Effects of crotamine in human prostate cancer cell line.

Our study presents the anticancer potential of crotamine from Crotalus durissus terrificus in human prostate cancer cell line DU-145. Crotamine isolation was conducted through RP-FPLC, its molecular mass analyzed by MALDI-TOF was 4881.4 kDa, and N-terminal sequencing confirmed crotamine identity. Crotamine demonstrated no toxicity and did not inhibit migration in HUVEC cells. Although no cell death occurred in DU-145 cells, crotamine inhibited their migration. Thus, crotamine presented potential to be a prototype of anticancer drug.

Venom Composition of Neglected Bothropoid Snakes from the Amazon Rainforest: Ecological and Toxinological Implications.

Snake venoms have evolved in several families of Caenophidae, and their toxins have been assumed to be biochemical weapons with a role as a trophic adaptation. However, it remains unclear how venom contributes to the success of venomous species for adaptation to different environments. Here we compared the venoms from Bothrocophias hyoprora, Bothrops taeniatus, Bothrops bilineatus smaragdinus, Bothrops brazili, and Bothrops atrox collected in the Amazon Rainforest, aiming to understand the ecological and toxinological consequences of venom composition. Transcriptomic and proteomic analyses indicated that the venoms presented the same toxin groups characteristic from bothropoids, but with distinct isoforms with variable qualitative and quantitative abundances, contributing to distinct enzymatic and toxic effects. Despite the particularities of each venom, commercial Bothrops antivenom recognized the venom components and neutralized the lethality of all species. No clear features could be observed between venoms from arboreal and terrestrial habitats, nor in the dispersion of the species throughout the Amazon habitats, supporting the notion that venom composition may not shape the ecological or toxinological characteristics of these snake species and that other factors influence their foraging or dispersal in different ecological niches.

Immunological Cross-Reactivity and Preclinical Assessment of a Colombian Anticoral Antivenom against the Venoms of Three Micrurus Species.

Snakebite accident treatment requires the administration of antivenoms that provide efficacy and effectiveness against several snake venoms of the same genus or family. The low number of immunogenic components in venom mixtures that allow the production of antivenoms consequently gives them partial neutralization and a suboptimal pharmacological response. This study evaluates the immunorecognition and neutralizing efficacy of the polyvalent anticoral antivenom from the Instituto Nacional de Salud (INS) of Colombia against the heterologous endemic venoms of Micrurus medemi, and M. sangilensis, and M. helleri by assessing immunoreactivity through affinity chromatography, ELISA, Western blot, and neutralization capability. Immunorecognition towards the venoms of M. medemi and M. sangilensis showed values of 62% and 68% of the protein composition according to the immunoaffinity matrix, respectively. The analysis by Western blot depicted the highest recognition patterns for M. medemi, followed by M. sangilensis, and finally by M. helleri. These findings suggest that the venom compositions are closely related and exhibit similar recognition by the antivenom. According to enzyme immunoassays, M. helleri requires a higher amount of antivenom to achieve recognition than the others. Besides reinforcing the evaluation of INS antivenom capability, this work recommends the use of M. helleri in the production of Colombian antisera.

A novel metalloproteinase-derived cryptide from Bothrops cotiara venom inhibits angiotensin-converting enzyme activity.

Snake venoms are primarily composed of proteins and peptides, which selectively interact with specific molecular targets, disrupting prey homeostasis. Identifying toxins and the mechanisms involved in envenoming can lead to the discovery of new drugs based on natural peptide scaffolds. In this study, we used mass spectrometry-based peptidomics to sequence 197 peptides in the venom of Bothrops cotiara, including a novel 7-residue peptide derived from a snake venom metalloproteinase. This peptide, named Bc-7a, features a pyroglutamic acid at the N-terminal and a PFR motif at the C-terminal, homologous to bradykinin. Using FRET (fluorescence resonance energy transfer) substrate assays, we demonstrated that Bc-7a strongly inhibits the two domains of angiotensin converting enzyme (Ki < 1 µM). Our findings contribute to the repertoire of biologically active peptides from snake venoms capable of inhibiting angiotensin-converting enzyme (ACE), beyond current known structural motifs and precursors. In summary, we report a novel snake venom peptide with ACE inhibitory activity, suggesting its potential contribution to the hypotensive effect observed in envenomation.

Snake and arthropod venoms: Search for inflammatory activity in human cells involved in joint diseases.

Most anti-inflammatory drugs currently adopted to treat chronic inflammatory joint diseases can alleviate symptoms but they do not lead to remission. Therefore, new and more efficient drugs are needed to block the course of joint inflammatory diseases. Animal venoms, rich in bioactive compounds, can contribute as valuable tools in this field of research. In this study, we first demonstrate the direct action of venoms on cells that constitute the articular joints. We established a platform consisting of cell-based assays to evaluate the release of cytokines (IL-6, IL-8, TNFα, IL-1ß, and IL-10) by human chondrocytes, synoviocytes and THP1 macrophages, as well as the release of neuropeptides (substance-P and ß-endorphin) by differentiated sensory neuron-like cells, 24 h after stimulation of cells with 21 animal venoms from snake and arthropod species, sourced from different taxonomic families and geographic origins. Results demonstrated that at non-cytotoxic concentrations, the venoms activate at varying degrees the secretion of inflammatory mediators involved in the pathology of articular diseases, such as IL-6, IL-8, and TNF-α by chondrocytes, synoviocytes, and macrophages and of substance P by neuron-like cells. Venoms of the Viperidae snake family were more inflammatory than those of the Elapidae family, while venoms of Arthropods were less inflammatory than snake venoms. Notably, some venoms also induced the release of the anti-inflammatory IL-10 by macrophages. However, the scorpion Buthus occitanus venom induced the release of IL-10 without increasing the release of inflammatory cytokines by macrophages. Since the cell types used in the experiments are crucial elements in joint inflammatory processes, the results of this work may guide future research on the activation of receptors and inflammatory signaling pathways by selected venoms in these particular cells, aiming at discovering new targets for therapeutic intervention.

Venom composition of neglected Bothropoid snakes from the Amazon Rainforest: ecological and toxinological implications

Snake venoms have evolved in several families of Caenophidae, and their toxins have been assumed to be biochemical weapons with a role as a trophic adaptation. However, it remains unclear how venom contributes to the success of venomous species for adaptation to different environments. Here we compared the venoms from Bothrocophias hyoprora, Bothrops taeniatus, Bothrops bilineatus smaragdinus, Bothrops brazili, and Bothrops atrox collected in the Amazon Rainforest, aiming to understand the ecological and toxinological consequences of venom composition. Transcriptomic and proteomic analyses indicated that the venoms presented the same toxin groups characteristic from bothropoids, but with distinct isoforms with variable qualitative and quantitative abundances, contributing to distinct enzymatic and toxic effects. Despite the particularities of each venom, commercial Bothrops antivenom recognized the venom components and neutralized the lethality of all species. No clear features could be observed between venoms from arboreal and terrestrial habitats, nor in the dispersion of the species throughout the Amazon habitats, supporting the notion that venom composition may not shape the ecological or toxinological characteristics of these snake species and that other factors influence their foraging or dispersal in different ecological niches.

Snake and arthropod venoms: search for inflammatory activity in human cells involved in joint diseases

Most anti-inflammatory drugs currently adopted to treat chronic inflammatory joint diseases can alleviate symptoms but they do not lead to remission. Therefore, new and more efficient drugs are needed to block the course of joint inflammatory diseases. Animal venoms, rich in bioactive compounds, can contribute as valuable tools in this field of research. In this study, we first demonstrate the direct action of venoms on cells that constitute the articular joints. We established a platform consisting of cell-based assays to evaluate the release of cytokines (IL-6, IL-8, TNFα, IL-1β, and IL-10) by human chondrocytes, synoviocytes and THP1 macrophages, as well as the release of neuropeptides (substance-P and β-endorphin) by differentiated sensory neuron-like cells, 24 h after stimulation of cells with 21 animal venoms from snake and arthropod species, sourced from different taxonomic families and geographic origins. Results demonstrated that at non-cytotoxic concentrations, the venoms activate at varying degrees the secretion of inflammatory mediators involved in the pathology of articular diseases, such as IL-6, IL-8, and TNF-α by chondrocytes, synoviocytes, and macrophages and of substance P by neuron-like cells. Venoms of the Viperidae snake family were more inflammatory than those of the Elapidae family, while venoms of Arthropods were less inflammatory than snake venoms. Notably, some venoms also induced the release of the anti-inflammatory IL-10 by macrophages. However, the scorpion Buthus occitanus venom induced the release of IL-10 without increasing the release of inflammatory cytokines by macrophages. Since the cell types used in the experiments are crucial elements in joint inflammatory processes, the results of this work may guide future research on the activation of receptors and inflammatory signaling pathways by selected venoms in these particular cells, aiming at discovering new targets for therapeutic intervention.

A novel metalloproteinase-derived cryptide from Bothrops cotiara venom inhibits angiotensin-converting enzyme activity

Snake venoms are primarily composed of proteins and peptides, which selectively interact with specific molecular targets, disrupting prey homeostasis. Identifying toxins and the mechanisms involved in envenoming can lead to the discovery of new drugs based on natural peptide scaffolds. In this study, we used mass spectrometry-based peptidomics to sequence 197 peptides in the venom of Bothrops cotiara, including a novel 7-residue peptide derived from a snake venom metalloproteinase. This peptide, named Bc-7a, features a pyroglutamic acid at the N-terminal and a PFR motif at the C-terminal, homologous to bradykinin. Using FRET (fluorescence resonance energy transfer) substrate assays, we demonstrated that Bc-7a strongly inhibits the two domains of angiotensin converting enzyme (Ki < 1 μM). Our findings contribute to the repertoire of biologically active peptides from snake venoms capable of inhibiting angiotensin-converting enzyme (ACE), beyond current known structural motifs and precursors. In summary, we report a novel snake venom peptide with ACE inhibitory activity, suggesting its potential contribution to the hypotensive effect observed in envenomation.

Bothrops Moojeni Snake Venom: A Source of Potential Therapeutic Agents Against Hemostatic Disorders

Abstract Hemostasis is a complex set of biological processes responsible for blood fluidity within normal vessels and for the physiological interruption of bleeding in cases of vascular injury. Bothrops moojeni snake venom is rich in bioactive compounds of pharmacological and clinical interest since its protein components are capable of interfering with many points of the hemostatic process. Here, we present the B. moojeni venom proteins that affect hemostasis and discuss their pharmacological and clinical potential. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Data were obtained from the CAPES Journal Portal database, using the terms "Bothrops" AND "hemostasis", in a search for scientific articles made available in the last 20 years. Many components isolated from B. moojeni snake venom are characterized for their effect on hemostasis and possible application in the diagnosis and treatment of hemostatic disorders.

Pictolysin-III, a Hemorrhagic Type-III Metalloproteinase Isolated from Bothrops pictus (Serpentes: Viperidae) Venom, Reduces Mitochondrial Respiration and Induces Cytokine Secretion in Epithelial and Stromal Cell Lines.

From the venom of the Bothrops pictus snake, an endemic species from Peru, we recently have described toxins that inhibited platelet aggregation and cancer cell migration. In this work, we characterize a novel P-III class snake venom metalloproteinase, called pictolysin-III (Pic-III). It is a 62 kDa proteinase that hydrolyzes dimethyl casein, azocasein, gelatin, fibrinogen, and fibrin. The cations Mg2+ and Ca2+ enhanced its enzymatic activity, whereas Zn2+ inhibited it. In addition, EDTA and marimastat were also effective inhibitors. The amino acid sequence deduced from cDNA shows a multidomain structure that includes a proprotein, metalloproteinase, disintegrin-like, and cysteine-rich domains. Additionally, Pic-III reduces the convulxin- and thrombin-stimulated platelet aggregation and in vivo, it has hemorrhagic activity (DHM = 0.3 µg). In epithelial cell lines (MDA-MB-231 and Caco-2) and RMF-621 fibroblast, it triggers morphological changes that are accompanied by a decrease in mitochondrial respiration, glycolysis, and ATP levels, and an increase in NAD(P)H, mitochondrial ROS, and cytokine secretion. Moreover, Pic-III sensitizes to the cytotoxic BH3 mimetic drug ABT-199 (Venetoclax) in MDA-MB-231 cells. To our knowledge, Pic-III is the first SVMP reported with action on mitochondrial bioenergetics and may offer novel opportunities for promising lead compounds that inhibit platelet aggregation or ECM-cancer-cell interactions.

In Silico Evaluation of Quercetin Methylated Derivatives on the Interaction with Secretory Phospholipases A2 from Crotalus durissus terrificus and Bothrops jararacussu.

Quercetin derivatives have already shown their anti-inflammatory potential, inhibiting essential enzymes involved in this process. Among diverse pro-inflammatory toxins from snake venoms, phospholipase A2 is one of the most abundant in some species, such as Crotalus durissus terrificus and Bothrops jararacussu from the Viperidae family. These enzymes can induce the inflammatory process through hydrolysis at the sn-2 position of glycerophospholipids. Hence, elucidating the main residues involved in the biological effects of these macromolecules can help to identify potential compounds with inhibitory activity. In silico tools were used in this study to evaluate the potential of quercetin methylated derivatives in the inhibition of bothropstoxin I (BthTX-I) and II (BthTX-II) from Bothrops jararacussu and phospholipase A2 from Crotalus durissus terrificus. The use of a transitional analogous and two classical inhibitors of phospholipase A2 guided this work to find the role of residues involved in the phospholipid anchoring and the subsequent development of the inflammatory process. First, main cavities were studied, revealing the best regions to be inhibited by a compound. Focusing on these regions, molecular docking assays were made to show main interactions between each compound. Results reveal that analogue and inhibitors, Varespladib (Var) and p-bromophenacyl bromide (BPB), guided quercetins derivatives analysis, revealing that Leu2, Phe5, Tyr28, glycine in the calcium-binding loop, His48, Asp49 of BthTX-II and Cdtspla2 were the main residues to be inhibited. 3MQ exhibited great interaction with the active site, similar to Var results, while Q anchored better in the BthTX-II active site. However, strong interactions in the C-terminal region, highlighting His120, seem to be crucial to decreasing contacts with phospholipid and BthTX-II. Hence, quercetin derivatives anchor differently with each toxin and further in vitro and in vivo studies are essential to elucidate these data.

Past, Present, and Future of Naturally Occurring Antimicrobials Related to Snake Venoms.

This review focuses on proteins and peptides with antimicrobial activity because these biopolymers can be useful in the fight against infectious diseases and to overcome the critical problem of microbial resistance to antibiotics. In fact, snakes show the highest diversification among reptiles, surviving in various environments; their innate immunity is similar to mammals and the response of their plasma to bacteria and fungi has been explored mainly in ecological studies. Snake venoms are a rich source of components that have a variety of biological functions. Among them are proteins like lectins, metalloproteinases, serine proteinases, L-amino acid oxidases, phospholipases type A2, cysteine-rich secretory proteins, as well as many oligopeptides, such as waprins, cardiotoxins, cathelicidins, and ß-defensins. In vitro, these biomolecules were shown to be active against bacteria, fungi, parasites, and viruses that are pathogenic to humans. Not only cathelicidins, but all other proteins and oligopeptides from snake venom have been proteolyzed to provide short antimicrobial peptides, or for use as templates for developing a variety of short unnatural sequences based on their structures. In addition to organizing and discussing an expressive amount of information, this review also describes new ß-defensin sequences of Sistrurus miliarius that can lead to novel peptide-based antimicrobial agents, using a multidisciplinary approach that includes sequence phylogeny.

O misterioso perfil tóxico da tribo Philodryadini: Técnicas ‘ômicas’ revelam variabilidade nos venenos destas serpentes

Philodryadini snakes belong to one of the most diverse families in the world and are the main opisthoglyphic snakes involved in human envenomation. These snakes play a fundamental ecological role, with most of them having a generalist feeding habit, but on the other hand, the species Philodryas agassizii feeds exclusively on arthropods. Despite all the diversity found in this group, there are still few studies on the composition and variability of the venoms of this tribe. Thus, this work aims to carry out the biochemical and functional characterization of the venom of five species of the genus Philodryas (P. patagoniensis, P. olfersii, P. nattereri, P. mattogrossensis e P. agassizii), two species of the genus Chlorosoma (C. viridissimum, previously known as Philodryas viridissima and C. laticeps, formerly known as Philodryas laticeps) and a species of the genus Xenoxybelis (X. argenteus), through transcriptomic analysis combined with proteomics and functional analysis of venoms through enzymatic assays. The most abundant components identified in the venoms were Snake Venom Metalloproteinases (SVMPs), Cysteine-rich Secretory Proteins (CRISPs) and C-type Lectins (CTLs), Snake Endogenous Matrix Metalloproteinases type 9 (seMMP-9) and Snake Venom Serinoproteinases (SVSPs). However, these protein families showed quantitative variability and a different expression profile in each analyzed genus. SVMPs were the most abundant components in Philodryas, while seMMP-9 were the most expressed in Chlorosoma and CRISPs in Xenoxybelis. Furthermore, we can observe variability within the same genus, where P. olfersii presented a greater amount of SVSPs than the other species of the genus. The composition of the venoms also reflected differences in the functional assays, as expected, only P. olfersii showed proteolytic activity for the substrate of SVSPs, while the other Philodryas were the most active on the substrate of SVMPs. Chlorosoma species showed higher activity in gelatin degradation with activity only partially inhibited by EDTA. The gel bands with the greatest degradation were identified by mass spectrometry and indicated the presence of seMMP-9, confirming the hypothesis that the proteolytic character of these proteins is maintained. Thus, the results indicate that within the Philodryadini tribe the Philodryas, Chlorosoma and Xenoxybelis genera are not distinguished only by morphological characteristics, but also by the biochemical composition of their venoms. In addition, we describe here for the first time the complete transcriptome of 7 species of the Philodryadini tribe and the proteome of 5 individuals of different species of this tribe.

As serpentes da tribo Philodryadini pertencem a uma das famílias mais diversas do mundo e são as principais serpentes opistóglifas envolvidas em envenenamentos humanos. Estas serpentes desempenham papel ecológico fundamental, sendo a maioria de hábito alimentar generalista, mas em contrapartida, a espécie Philodryas agassizii se alimenta exclusivamente de artrópodes. Apesar de toda a diversidade encontrada neste grupo, ainda há poucos estudos sobre a composição e variabilidade dos venenos desta tribo. Assim, este trabalho visa realizar a caracterização bioquímica e funcional do veneno de cinco espécies do gênero Philodryas (P. patagoniensis, P. olfersii, P. nattereri, P. mattogrossensis e P. agassizii), duas espécies do gênero Chlorosoma (C. viridissimum, anteriormente nomeada como Philodryas viridissima e C. laticeps, anteriormente conhecida como Philodryas laticeps) e uma espécie do gênero Xenoxybelis (X. argenteus), através da análise transcriptômica combinada à proteômica e análise funcional dos venenos através de ensaios enzimáticos. Os componentes mais abundantes identificados nos venenos foram as Metaloproteinases de Veneno de Serpente (SVMPs), Proteínas Secretoras Ricas em Cisteína (CRISPs) e Lectinas do tipo C (CTLs), Metaloproteinases de Matriz do tipo 9 Endógenas de Serpente (seMMP-9) e Serinoproteinases de Veneno de Serpente (SVSPs). No entanto, essas famílias de proteínas apresentaram variabilidade quantitativa e um perfil de expressão diferente em cada gênero analisado. As SVMPs foram os componentes mais abundantes em Philodryas, enquanto que as seMMP-9 foram as mais expressas em Chlorosoma e as CRISPs em Xenoxybelis. Além disso, podemos observar variabilidade dentro do mesmo gênero, onde P. olfersii apresentou uma maior quantidade de SVSPs que as outras espécies do gênero. A composição dos venenos também refletiu diferenças nos ensaios funcionais, como já era esperado, apenas P. olfersii apresentou atividade proteolítica para o substrato de SVSPs, enquanto que as demais Philodryas foram as mais ativas no substrato de SVMPs. As espécies de Chlorosoma apresentaram maior atividade na degradação da gelatina com atividade apenas parcialmente inibida pelo EDTA. As bandas do gel com maior degradação foram identificadas por espectrometria de massas e indicaram a presença de seMMP-9, confirmando a hipótese de que o caráter proteolítico destas proteínas é mantido. Dessa forma, os resultados indicam que dentro da tribo Philodryadini os gêneros Philodryas, Chlorosoma e Xenoxybelis não se distinguem apenas por características morfológicas, mas também pela composição bioquímica de seus venenos. Além disso, descrevemos aqui pela primeira vez o transcriptoma completo de 7 espécies da tribo Philodryadini e o proteoma de 5 indivíduos de espécies diferentes dessa tribo.

Caracterização estrutural e funcional de uma metaloproteinase de classe P-I do veneno de Lachesis muta rhombeata

Rhomb-I, a 23-kDa metalloproteinase was isolated from L. m. rhombeata venom. Its dimethylcasein proteolysis was abolished by metal chelators, and slightly enhanced by Ca2+ and Mg2+ ions, but inhibited by Co2+ , Zn2+ and α2-macroglobulin. In aqueous solution, rhomb-I autoproteolyzed to a 20- and 11-kDa fragments at 37 oC. The amino acid sequence showed high homology with other SVMPs. Rhomb-I causes hemorrhage that may be ascribed to hydrolysis of essential BM, ECM and plasma proteins. It preferentially cleaves the α-chains of fibrin(ogen). Rhomb-I inhibited convulxin- and vWF-induced aggregation on human platelets without significant effect on collagen-stimulated aggregation or other effectors. It digests vWF into a low- molecular-mass multimers of vWF and a rvWF-A1 domain to a 27-kDa fragment as revealed by western blotting with mouse anti-rvWF A1-domain IgG. Incubation of platelets with rhomb-I resulted in adhesion to and cleavage of platelet receptors GPIbα and GPVI to release a 130-kDa and 55-kDa soluble form. Both membrane glycoproteins, GPIbα that binds vWF, together with GPVI which binds collagen, play a key role in mediating platelet adhesion/activation and can initiate (patho)physiological thrombus formation. Conclusions: rhomb-I is implicated in the pathophysiology of Lachesis envenoming by disrupting vasculature, hemostasis and platelet aggregation through impairing vWF-GPIb axis and blocking GPVI-collagen binding.

Rhomb-I, uma metaloproteinase de 23 kDa foi isolada do veneno de L. m. rhombata. Sua ação proteolítica sobre dimetilcaseína foi inibida por α2-macroglobulina, quelantes de metais e por cátions Co2+ e Zn2+ e levemente estimulada por Ca2+ e Mg2+ . Em solução aquosa a 37 oC, rhomb-I sofreu autoproteólise gerando fragmentos de aproximadamente 20 e 11 kDa. A sequência de aminoácidos apresentou alta similaridade com outras SVMPs P-I. Rhomb-I causa hemorragia que pode ser atribuída à hidrólise de proteínas da membrana basal, da matriz extracelular e proteínas plasmáticas. Rhomb-I cliva, preferencialmente, as cadeias Aα da fibrina e do fibrinogênio. Rhomb-I inibiu a agregação induzida por convulxina e pelo fator de von Willebrand (vWF) em plaquetas humanas, sem efeito significativo na agregação estimulada por colágeno ou outros agonistas. Ela digere vWF em multímeros de massas moleculares menores bem como o domínio A1 recombinante de vWF (rvWF- A1) gerando um fragmento de aproximadamente 27 kDa, conforme evidenciado por western blot com IgG anti-rvWF-A1, produzido em camundongos. Após incubar plaquetas lavadas com rhomb-I, foi possível observar por western blot que a proteína liga e cliva as glicoproteínas de plaquetas GPIb e GPVI, liberando as formas solúveis de 130 kDa e 55 kDa, respectivamente. Ambas glicoproteínas, GPIbα que se liga ao vWF, e GPVI que se liga ao colágeno, desempenham um papel fundamental na mediação da adesão/ativação plaquetária e podem iniciar a formação fisiológica ou patológica de trombos. Conclusões: Rhomb-I é uma metaloproteinase classe P-I, hemorrágica, fibrino(geno)lítica que degrada proteínas da matriz extracelular e interfere na função plaquetária pela clivagem de vWF, GPIb e GPVI. Estes resultados indicam que rhomb-I pode estar envolvida na fisiopatologia do envenenamento por Lachesis, perturbando a hemostasia e agregação plaquetária e causando danos à vasculatura.

Past, present, and future of naturally occurring antimicrobials related to snake venoms

This review focuses on proteins and peptides with antimicrobial activity because these biopolymers can be useful in the fight against infectious diseases and to overcome the critical problem of microbial resistance to antibiotics. In fact, snakes show the highest diversification among reptiles, surviving in various environments; their innate immunity is similar to mammals and the response of their plasma to bacteria and fungi has been explored mainly in ecological studies. Snake venoms are a rich source of components that have a variety of biological functions. Among them are proteins like lectins, metalloproteinases, serine proteinases, L-amino acid oxidases, phospholipases type A2, cysteine-rich secretory proteins, as well as many oligopeptides, such as waprins, cardiotoxins, cathelicidins, and β-defensins. In vitro, these biomolecules were shown to be active against bacteria, fungi, parasites, and viruses that are pathogenic to humans. Not only cathelicidins, but all other proteins and oligopeptides from snake venom have been proteolyzed to provide short antimicrobial peptides, or for use as templates for developing a variety of short unnatural sequences based on their structures. In addition to organizing and discussing an expressive amount of information, this review also describes new β-defensin sequences of Sistrurus miliarius that can lead to novel peptide-based antimicrobial agents, using a multidisciplinary approach that includes sequence phylogeny.

Mordeduras de ofidios en mano pediátrica y sus complicaciones locales / Snake bites in pediatric hand and their local complications / Mordidas de serpentes de mão pediátricas e suas complicações locais

Introducción: el envenenamiento por mordedura de ofidios es reconocido como un problema de salud pública según la Organización Mundial de la Salud. La baja incidencia sumada a la diversidad de presentaciones clínicas, edades, topografías afectadas, así como los diferentes protocolos en la bibliografía existente sobre algunos aspectos del tratamiento, hacen difícil el manejo sistematizado de estos pacientes. El objetivo de este trabajo es realizar una revisión sistemática de la literatura sobre mordedura de serpientes en pacientes pediátricos con afectación en mano y miembro superior, haciendo hincapié en la conducta frente las complicaciones loco-regionales. Por importancia y frecuencia destacamos al síndrome compartimental, las flictenas y las infecciones. Metodología: se realizó una búsqueda bibliográfica en MedLine/PubMed con las palabras clave: "Snake Bite hand Children" y "Snake Bite compartimental syndrome". Se incluyeron los artículos publicados en los últimos 10 años (2012 al 2022). Resultados: la búsqueda de artículos ante las palabras "Snake Bite hand Children" resultó en 20 articulos y la busqueda ante las palabras "Snake Bite compartimental syndrome" derivó en 34. Luego de aplicar los criterios de inclusión y exclusión se obtuvieron 30 artículos para el análisis. Conclusiones: la población pediátrica se encuentra más expuesta a las mordeduras por serpientes y a su vez a presentar lesiones más severas. El tratamiento del síndrome compartimental continúa siendo un tema de debate. El veneno inoculado puede simular un síndrome compartimental que puede revertir sin fasciotomías con el tratamiento adecuado. Igualmente, ante síntomas y signos claros de síndrome compartimental se sugiere realizar fasciotomías frente a las graves secuelas potenciales. Ante la aparición de flictenas, el destechado cuidadoso de la misma es un tratamiento adecuado. La mayoría de los autores coinciden con el tratamiento profiláctico con antibioticoterapia.

Introduction: Ophidian bite poisoning is recognized as a public health problem by the World Health Organization. The low incidence added to the diversity of clinical presentations, ages, affected topographies, as well as the different protocols in the existing literature on some aspects of treatment, make the systematized management of these patients difficult. The aim of this work is to carry out a systematic review of the literature on snakebite in pediatric patients with hand and upper limb involvement, with emphasis on the management of loco-regional complications. In terms of importance and frequency, we highlight compartment syndrome, phlyctenas and infections. Methodology: a literature search was carried out in MedLine/PubMed with the keywords: "Snake Bite hand Children" and "Snake Bite compartment syndrome". Articles published in the last 10 years (2012 to 2022) were included. Results: the search for articles with the words "Snake Bite hand Children" resulted in 20 articles and the search for the words "Snake Bite compartment syndrome" resulted in 34 articles. After applying the inclusion and exclusion criteria, 30 articles were obtained for the analysis. Conclusions: the pediatric population is more exposed to snake bites and in turn to present more severe lesions. The treatment of compartment syndrome continues to be a subject of debate. Inoculated venom can simulate a compartment syndrome that can be reversed without fasciotomies with proper treatment. Likewise, in the presence of clear symptoms and signs of compartment syndrome, fasciotomies are suggested because of the serious sequelae generated. In the event of the appearance of phlyctenas, careful unroofing of the phlyctenas would be an appropriate treatment. Most authors agree with prophylactic treatment with antibiotic therapy.

Introdução: O envenenamento por mordidas ofídias é reconhecido como um problema de saúde pública pela Organização Mundial da Saúde. A baixa incidência, juntamente com a diversidade de apresentações clínicas, idades, topografias afetadas, bem como os diferentes protocolos da literatura existente sobre alguns aspectos do tratamento, tornam difícil o gerenciamento sistemático desses pacientes. O objetivo deste trabalho é realizar uma revisão sistemática da literatura sobre mordida de cobra em pacientes pediátricos com envolvimento de mãos e membros superiores, com ênfase no gerenciamento de complicações loco-regionais. Em termos de importância e freqüência, destacamos a síndrome compartimental, as flectenas e as infecções. Metodologia: foi realizada uma pesquisa bibliográfica no MedLine/PubMed com as palavras-chave: "Snake Bite hand Children" e "Snake Bite compartment syndrome". Os artigos publicados nos últimos 10 anos (2012 a 2022) foram incluídos. Resultados: a busca de artigos usando as palavras "Snake Bite hand Children" resultou em 20 artigos e a busca das palavras "Snake Bite compartment syndrome" resultou em 34 artigos. Após a aplicação dos critérios de inclusão e exclusão, foram obtidos 30 artigos para análise. Conclusões: a população pediátrica está mais exposta às picadas de cobra e, por sua vez, a lesões mais graves. O tratamento da síndrome compartimental continua a ser motivo de debate. O veneno inoculado pode simular uma síndrome de compartimento que pode ser revertida sem fasciotomias com tratamento apropriado. Da mesma forma, se houver sinais e sintomas claros de síndrome compartimental, são sugeridas fasciotomias por causa das severas seqüelas. Se as flectenas aparecerem, o desenrolamento cuidadoso das flectenas seria um tratamento apropriado. A maioria dos autores concorda com o tratamento profilático com a antibioticoterapia.

Massive acute ischemic stroke after Bothrops spp. envenomation in southwestern Colombia: Case report and literature review. / Accidente cerebrovascular isquémico agudo masivo por veneno de Bothrops spp. en el suroccidente de Colombia: reporte de caso y revisión de la literatura

Bothrops spp. envenomation and its relationship with ischemic stroke has complex pathogenesis. Local effects such as edema, pain, redness, necrosis, and systemic manifestations like coagulation disorders, thrombosis, renal failure, and hemorrhage have been reported. Hemorrhagic stroke is a common neurological complication but ischemic stroke is poorly understood. We present here the case of a 50-year-old male with no comorbidities referred from a rural area in southwest Colombia with a Bothrops spp. snakebite on the left hand. On admission, the patient presented with a deterioration of consciousness and required mechanical ventilation assistance. The MRI showed multiple ischemic areas in the bilateral frontaltemporal and occipital regions. Two months later, the patient had a favorable resolution, although central paresis in the III and VI cranial nerves and positive Babinski's sign persisted. As already mentioned, the pathophysiology of ischemic stroke due to snakebite is complex but the procoagulant activity of the venom components, the hypovolemic shock, the endothelial damage, and the thromboinflammation can explain it, and although it rarely occurs, it should be considered as a complication of ophidian accidents caused by Bothrops spp.

La mordedura de serpientes Bothrops spp. y el ataque cerebrovascular isquémico tienen una patogenia compleja. Se reconocen efectos locales como edema, dolor, enrojecimiento y necrosis, así como manifestaciones sistémicas como trastornos de la coagulación, trombosis, insuficiencia renal y hemorragia, por lo que el accidente cerebrovascular hemorrágico es una complicación neurológica común, pero, en cambio, el accidente cerebrovascular isquémico es poco conocido. Se presenta el caso de un paciente de 50 años, sin comorbilidades, remitido de una zona rural del suroccidente de Colombia debido a la mordedura de una serpiente Bothrops spp. en su mano izquierda. En el momento del ingreso, el paciente presentaba deterioro de la conciencia y requirió asistencia respiratoria mecánica. Mediante resonancia magnética, se observaron múltiples áreas isquémicas bilaterales en la región fronto-temporal y en la occipital. Dos meses después, el paciente había evolucionado favorablemente, pero persistían la paresia en los pares craneales III y VI y el signo de Babinski. La fisiopatología del accidente cerebrovascular isquémico por mordedura de serpiente es compleja. La actividad procoagulante de los componentes del veneno, el choque hipovolémico, el daño endotelial y la tromboinflamación pueden explicar el accidente cerebrovascular isquémico que, aunque raro, debe considerarse como una complicación del accidente ofídico causado por serpientes Bothrops spp.

Cytotoxic activity in basal and tumoral cell lines of the C0K3N3 protein from the snake venom Crotalus durissus collilineatus, variety crotamine negative.

Snake venoms are natural sources of bioactive substances with therapeutic potential. In this work, we evaluated the cytotoxicity of the Crotalus durissus collilineatus, negative crotamine variety and the isolated fraction C0K3N3 in BALB C/3T3 and K562 cell lines. The results indicate that the C0K3N3 protein is more cytotoxic against the K562 tumor cell line than in the 3T3 baseline.

Massive acute ischemic stroke after Bothrops spp. envenomation in southwestern Colombia: Case report and literature review / Accidente cerebrovascular isquémico agudo masivo por veneno de Bothrops spp. en el suroccidente de Colombia: reporte de caso y revisión de la literatura

Bothrops spp. envenomation and its relationship with ischemic stroke has complex pathogenesis. Local effects such as edema, pain, redness, necrosis, and systemic manifestations like coagulation disorders, thrombosis, renal failure, and hemorrhage have been reported. Hemorrhagic stroke is a common neurological complication but ischemic stroke is poorly understood. We present here the case of a 50-year-old male with no comorbidities referred from a rural area in southwest Colombia with a Bothrops spp. snakebite on the left hand. On admission, the patient presented with a deterioration of consciousness and required mechanical ventilation assistance. The MRI showed multiple ischemic areas in the bilateral frontal- temporal and occipital regions. Two months later, the patient had a favorable resolution, although central paresis in the III and VI cranial nerves and positive Babinski's sign persisted. As already mentioned, the pathophysiology of ischemic stroke due to snakebite is complex but the procoagulant activity of the venom components, the hypovolemic shock, the endothelial damage, and the thromboinflammation can explain it, and although it rarely occurs, it should be considered as a complication of ophidian accidents caused by Bothrops spp.

La mordedura de serpientes Bothrops spp. y el ataque cerebrovascular isquémico tienen una patogenia compleja. Se reconocen efectos locales como edema, dolor, enrojecimiento y necrosis, así como manifestaciones sistémicas como trastornos de la coagulación, trombosis, insuficiencia renal y hemorragia, por lo que el accidente cerebrovascular hemorrágico es una complicación neurológica común, pero, en cambio, el accidente cerebrovascular isquémico es poco conocido. Se presenta el caso de un paciente de 50 años, sin comorbilidades, remitido de una zona rural del suroccidente de Colombia debido a la mordedura de una serpiente Bothrops spp. en su mano izquierda. En el momento del ingreso, el paciente presentaba deterioro de la conciencia y requirió asistencia respiratoria mecánica. Mediante resonancia magnética, se observaron múltiples áreas isquémicas bilaterales en la región fronto-temporal y en la occipital. Dos meses después, el paciente había evolucionado favorablemente, pero persistían la paresia en los pares craneales III y VI y el signo de Babinski. La fisiopatología del accidente cerebrovascular isquémico por mordedura de serpiente es compleja. La actividad procoagulante de los componentes del veneno, el choque hipovolémico, el daño endotelial y la tromboinflamación pueden explicar el accidente cerebrovascular isquémico que, aunque raro, debe considerarse como una complicación del accidente ofídico causado por serpientes Bothrops spp.