Abstract

Skin blistering as a result of snakebite envenomation is characteristic of some bites, however little is known regarding the mechanism of blister formation or the composition of the blister fluid. In order to investigate if blister fluid proteomes from humans suffering snakebite envenomation could provide insights on the pathophysiology of these skin alterations, blister fluid was collected from six patients upon presentation at a clinic in India bitten by three species of snakes, Daboia russelii (3), Hypnale hypnale (2), or Naja naja (1). Standard clinical data were recorded throughout the treatment. Approximately 805 proteins were identified in blister fluids using proteomic analyses. Informatics analyses of the proteomes identified the top biological response categories as: platelet degranulation, innate immune response, receptor-mediated endocytosis, complement activation, and blood coagulation. Hierarchical clustering did not show a clear segregation of patients’ proteomes being associated with the species of snake involved, suggesting that either the proteomic profiles described reflect a general response to venom-induced tissue damage or more patient data sets will be required to observe significant differences. Finally, it is of interest that venom proteins were also identified in the blister fluids suggesting that this fluid may serve as a reservoir of venom biologically active proteins/toxins, and as such, may indicate the clinical value of removing blister fluid to attenuate further tissue damage.

Highlights

  • Snakebite envenomations represent a significant public health problem observed on a global basis, but in sub-Saharan Africa, Asia, Latin America, and parts of Oceania, and have been included by the World Health Organization (WHO) in the list of neglected tropical diseases [1]

  • In this study, utilizing mass spectrometry, we investigated the composition of blister fluid collected from patients envenomated by three species of Indian snakes, i.e., Daboia russelii and Hypnale sp., or Naja naja

  • Previous studies carried out in mice have described the potential of proteomics analysis of wound exudate fluid to provide a “window” to explore the pathological and inflammatory events occurring in tissues injected with snake venoms

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Summary

Introduction

Snakebite envenomations represent a significant public health problem observed on a global basis, but in sub-Saharan Africa, Asia, Latin America, and parts of Oceania, and have been included by the World Health Organization (WHO) in the list of neglected tropical diseases [1]. Polyvalent snake antivenoms (SAV) are produced by several manufacturers in India against venoms of the “big four” species, envenomations continue to cause fatalities and pathophysiological sequelae in thousands of people a year. There is a need to further expand our knowledge on the various aspects of snakebite envenomation in this country, including a better understanding of the pathophysiology and mechanisms of action of venom-induced effects. Efforts have been directed at the identification of markers of tissue damage, especially at the injury site, since they may provide valuable information about the mechanisms of disease and the condition and prognosis of the patient, all of which may lead to a more effective treatment [5,6,7]

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