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A lipidomics approach reveals new insights into Crotalus durissus terrificus and Bothrops moojeni snake venoms

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Abstract

Snakebite envenomation causes > 81,000 deaths and incapacities in another 400,000 people worldwide every year. Snake venoms are complex natural secretions comprised of hundreds of different molecules with a wide range of biological functions that after injection cause local and systemic manifestations. Although several studies have investigated snake venoms, the majority have focused on the protein portion (toxins), without significant attention paid to the lipid fraction. Therefore, an untargeted lipidomic approach based on liquid chromatography with high-resolution mass spectrometry (LC-HRMS) was applied to investigate the lipid constituents of venoms of the snake species Crotalus durissus terrificus and Bothrops moojeni. Phosphatidylcholines (PC), Lyso-PCs, phosphatidylethanolamines (PE), Lyso-PE, phosphatidylserine (PS), phosphatidylinositol (PI), ceramides (Cer), and sphingomyelin (SM) species were detected in the analyzed snake venoms. The identified lipids included bioactive compounds such as platelet-activating factor (PAF) precursor, PAF-like molecules, plasmalogens, ceramides, and sphingomyelins with long fatty acid chain lengths, which may be associated with the systemic responses triggered by C. d. terrificus and B. moojeni envenomation. These responses include platelet aggregation, activation of intercellular adhesion molecule 1 (ICAM1), apoptosis, as well as the production of pro-inflammatory lipid mediators, cytokines, and reactive species. The newly proposed lipidomics strategy provided valuable information regarding the lipid profiles of viperid venoms, which could lead to increased understanding of the complex pathology promoted by snakebite envenomation.

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All data is contained in the manuscript or the supplemental material, and are available from the corresponding author upon request.

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Acknowledgements

This work was supported by the São Paulo Research Foundation (FAPESP, Grants #2014/07125-6, and EMU #2015/00658-1) and the National Council for Scientific and Technological Development (CNPq, Research Grant 302514/2015-5). T.A. thanks the FAPESP for the post-doctoral fellowship (Grants #2018/25704-4). The authors would like to thank the biologist Luiz Henrique Anzaloni Pedrosa for extracting the snake venoms.

Funding

This work was supported by the São Paulo Research Foundation (FAPESP, Grants #2018/25704-4, #2014/07125-6, and EMU #2015/00658-1) and the National Council for Scientific and Technological Development (CNPq, Research Grant 302514/2015-5).

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TA: conceived of/designed the study, performed research, analyzed data and wrote the paper. VN: analyzed data and reviewed and edited the paper. LHF: conceived of/designed the study and reviewed and edited the paper.

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Correspondence to Lúcia Helena Faccioli.

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Acunha, T., Nardini, V. & Faccioli, L.H. A lipidomics approach reveals new insights into Crotalus durissus terrificus and Bothrops moojeni snake venoms. Arch Toxicol 95, 345–353 (2021). https://doi.org/10.1007/s00204-020-02896-y

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  • DOI: https://doi.org/10.1007/s00204-020-02896-y

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