RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Species of the Jatropha genus (Euphorbiaceae) are used indiscriminately in traditional medicine to treat accidents involving venomous animals. Jatropha mutabilis Baill., popularly known as "pinhão-de-seda," is found in the semi-arid region of Northeastern Brazil. It is widely used as a vermifuge, depurative, laxative, and antivenom. AIM OF THE STUDY: Obtaining the phytochemical profile of the latex of Jatropha mutabilis (JmLa) and evaluate its acute oral toxicity and inhibitory effects against the venom of the scorpion Tityus stigmurus (TstiV). MATERIALS AND METHODS: The latex of J. mutabilis (JmLa) was obtained through in situ incisions in the stem and characterized using HPLC-ESI-QToF-MS. Acute oral toxicity was investigated in mice. The protein profile of T. stigmurus venom was obtained by electrophoresis. The ability of latex to interact with venom components (TstiV) was assessed using SDS-PAGE, UV-Vis scanning spectrum, and the neutralization of fibrinogenolytic and hyaluronidase activities. Additionally, the latex was evaluated in vivo for its ability to inhibit local edematogenic and nociceptive effects induced by the venom. RESULTS: The phytochemical profile of the latex revealed the presence of 75 compounds, including cyclic peptides, glycosides, phenolic compounds, alkaloids, coumarins, and terpenoids, among others. No signs of acute toxicity were observed at a dose of 2000 mg/kg (p.o.). The latex interacted with the protein profile of TstiV, inhibiting the venom's fibrinogenolytic and hyaluronidase activities by 100%. Additionally, the latex was able to mitigate local envenomation effects, reducing nociception by up to 56.5% and edema by up to 50% compared to the negative control group. CONCLUSIONS: The latex of Jatropha mutabilis exhibits a diverse phytochemical composition, containing numerous classes of metabolites. It does not present acute toxic effects in mice and has the ability to inhibit the enzymatic effects of Tityus stigmurus venom in vitro. Additionally, it reduces nociception and edema in vivo. These findings corroborate popular reports regarding the antivenom activity of this plant and indicate that the latex has potential for treating scorpionism.
Assuntos
Antivenenos , Jatropha , Látex , Extratos Vegetais , Venenos de Escorpião , Escorpiões , Animais , Antivenenos/farmacologia , Antivenenos/química , Camundongos , Látex/química , Látex/farmacologia , Jatropha/química , Venenos de Escorpião/toxicidade , Venenos de Escorpião/química , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Feminino , Animais PeçonhentosRESUMO
Alternative recombinant sources of antivenoms have been successfully generated. The application of such strategies requires the characterization of the venoms for the development of specific neutralizing molecules against the toxic components. Five toxic peptides to mammals from the Mexican scorpion Centruroides villegasi were isolated by chromatographic procedures by means of gel filtration on Sephadex G-50, followed by ion-exchange columns on carboxy-methyl-cellulose (CMC) resins and finally purified by high-performance chromatography (HPLC) columns. Their primary structures were determined by Edman degradation. They contain 66 amino acids and are maintained well packed by four disulfide bridges, with molecular mass from 7511.3 to 7750.1 Da. They are all relatively toxic and deadly to mice and show high sequence identity with known peptides that are specific modifiers of the gating mechanisms of Na+ ion channels of type beta-toxin (ß-ScTx). They were named Cv1 to Cv5 and used to test their recognition by single-chain variable fragments (scFv) of antibodies, using surface plasmon resonance. Three different scFvs generated in our laboratory (10FG2, HV, LR) were tested for recognizing the various new peptides described here, paving the way for the development of a novel type of scorpion antivenom.
Assuntos
Peptídeos , Venenos de Escorpião , Escorpiões , Anticorpos de Cadeia Única , Animais , Venenos de Escorpião/química , Venenos de Escorpião/toxicidade , Venenos de Escorpião/imunologia , Peptídeos/química , Anticorpos de Cadeia Única/química , Humanos , Camundongos , Sequência de Aminoácidos , Antivenenos/imunologia , Antivenenos/química , Antivenenos/farmacologia , Animais PeçonhentosRESUMO
In this study, we report the innovative application of whole-cell patch-clamp electrophysiology in assessing broad-spectrum neutralisation by three different antivenoms, of venoms from the medically significant scorpion genus Centruroides. Envenomations by as many as 21 species from the Centruroides genus result in up to 300,000 envenomations per year in Mexico, which poses significant and potentially life-threatening pathophysiology. We first evaluated the in vitro manifestation of envenomation against two human voltage-gated sodium (hNaV) channel subtypes: hNaV1.4 and hNaV1.5, which are primarily expressed in skeletal muscles and cardiomyocytes, respectively. The neutralisation of venom activity was then characterised for three different antivenoms using a direct competition model against the more potent target, hNaV1.4. While broad-spectrum neutralisation was identified, variation in neutralisation arose for Centruroides elegans, C. limpidus, C. noxius and C. suffusus venoms, despite the presence of a number of these venoms within the immunising mixture. This raises questions regarding the truly "broad" neutralisation capacity of the antivenoms. This study not only extends previous validation of the in vitro investigation of antivenom efficacy utilising the whole-cell patch-clamp technique but also underscores the potential of this animal-free model in exploring cross-reactivity, experimental scalability, and most importantly, informing clinical management practices regarding the administration of antivenom in Mexico.
Assuntos
Antivenenos , Venenos de Escorpião , Escorpiões , Animais , Venenos de Escorpião/toxicidade , Antivenenos/farmacologia , Humanos , Picadas de Escorpião/tratamento farmacológico , Técnicas de Patch-Clamp , Especificidade da Espécie , México , Animais PeçonhentosRESUMO
The Brazilian Amazon is home to a rich fauna of scorpion species of medical importance, some of them still poorly characterized regarding their biological actions and range of clinical symptoms after envenoming. The Amazonian scorpion species Tityus strandi and Tityus dinizi constitute some of the scorpions in this group, with few studies in the literature regarding their systemic repercussions. In the present study, we characterized the clinical, inflammatory, and histopathological manifestations of T. strandi and T. dinizi envenoming in a murine model using Balb/c mice. The results show a robust clinical response based on clinical score, hyperglycemia, leukocytosis, increased cytokines, and histopathological changes in the kidneys and lungs. Tityus strandi envenomed mice presented more prominent clinical manifestations when compared to Tityus dinizi, pointing to the relevance of this species in the medical scenario, with both species inducing hyperglycemia, leukocytosis, increased cytokine production in the peritoneal lavage, increased inflammatory infiltrate in the lungs, and acute tubular necrosis after T. strandi envenoming. The results presented in this research can help to understand the systemic manifestations of scorpion accidents in humans caused by the target species of the study and point out therapeutic strategies in cases of scorpionism in remote regions of the Amazon.
Assuntos
Camundongos Endogâmicos BALB C , Picadas de Escorpião , Venenos de Escorpião , Escorpiões , Animais , Venenos de Escorpião/toxicidade , Camundongos , Modelos Animais de Doenças , Citocinas/metabolismo , Brasil , Leucocitose/induzido quimicamente , Pulmão/patologia , Pulmão/efeitos dos fármacos , Masculino , Rim/patologia , Rim/efeitos dos fármacos , FemininoRESUMO
The venom fractions of three buthid scorpion species from Colombia, C. margaritatus, T. pachyurus and T. n. sp. aff. metuendus, were examined for antimicrobial and toxicity toward mice and insects. The three venoms were separated into individual fractions using RP-HPLC, resulting in 85 fractions from C. margaritatus, 106 from T. pachyurus, and 70 from T. n. sp. aff. metuendus. The major fractions from the three scorpion venoms, which were eluted between 35 and 50 min, were tested for antimicrobial activity and toxicity. It was confirmed that the venom of the three species contains fractions with antimicrobial peptides that were evaluated against two bacterial strains of public health importance, Pseudomonas aeruginosa and Staphylococcus aureus. The venom of C. margaritatus had two antimicrobial fractions that showed activity against the named tested strains. The venom of T. pachyurus had three fractions that showed activity against S. aureus and two against both bacterial strains. Finally, the venom of T. n. sp. aff. metuendus had one fraction that showed activity against S. aureus, and five fractions showed activity against both bacterial strains. Also, some peptide fractions from the three venoms were toxic to mice. Last, the venoms of C. margaritatus and T. pachyurus were used as immunogens to obtain neutralizing antibodies against its respective venoms and to observe antibody recognition to related and unrelated scorpion venoms. A total of 15 mg of lyophilized antibodies were able to neutralize 1.5â LD50 of the venoms from T. n. sp. aff. metuendus, T. pachyurus and C. margaritatus, respectively. This information provides valuable insights into the diversity of each species' venom and their potential role in antimicrobial and venom toxicity.
Assuntos
Animais Peçonhentos , Anti-Infecciosos , Venenos de Escorpião , Camundongos , Animais , Sequência de Aminoácidos , Escorpiões , Venenos de Escorpião/toxicidade , Colômbia , Staphylococcus aureusRESUMO
Background: In Colombia, several species of Buthidae scorpions belonging to the genera Centruroides and Tityus coexist, and their stings are considered life-threatening to humans because of their venom neurotoxins. Despite previous studies focusing on neurotoxins from these scorpion genera, little is known about the enzymes present in their venoms and their relationship with whole venom toxicity. Methods: Here, using proteomic and biochemical protocols the enzymatic activities of the venoms of three Colombian scorpion species, C. margaritatus, T. pachyurus, and T. n. sp. aff. metuendus, were compared to establish the presence and absence of enzymes such as phospholipases, hyaluronidases, and proteases that could be related to venom toxicity. Results: C. margaritatus was positive for hyaluronidases, T. n. sp. aff. metuendus for proteases, and T. pachyurus exhibited activity for all three mentioned enzymes. Conclusion: This information provides valuable insights into the specific enzyme diversity of each species' venom and their potential role in venom toxicity, which could contribute to the development of better treatments and prevention strategies for scorpion envenomation.
Assuntos
Venenos de Escorpião/enzimologia , Venenos de Escorpião/toxicidade , ColômbiaRESUMO
OBJECTIVE: We aimed to elucidate the potential differences in the venom peptide sequences of three Tityus species from Costa Rican rainforests: T. jaimei, T. championi and T. dedoslargos, compared to T. cf. asthenes from Colombia, which could explain the low level of scorpionism in Costa Rica, evidenced by the lack of epidemiological data. METHODOLOGY: We applied venom proteomics of peptides purified by RP-HPLC and compared the obtained sequences from venoms of these Tityus species to the sequences previously identified from Tityus inhabiting other Central and South American regions. RESULTS: Venom proteome analysis evidences that most of the putative peptide toxins identified in Costa Rican dark-colored Tityus are very similar to those present in other T. (Atreus) from the region. CONCLUSIONS: Our study suggests that, in the case of potential envenomation by Tityus in Costa Rica, the same level of toxicity should be observed, compared to other cases caused by members of the subgenus from other geographical localities. On the other hand, compared to countries with more accelerated urban expansion, Costa Rican Tityus still inhabit secondary rainforests and do not commonly share the same spaces with humans, so the lack of epidemiological evidence of medical emergencies caused by envenoming by this scorpion group could be more related to ecological and demographic factors and less attributed to the characteristics of the venom.
Assuntos
Floresta Úmida , Venenos de Escorpião , Humanos , Animais , Costa Rica , Escorpiões , Proteômica , Peptídeos , Venenos de Escorpião/toxicidadeRESUMO
There are several scorpion species of medical relevance around the world. Some of them are well characterized by their toxins and clinical outcomes. Brazilian Amazon has a great amount of these arthropods that have an impact in the scorpionism events specifically in this region of Brazil. Recently, several studies pointed out the immune system activation during scorpion envenouming as an important facet of scorpionism, inducing a sepsis-like state that culminates in clinical severity and death. In this work, we characterized the macrophage response of three species of clinical relevance in Brazilian Amazon: Tityus silvestris, T. metuendus and T. obscurus and one specie with no toxic effects to humans, Brotheas amazonicus. All the four species analyzed were able to induce pro- and anti-inflammatory cytokine production in a J774.1 murine macrophage model. This activation was dependent on TLR2/TLR4/MyD88 activation and abolished by TLRs antagonists. These results suggest that the venoms of the four species analyzed were able to induce macrophage response in agreement to the well-established immune activation by T. serrulatus venom. Our findings provide new insights into the clinical repercussions of scorpionism of uncharacterized species and point to new biotechnological applications of these venoms and possible supportive therapies in scorpionism.
Assuntos
Picadas de Escorpião , Venenos de Escorpião , Humanos , Camundongos , Animais , Brasil , Venenos de Escorpião/toxicidade , Escorpiões , MacrófagosRESUMO
Due to the high prevalence and clinical relevance, scorpionism is a critical public health issue in several Brazilian regions. Tityus serrulatus, commonly known as the Brazilian yellow scorpion, is the most venomous genus found in Brazilian fauna and associated with severe clinical manifestations such as localized pain, hypertension, sweating, tachycardia and complex hyperinflammatory responses. In general, T. serrulatus venom contains a complex mixture of active compounds, including proteins, peptides, and amino acids. Although knowledge of the protein fractions of scorpion venom is available, venom lipid components are not yet comprehensively known. The aim of the present study was to determine and characterize the lipid constituents/profile of the T. serratus venom utilizing liquid chromatography coupled with high-resolution mass spectrometry. Lipid species (164 in total) belonging to 3 different lipid categories, glycerophospholipids, sphingolipids, and glycerolipids, were identified. A further search on MetaCore/MetaDrug platform, which is based upon a manually curated database of molecular interactions, molecular pathways, gene-disease associations, chemical metabolism, and toxicity information, exhibited several metabolic pathways for 24 of previously identified lipid species, including activation of nuclear factor kappa B and oxidative stress pathways. Further several bioactive compounds, such as plasmalogens, lyso-platelet-activating factors, and sphingomyelins, associated with systemic responses triggered by T. serrulatus envenomation were detected. Finally, lipidomic data presented provide advanced and valuable information to better comprehend the mechanisms underlying the complex pathophysiology induced by T. serrulatus envenomation.
Assuntos
Venenos de Escorpião , Animais , Venenos de Escorpião/toxicidade , Venenos de Escorpião/química , Escorpiões , Brasil , Lipidômica , LipídeosRESUMO
Scorpion sting envenomations (SSE) are feared by the intense pain that they produce in victims. Pain from SSE is triggered mainly by the presence of neurotoxins in the scorpion venom that modulates voltage-gated ion channels. In Brazil, SSE is mostly caused by Tityus serrulatus, popularly known as yellow scorpion. Here, we evaluated experimental spontaneous nociception induced by T. serrulatus venom as well as its isolated neurotoxins Ts1, Ts5, Ts6, Ts8, and Ts19 frag II, evidencing different degrees of pain behavior in mice. In addition, we developed a mice-derived polyclonal antibody targeting Ts5 able to neutralize the effect of this neurotoxin, showing that Ts5 presents epitopes capable of activating the immune response, which decreased considerably the nociception produced by the whole venom. This is the pioneer study to explore nociception using different classes of T. serrulatus neurotoxins on nociception (α-NaTx, ß-NaTx, α-KTx, and ß-KTx), targeting potassium and sodium voltage-gated channels, besides demonstrating that Ts5 plays an important role in the scorpion sting induced-pain.
Assuntos
Picadas de Escorpião , Venenos de Escorpião , Camundongos , Animais , Neurotoxinas/toxicidade , Nociceptividade , Peçonhas , Escorpiões , Dor/induzido quimicamente , Venenos de Escorpião/toxicidadeRESUMO
Centruroides huichol scorpion venom is lethal to mammals. Analysis of the venom allowed the characterization of four lethal toxins named Chui2, Chui3, Chui4, and Chui5. scFv 10FG2 recognized well all toxins except Chui5 toxin, therefore a partial neutralization of the venom was observed. Thus, scFv 10FG2 was subjected to three processes of directed evolution and phage display against Chui5 toxin until obtaining scFv HV. Interaction kinetic constants of these scFvs with the toxins were determined by surface plasmon resonance (SPR) as well as thermodynamic parameters of scFv variants bound to Chui5. In silico models allowed to analyze the molecular interactions that favor the increase in affinity. In a rescue trial, scFv HV protected 100% of the mice injected with three lethal doses 50 (LD50) of venom. Moreover, in mix-type neutralization assays, a combination of scFvs HV and 10FG2 protected 100% of mice injected with 5 LD50 of venom with moderate signs of intoxication. The ability of scFv HV to neutralize different toxins is a significant achievement, considering the diversity of the species of Mexican venomous scorpions, so this scFv is a candidate to be part of a recombinant anti-venom against scorpion stings in Mexico.
Assuntos
Venenos de Escorpião , Escorpiões , Sequência de Aminoácidos , Animais , Fragmentos de Imunoglobulinas , Mamíferos , México , Camundongos , Proteínas Recombinantes , Venenos de Escorpião/toxicidadeRESUMO
Enzymes are an integral part of animal venoms. Unlike snakes, in which enzymes play a primary role in envenomation, in scorpions, their function appears to be ancillary in most species. Due to this, studies on the diversity of scorpion venom components have focused primarily on the peptides responsible for envenomation (toxins) and a few others (e.g., antimicrobials), while enzymes have been overlooked. In this work, a comprehensive study on enzyme diversity in scorpion venoms was performed by transcriptomic and proteomic techniques. Enzymes of 63 different EC types were found, belonging to 330 orthogroups. Of them, 24 ECs conform the scorpion venom enzymatic core, since they were determined to be present in all the studied scorpion species. Transferases and lyases are reported for the first time. Novel enzymes, which can play different roles in the venom, including direct toxicity, as venom spreading factors, activators of venom components, venom preservatives, or in prey pre-digestion, were described and annotated. The expression profile for transcripts coding for venom enzymes was analyzed, and shown to be similar among the studied species, while being significantly different from their expression pattern outside the telson.
Assuntos
Venenos de Escorpião , Animais , Peptídeos/metabolismo , Proteômica/métodos , Venenos de Escorpião/metabolismo , Venenos de Escorpião/toxicidade , Escorpiões/genética , TranscriptomaRESUMO
The Tityus serrulatus scorpion is considered the most dangerous of the Brazilian fauna due to the severe clinical manifestations in injured victims. Despite being abundant components of the venom, few linear peptides have been characterized so far, such as hypotensins. In vivo studies have demonstrated that hypotensin I (TsHpt-I) exerts hypotensive activity, with an angiotensin-converting enzyme (ACE)-independent mechanism of action. Since experiments have not yet been carried out to analyze the direct interaction of hypotensins with ACE, and to deepen the knowledge about these peptides, hypotensins I and II (TsHpt-II) were studied regarding their modulatory action over the activities of ACE and neprilysin (NEP), which are the peptidases involved in blood pressure control. Aiming to search for indications of possible pro-inflammatory action, hypotensins were also analyzed for their role in murine macrophage viability, the release of interleukins and phagocytic activity. TsHpt-I and -II were used in kinetic studies with the metallopeptidases ACE and NEP, and both hypotensins were able to increase the activity of ACE. TsHpt-I presented itself as an inhibitor of NEP, whereas TsHpt-II showed weak inhibition of the enzyme. The mechanism of inhibition of TsHpt-I in relation to NEP was defined as non-competitive, with an inhibition constant (Ki) of 4.35 µM. Concerning the analysis of cell viability and modulation of interleukin levels and phagocytic activity, BALB/c mice's naïve macrophages were used, and an increase in TNF production in the presence of TsHpt-I and -II was observed, as well as an increase in IL-6 production in the presence of TsHpt-II only. Both hypotensins were able to increase the phagocytic activity of murine macrophages in vitro. The difference between TsHpt-I and -II is the residue at position 15, with a glutamine in TsHpt-I and a glutamic acid in TsHpt-II. Despite this, kinetic analyzes and cell assays indicated different actions of TsHpt-I and -II. Taken together, these results suggest a new mechanism for the hypotensive effects of TsHpt-I and -II. Furthermore, the release of some interleukins also suggests a role for these peptides in the venom inflammatory response. Even though these molecules have been well studied, the present results suggest a new mechanism for the hypotensive effects of TsHpt-I.
Assuntos
Inflamação/induzido quimicamente , Macrófagos Peritoneais/efeitos dos fármacos , Metaloproteases/metabolismo , Venenos de Escorpião/química , Animais , Citocinas/genética , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Venenos de Escorpião/toxicidadeRESUMO
Few data are available in the literature describing the long-term effects of envenoming in the perinatal period. In this study, the relationship between envenoming of lactating rats and possible behavioral changes in the mother and in her offspring were investigated. Lactating Wistar rats received a single dose of T. serrulatus crude venom on postnatal days 2 (V2), 10 (V10) or 16 (V16), and had their maternal behavior evaluated. The seizure threshold was evaluated in adulthood offspring. A decrease in maternal care during envenoming was observed in V2 and V10 groups. The retrieval behavior was absent in the V2 group, and a lower seizure threshold in the adult offspring of all groups was observed. During envenoming, mothers stayed away from their offspring for a relatively long time. Maternal deprivation during the early postnatal period is one of the most potent stressors for pups and could be responsible, at least in part, for the decrease in the convulsive threshold of the offspring since stress is pointed to as a risk factor for epileptogenesis. Furthermore, the scorpionic accident generates an intense immune response, and inflammation in neonates increases the susceptibility to seizures in adulthood. Therefore, maternal envenoming during lactation can have adverse effects on offspring in adulthood.
Assuntos
Lactação , Comportamento Materno/efeitos dos fármacos , Venenos de Escorpião/toxicidade , Convulsões/induzido quimicamente , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Convulsivantes/administração & dosagem , Feminino , Masculino , Exposição Materna/efeitos adversos , Pentilenotetrazol/administração & dosagem , Ratos WistarRESUMO
Multidrug-resistant bacteria represent a global health problem increasingly leading to infections that are untreatable with our existing antibiotic arsenal. Therefore, it is critical to identify novel effective antimicrobials. Venoms represent an underexplored source of potential antibiotic molecules. Here, we engineered a peptide (IsCT1-NH2) derived from the venom of the scorpion Opisthacanthus madagascariensis, whose application as an antimicrobial had been traditionally hindered by its high toxicity. Through peptide design and the knowledge obtained in preliminary studies with single and double-substituted analogs, we engineered IsCT1 derivatives with multiple amino acid substitutions to assess the impact of net charge on antimicrobial activity and toxicity. We demonstrate that increased net charge (from +3 to +6) significantly reduced toxicity toward human erythrocytes. Our lead synthetic peptide, [A]1[K]3[F]5[K]8-IsCT1-NH2 (net charge of +4), exhibited increased antimicrobial activity against Gram-negative and Gram-positive bacteria in vitro and enhanced anti-infective activity in a mouse model. Mechanism of action studies revealed that the increased antimicrobial activity of our lead molecule was due, at least in part, to its enhanced ability to permeabilize the outer membrane and depolarize the cytoplasmic membrane. In summary, we describe a simple method based on net charge tuning to turn highly toxic venom-derived peptides into viable therapeutics.
Assuntos
Anti-Infecciosos , Venenos de Escorpião , Animais , Camundongos , Testes de Sensibilidade Microbiana , Modelos Animais , Peptídeos/farmacologia , Venenos de Escorpião/toxicidadeRESUMO
Scorpion venom is a Chinese medicine for epilepsy treatment, but the underlying mechanism is not clear. Scorpion venom heat-resistant peptide (SVHRP), a peptide isolated from the venom of Buthus martensii Karsch, has an anti-epileptic effect by reducing seizure behavior according to a modified Racine scale. The present study aimed to investigate the molecular mechanism of SVHRP on temporal lobe epilepsy. The hippocampus and hippocampal neurons from kainic acid-induced epileptic rats were treated with SVHRP at different doses and duration. Quantitative RT-PCR and immunoblotting were used to detect the expression level of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), cAMP-response element binding protein (CREB), stromal interaction molecule (STIM), and calcium release-activated calcium channel protein 1 (ORAI1). In the hippocampal tissues and primary hippocampal neuron cultures, SVHRP treatment resulted in increased mRNA and protein levels of BDNF and NPY under the epileptic condition. The upregulation of BDNF and NPY expression was positively correlated with the dose level and treatment duration of SVHRP in hippocampal tissues from kainic acid-induced epileptic rats. On the other hand, no significant changes in the levels of CREB, STIM, or ORAI1 were observed. SVHRP may exhibit an anti-epileptic effect by upregulating the expression of BDNF and NPY in the epileptic hippocampus.
Assuntos
Epilepsia , Venenos de Escorpião , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Hipocampo/metabolismo , Temperatura Alta , Ácido Caínico/toxicidade , Neurônios , Peptídeos , Ratos , Venenos de Escorpião/toxicidadeRESUMO
Cases of human envenomation by Centruroides pococki are exceptionally reported in human. We report a Class III human envenomation by C. pococki in Guadeloupe, French West Indies, with neuromuscular toxicity that has never been described before. Symptoms resolved within a few hours, without the need for intravenous scorpion-specific antivenom.
Assuntos
Sistema Nervoso/efeitos dos fármacos , Venenos de Escorpião/toxicidade , Escorpiões , Administração Intravenosa , Adulto , Animais , Antivenenos , Feminino , Guadalupe , Humanos , Picadas de Escorpião , Índias OcidentaisRESUMO
Centruroides margaritatus scorpion stings are common in Colombia. However, the cardiovascular toxicity of the venom has not been clarified. AIM: To study the effect and mechanisms of action of the complete venom of C. margaritatus (CmV) on the murine cardiovascular system. METHODS: We evaluated the in vivo effect of CmV LD50 on the mean arterial pressure (MABP), heart rate, and surface electrocardiogram in male adult normotensive Wistar rats. Ex vivo, we evaluated the vascular reactivity of rat aortic rings to increasing concentrations (1 to 60 µg/mL) of CmV using the blockers L-NAME, indomethacin, seratrodast, and prazosin. RESULTS: In the first hour of poisoning, CmV increased the MABP. In the second hour after poisoning, the heart rate decreased as the normalized PR interval and QT corrected increased. After that, cardiovascular shock was demonstrated by a drastic fall in the MABP and signs of cardiac conduction system block. In aortic rings, CmV caused a direct vasoconstrictor effect mediated by alpha-1 adrenergic receptors and counteracted by nitric oxide. CONCLUSION: The direct vascular and probably the cardiac alpha-1 effects likely explain the transient hypertension and the maintenance of cardiac function, while interval lengthening may be due to K+ channel blockage. Afterwards, the effects of both the alpha-1 pathway and the K+ channel pathway converged, resulting in fatal cardiovascular shock. This knowledge could aid in understanding the dynamics of the effects of the venom and in designing treatments to address its cardiovascular effects.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Receptores Adrenérgicos alfa 1/metabolismo , Venenos de Escorpião/toxicidade , Escorpiões/química , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Eletrocardiografia/métodos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
Scorpion venom is a Chinese medicine for epilepsy treatment, but the underlying mechanism is not clear. Scorpion venom heat-resistant peptide (SVHRP), a peptide isolated from the venom of Buthus martensii Karsch, has an anti-epileptic effect by reducing seizure behavior according to a modified Racine scale. The present study aimed to investigate the molecular mechanism of SVHRP on temporal lobe epilepsy. The hippocampus and hippocampal neurons from kainic acid-induced epileptic rats were treated with SVHRP at different doses and duration. Quantitative RT-PCR and immunoblotting were used to detect the expression level of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), cAMP-response element binding protein (CREB), stromal interaction molecule (STIM), and calcium release-activated calcium channel protein 1 (ORAI1). In the hippocampal tissues and primary hippocampal neuron cultures, SVHRP treatment resulted in increased mRNA and protein levels of BDNF and NPY under the epileptic condition. The upregulation of BDNF and NPY expression was positively correlated with the dose level and treatment duration of SVHRP in hippocampal tissues from kainic acid-induced epileptic rats. On the other hand, no significant changes in the levels of CREB, STIM, or ORAI1 were observed. SVHRP may exhibit an anti-epileptic effect by upregulating the expression of BDNF and NPY in the epileptic hippocampus.
Assuntos
Animais , Ratos , Venenos de Escorpião/toxicidade , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Peptídeos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Temperatura Alta , Hipocampo/metabolismo , Ácido Caínico/toxicidade , NeurôniosRESUMO
Envenoming by scorpions in genus Tityus is a public health problem in Tropical America. One of the most medically significant species is Tityus trivittatus, which is known to occur from southwest Brazil to central-northern and eastern Argentina. In this work, we studied the lethality, composition, antigenicity, and enzymatic activity of venom from a T. trivittatus population found further north in urban areas of eastern Paraguay, where it has caused serious envenomation of children. Our results indicate that the population is of medical importance as it produces a potently toxic venom with an LD50 around 1.19 mg/kg. Venom neutralization in preliminary mouse bioassays was complete when using Brazilian anti-T. serrulatus antivenom but only partial when using Argentinean anti-T. trivittatus antivenom. Venom competitive solid-phase enzyme immunoassays and immunoblotting from Argentinean and Paraguayan T. trivittatus populations indicated that antigenic differences exist across the species range. SDS-PAGE showed variations in type and relative amounts of venom proteins between T. trivitattus samples from Argentina and Paraguay. MALDI-TOF mass spectrometry indicated that while some sodium channel toxins are shared, including ß-toxin Tt1g, others are population-specific. Proteolytic activity by zymography and peptide identification through nESI-MS/MS also point out that population-specific proteases may exist in T. trivitattus, which are postulated to be involved in the envenoming process. A time-calibrated molecular phylogeny of mitochondrial COI sequences revealed a significant (8.14%) genetic differentiation between the Argentinean and Paraguayan populations, which appeared to have diverged between the mid Miocene and early Pliocene. Altogether, toxinological and genetic evidence indicate that T. trivitattus populations from Paraguay and Argentina correspond to distinct, unique cryptic species, and suggest that further venom and taxonomic diversity exists in synanthropic southern South American Tityus than previously thought.