Delayed oral LY333013 rescues mice from highly neurotoxic, lethal doses of Papuan Taipan (Oxyuranus scutellatus) venom
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...
| Main Authors: | , , , , , , , |
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| Format: | Artículo |
| Language: | Inglés |
| Published: |
2019
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| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/10/10/380 https://hdl.handle.net/10669/76387 |
| Summary: | 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 |
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