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Snakebite envenoming is one of the most significantly neglected tropical diseases in the world. The lack of diagnosis/prognosis methods for snakebite is one of our motivations to develop innovative technological solutions for Brazilian health. The objective of this work was to evaluate the protein and metallic ion composition of Crotalus durissus terrificus, Bothrops jararaca, B. alternatus, B. jararacussu, B. moojeni, B. pauloensis, and Lachesis muta muta snake venoms. Brazilian snake venoms were subjected to the shotgun proteomic approach using mass spectrometry, and metal ion analysis was performed by atomic spectrometry. Shotgun proteomics has shown three abundant toxin classes (PLA2, serine proteases, and metalloproteinases) in all snake venoms, and metallic ions analysis has evidenced that the Cu2+ ion is present exclusively in the L. m. muta venom; Ca2+ and Mg2+ ions have shown a statistical difference between the species of Bothrops and Crotalus genus, whereas the Zn2+ ion presented a statistical difference among all species studied in this work. In addition, Mg2+ ions have shown 42 times more in the C. d. terrificus venom when compared to the average concentration in the other genera. Though metal ions are a minor fraction of snake venoms, several venom toxins depend on them. We believe that these non-protein fractions are capable of assisting in the development of unprecedented diagnostic devices for Brazilian snakebites. [ABSTRACT FROM AUTHOR]

Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 animals intraperitoneally inoculated with saline solution in the control group (CG), as well as venom in the experimental group (EG). The animals were euthanized at predetermined intervals (1 h, 3 h, 6 h, 12 h, 24 h, and 48 h), and lung fragments were collected for H&E and Masson histological analysis. The CG did not present inflammatory alterations in pulmonary parenchyma. In the EG, interstitial and alveolar swelling, necrosis, septal losses followed by alveolar distensions, and areas of atelectasis in the pulmonary parenchyma were observed after three hours. The EG morphometric analysis presented pulmonary inflammatory infiltrates at all time intervals, being more significant at three and six (p = 0.035) and six and 12 h (p = 0.006). The necrosis zones were significant at intervals of one and 24 h (p = 0.001), one and 48 h (p = 0.001), and three and 48 h (p = 0.035). Crotalus durissus cascavella venom induces a diffuse, heterogeneous, and acute inflammatory injury in the pulmonary parenchyma, with potential clinical implications for respiratory mechanics and gas exchange. The early recognition and prompt treatment of this condition are essential to prevent further lung injury and to improve outcomes. [ABSTRACT FROM AUTHOR]

This study investigated the systemic inflammatory response and mechanism of pulmonary lesions induced by Crotalus durissus cascavella venom in murine in the state of Bahia. In order to investigate T helper Th1, Th2 and Th17 lymphocyte profiles, we measured interleukin (IL) -2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF) and interferon gamma (IFN-γ) levels in the peritoneal fluid and macerated lungs of mice and histopathological alterations at the specific time windows of 1h, 3h, 6h, 12h, 24h and 48h after inoculation with Crotalus durissus cascavella venom. The data demonstrated an increase of acute-phase cytokines (IL-6 and TNF) in the first hours after inoculation, with a subsequent increase in IL-10 and IL-4, suggesting immune response modulation for the Th2 profile. The histopathological analysis showed significant morphological alterations, compatible with acute pulmonary lesions, with polymorphonuclear leukocyte (PMN) infiltration, intra-alveolar edema, congestion, hemorrhage and atelectasis. These findings advance our understanding of the dynamics of envenomation and contribute to improve clinical management and antiophidic therapy for individuals exposed to venom. [ABSTRACT FROM AUTHOR]

Bothrops leucurus is considered as a snake of medical interest in the State of Bahia, Brazil. However, so far, there are no studies that provide a refined mapping of the composition of this venom. The aim of this work was to better understand the protein composition of B. leucurus snake venom and to isolate and biologically characterize the most abundant toxin, a basic PLA 2 -like. Shotgun proteomics approach identified 137 protein hits in B. leucurus venom subdivided into 19 protein families. The new basic PLA 2- like toxin identified was denominated Bleu-PLA 2 -like, it and other proteoforms represents about 25% of the total proteins in the venom of B. leucurus and induces myotoxicity, inflammation and muscle damage. Immunoreactivity assays demonstrated that B. leucurus venom is moderately recognized by bothropic and crotalic antivenoms, and on the other hand, Bleu-PLA 2 -like and its proteoforms are poorly recognized. Our findings open doors for future studies in order to assess the systemic effects caused by this snake venom in order to better understand the toxinological implications of this envenomation and, consequently, to assist in the clinical treatment of victims. [Display omitted] • Proteomics approaches have expanded the knowledge about the Bothrops leucurus venom. • Bleu-PLA 2 -like induces inflammatory, myotoxic and edematogenic effects. • Bothrops leucurus snake venom is moderately recognized by Brazilian antivenoms. [ABSTRACT FROM AUTHOR]

Abstract: Tarantulas are included in the mygalomorph spider family Theraphosidae. Although the pharmacological diversity of theraphosid toxins (theraphotoxins) is broad, studies dedicated to the characterization of biologically active molecules from the theraphosid genus Acanthoscurria have been restricted to the investigation of antimicrobial peptides and polyamines produced by the hemocytes of Acanthoscurria gomesiana. The present study reports the purification, primary structure determination and electrophysiological effects of an anti-insect toxin, named μ-theraphotoxin-An1a (μ-TRTX-An1a), from the venom of Acanthoscurria natalensis – a tarantula species occurring in the Brazilian biomes caatinga and cerrado. The analysis of the primary structure of μ-TRTX-An1a revealed the similarity of this toxin to theraphosid toxins bearing a huwentoxin-II-like fold. Electrophysiological experiments showed that μ-TRTX-An1a (100 nM) induces membrane depolarization, increases the spontaneous firing frequency and reduces spike amplitude of cockroach dorsal unpaired median (DUM) neurons. In addition, under voltage-clamp conditions, μ-TRTX-An1a (100 nM) only partially blocks voltage-dependent sodium current amplitudes in DUM neurons without any effect on their voltage dependence. This effect correlates well with the reduction of the spontaneous action potential amplitudes. Altogether, these last results suggest that μ-TRTX-An1a affects insect neuronal voltage-dependent sodium channels, which are among possible channels targeted by this promiscuous toxin. [Copyright &y& Elsevier]

Abstract: The Buthidae is the most clinically important scorpion family, with over 500 species distributed worldwide. Taxonomical positions and phylogenetic relationships concerning the representative genera and species of this family have been mostly inferred based upon comparisons between morphological characters. Yet, some authors have performed such inferences by comparing some structural properties of a few selected molecules found in the venoms from these scorpions. Here, we propose a novel methodology pipeline designed to address these issues. We have analyzed the whole venoms from some species that exemplify peculiar cases in the Buthidae family (Tityus stigmurus, Tityus serrulatus, Tityus bahiensis, Leiurus quinquestriatus quinquestriatus and Leiurus quinquestriatus hebraeus), by means of a proteomic approach using a 2D-LC/MS technique. The molecules found in these venoms were clustered according to their physicochemical properties (molecular mass and hydrophobicity), by using the machine learning-based Weka software. The clusters assessment, along with the number of molecules found in a given cluster for each scorpion, which assigns for the venom and structural family complexities, respectively, was used to generate a phenetic correlation tree for positioning these species. Our results were in accordance with the classical taxonomy viewpoint, which places T. serrulatus and T. stigmurus as very close species, T. bahiensis as a less related species in the Tityus genus and L. q. quinquestriatus and L. q. hebraeus with small differences within the same species (L. quinquestriatus). Therefore, we believe that this is a well-suited method to determine venom complexities that reflect the scorpions'' evolutionary history, which can be crucial to reconstruct their phylogeny through the molecular evolution of their venoms. [Copyright &y& Elsevier]