Zebrafish as a translational model for Bitis arietans envenomation: Integrative proteomic and histopathological insights.

Abstract

The genus Bitis, especially the species Bitis arietans, significantly contributes to snakebite incidents in Africa, causing a range of serious medical conditions. This study aimed to explore the pathological mechanisms underlying envenomations by B. arietans using zebrafish (Danio rerio) as a model organism. Blood samples were collected at 3- and 6-h post-envenomation, followed by plasma analysis through mass spectrometry. Key findings indicated that B. arietans venom caused a hemolytic effect leading to acute severe anemia by 6 h post-envenomation. A hematopoietic response was also observed, characterized by an increase in precursor blood cells and leukocytosis with elevated myelomonocytic cell counts. Mass spectrometry analysis identified 558 plasma proteins with differential abundance between the experimental groups, many of which play crucial roles in biological processes such as immune response, hemostasis, coagulation cascade, complement system activation, neutrophil degranulation, and oxidative stress regulation. Additionally, proteins associated with cellular extravasation and regulatory functions were detected, correlating with histopathological lesions observed locally and indicating systemic effects of envenomation affecting vital organs such as the kidneys, heart, liver, and gills. Our results suggest that the plasma protein profile identified may serve as potential biomarkers for assessing lesions resulting from B. arietans envenomation. Overall, these findings enhance our understanding of the toxic impacts of B. arietans venom and underscore the utility of zebrafish as a model for further research into snakebite pathophysiology.