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The role of natural selection in the evolution of trait complexity can be characterized by testing hypothesized links between complex forms and their functions across species. Predatory venoms are composed of multiple proteins that collectively function to incapacitate prey. Venom complexity fluctuates over evolutionary timescales, with apparent increases and decreases in complexity, and yet the causes of this variation are unclear. We tested alternative hypotheses linking venom complexity and ecological sources of selection from diet in the largest clade of front-fanged venomous snakes in North America: the rattlesnakes, copperheads, cantils, and cottonmouths. We generated independent transcriptomic and proteomic measures of venom complexity and collated several natural history studies to quantify dietary variation. We then constructed genome-scale phylogenies for these snakes for comparative analyses. Strikingly, prey phylogenetic diversity was more strongly correlated to venom complexity than was overall prey species diversity, specifically implicating prey species’ divergence, rather than the number of lineages alone, in the evolution of complexity. Prey phylogenetic diversity further predicted transcriptomic complexity of three of the four largest gene families in viper venom, showing that complexity evolution is a concerted response among many independent gene families. We suggest that the phylogenetic diversity of prey measures functionally relevant divergence in the targets of venom, a claim supported by sequence diversity in the coagulation cascade targets of venom. Our results support the general concept that the diversity of species in an ecological community is more important than their overall number in determining evolutionary patterns in predator trait complexity.
Matthew L. Holding; Jason L. Strickland; Rhett M. Rautsaw; Erich P. Hofmann; Andrew J. Mason; Michael P. Hogan; Gunnar S. Nystrom; Schyler A. Ellsworth; Timothy J. Colston; Miguel Borja; Gamaliel Castañeda-Gaytán; Christoph I. Grünwald; Jason M. Jones; Luciana A. Freitas-De-Sousa; Vincent Louis Viala; Mark J. Margres; Erika Hingst-Zaher; Inácio L. M. Junqueira-De-Azevedo; Ana M. Moura-Da-Silva; Felipe G. Grazziotin; H. Lisle Gibbs; Darin R. Rokyta; Christopher L. Parkinson. Phylogenetically diverse diets favor more complex venoms in North American pitvipers. Proceedings of the National Academy of Sciences 2021, 118, 1 .
AMA StyleMatthew L. Holding, Jason L. Strickland, Rhett M. Rautsaw, Erich P. Hofmann, Andrew J. Mason, Michael P. Hogan, Gunnar S. Nystrom, Schyler A. Ellsworth, Timothy J. Colston, Miguel Borja, Gamaliel Castañeda-Gaytán, Christoph I. Grünwald, Jason M. Jones, Luciana A. Freitas-De-Sousa, Vincent Louis Viala, Mark J. Margres, Erika Hingst-Zaher, Inácio L. M. Junqueira-De-Azevedo, Ana M. Moura-Da-Silva, Felipe G. Grazziotin, H. Lisle Gibbs, Darin R. Rokyta, Christopher L. Parkinson. Phylogenetically diverse diets favor more complex venoms in North American pitvipers. Proceedings of the National Academy of Sciences. 2021; 118 (17):1.
Chicago/Turabian StyleMatthew L. Holding; Jason L. Strickland; Rhett M. Rautsaw; Erich P. Hofmann; Andrew J. Mason; Michael P. Hogan; Gunnar S. Nystrom; Schyler A. Ellsworth; Timothy J. Colston; Miguel Borja; Gamaliel Castañeda-Gaytán; Christoph I. Grünwald; Jason M. Jones; Luciana A. Freitas-De-Sousa; Vincent Louis Viala; Mark J. Margres; Erika Hingst-Zaher; Inácio L. M. Junqueira-De-Azevedo; Ana M. Moura-Da-Silva; Felipe G. Grazziotin; H. Lisle Gibbs; Darin R. Rokyta; Christopher L. Parkinson. 2021. "Phylogenetically diverse diets favor more complex venoms in North American pitvipers." Proceedings of the National Academy of Sciences 118, no. 17: 1.
Ontogenetic changes in venom composition have been described in Bothrops snakes, but only a few studies have attempted to identify the targeted paralogues or the molecular mechanisms involved in modifications of gene expression during ontogeny. In this study, we decoded B. jararacussu venom gland transcripts from six specimens of varying sizes and analyzed the variability in the composition of independent venom proteomes from 19 individuals. We identified 125 distinct putative toxin transcripts, and of these, 73 were detected in venom proteomes and only 10 were involved in the ontogenetic changes. Ontogenetic variability was linearly related to snake size and did not correspond to the maturation of the reproductive stage. Changes in the transcriptome were highly predictive of changes in the venom proteome. The basic myotoxic phospholipases A2 (PLA2s) were the most abundant components in larger snakes, while in venoms from smaller snakes, PIII-class SVMPs were the major components. The snake venom metalloproteinases (SVMPs) identified corresponded to novel sequences and conferred higher pro-coagulant and hemorrhagic functions to the venom of small snakes. The mechanisms modulating venom variability are predominantly related to transcriptional events and may consist of an advantage of higher hematotoxicity and more efficient predatory function in the venom from small snakes.
Luciana A. Freitas-De-Sousa; Pedro G. Nachtigall; José A. Portes-Junior; Matthew L. Holding; Gunnar S. Nystrom; Schyler A. Ellsworth; Noranathan C. Guimarães; Emilly Tioyama; Flora Ortiz; Bruno R. Silva; Tobias S. Kunz; Inácio L. M. Junqueira-De-Azevedo; Felipe G. Grazziotin; Darin R. Rokyta; Ana M. Moura-Da-Silva. Size Matters: An Evaluation of the Molecular Basis of Ontogenetic Modifications in the Composition of Bothrops jararacussu Snake Venom. Toxins 2020, 12, 791 .
AMA StyleLuciana A. Freitas-De-Sousa, Pedro G. Nachtigall, José A. Portes-Junior, Matthew L. Holding, Gunnar S. Nystrom, Schyler A. Ellsworth, Noranathan C. Guimarães, Emilly Tioyama, Flora Ortiz, Bruno R. Silva, Tobias S. Kunz, Inácio L. M. Junqueira-De-Azevedo, Felipe G. Grazziotin, Darin R. Rokyta, Ana M. Moura-Da-Silva. Size Matters: An Evaluation of the Molecular Basis of Ontogenetic Modifications in the Composition of Bothrops jararacussu Snake Venom. Toxins. 2020; 12 (12):791.
Chicago/Turabian StyleLuciana A. Freitas-De-Sousa; Pedro G. Nachtigall; José A. Portes-Junior; Matthew L. Holding; Gunnar S. Nystrom; Schyler A. Ellsworth; Noranathan C. Guimarães; Emilly Tioyama; Flora Ortiz; Bruno R. Silva; Tobias S. Kunz; Inácio L. M. Junqueira-De-Azevedo; Felipe G. Grazziotin; Darin R. Rokyta; Ana M. Moura-Da-Silva. 2020. "Size Matters: An Evaluation of the Molecular Basis of Ontogenetic Modifications in the Composition of Bothrops jararacussu Snake Venom." Toxins 12, no. 12: 791.
Bleeding is a common hemostatic disorder that occurs in Bothrops envenomations. We evaluated the changes in coagulation, fibrinolysis components, and platelets in Bothrops atrox envenomations with bleeding. This is an observational study with B. atrox snakebite patients (n = 100) treated in Manaus, Brazilian Amazon. Bleeding was recorded on admission and during hospitalization. We found that the platelet count in our patients presented a weak correlation to tissue factor, factor II, and plasminogen. Tissue factor presented weak correlation to factor V, II, D-dimer, plasminogen, alpha 2-antiplasmin, and moderate correlation to fibrinogen and fibrin/fibrinogen degradation product (FDP). Patients with systemic bleeding (n = 20) presented low levels of factor V, II, fibrinogen, plasminogen, and alpha 2-antiplasmin, and high levels of tissue factor and FDP compared to those without bleeding. Patients with only local bleeding (n = 41) and without bleeding showed similar levels of hemostatic factors. Thrombocytopenia was observed mainly in patients with systemic bleeding and increased levels of serum venom. No association was found between venom levels and systemic bleeding, or between venom levels and clinical severity of envenomation. This is the first report that shows the participation of the extrinsic coagulation pathway in the consumption coagulopathy of B. atrox envenomations with systemic bleeding due to tissue factor release.
Sâmella S. Oliveira; Eliane C. Alves; Alessandra S. Santos; Elizandra F. Nascimento; João T. Pereira; Iran M. Silva; Jacqueline A. G. Sachett; Lybia S. Sarraff; Luciana Freitas-De-Sousa; Mônica Colombini; Hedylamar O. Marques; Marcus V. G. Lacerda; Marco Sartim; Ana Moura-Da-Silva; Luiz L. Ferreira; Ida S. Sano-Martins; Wuelton M. Monteiro. Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor. Toxins 2020, 12, 554 .
AMA StyleSâmella S. Oliveira, Eliane C. Alves, Alessandra S. Santos, Elizandra F. Nascimento, João T. Pereira, Iran M. Silva, Jacqueline A. G. Sachett, Lybia S. Sarraff, Luciana Freitas-De-Sousa, Mônica Colombini, Hedylamar O. Marques, Marcus V. G. Lacerda, Marco Sartim, Ana Moura-Da-Silva, Luiz L. Ferreira, Ida S. Sano-Martins, Wuelton M. Monteiro. Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor. Toxins. 2020; 12 (9):554.
Chicago/Turabian StyleSâmella S. Oliveira; Eliane C. Alves; Alessandra S. Santos; Elizandra F. Nascimento; João T. Pereira; Iran M. Silva; Jacqueline A. G. Sachett; Lybia S. Sarraff; Luciana Freitas-De-Sousa; Mônica Colombini; Hedylamar O. Marques; Marcus V. G. Lacerda; Marco Sartim; Ana Moura-Da-Silva; Luiz L. Ferreira; Ida S. Sano-Martins; Wuelton M. Monteiro. 2020. "Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor." Toxins 12, no. 9: 554.
Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.
Ana Maria Moura-Da-Silva; Jorge Carlos Contreras-Bernal; Sarah Natalie Cirilo Gimenes; Luciana Aparecida Freitas-De-Sousa; José Antonio Portes-Junior; Pedro Da Silva Peixoto; Leo Kei Iwai; Valéria Mourão De Moura; Pedro Ferreira Bisneto; Marcus Lacerda; Iran Mendonça Da Silva; Luiz Carlos De Lima Ferreira; Sâmella Silva De Oliveira; Fan Hui Wen; Jacqueline De Almeida Gonçalves Sachett; Wuelton M. Monteiro. The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox). PLOS Neglected Tropical Diseases 2020, 14, e0008299 .
AMA StyleAna Maria Moura-Da-Silva, Jorge Carlos Contreras-Bernal, Sarah Natalie Cirilo Gimenes, Luciana Aparecida Freitas-De-Sousa, José Antonio Portes-Junior, Pedro Da Silva Peixoto, Leo Kei Iwai, Valéria Mourão De Moura, Pedro Ferreira Bisneto, Marcus Lacerda, Iran Mendonça Da Silva, Luiz Carlos De Lima Ferreira, Sâmella Silva De Oliveira, Fan Hui Wen, Jacqueline De Almeida Gonçalves Sachett, Wuelton M. Monteiro. The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox). PLOS Neglected Tropical Diseases. 2020; 14 (6):e0008299.
Chicago/Turabian StyleAna Maria Moura-Da-Silva; Jorge Carlos Contreras-Bernal; Sarah Natalie Cirilo Gimenes; Luciana Aparecida Freitas-De-Sousa; José Antonio Portes-Junior; Pedro Da Silva Peixoto; Leo Kei Iwai; Valéria Mourão De Moura; Pedro Ferreira Bisneto; Marcus Lacerda; Iran Mendonça Da Silva; Luiz Carlos De Lima Ferreira; Sâmella Silva De Oliveira; Fan Hui Wen; Jacqueline De Almeida Gonçalves Sachett; Wuelton M. Monteiro. 2020. "The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox)." PLOS Neglected Tropical Diseases 14, no. 6: e0008299.
Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products of Matrigel. BALB/c mice were injected with SVMPs (2 μg), for assessment of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, representing an increase of ~70% of the paw size. Leukocyte infiltrates reached levels of 6 × 106 with ATXL and 5 × 106 with BATXH. TNF-α was identified in the supernatant of BATXH—or venom-stimulated MPAC cells. Incubation of Matrigel with the SVMPs generated fragments, including peptides from Laminin, identified by LC–MS/MS. The Matrigel hydrolysis peptides caused edema that increased 30% the paw size and promoted leukocyte accumulation (4–5 × 106) to the peritoneal cavity, significantly higher than Matrigel control peptides 1 and 4 h after injection. Our findings suggest that ATXL and BATXH are involved in the inflammatory reaction observed in B. atrox envenomings by direct action on inflammatory cells or by releasing proinflammatory peptides from BM proteins that may amplify the direct action of SVMPs through activation of endogenous signaling pathways.
Michelle Teixeira De Almeida; Luciana Aparecida Freitas-De-Sousa; Monica Colombini; Sarah Gimenes; Eduardo S. Kitano; Eliana L. Faquim-Mauro; Solange M. T. Serrano; Ana Maria Moura-Da-Silva. Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components. Toxins 2020, 12, 96 .
AMA StyleMichelle Teixeira De Almeida, Luciana Aparecida Freitas-De-Sousa, Monica Colombini, Sarah Gimenes, Eduardo S. Kitano, Eliana L. Faquim-Mauro, Solange M. T. Serrano, Ana Maria Moura-Da-Silva. Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components. Toxins. 2020; 12 (2):96.
Chicago/Turabian StyleMichelle Teixeira De Almeida; Luciana Aparecida Freitas-De-Sousa; Monica Colombini; Sarah Gimenes; Eduardo S. Kitano; Eliana L. Faquim-Mauro; Solange M. T. Serrano; Ana Maria Moura-Da-Silva. 2020. "Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components." Toxins 12, no. 2: 96.
Variability in snake venom composition has been frequently reported and correlated to the adaptability of snakes to environmental conditions. Previous studies report plasticity for the venom phenotype. However, these observations are not conclusive, as the results were based on pooled venoms, which present high individual variability. Here we tested the hypothesis of plasticity by influence of confinement and single diet type in the venom composition of 13 adult specimens of Bothrops atrox snakes, maintained under captivity for more than three years. Individual variability in venom composition was observed in samples extracted just after the capture of the snakes. However, composition was conserved in venoms periodically extracted from nine specimens, which presented low variability restricted to the less abundant components. In a second group, composed of four snakes, drastic changes were observed in the venom samples extracted at different periods, mostly related to snake venom metalloproteinases (SVMPs), the core function toxins of B. atrox venom, which occurred approximately between 400 and 500 days in captivity. These data show plasticity in the venom phenotype during the lifetime of adult snakes maintained under captive conditions. Causes or functional consequences involved in the phenotype modification require further investigations.
Diana R. Amazonas; Luciana A. Freitas-De-Sousa; Daniele P. Orefice; Leijiane F. De Sousa; Melissa G. Martinez; Rosa H. V. Mourão; Hipócrates M. Chalkidis; Plínio B. Camargo; Ana M. Moura-Da-Silva. Evidence for Snake Venom Plasticity in a Long-Term Study with Individual Captive Bothrops atrox. Toxins 2019, 11, 294 .
AMA StyleDiana R. Amazonas, Luciana A. Freitas-De-Sousa, Daniele P. Orefice, Leijiane F. De Sousa, Melissa G. Martinez, Rosa H. V. Mourão, Hipócrates M. Chalkidis, Plínio B. Camargo, Ana M. Moura-Da-Silva. Evidence for Snake Venom Plasticity in a Long-Term Study with Individual Captive Bothrops atrox. Toxins. 2019; 11 (5):294.
Chicago/Turabian StyleDiana R. Amazonas; Luciana A. Freitas-De-Sousa; Daniele P. Orefice; Leijiane F. De Sousa; Melissa G. Martinez; Rosa H. V. Mourão; Hipócrates M. Chalkidis; Plínio B. Camargo; Ana M. Moura-Da-Silva. 2019. "Evidence for Snake Venom Plasticity in a Long-Term Study with Individual Captive Bothrops atrox." Toxins 11, no. 5: 294.
Extracts of leaves and bark of Aniba fragrans are used as tea (decoction) to treat snakebites in communities in the Brazilian Amazon. The aqueous extract of the leaves of A. fragrans has been proven to be effective against Bothrops venom, but only when pre-incubated with the venom. This study sought to assess the potential of different types of extract of this species to inhibit the biological activities of Bothrops atrox venom (BaV) when used the same way as in folk medicine. The main classes of secondary metabolites and the concentrations of phenolics in the extracts were also determined.Four types of extract of A. fragrans were prepared: aqueous extract of the leaf (AEL), aqueous extract of the bark (AEB), hydroalcoholic leaf extract (HLE) and extract of the residue from hydrodistillation of the leaf (ERHL). The phytochemical profiles of the aqueous extracts were determined using thin layer chromatography (TLC), and the concentrations of phenolics were measured by colorimetric assays. To investigate the potential of the extracts to inhibit the biological activities of BaV, in vitro tests for antiphospholipase and antifibrinolytic activities were performed. In vivo tests for antihemorrhagic and antidefibrinating activities were also carried out, as well as antimicrobial tests for activity against the main bacteria found in the oral cavity of snakes. Interaction between the extracts and the proteins in BaV was assessed by electrophoresis (SDS-PAGE) and Western blot (WB). The cytotoxicity of the extracts was assessed in a strain of MRC-5 human fibroblasts.Terpenoids, flavonoids and condensed and hydrolysable tannins were detected in all the extracts. Metabolites such as coumarins, fatty acids and alkaloids were present in some extracts but not in others, indicating different phytochemical profiles. Phenolics content varied between extracts, and there were more tannins in AEB and HLE. In the in vitro tests, the extracts inhibited the phospholipase and fibrinolytic activities of BaV in the two ratios of venom to extract used. HLE exhibited effective antimicrobial action as it inhibited growth of 11 of the 15 bacteria investigated, including Morganella morganii, the main bacteria described in the oral cavity of snakes. The extracts failed to inhibit the defibrinating activity of BaV, and only the Bothrops antivenom had a significant effect (96.1%) on this activity. BaV-induced hemorrhage was completely inhibited by AEL and AEB when the pre-incubation (venom:extract) protocol was used. When administered orally, as in folk medicine, both AEB and AEL produced significant inhibition of hemorrhagic activity (maximum inhibition 46.5% and 39.2%, respectively). SDS-PAGE and WB of the extracts pre-incubated with BaV showed that the main proteins in the venom had been precipitated by the extracts. None of the four extracts showed cytotoxic effects in the tests carried out with a human fibroblast cell line.In addition to being effective in reducing hemorrhage when administered orally, the extracts displayed a high antimicrobial potential against microorganisms involved in secondary infections at the site of the snakebite. Once the extracts have been tested in accordance with the appropriate regulations, this species could potentially be used to produce a phytomedicine for complementary treatment of the secondary infections due to bacteria that aggravate the local signs and symptoms after snakebite envenomation.
Valéria Mourão de Moura; Noranathan Da Costa Guimarães; Luana Travassos Batista; Luciana A. Freitas-De-Sousa; Joanderson De Sousa Martins; Maria Carolina Scheffer de Souza; Patrícia D. Oliveira de Almeida; Wuelton Marcelo Monteiro; Ricardo Bezerra de Oliveira; Maria Cristina Dos-Santos; Rosa Helena Veras Mourão. Assessment of the anti-snakebite properties of extracts of Aniba fragrans Ducke (Lauraceae) used in folk medicine as complementary treatment in cases of envenomation by Bothrops atrox. Journal of Ethnopharmacology 2018, 213, 350 -358.
AMA StyleValéria Mourão de Moura, Noranathan Da Costa Guimarães, Luana Travassos Batista, Luciana A. Freitas-De-Sousa, Joanderson De Sousa Martins, Maria Carolina Scheffer de Souza, Patrícia D. Oliveira de Almeida, Wuelton Marcelo Monteiro, Ricardo Bezerra de Oliveira, Maria Cristina Dos-Santos, Rosa Helena Veras Mourão. Assessment of the anti-snakebite properties of extracts of Aniba fragrans Ducke (Lauraceae) used in folk medicine as complementary treatment in cases of envenomation by Bothrops atrox. Journal of Ethnopharmacology. 2018; 213 ():350-358.
Chicago/Turabian StyleValéria Mourão de Moura; Noranathan Da Costa Guimarães; Luana Travassos Batista; Luciana A. Freitas-De-Sousa; Joanderson De Sousa Martins; Maria Carolina Scheffer de Souza; Patrícia D. Oliveira de Almeida; Wuelton Marcelo Monteiro; Ricardo Bezerra de Oliveira; Maria Cristina Dos-Santos; Rosa Helena Veras Mourão. 2018. "Assessment of the anti-snakebite properties of extracts of Aniba fragrans Ducke (Lauraceae) used in folk medicine as complementary treatment in cases of envenomation by Bothrops atrox." Journal of Ethnopharmacology 213, no. : 350-358.
Bothrops atrox is the snake responsible for the majority of snakebites in the Brazilian Amazon. Patients generally evolve to local manifestations such as edema, pain and ecchymoses. Systemic effects of B. atrox venom are usually restricted to blood incoagulability and spontaneous bleeding. However, in a few cases, bleeding in the central nervous system may occur, which can lead to sequels and deaths. Here, we report a case of a 59 year-old woman who presented edema, pain and ecchymoses on the right foot, headache, nausea, diarrhea, hypertension and blood incoagulability after the bite by Bothrops snake in the Brazilian Amazon. This case evolved with stroke resulting in death despite the antivenom and conservative therapy employed. In addition, we were able to identify the presence of venom in the patient's brain tissue after death. Direct action of toxins present in the snake's venom in the induction of systemic hemorrhage allied to blood incoagulability and hypertension presented by the patient could be involved in the mechanism of stroke in this case.
Sâmella Silva de Oliveira; Luciana Freitas-De-Sousa; Eliane Campos Alves; Luiz Carlos De Lima Ferreira; Iran Mendonça da Silva; Marcus Vinícius Guimarães de Lacerda; Hui Wen Fan; Ana Maria Moura-Da-Silva; Wuelton Marcelo Monteiro. Fatal stroke after Bothrops snakebite in the Amazonas state, Brazil: A case report. Toxicon 2017, 138, 102 -106.
AMA StyleSâmella Silva de Oliveira, Luciana Freitas-De-Sousa, Eliane Campos Alves, Luiz Carlos De Lima Ferreira, Iran Mendonça da Silva, Marcus Vinícius Guimarães de Lacerda, Hui Wen Fan, Ana Maria Moura-Da-Silva, Wuelton Marcelo Monteiro. Fatal stroke after Bothrops snakebite in the Amazonas state, Brazil: A case report. Toxicon. 2017; 138 ():102-106.
Chicago/Turabian StyleSâmella Silva de Oliveira; Luciana Freitas-De-Sousa; Eliane Campos Alves; Luiz Carlos De Lima Ferreira; Iran Mendonça da Silva; Marcus Vinícius Guimarães de Lacerda; Hui Wen Fan; Ana Maria Moura-Da-Silva; Wuelton Marcelo Monteiro. 2017. "Fatal stroke after Bothrops snakebite in the Amazonas state, Brazil: A case report." Toxicon 138, no. : 102-106.
Hemorrhage is the most prominent effect of snake venom metalloproteinases (SVMPs) in human envenomation. The capillary injury is a multifactorial effect caused by hydrolysis of the components of the basement membrane (BM). The PI and PIII classes of SVMPs are abundant in viperid venoms and hydrolyze BM components. However, hemorrhage is associated mostly with PIII-class SVMPs that contain non-catalytic domains responsible for the binding of SVMPs to BM proteins, facilitating enzyme accumulation in the tissue and enhancing its catalytic efficiency. Here we report on Atroxlysin-Ia, a PI-class SVMP that induces hemorrhagic lesions in levels comparable to those induced by Batroxrhagin (PIII-class), and a unique SVMP effect characterized by the rapid onset of dermonecrotic lesions. Atroxlysin-Ia was purified from B. atrox venom, and sequence analyses indicated that it is devoid of non-catalytic domains and unable to bind to BM proteins as collagen IV and laminin in vitro or in vivo. The presence of Atroxlysin-Ia was diffuse in mice skin, and localized mainly in the epidermis with no co-localization with BM components. Nevertheless, the skin lesions induced by Atroxlysin-Ia were comparable to those induced by Batroxrhagin, with induction of leukocyte infiltrates and hemorrhagic areas soon after toxin injection. Detachment of the epidermis was more intense in skin injected with Atroxlysin-Ia. Comparing the catalytic activity of both toxins, Batroxrhagin was more active in the hydrolysis of a peptide substrate while Atroxlysin-Ia hydrolyzed more efficiently fibrin, laminin, collagen IV and nidogen. Thus, the results suggest that Atroxlysin-Ia bypasses the binding step to BM proteins, essential for hemorrhagic lesions induced by PII- and P-III class SVMPs, causing a significantly fast onset of hemorrhage and dermonecrosis, due to its higher proteolytic capacity on BM components.
Luciana Aparecida Freitas-De-Sousa; Mônica Colombini; Mônica Lopes-Ferreira; Solange M. T. Serrano; Ana Maria Moura-Da-Silva. Insights into the Mechanisms Involved in Strong Hemorrhage and Dermonecrosis Induced by Atroxlysin-Ia, a PI-Class Snake Venom Metalloproteinase. Toxins 2017, 9, 239 .
AMA StyleLuciana Aparecida Freitas-De-Sousa, Mônica Colombini, Mônica Lopes-Ferreira, Solange M. T. Serrano, Ana Maria Moura-Da-Silva. Insights into the Mechanisms Involved in Strong Hemorrhage and Dermonecrosis Induced by Atroxlysin-Ia, a PI-Class Snake Venom Metalloproteinase. Toxins. 2017; 9 (8):239.
Chicago/Turabian StyleLuciana Aparecida Freitas-De-Sousa; Mônica Colombini; Mônica Lopes-Ferreira; Solange M. T. Serrano; Ana Maria Moura-Da-Silva. 2017. "Insights into the Mechanisms Involved in Strong Hemorrhage and Dermonecrosis Induced by Atroxlysin-Ia, a PI-Class Snake Venom Metalloproteinase." Toxins 9, no. 8: 239.
In this report, we compared isoforms present in venoms from snakes collected at different Amazonian habitats. By means of a species venom gland transcriptome and the in silico functional prediction of each isoform, we were able to predict the principal venom activities in vitro and in animal models. We also showed remarkable differences in the venom pools from snakes collected at the floodplain (várzea habitat) compared to other habitats. Not only was this venom less hemorrhagic and more procoagulant, when compared to the venom pools from the other three habitats studied, but also this enhanced procoagulant activity was not efficiently neutralized by Bothrops antivenom. Thus, using a functional proteomic approach, we highlighted intraspecific differences in B. atrox venom that could impact both in the ecology of snakes but also in the treatment of snake bite patients in the region.
Leijiane de Sousa; Milton Nishiyama Junior; Carolina A Nicolau; Juliana L Bernardoni; Milton Y Nishiyama-Jr; Diana R Amazonas; Luciana Freitas-De-Sousa; Rosa Hv Mourão; Hipócrates Chalkidis; Richard H Valente; Ana M Moura-Da-Silva. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon. Journal of Proteomics 2017, 159, 32 -46.
AMA StyleLeijiane de Sousa, Milton Nishiyama Junior, Carolina A Nicolau, Juliana L Bernardoni, Milton Y Nishiyama-Jr, Diana R Amazonas, Luciana Freitas-De-Sousa, Rosa Hv Mourão, Hipócrates Chalkidis, Richard H Valente, Ana M Moura-Da-Silva. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon. Journal of Proteomics. 2017; 159 ():32-46.
Chicago/Turabian StyleLeijiane de Sousa; Milton Nishiyama Junior; Carolina A Nicolau; Juliana L Bernardoni; Milton Y Nishiyama-Jr; Diana R Amazonas; Luciana Freitas-De-Sousa; Rosa Hv Mourão; Hipócrates Chalkidis; Richard H Valente; Ana M Moura-Da-Silva. 2017. "Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon." Journal of Proteomics 159, no. : 32-46.
Ethnobotanical studies have shown that Plathymenia reticulata Benth. (Fabaceae) has been widely used in cases of snake envenomation, particularly in Northern Brazil. In light of this, the aim of this study was to evaluate the inhibitory potential of the condensed-tannin-rich fraction obtained from the bark of P. reticulata against the main biological activities induced by Bothrops atrox venom (BaV). The chemical composition of the aqueous extract of P. reticulata (AEPr) was first investigated by thin-layer chromatography (TLC) and the extract was then fractionated by column chromatography on Sephadex LH-20. This yielded five main fractions (Pr1, Pr2, Pr3, Pr4 and Pr5), which were analyzed by colorimetry to determine their concentrations of total phenolics, total tannins and condensed tannins and to assess their potential for blocking the phospholipase activity of BaV. The Pr5 fraction was defined as the fraction rich in condensed tannins (CTPr), and its inhibitory potential against the activities of the venom was evaluated. CTPr was evaluated in different in vivo and in vitro experimental protocols. The in vivo protocols consisted of (1) pre-incubation (venom:CTPr, w/w), (2) pre-treatment (orally administered) and (3) post-treatment (orally administered) to evaluate the effect on the hemorrhagic and edematogenic activities of BaV; in the in vitro protocol the effect on phospholipase and coagulant activity using pre-incubation in both tests was evaluated. There was statistically significant inhibition (p<0.05) of hemorrhagic activity by CTPr when the pre-incubation protocol was used [55% (1:5, w/w) and 74% (1:10, w/w)] and when pre-treatment with doses of 50 and 100 mg/kg was used (19% and 13%, respectively). However, for the concentrations tested, there was no statistically significant inhibition in the group subjected to post-treatment administered orally. CTPr blocked 100% of phospholipase activity and 63.3% (1:10, w/w) of coagulant activity when it was pre-incubated with BaV. There was a statistically significant reduction (p<0.05) in edema induced by BaV in the oral protocols. Maximum inhibition was 95% (pre-treatment). Our findings indicate that CTPr could be a good source of natural inhibitors of the components of snake venom responsible for inducing local inflammation.
Valéria Mourão de Moura; Wania Cristina Rodrigues da Silva; Juliana D.A. Raposo; Luciana A. Freitas-De-Sousa; Maria Cristina Dos-Santos; Ricardo Bezerra de Oliveira; Rosa Helena Veras Mourão. The inhibitory potential of the condensed-tannin-rich fraction of Plathymenia reticulata Benth. (Fabaceae) against Bothrops atrox envenomation. Journal of Ethnopharmacology 2016, 183, 136 -142.
AMA StyleValéria Mourão de Moura, Wania Cristina Rodrigues da Silva, Juliana D.A. Raposo, Luciana A. Freitas-De-Sousa, Maria Cristina Dos-Santos, Ricardo Bezerra de Oliveira, Rosa Helena Veras Mourão. The inhibitory potential of the condensed-tannin-rich fraction of Plathymenia reticulata Benth. (Fabaceae) against Bothrops atrox envenomation. Journal of Ethnopharmacology. 2016; 183 ():136-142.
Chicago/Turabian StyleValéria Mourão de Moura; Wania Cristina Rodrigues da Silva; Juliana D.A. Raposo; Luciana A. Freitas-De-Sousa; Maria Cristina Dos-Santos; Ricardo Bezerra de Oliveira; Rosa Helena Veras Mourão. 2016. "The inhibitory potential of the condensed-tannin-rich fraction of Plathymenia reticulata Benth. (Fabaceae) against Bothrops atrox envenomation." Journal of Ethnopharmacology 183, no. : 136-142.
The poor distribution and limited availability of antivenoms in Brazil have led to greater use of plants to treat snakebites. Very often such plants are the only alternative available to riverside communities.Direct questionnaire-based interviews were conducted with members of the Cucurunã, São Pedro and Alter do Chão communities in Santarém, Pará, Brazil. For each of the 12 most frequently mentioned species aqueous extracts were prepared and the phytochemical profiles determined by thin layer chromatography. The concentrations of phenolic compounds (tannins and flavonoids) in the aqueous extracts were determined by colorimetric assays. To assess inhibition of the hemorrhagic activity of Bothrops jararaca venom, solutions containing the venom mixed with aqueous extracts in the ratios 1:12 and 1:48 were tested (w/w). SDS-PAGE and Western blot were used to assess the action of the extracts on Bothrops jararaca venom.In all, 24 plants belonging to 19 families were mentioned in the survey as being used to treat snakebites. Leaves (84%), seeds (60.9%) and inner bark (53%) were cited as the most frequently used parts in folk remedies, which were usually prepared in the form of a decoction (62.5%), tincture (45%) or maceration (22.5%). Hemorrhage induced by Bothrops jararaca venom was completely inhibited by aqueous extracts of Bellucia dichotoma, Connarus favosus, Plathymenia reticulata and Philodendron megalophyllum, which had a high phenolic content and contained condensed and hydrolyzable tannins. The results of SDS-PAGE showed that some venom protein bands were not visible when the venom was preincubated with the extracts that had completely inhibited hemorrhagic activity of the venom. Western blot showed that the extracts did not have any enzymatic action on the proteins in the venom as it failed to detect low-molecular-weight bands, which are indicative of possible enzymatic cleavage.Traditional use of plants to treat snakebites is a common practice in the western region of Pará, Brazil. Our findings show that some plant extracts were able to inhibit snake venom-induced hemorrhage in vitro. In vivo studies are being carried out to validate the traditional use of these species to treat snakebites.
Valéria Mourão de Moura; Luciana Freitas-De-Sousa; Maria Cristina Dos-Santos; Juliana Divina Almeida Raposo; Aline Evangelista Lima; Ricardo Bezerra de Oliveira; Milton Nascimento da Silva; Rosa Helena Veras Mourão. Plants used to treat snakebites in Santarém, western Pará, Brazil: An assessment of their effectiveness in inhibiting hemorrhagic activity induced by Bothrops jararaca venom. Journal of Ethnopharmacology 2015, 161, 224 -232.
AMA StyleValéria Mourão de Moura, Luciana Freitas-De-Sousa, Maria Cristina Dos-Santos, Juliana Divina Almeida Raposo, Aline Evangelista Lima, Ricardo Bezerra de Oliveira, Milton Nascimento da Silva, Rosa Helena Veras Mourão. Plants used to treat snakebites in Santarém, western Pará, Brazil: An assessment of their effectiveness in inhibiting hemorrhagic activity induced by Bothrops jararaca venom. Journal of Ethnopharmacology. 2015; 161 ():224-232.
Chicago/Turabian StyleValéria Mourão de Moura; Luciana Freitas-De-Sousa; Maria Cristina Dos-Santos; Juliana Divina Almeida Raposo; Aline Evangelista Lima; Ricardo Bezerra de Oliveira; Milton Nascimento da Silva; Rosa Helena Veras Mourão. 2015. "Plants used to treat snakebites in Santarém, western Pará, Brazil: An assessment of their effectiveness in inhibiting hemorrhagic activity induced by Bothrops jararaca venom." Journal of Ethnopharmacology 161, no. : 224-232.