A fingerprint of plasma proteome alteration after local tissue damage induced by Bothrops leucurus snake venom in mice

Cavalcante, Joeliton dos Santos; Almeida, Cayo; Clasen, Milan A; Silva, Emerson Lucena da; Barros, Luciana Curtolo de; Rossini, Bruno César; Marino, Celso Luís; Carvalho, Paulo C.; Jorge, Roberta Jeane Bezerra; Santos, Lucilene Delazari dos

doi:10.1016/j.jprot.2021.104464

Cited by 13 publications

(20 citation statements)

References 115 publications

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“…30,33,34 Regardless of the mechanism of induction, immune system processes dominated the top 20 enriched pathways for both unique and upregulated proteins and we further identified multiple signatures associated with inflammatory signalling and response (Table 1 and complement system, coagulation, oxidative stress, neutrophil degranulation, and platelet degranulation. 12,13,35 Inflammation is a common response to envenomation. However, we did not detect the same proteins that were suggested to indicate the severity of inflammation, perhaps due to the development of anaphylaxis in this case as opposed to a less severe localized inflammatory reaction.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of detecting snake envenomation biomarkers from dried blood spots

Smith

Brandehoff

Pepin

et al. 2023

Analytical Science Advances

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Biofluid proteomics is a sensitive and high throughput technique that provides vast amounts of molecular data for biomarker discovery. More recently, dried blood spots (DBS) have gained traction as a stable, noninvasive, and relatively cheap source of proteomic data for biomarker identification in disease and injury. Snake envenomation is responsible for significant morbidity and mortality worldwide; however, much remains unknown about the systemic molecular response to envenomation and acquiring biological samples for analysis is a major hurdle. In this study, we utilized DBS acquired from a case of lethal rattlesnake envenomation to determine the feasibility of discovering biomarkers associated with human envenomation. We identified proteins that were either unique or upregulated in envenomated blood compared to non‐envenomated blood and evaluated if physiological response pathways and protein markers that correspond to the observed syndromes triggered by envenomation could be detected. We demonstrate that DBS provide useful proteomic information on the systemic processes that resulted from envenomation in this case and find evidence for a massive and systemic inflammatory cascade, combined with coagulation dysregulation, complement system activation, hypoxia response activation, and apoptosis. We also detected potential markers indicative of lethal anaphylaxis, cardiac arrest, and brain death. Ultimately, DBS proteomics has the potential to provide stable and sensitive molecular data on envenomation syndromes and response pathways, which is particularly relevant in low‐resource areas which may lack the materials for biofluid processing and storage.

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Section: Discussionmentioning

confidence: 99%

Feasibility of detecting snake envenomation biomarkers from dried blood spots

Smith

Brandehoff

Pepin

et al. 2023

Analytical Science Advances

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“…Human envenomation by venomous animals causes changes in plasma protein abundance that are currently monitored by assays that primarily assess changes in hemostasis [ 20 , 21 ]. Additionally, other proteins that are or are not involved in hemostasis have already been identified as potential biomarker candidates but require validation for monitoring clinical complications associated with envenomation [ 67 , 68 , 69 , 70 ]. Furthermore, the possibility of identifying circulating animal toxins in plasma samples from patients after multiple bee stings [ 50 ] and snake bites [ 41 , 71 ] using proteomics tools has already been reported.…”

Section: Biomarkers For Envenomation By Venomous Animals: What To Loo...mentioning

confidence: 99%

“…Studies involving mass spectrometry in toxinology have focused on the study of proteins present in animal venoms, converging on (i) the identification of isolated and purified proteins from venoms [ 72 , 73 , 74 ], (ii) the description of the composition of venoms [ 75 , 76 , 77 , 78 , 79 , 80 , 81 ], and (iii) the identification of altered biological processes in tissues after tissue damage caused by snake venom [ 41 , 67 , 68 , 69 , 70 , 82 , 83 ]. MS can assist in the development and tracking of target toxins and improve the sensitivity and specificity of ELISA and Western blot assays by identifying toxins circulating in the blood of the victims.…”

Section: Biomarkers For Envenomation By Venomous Animals: What To Loo...mentioning

confidence: 99%

“…The number of species within the same genus can be a critical challenge for studies of biomarkers in envenomation by venomous animals. As observed in experimental studies, different biomarker candidates may be associated with the species that caused the envenomation, requiring the search for candidates that overlap at the genus level [ 67 , 68 , 69 ]. There is an opportunity for high specificity if the biomarker target is not endogenous, for example, specific toxins with markers [ 41 , 50 , 71 ].…”

Section: Other Directions For Studies Of Biomarkers In Envenomationsmentioning

confidence: 99%

“…Furthermore, the ability to actually target and separate the biomarkers associated with clinical complications from those that are not could be a potential challenge. One of the limitations encountered so far in studies is that they display a map of the proteome differentially expressed at a single moment during disease progression compared to healthy individuals or individuals who did not present a specific event [ 37 , 67 , 68 , 69 , 70 ]. Single-point analysis (case versus control) in the case of envenomations by venomous animals, which involves obtaining an overview of biomarkers at the moment the patient enters the hospital service, will help to identify possible diagnostic markers.…”

Section: Other Directions For Studies Of Biomarkers In Envenomationsmentioning

confidence: 99%

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Challenges and Opportunities in Clinical Diagnostic Routine of Envenomation Using Blood Plasma Proteomics

Cavalcante

Almeida

Moraes

et al. 2023

Toxins

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Specific and sensitive tools for the diagnosis and monitoring of accidents by venomous animals are urgently needed. Several diagnostic and monitoring assays have been developed; however, they have not yet reached the clinic. This has resulted in late diagnoses, which represents one of the main causes of progression from mild to severe disease. Human blood is a protein-rich biological fluid that is routinely collected in hospital settings for diagnostic purposes, which can translate research progress from the laboratory to the clinic. Although it is a limited view, blood plasma proteins provide information about the clinical picture of envenomation. Proteome disturbances in response to envenomation by venomous animals have been identified, allowing mass spectrometry (MS)-based plasma proteomics to emerge as a tool in a range of clinical diagnostics and disease management that can be applied to cases of venomous animal envenomation. Here, we provide a review of the state of the art on routine laboratory diagnoses of envenomation by snakes, scorpions, bees, and spiders, as well as a review of the diagnostic methods and the challenges encountered. We present the state of the art on clinical proteomics as the standardization of procedures to be performed within and between research laboratories, favoring a more excellent peptide coverage of candidate proteins for biomarkers. Therefore, the selection of a sample type and method of preparation should be very specific and based on the discovery of biomarkers in specific approaches. However, the sample collection protocol (e.g., collection tube type) and the processing procedure of the sample (e.g., clotting temperature, time allowed for clotting, and anticoagulant used) are equally important to eliminate any bias.

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