LY333013 rescues mice from highly neurotoxic, lethal doses of Papuan Taipan (Oxyuranus scutellatus) venom

 

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Detalles Bibliográficos
Autores: Gutiérrez, José María, Samuel, Stephen P., Herrera Vega, María, Bryan Quirós, Wendy, Lomonte, Bruno, Bickler, Philip E., Bulfone, Tommaso C., Williams, David J.
Formato: artículo original
Fecha de Publicación:2018
Descripción: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
País:Kérwá
Institución:Universidad de Costa Rica
Repositorio:Kérwá
OAI Identifier:oai:https://www.kerwa.ucr.ac.cr:10669/76387
Acceso en línea:https://www.mdpi.com/2072-6651/10/10/380
https://hdl.handle.net/10669/76387
Access Level:acceso abierto
Palabra clave:Snakebite
Envenoming
Neglected tropical disease
Field antidote
Inhibitor
Taipan
PLA2
Phospholipase A2
Neurotoxicity
Antivenom
615.94 Venenos animales