Autor(es)

Silva, Ana Luiza T. ; de Barros, Bianca C. S. C. ; da Silva, Joanderson P. C. ; Carvalho, Isabel S. ; Santoro, Marcelo L. ; Chaves, Alison F. A. ; Serrano, Solange M. T.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PROTEOMICS; v. 325, p. 13-pg., 2026-03-15.

Resumo

Snakebite envenomation is a critical yet underexplored public health issue, particularly in tropical and subtropical regions. Bothrops jararaca venom induces severe local and systemic effects, including pulmonary injury, however, the molecular mechanisms underlying lung tissue damage remain poorly understood. This study employed label- free quantitative proteomics to map protein alterations in the lung tissue in a mouse model of envenomation. Using Data-Dependent Acquisition (DDA) and Data-Independent Acquisition (DIA) approaches combined with different sample preparation methods, we provide a comprehensive proteomic profile of venominduced pulmonary damage. Our findings reveal significant changes in proteins involved in inflammatory responses, extracellular matrix remodeling, oxidative stress, and blood coagulation. Comparative analyses highlight the superior performance of DIA over DDA, with DIA offering deeper proteome coverage, enhanced detection of low-abundance proteins, and improved resolution of venom-induced alterations. This benchmark study underscores the potential of DIA as a robust tool for elucidating complex, systemic, mammalian molecular responses to animal toxins. By bridging the gap between proteomic methodologies and pathophysiological insights, our findings contribute to a deeper understanding of viperid snake venom-induced lung injury and give insights for improved clinical management strategies. Significance: Bothrops snakebites remain a major neglected health problem, causing severe local and systemic complications. While the impact of viperid venoms on muscle and kidney tissues is well documented, the effects on the lungs - an organ critically involved in systemic envenomation outcomes - remain poorly understood. Our study provides the first comprehensive proteomic characterization of lung responses to B. jararaca venom in a murine model, revealing alterations in pathways related to inflammation, extracellular matrix remodeling, oxidative stress, and coagulation. These molecular insights fill an important knowledge gap by showing that proteomic disturbances occur even in the absence of overt lung pathology, highlighting the lungs as a key systemic target of envenomation. Moreover, by demonstrating that antivenom administration mitigates many of these changes, our findings underscore both the therapeutic efficacy of antivenom and the need to better understand its broader systemic footprint. This work advances both toxinology and proteomics by linking molecular-level disturbances to clinically relevant systemic outcomes. (AU)

• Processo FAPESP: 23/08327-0 - O veneno de Bothrops jararaca e o dano tecidual: análise proteômica e peptidômica da toxicidade em fibroblastos humanos.
• Beneficiário: Isabel de Souza Carvalho
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 19/07618-6 - Interação hemostasia-inflamação no envenenamento pela serpente Bothrops jararaca: patogênese da plaquetopenia e mecanismos terapêuticos antiofídicos da quercetina-3-rutinosídeo (rutina)
• Beneficiário: Marcelo Larami Santoro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/12317-2 - Análise proteômica dos efeitos sistêmicos do veneno da Bothrops jararaca em modelo murino.
• Beneficiário: Alison Felipe Alencar Chaves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/26476-8 - Análise proteômica e metabolômica sistêmica do envenenemento por serpentes do gênero Bothrops e dos efeitos do antiveneno, utilizando um modelo murino
• Beneficiário: Solange Maria de Toledo Serrano
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/16146-3 - Caracterização molecular dos efeitos do veneno de Bothrops jararaca: análise de células pulmonares em cultura e tecido pulmonar de camundongo por abordagens proteômica e imuno-histoquímica.
• Beneficiário: Ana Luiza Teixeira Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 21/10570-5 - Caracterização molecular dos efeitos in vivo do veneno da Bothrops jararaca: análises do tecido muscular e do plasma de camundongos, por abordagens de proteômica e imuno-histoquímica
• Beneficiário: Bianca Carla Silva Campitelli de Barros
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado