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Sample records for quinquestriatus scorpion venom

  1. Chloride channel inhibition by the venom of the scorpion Leiurus quinquestriatus.

    PubMed

    DeBin, J A; Strichartz, G R

    1991-01-01

    The venom of the scorpion Leiurus quinquestriatus produced a significant, reversible inhibition of reconstituted Cl- channels of the small conductance type found in rat colonic epithelial cells. The kinetics of single-channel block by this venom were consistent with a first-order binding reaction in which the binding of one ligand molecule is sufficient to induce channel block. Single-channel mean block times were c.6 sec at -20 mV, and a KI in the submicromolar range is predicted. The active component has a mol. wt of roughly 5000 as judged by molecular sieve chromatography. PMID:1726031

  2. Comparative study between the protective effects of Saudi and Egyptian antivenoms, alone or in combination with ion channel modulators, against deleterious actions of Leiurus quinquestriatus scorpion venom.

    PubMed

    Fatani, Amal J; Ahmed, Amany A E; Abdel-Halim, Rabab M; Abdoon, Nozha A; Darweesh, Amal Q

    2010-04-01

    This study compared efficacy of two polyvalent antivenoms (Saudi Arabian and Egyptian), against lethality and pathophysiological changes of Leiurus quinquestriatus quinquestriatus (LQQ) scorpion venom in mice. Additionally, the study examined whether treatment with selected ion channel modulators, lidocaine, nimodipine or amiodarone would be effective, alone or combined with the antivenoms. The protein concentration of the Saudi antivenom was 1/3 of Egyptian, indicating lesser immunogenicity, while both preservative contents were within limits. In immunodiffusion experiments, both exhibited prominent precipitin bands indicating high concentrations of specific antibodies. Neutralizing capacities (60-70 LD(50)) stated on labels were confirmed. Both antivenoms significantly (P < 0.001) prolonged survival time (from 26.9 +/- 1.18 min, 100% dead with venom to 224-300 min, 0-30% dead) of envenomed mice, whether injected iv before or 5 min after venom. Injection of either antivenom plus ion channel modulators, gave comparable results to that observed in mice treated with antivenoms alone. The Na(+) channel blocker lidocaine and the Ca(2+) channel blocker nimodipine on their own significantly protected the animals (P < 0.05), but to a lesser extent. The two antivenoms, significantly ameliorated the venom-evoked changes in serum LDH (P < 0.001) and CKMB (P < 0.01) plus cardiac TNFalpha and nitrate/nitrite levels (P < 0.001). When combined with lidocaine or nimodipine, the effects were not greater than antivenom alone. Moreover, the antivenoms ameliorated characteristic venom-evoked changes in the isolated perfused Langendorff hearts. Lidocaine and amiodarone were more effective than nimodipine. In Conclusion both Saudi and Egyptian antivenoms protected mice from the pathological and lethal effects of LQQ scorpion. Sodium and calcium channel blockers, lidocaine and nimodipine, may be useful when antivenoms are not available. PMID:19931297

  3. Leiurus quinquestriatus venom inhibits BRL 34915-induced /sup 86/Rb/sup +/ efflux from the rat portal vein

    SciTech Connect

    Quast, U.; Cook, N.S.

    1988-01-01

    The effect of the crude venom of the Israeli scorpion Leiurus quinquestriatus hebraeus on the /sup 86/Rb/sup +/ efflux stimulated by the K/sup +/ channel opener BRL 34915 in the rat portal vein was examined. Applied alone, the venom greatly increased the spontaneous mechanical activity of and the concomitant /sup 86/Rb/sup +/ efflux from the vessel. When the excitability of the vein was suppressed by the dihydropyridine calcium antagonist, PN 200-110, the /sup 86/Rb/sup +/ efflux stimulated by BRL 34915 could be shown to be inhibited by the venom. From the concentration dependence of this inhibition an IC/sub 50/ value of 0.17 +/- 0.01 mg/ml was estimated. This venom is thus the most potent blocker of BRL 34915-evoked /sup 86/Rb/sup +/ efflux reported so far. 17 references, 2 figures.

  4. Moving pieces in a taxonomic puzzle: venom 2D-LC/MS and data clustering analyses to infer phylogenetic relationships in some scorpions from the Buthidae family (Scorpiones).

    PubMed

    Nascimento, Danielle G; Rates, Breno; Santos, Daniel M; Verano-Braga, Thiago; Barbosa-Silva, Adriano; Dutra, Alexandre A A; Biondi, Ilka; Martin-Eauclaire, Marie France; De Lima, Maria Elena; Pimenta, Adriano M C

    2006-05-01

    The Buthidae is the most clinically important scorpion family, with over 500 species distributed worldwide. Taxonomical positions and phylogenetic relationships concerning the representative genera and species of this family have been mostly inferred based upon comparisons between morphological characters. Yet, some authors have performed such inferences by comparing some structural properties of a few selected molecules found in the venoms from these scorpions. Here, we propose a novel methodology pipeline designed to address these issues. We have analyzed the whole venoms from some species that exemplify peculiar cases in the Buthidae family (Tityus stigmurus, Tityus serrulatus, Tityus bahiensis, Leiurus quinquestriatus quinquestriatus and Leiurus quinquestriatus hebraeus), by means of a proteomic approach using a 2D-LC/MS technique. The molecules found in these venoms were clustered according to their physicochemical properties (molecular mass and hydrophobicity), by using the machine learning-based Weka software. The clusters assessment, along with the number of molecules found in a given cluster for each scorpion, which assigns for the venom and structural family complexities, respectively, was used to generate a phenetic correlation tree for positioning these species. Our results were in accordance with the classical taxonomy viewpoint, which places T. serrulatus and T. stigmurus as very close species, T. bahiensis as a less related species in the Tityus genus and L. q. quinquestriatus and L. q. hebraeus with small differences within the same species (L. quinquestriatus). Therefore, we believe that this is a well-suited method to determine venom complexities that reflect the scorpions' evolutionary history, which can be crucial to reconstruct their phylogeny through the molecular evolution of their venoms. PMID:16551474

  5. [The threat of snake and scorpion venoms].

    PubMed

    Płusa, Tadeusz; Smędzik, Katarzyna

    2015-09-01

    Venoms of snakes and scorpions pose a significant threat to the health and life of humans. The speed and range of their actions causes damage of the organ responsible for the maintenance of vital signs. Venomous snake venoms cause blood clotting disorders, tissue necrosis and hemolysis, and the release of a number of proinflammatory cytokines and impair antibody synthesis. Availability of antitoxins is limited and in the most cases supportive treatment is recommended. In turn, the venom of scorpions beside intestinal symptoms cause significant impairment of neuromuscular conduction, causing severe respiratory disorders. Action venom poses a particular threat to sensitive patients. The degree of threat to life caused by the venom of snakes and scorpions authorizes the treatment of these substances as a potential biological weapon. PMID:26449581

  6. Inhibition of ClC-2 chloride channels by a peptide component or components of scorpion venom.

    PubMed

    Thompson, C H; Fields, D M; Olivetti, P R; Fuller, M D; Zhang, Z R; Kubanek, J; McCarty, N A

    2005-11-01

    ClC chloride channels play essential roles in membrane excitability and maintenance of osmotic balance. Despite the recent crystallization of two bacterial ClC-like proteins, the gating mechanism for these channels remains unclear. In this study we tested scorpion venom for the presence of novel peptide inhibitors of ClC channels, which might be useful tools for dissecting the mechanisms underlying ClC channel gating. Recently, it has been shown that a peptide component of venom from the scorpion L. quinquestriatus hebraeus inhibits the CFTR chloride channel from the intracellular side. Using two-electrode voltage clamp we studied the effect of scorpion venom on ClC-0, -1, and -2, and found both dose- and voltage-dependent inhibition only of ClC-2. Comparison of voltage-dependence of inhibition by venom to that of known pore blockers revealed opposite voltage dependencies, suggesting different mechanisms of inhibition. Kinetic data show that venom induced slower activation kinetics compared to pre-venom records, suggesting that the active component(s) of venom may function as a gating modifier at ClC-2. Trypsinization abolished the inhibitory activity of venom, suggesting that the component(s) of scorpion venom that inhibits ClC-2 is a peptide. PMID:16596447

  7. Transcriptome analysis of the venom gland of the scorpion Scorpiops jendeki: implication for the evolution of the scorpion venom arsenal

    PubMed Central

    Ma, Yibao; Zhao, Ruiming; He, Yawen; Li, Songryong; Liu, Jun; Wu, Yingliang; Cao, Zhijian; Li, Wenxin

    2009-01-01

    Background The family Euscorpiidae, which covers Europe, Asia, Africa, and America, is one of the most widely distributed scorpion groups. However, no studies have been conducted on the venom of a Euscorpiidae species yet. In this work, we performed a transcriptomic approach for characterizing the venom components from a Euscorpiidae scorpion, Scorpiops jendeki. Results There are ten known types of venom peptides and proteins obtained from Scorpiops jendeki. Great diversity is observed in primary sequences of most highly expressed types. The most highly expressed types are cytolytic peptides and serine proteases. Neurotoxins specific for sodium channels, which are major groups of venom components from Buthidae scorpions, are not detected in this study. In addition to those known types of venom peptides and proteins, we also obtain nine atypical types of venom molecules which haven't been observed in any other scorpion species studied to date. Conclusion This work provides the first set of cDNAs from Scorpiops jendeki, and one of the few transcriptomic analyses from a scorpion. This allows the characterization of a large number of venom molecules, belonging to either known or atypical types of scorpion venom peptides and proteins. Besides, our work could provide some clues to the evolution of the scorpion venom arsenal by comparison with venom data from other scorpion lineages. PMID:19570192

  8. Scorpion venom and the inflammatory response.

    PubMed

    Petricevich, Vera L

    2010-01-01

    Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability. PMID:20300540

  9. Scorpion Venom and the Inflammatory Response

    PubMed Central

    Petricevich, Vera L.

    2010-01-01

    Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. These venoms are associated with high morbility and mortality, especially among children. Victims of envenoming by a scorpion suffer a variety of pathologies, involving mainly both sympathetic and parasympathetic stimulation as well as central manifestations such as irritability, hyperthermia, vomiting, profuse salivation, tremor, and convulsion. The clinical signs and symptoms observed in humans and experimental animals are related with an excessive systemic host inflammatory response to stings and stings, respectively. Although the pathophysiology of envenomation is complex and not yet fully understood, venom and immune responses are known to trigger the release of inflammatory mediators that are largely mediated by cytokines. In models of severe systemic inflammation produced by injection of high doses of venom or venoms products, the increase in production of proinflammatory cytokines significantly contributes to immunological imbalance, multiple organ dysfunction and death. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and also physiological events in the host such as activation of vasodilatation, hypotension, and increased of vessel permeability. PMID:20300540

  10. Analysis of scorpion venom composition by Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Martínez-Zérega, Brenda E.; González-Solís, José L.

    2015-01-01

    In this work we study the venom of two Centruroides scorpion species using Raman spectroscopy. The spectra analysis allows to determine the venoms chemical composition and to establish the main differences and similarities among the species. It is also shown that the use of Principal Component Analysis may help to tell apart between the scorpion species.

  11. The Block of CFTR by Scorpion Venom is State-Dependent

    PubMed Central

    Fuller, Matthew D.; Zhang, Zhi-Ren; Cui, Guiying; McCarty, Nael A.

    2005-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) adenosine triphosphate-dependent chloride channels are expressed in epithelial cells and are associated with a number of genetic disorders, including cystic fibrosis. Venom of the scorpion Leirus quinquestriatus hebraeus reversibly inhibits CFTR when applied to its cytoplasmic surface. To examine the state-dependence of inhibition we recorded wild-type and mutant CFTR channel currents using inside-out membrane patches from Xenopus oocytes. Application of either venom or diphenylamine-2-carboxylate to channels that were either activated (open) or resting (closed) indicate primarily closed state-dependent inhibition of CFTR by venom, whereas diphenylamine-2-carboxylate showed no state-dependence of block. Efficacy of venom-mediated macroscopic current inhibition was inversely related to channel activity. Analysis of single-channel and macropatch data indicated that venom could either inhibit channel opening, if it binds during an interburst closed state or in the absence of cytosolic adenosine triphosphate, or introduce new intraburst closed states, if it binds during an open event. The on-rate of venom binding for intraburst block could be modulated by changing CFTR activity with vanadate or adenylyl-imidodiphosphate, or by introducing the Walker A mutation K1250A. These findings represent the first description of state-dependent inhibition of CFTR and suggest that the active toxin could be used as a tool to study the conformational changes that occur during CFTR gating. PMID:16183882

  12. The block of CFTR by scorpion venom is state-dependent.

    PubMed

    Fuller, Matthew D; Zhang, Zhi-Ren; Cui, Guiying; McCarty, Nael A

    2005-12-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) adenosine triphosphate-dependent chloride channels are expressed in epithelial cells and are associated with a number of genetic disorders, including cystic fibrosis. Venom of the scorpion Leirus quinquestriatus hebraeus reversibly inhibits CFTR when applied to its cytoplasmic surface. To examine the state-dependence of inhibition we recorded wild-type and mutant CFTR channel currents using inside-out membrane patches from Xenopus oocytes. Application of either venom or diphenylamine-2-carboxylate to channels that were either activated (open) or resting (closed) indicate primarily closed state-dependent inhibition of CFTR by venom, whereas diphenylamine-2-carboxylate showed no state-dependence of block. Efficacy of venom-mediated macroscopic current inhibition was inversely related to channel activity. Analysis of single-channel and macropatch data indicated that venom could either inhibit channel opening, if it binds during an interburst closed state or in the absence of cytosolic adenosine triphosphate, or introduce new intraburst closed states, if it binds during an open event. The on-rate of venom binding for intraburst block could be modulated by changing CFTR activity with vanadate or adenylyl-imidodiphosphate, or by introducing the Walker A mutation K1250A. These findings represent the first description of state-dependent inhibition of CFTR and suggest that the active toxin could be used as a tool to study the conformational changes that occur during CFTR gating. PMID:16183882

  13. Determination of the Median Lethal Dose and Electrophoretic Pattern of Hottentotta saulcyi (Scorpiones, Buthidae) Scorpion Venom

    PubMed Central

    Yağmur, Ersen Aydın; Özkan, Özcan; Karaer, K Zafer

    2015-01-01

    Background: In this study, we investigated the lethal potency, electrophoretic protein pattern and in vivo effects of Hottentotta saulcyi scorpion venom in mice. Methods: Scorpions were collected at night, by using a UV lamp from Mardin Province, Turkey. Venom was obtained from mature H. saulcyi scorpions by electrical stimulation of the telson. The lethality of the venom was determined by i.v. injections using Swiss mice. In vivo effects of the venom were assessed by using the intraperitoneal route (ip) injections into mice (20±1g) and monitored for 24 h. The protein profiles of the scorpion venom were analyzed by NuPAGE® Novex® 4–12 % gradient Bis-Tris gel followed by Coomassie blue staining. Results: The lethal assay of the venom was 0.73 mg/kg in mice. We determined the electrophoretic protein pattern of this scorpion venom to be 4, 6, 9, 31, 35, 40, 46 and 69 kDa by SDS-PAGE. Analysis of electrophoresis indicated that H. saulcyi scorpion intoxicated mice exhibited autonomic nervous system symptoms (tachypnea, restlessness, hyperexcitability, convulsions, salivation, lacrimation, weakness). Conclusions: Hottentotta saulcyi scorpion venom includes short-chain neurotoxins and long-chain neurotoxins according to the electrophoretic protein patterns. The stings of H. saulcyi scorpion must be considered of risk for humans in the southeastern region, Turkey. PMID:26623435

  14. [Use of medicinal plants against scorpionic and ophidian venoms].

    PubMed

    Memmi, A; Sansa, G; Rjeibi, I; El Ayeb, M; Srairi-Abid, N; Bellasfer, Z; Fekhih, A

    2007-01-01

    The scorpionic and ophidian envenomations are a serious public health problem in Tunisia especially in Southeastern regions. In these regions Artemisia campestris L is a plant well known which has a very important place in traditional medicine for its effectiveness against alleged venom of scorpions and snakes. In this work, we tested for the first time, the anti-venomous activity of Artemisia campestris L against the scorpion Androctonus australis garzonii and the viper Macrovipera lebetina venoms. Assays were conducted by fixing the dose of extract to3 mg/mouse while doses of venom are variable. The leaves of Artemisia campestris L were extracted by various organic solvents (Ether of oil, ethyl acetate, methanol and ethanol) and each extract was tested for its venom neutralizing capacity. For the ethanolic extract, a significant activity with respect to the venoms of scorpion Androctonus australis garzonii (Aag), was detected. Similarly, a significant neutralizing activity against the venom of a viper Macrovipera lebetina (Ml), was obtained with the dichloromethane extract. These results suggest the presence of two different type of chemical components in this plant: those neutralizing the venom of scorpion are soluble in ethanol whereas those neutralizing the venom of viper are soluble in dichloromethane. PMID:19388583

  15. Scorpions

    MedlinePlus

    ... 222-1222) from anywhere in the United States. Poisonous Ingredient Scorpion venom contains the poison. Where Found ... most varieties of North American scorpions are NOT poisonous. The poisonous ones in the United States live ...

  16. Whole Transcriptome of the Venom Gland from Urodacus yaschenkoi Scorpion

    PubMed Central

    Juárez-González, Víctor Rivelino; Possani, Lourival D.

    2015-01-01

    Australian scorpion venoms have been poorly studied, probably because they do not pose an evident threat to humans. In addition, the continent has other medically important venomous animals capable of causing serious health problems. Urodacus yaschenkoi belongs to the most widely distributed family of Australian scorpions (Urodacidae) and it is found all over the continent, making it a useful model system for studying venom composition and evolution. This communication reports the whole set of mRNA transcripts produced by the venom gland. U. yaschenkoi venom is as complex as its overseas counterparts. These transcripts certainly code for several components similar to known scorpion venom components, such as: alpha-KTxs, beta-KTxs, calcins, protease inhibitors, antimicrobial peptides, sodium-channel toxins, toxin-like peptides, allergens, La1-like, hyaluronidases, ribosomal proteins, proteasome components and proteins related to cellular processes. A comparison with the venom gland transcriptome of Centruroides noxius (Buthidae) showed that these two scorpions have similar components related to biological processes, although important differences occur among the venom toxins. In contrast, a comparison with sequences reported for Urodacus manicatus revealed that these two Urodacidae species possess the same subfamily of scorpion toxins. A comparison with sequences of an U. yaschenkoi cDNA library previously reported by our group showed that both techniques are reliable for the description of the venom components, but the whole transcriptome generated with Next Generation Sequencing platform provides sequences of all transcripts expressed. Several of which were identified in the proteome, but many more transcripts were identified including uncommon transcripts. The information reported here constitutes a reference for non-Buthidae scorpion venoms, providing a comprehensive view of genes that are involved in venom production. Further, this work identifies new putative

  17. Scorpions from Mexico: From Species Diversity to Venom Complexity

    PubMed Central

    Santibáñez-López, Carlos E.; Francke, Oscar F.; Ureta, Carolina; Possani, Lourival D.

    2015-01-01

    Scorpions are among the oldest terrestrial arthropods, which are distributed worldwide, except for Antarctica and some Pacific islands. Scorpion envenomation represents a public health problem in several parts of the world. Mexico harbors the highest diversity of scorpions in the world, including some of the world’s medically important scorpion species. The systematics and diversity of Mexican scorpion fauna has not been revised in the past decade; and due to recent and exhaustive collection efforts as part of different ongoing major revisionary systematic projects, our understanding of this diversity has changed compared with previous assessments. Given the presence of several medically important scorpion species, the study of their venom in the country is also important. In the present contribution, the diversity of scorpion species in Mexico is revised and updated based on several new systematic contributions; 281 different species are recorded. Commentaries on recent venomic, ecological and behavioral studies of Mexican scorpions are also provided. A list containing the most important peptides identified from 16 different species is included. A graphical representation of the different types of components found in these venoms is also revised. A map with hotspots showing the current knowledge on scorpion distribution and areas explored in Mexico is also provided. PMID:26712787

  18. Scorpions from Mexico: From Species Diversity to Venom Complexity.

    PubMed

    Santibáñez-López, Carlos E; Francke, Oscar F; Ureta, Carolina; Possani, Lourival D

    2016-01-01

    Scorpions are among the oldest terrestrial arthropods, which are distributed worldwide, except for Antarctica and some Pacific islands. Scorpion envenomation represents a public health problem in several parts of the world. Mexico harbors the highest diversity of scorpions in the world, including some of the world's medically important scorpion species. The systematics and diversity of Mexican scorpion fauna has not been revised in the past decade; and due to recent and exhaustive collection efforts as part of different ongoing major revisionary systematic projects, our understanding of this diversity has changed compared with previous assessments. Given the presence of several medically important scorpion species, the study of their venom in the country is also important. In the present contribution, the diversity of scorpion species in Mexico is revised and updated based on several new systematic contributions; 281 different species are recorded. Commentaries on recent venomic, ecological and behavioral studies of Mexican scorpions are also provided. A list containing the most important peptides identified from 16 different species is included. A graphical representation of the different types of components found in these venoms is also revised. A map with hotspots showing the current knowledge on scorpion distribution and areas explored in Mexico is also provided. PMID:26712787

  19. Inhibition of CFTR channels by a peptide toxin of scorpion venom.

    PubMed

    Fuller, Matthew D; Zhang, Zhi-Ren; Cui, Guiying; Kubanek, Julia; McCarty, Nael A

    2004-11-01

    Peptide toxins have been valuable probes in efforts to identify amino acid residues that line the permeation pathway of cation-selective channels. However, no peptide toxins have been identified that interact with known anion-selective channels such as the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR channels are expressed in epithelial cells and are associated with several genetic disorders, including cystic fibrosis and polycystic kidney disease. Several organic inhibitors have been used to investigate the structure of the Cl- permeation pathway in CFTR. However, investigations of the wider cytoplasmic vestibule have been hindered by the lack of a high-affinity blocker that interacts with residues in this area. In this study we show that venom of the scorpion Leiurus quinquestriatus hebraeus reversibly inhibits CFTR, in a voltage-independent manner, by decreasing single-channel mean burst duration and open probability only when applied to the cytoplasmic surface of phosphorylated channels. Venom was able to decrease burst duration and open probability even when CFTR channels were locked open by treatment with either vanadate or adenosine 5'-(beta,gamma-imido)triphosphate, and block was strengthened on reduction of extracellular Cl- concentration, suggesting inhibition by a pore-block mechanism. Venom had no effect on ATP-dependent macroscopic opening rate in channels studied by inside-out macropatches. Interestingly, the inhibitory activity was abolished by proteinase treatment. We conclude that a peptide toxin contained in the scorpion venom inhibits CFTR channels by a pore-block mechanism; these experiments provide the first step toward isolation of the active component, which would be highly valuable as a probe for CFTR structure and function. PMID:15240343

  20. Protease inhibitor in scorpion (Mesobuthus eupeus) venom prolongs the biological activities of the crude venom.

    PubMed

    Ma, Hakim; Xiao-Peng, Tang; Yang, Shi-Long; Lu, Qiu-Min; Lai, Ren

    2016-08-01

    It is hypothesized that protease inhibitors play an essential role in survival of venomous animals through protecting peptide/protein toxins from degradation by proteases in their prey or predators. However, the biological function of protease inhibitors in scorpion venoms remains unknown. In the present study, a trypsin inhibitor was purified and characterized from the venom of scorpion Mesobuthus eupeus, which enhanced the biological activities of crude venom components in mice when injected in combination with crude venom. This protease inhibitor, named MeKTT-1, belonged to Kunitz-type toxins subfamily. Native MeKTT-1 selectively inhibited trypsin with a Kivalue of 130 nmol·L(-1). Furthermore, MeKTT-1 was shown to be a thermo-stable peptide. In animal behavioral tests, MeKTT-1 prolonged the pain behavior induced by scorpion crude venom, suggesting that protease inhibitors in scorpion venom inhibited proteases and protect the functionally important peptide/protein toxins from degradation, consequently keeping them active longer. In conclusion, this was the first experimental evidence about the natural existence of serine protease inhibitor in the venom of scorpion Mesobuthus eupeus, which preserved the activity of venom components, suggests that scorpions may use protease inhibitors for survival. PMID:27608950

  1. Preparation of a potent anti-scorpion-venom-serum against the venom of red scorpion (Buthus tamalus).

    PubMed

    Kankonkar, R C; Kulkurni, D G; Hulikavi, C B

    1998-01-01

    A number of children and adults, especially pregnant women succumb to the sting by red Scorpion (Buthus tamalus) in Konkan region--particularly on the coastal line. No specific antiserum or any other antidote is available to treat a victim of scorpion bite and hence the need to prepare a potent antiserum. Red Scorpion (B. tamalus) venom is a mixture of a number of protein moieties and neurotoxins of low molecular weight. Therefore, the venom is poor in antigenic composition and it is difficult to get antibodies specific to neutralise lethal factor/factors. Using Bentonite as an adjuvant and extending the period of immunization a potent antiserum has been prepared capable of neutralising the lethal factor/factors. In vivo testing carried out in albino mice, guinea pigs, dogs and langurs confirms this finding and shows that the antiserum is quite effective in neutralising the scorpion venom to save the life of envenomated animals. PMID:10703580

  2. Transcriptome analysis of the venom gland of the Mexican scorpion Hadrurus gertschi (Arachnida: Scorpiones)

    PubMed Central

    Schwartz, Elisabeth F; Diego-Garcia, Elia; Rodríguez de la Vega, Ricardo C; Possani, Lourival D

    2007-01-01

    Background Scorpions like other venomous animals posses a highly specialized organ that produces, secretes and disposes the venom components. In these animals, the last postabdominal segment, named telson, contains a pair of venomous glands connected to the stinger. The isolation of numerous scorpion toxins, along with cDNA-based gene cloning and, more recently, proteomic analyses have provided us with a large collection of venom components sequences. However, all of them are secreted, or at least are predicted to be secretable gene products. Therefore very little is known about the cellular processes that normally take place inside the glands for production of the venom mixture. To gain insights into the scorpion venom gland biology, we have decided to perform a transcriptomic analysis by constructing a cDNA library and conducting a random sequencing screening of the transcripts. Results From the cDNA library prepared from a single venom gland of the scorpion Hadrurus gertschi, 160 expressed sequence tags (ESTs) were analyzed. These transcripts were further clustered into 68 unique sequences (20 contigs and 48 singlets), with an average length of 919 bp. Half of the ESTs can be confidentially assigned as homologues of annotated gene products. Annotation of these ESTs, with the aid of Gene Ontology terms and homology to eukaryotic orthologous groups, reveals some cellular processes important for venom gland function; including high protein synthesis, tuned posttranslational processing and trafficking. Nonetheless, the main group of the identified gene products includes ESTs similar to known scorpion toxins or other previously characterized scorpion venom components, which account for nearly 60% of the identified proteins. Conclusion To the best of our knowledge this report contains the first transcriptome analysis of genes transcribed by the venomous gland of a scorpion. The data were obtained for the species Hadrurus gertschi, belonging to the family

  3. Enzymatic analysis of venom from Cuban scorpion Rhopalurus junceus

    PubMed Central

    Díaz-García, Alexis; Ruiz-Fuentes, Jenny Laura; Yglesias-Rivera, Arianna; Rodríguez-Sánchez, Hermis; Riquenes Garlobo, Yanelis; Fleitas Martinez, Osmel; Fraga Castro, José A

    2015-01-01

    Rhopalurus junceus scorpion venom has been identified as a natural extract with anticancer potential. Interestingly, this scorpion venom does not cause adverse symptoms in humans. However, there is scarce information about its composition and enzymatic activity. In this work, we determined the electrophoretic profile of the venom, the gelatinase and caseinolytic activity, and the phospholipase A2 (PLA2) and hemolytic activity. The effect of different venom doses (6.25, 12.5 and 25 mg/kg) on gastrocnemius muscle was also measured as CK and LDH activity in serum. The presence of hyaluronidase was determined by turbidimetric assay. The effect of different fractions obtained by gel filtration chromatography were evaluated at different concentrations (0.05, 0.1, 0.2, 0.4, 0.6mg/ml) against lung cancer cell A549 and lung normal cell MRC-5 using MTT assay. The electrophoretic profile demonstrated the presence of proteins bands around 67kDa, 43kDa, 18.4kDa and a majority band below 14.3kDa. The venom did not showed caseinolytic, gelatinase, PLA2 and hemolytic activity even at highest venom concentration used in the study. Scorpion venom only showed a significant toxic effect on gastrocnemius muscles identified by CK and LDH release after subcutaneous injection of 12.5 and 25mg/kg. Low molecular weight fractions (<4kDa) induced a significant cytotoxicity in A549 cells while high molecular weight proteins (45–60kDa) were responsible for hyaluronidase activity and toxic effect against MRC-5. Experiments indicate that Rhopalurus junceus scorpion venom has low enzymatic activity, which could contribute to the low toxic potential of this scorpion venom. PMID:26605039

  4. Enzymatic analysis of venom from Cuban scorpion Rhopalurus junceus.

    PubMed

    Díaz-García, Alexis; Ruiz-Fuentes, Jenny Laura; Yglesias-Rivera, Arianna; Rodríguez-Sánchez, Hermis; Riquenes Garlobo, Yanelis; Fleitas Martinez, Osmel; Fraga Castro, José A

    2015-01-01

    Rhopalurus junceus scorpion venom has been identified as a natural extract with anticancer potential. Interestingly, this scorpion venom does not cause adverse symptoms in humans. However, there is scarce information about its composition and enzymatic activity. In this work, we determined the electrophoretic profile of the venom, the gelatinase and caseinolytic activity, and the phospholipase A2 (PLA2) and hemolytic activity. The effect of different venom doses (6.25, 12.5 and 25 mg/kg) on gastrocnemius muscle was also measured as CK and LDH activity in serum. The presence of hyaluronidase was determined by turbidimetric assay. The effect of different fractions obtained by gel filtration chromatography were evaluated at different concentrations (0.05, 0.1, 0.2, 0.4, 0.6mg/ml) against lung cancer cell A549 and lung normal cell MRC-5 using MTT assay. The electrophoretic profile demonstrated the presence of proteins bands around 67kDa, 43kDa, 18.4kDa and a majority band below 14.3kDa. The venom did not showed caseinolytic, gelatinase, PLA2 and hemolytic activity even at highest venom concentration used in the study. Scorpion venom only showed a significant toxic effect on gastrocnemius muscles identified by CK and LDH release after subcutaneous injection of 12.5 and 25mg/kg. Low molecular weight fractions (<4kDa) induced a significant cytotoxicity in A549 cells while high molecular weight proteins (45-60kDa) were responsible for hyaluronidase activity and toxic effect against MRC-5. Experiments indicate that Rhopalurus junceus scorpion venom has low enzymatic activity, which could contribute to the low toxic potential of this scorpion venom. PMID:26605039

  5. Comparative venom gland transcriptome analysis of the scorpion Lychas mucronatus reveals intraspecific toxic gene diversity and new venomous components

    PubMed Central

    2010-01-01

    Background Lychas mucronatus is one scorpion species widely distributed in Southeast Asia and southern China. Anything is hardly known about its venom components, despite the fact that it can often cause human accidents. In this work, we performed a venomous gland transcriptome analysis by constructing and screening the venom gland cDNA library of the scorpion Lychas mucronatus from Yunnan province and compared it with the previous results of Hainan-sourced Lychas mucronatus. Results A total of sixteen known types of venom peptides and proteins are obtained from the venom gland cDNA library of Yunnan-sourced Lychas mucronatus, which greatly increase the number of currently reported scorpion venom peptides. Interestingly, we also identified nineteen atypical types of venom molecules seldom reported in scorpion species. Surprisingly, the comparative transcriptome analysis of Yunnan-sourced Lychas mucronatus and Hainan-sourced Lychas mucronatus indicated that enormous diversity and vastly abundant difference could be found in venom peptides and proteins between populations of the scorpion Lychas mucronatus from different geographical regions. Conclusions This work characterizes a large number of venom molecules never identified in scorpion species. This result provides a comparative analysis of venom transcriptomes of the scorpion Lychas mucronatus from different geographical regions, which thoroughly reveals the fact that the venom peptides and proteins of the same scorpion species from different geographical regions are highly diversified and scorpion evolves to adapt a new environment by altering the primary structure and abundance of venom peptides and proteins. PMID:20663230

  6. Venom proteomic and venomous glands transcriptomic analysis of the Egyptian scorpion Scorpio maurus palmatus (Arachnida: Scorpionidae).

    PubMed

    Abdel-Rahman, Mohamed A; Quintero-Hernandez, Veronica; Possani, Lourival D

    2013-11-01

    Proteomic analysis of the scorpion venom Scorpio maurus palmatus was performed using reverse-phase HPLC separation followed by mass spectrometry determination. Sixty five components were identified with molecular masses varying from 413 to 14,009 Da. The high percentage of peptides (41.5%) was from 3 to 5 KDa which may represent linear antimicrobial peptides and KScTxs. Also, 155 expressed sequence tags (ESTs) were analyzed through construction the cDNA library prepared from a pair of venomous gland. About 77% of the ESTs correspond to toxin-like peptides and proteins with definite open reading frames. The cDNA sequencing results also show the presence of sequences whose putative products have sequence similarity with antimicrobial peptides (24%), insecticidal toxins, β-NaScTxs, κ-KScTxs, α-KScTxs, calcines and La1-like peptides. Also, we have obtained 23 atypical types of venom molecules not recorded in other scorpion species. Moreover, 9% of the total ESTs revealed significant similarities with proteins involved in the cellular processes of these scorpion venomous glands. This is the first set of molecular masses and transcripts described from this species, in which various venom molecules have been identified. They belong to either known or unassigned types of scorpion venom peptides and proteins, and provide valuable information for evolutionary analysis and venomics. PMID:23998939

  7. A new Kunitz-type plasmin inhibitor from scorpion venom.

    PubMed

    Ding, Li; Wang, Xiaobo; Liu, Hongyan; San, Mingkui; Xu, Yue; Li, Jian; Li, Shan; Cao, Zhijian; Li, Wenxin; Wu, Yingliang; Chen, Zongyun

    2015-11-01

    Kunitz-type peptides from venomous animals are an important source of lead drug candidates towards human plasmin, a target of protease-associated diseases. However, no Kunitz-type plasmin inhibitor from venomous scorpion has been characterized. Here, we first investigated plasmin inhibiting activities of eight known Kunitz-type scorpion toxins Hg1, BmKTT-1, BmKTT-2, BmKTT-3, LmKTT-1a, LmKTT-1b, LmKTT-1c and BmKPI, and found a new plasmin inhibitor BmKTT-2, a Kunitz-type toxin peptide from the scorpion Buthus martensi karch. Protease inhibitory activity assay showed that BmKTT-2 potently inhibited plasmin with a Ki value of 8.75 ± 2.05 nM. Structure-function relationship studies between BmKTT-2 and plasmin showed that BmKTT-2 is a classical Kunitz-type plasmin inhibitor: Lys13 in BmKTT-2 is the P1 site, and Ala14 in BmKTT-2 is the P1' site. Interestingly, BmKTT-2 has potent inhibiting activities towards three important digestive serine proteases trypsin, chymotrypsin and elastase, suggesting a good stability for administering oral medications. To the best of our knowledge, BmKTT-2 is the first Kunitz-type human plasmin inhibitor from scorpion venom, providing novel insights into drug developments targeting human plasmin protease. PMID:26363290

  8. A scorpion venom neurotoxin paralytic to insects that affects sodium current inactivation: Purification, primary structure, and mode of action

    SciTech Connect

    Eitan, M.; Fowler, E.; Herrmann, R.; Duval, A.; Pelhate, M.; Zlotkin, E. )

    1990-06-26

    A new toxin, Lqh alpha IT, which caused a unique mode of paralysis of blowfly larvae, was purified from the venom of the scorpion Leiurus quinquestriatus hebraeus, and its structural and pharmacological properties were compared to those of three other groups of neurotoxins found in Buthinae scorpion venoms. Like the excitatory and depressant insect-selective neurotoxins, Lqh alpha IT was highly toxic to insects, but it differed from these toxins in two important characteristics: (a) Lqh alpha IT lacked strict selectivity for insects; it was highly toxic to crustaceans and had a measurable but low toxicity to mice. (b) It did not displace an excitatory insect toxin, 125I-AaIT, from its binding sites in the insect neuronal membrane; this indicates that the binding sites for Lqh alpha IT are different from those shared by the excitatory and depressant toxins. However, in its primary structure and its effect on excitable tissues, Lqh alpha IT strongly resembled the well-characterized alpha scorpion toxins, which affect mammals. The amino acid sequence was identical with alpha toxin sequences in 55%-75% of positions. This degree of similarity is comparable to that seen among the alpha toxins themselves. Voltage- and current-clamp studies showed that Lqh alpha IT caused an extreme prolongation of the action potential in both cockroach giant axon and rat skeletal muscle preparations as a result of the slowing and incomplete inactivation of the sodium currents. These observations indicate that Lqh alpha IT is an alpha toxin which acts on insect sodium channels.

  9. Tityus bahiensis scorpion venom injected to dams during pregnancy affects some cytokines of fetuses.

    PubMed

    Dorce, Ana L C; Frare, Eduardo O; Paulo, Maria E F V; Dorce, Valquiria A C; Nencioni, Ana L A

    2015-09-01

    Due to the high incidence of scorpion stings in Brazil, pregnant women are among the possible victims. Cytokines are important during the pregnancy, and scorpion venoms can change their release. We evaluated the levels of some cytokines in the fetuses after the treatment of pregnant rats with the Tityus bahiensis scorpion venom. The concentration of some of them is altered and can be responsible for the effects previously observed on innate reflexes, and the physical and behavioral development of the offspring. PMID:26140840

  10. Reproductive toxic effects of Tityus serrulatus scorpion venom in rats.

    PubMed

    Cruttenden, Karen; Nencioni, Ana Leonor A; Bernardi, Maria Martha; Dorce, Valquiria A C

    2008-08-01

    Tityus serrulatus is the most venomous scorpion in Brazil. Little is known about the effect of maternal exposure to the venom on fetal development. We investigated the effect of low to moderate doses of the venom (0.3 or 1.0 mg/kg s.c. on either day 5 or day 10 of gestation) on pregnant rats and on their offspring. For dams, we observed their body weight gain and reproductive parameters. For the offspring, we observed their body weight and weight of internal organs and the number of live and dead fetuses, and we investigated whether the venom caused external, visceral, skeletal or histopathological alterations in the offspring. The offspring were examined on gestational day 21. Injection of the venom on gestational day 5 did not change the reproductive parameters of the dams, their weight or fetuses' weight. Rats that received the high dose of the venom (1.0 mg/kg) on gestational day 10 had heavier placentas and heavier fetuses with heavier lungs. Injections on day 10 of gestation did not alter the reproductive parameters of the dams nor their weight gain at either dose. The venom did not cause malformations of the fetal skeleton or viscera and did not delay fetal development with either dose. In conclusion, subcutaneous administration of 0.3 or 1.0 mg/kg T. serrulatus venom to pregnant Wistar rats at either day 5 or day 10 of gestation did not cause maternal or clear fetal toxicity. Subtle increases in placental weight and fetal body and lung weights observed following treatment with 1.0 mg/kg on day 10 of gestation were not associated with histopathological findings. Whether these observations represent a reaction to treatment and, if so, the underlying mechanisms and their toxicological impact remain to be examined further in future studies. PMID:18550329

  11. The Cuban scorpion Rhopalurus junceus (Scorpiones, Buthidae): component variations in venom samples collected in different geographical areas

    PubMed Central

    2013-01-01

    Backgound The venom of the Cuban scorpion Rhopalurus junceus is poorly study from the point of view of their components at molecular level and the functions associated. The purpose of this article was to conduct a proteomic analysis of venom components from scorpions collected in different geographical areas of the country. Results Venom from the blue scorpion, as it is called, was collected separately from specimens of five distinct Cuban towns (Moa, La Poa, Limonar, El Chote and Farallones) of the Nipe-Sagua-Baracoa mountain massif and fractionated by high performance liquid chromatography (HPLC); the molecular masses of each fraction were ascertained by mass spectrometry analysis. At least 153 different molecular mass components were identified among the five samples analyzed. Molecular masses varied from 466 to 19755 Da. Scorpion HPLC profiles differed among these different geographical locations and the predominant molecular masses of their components. The most evident differences are in the relative concentration of the venom components. The most abundant components presented molecular weights around 4 kDa, known to be K+-channel specific peptides, and 7 kDa, known to be Na+-channel specific peptides, but with small molecular weight differences. Approximately 30 peptides found in venom samples from the different geographical areas are identical, supporting the idea that they all probably belong to the same species, with some interpopulational variations. Differences were also found in the presence of phospholipase, found in venoms from the Poa area (molecular weights on the order of 14 to 19 kDa). The only ubiquitous enzyme identified in the venoms from all five localities studied (hyaluronidase) presented the same 45 kD molecular mass, identified by gel electrophoresis analysis. Conclusions The venom of these scorpions from different geographical areas seem to be similar, and are rich in peptides that have of the same molecular masses of the peptides

  12. General biochemical and immunological characteristics of the venom from Peruvian scorpion Hadruroides lunatus.

    PubMed

    Costal-Oliveira, F; Duarte, C G; Machado de Avila, R A; Melo, M M; Bordon, K C F; Arantes, E C; Paredes, N C; Tintaya, B; Bonilla, C; Bonilla, R E; Suarez, W S; Yarleque, A; Fernandez, J M; Kalapothakis, E; Chávez-Olórtegui, Carlos

    2012-10-01

    This communication describes the general biochemical properties and some immunological characteristics of the venom from the Peruvian scorpion Hadruroides lunatus, which is the most medically relevant species in Peru. The soluble venom of this scorpion is toxic to mice, the LD₅₀ determined was 0.1 mg/kg and 21.55 mg/kg when the venom was injected intracranial or intraperitoneally, respectively. The soluble venom displayed proteolytic, hyaluronidasic, phospholipasic and cardiotoxic activities. High performance liquid chromatography of the soluble venom resulted in the separation of 20 fractions. Two peptides with phospholipasic activity were isolated to homogeneity and their molecular masses determined by mass spectrometry (MALDI TOF). Anti-H. lunatus venom sera were produced in rabbits. Western blotting analysis showed that most of the protein content of this venom is immunogenic. H. lunatus anti-venom displayed consistent cross-reactivity with venom antigens from the new World-scorpions Tityus serrulatus and Centruroides sculpturatus venoms; however, a weaker reactivity was observed against the venom antigens from the old World-scorpion Androctonus australis Hector. PMID:22750532

  13. General biochemical and immunological characterization of the venom from the scorpion Tityus trivittatus of Argentina.

    PubMed

    de Roodt, Adolfo R; Coronas, Fredy I V; Lago, Nestor; González, María E; Laskowicz, Rodrigo D; Beltramino, Juan C; Saavedra, Silvina; López, Raúl A; Reati, Gustavo J; Vucharchuk, Miriam G; Bazán, Eduardo; Varni, Liliana; Salomón, Oscar D; Possani, Lourival D

    2010-01-01

    Tityus trivittatus is the Argentinean scorpion reported to cause the majority of human fatalities in the country, however no systematic studies have been conducted with the venom of this species. This communication describes a general biochemical and immunological characterization of the venom obtained from T. trivittatus scorpions collected in the city of Buenos Aires and various provinces of Argentina: Catamarca, Cordoba, Entre Rios, La Rioja, Santa Fe and Santiago del Estero. These are places where human accidents were reported to occur due to this scorpion. For comparative purposes two types of samples were assayed: whole soluble venom obtained by electrical stimulation and supernatant from homogenized venomous glands. Two strains of mice (NIH and CF-1) were used for LD(50) determinations by two distinct routes of administration (intravenously and intraperitoneally). Important variations were found that goes from 0.5 to 12 mg/kg mouse body weight. Samples of soluble venom were always more potent than Telson homogenates. More complex pattern was observed in homogenates compared to soluble venom, as expected. This was supported by gel electrophoretic analysis and high performance liquid chromatographic (HPLC) separations. Additionally, the HPLC profile was enriched in proteins resolved at similar elution times as other known toxins from scorpion venoms studied. Immune enzymatic assays were also conducted comparatively, using four different anti-venoms commercially available for treatment of scorpion stings (Argentinean antidote from INPB, two anti-venoms from Butantan Institute of Brazil and Alacramyn from the Mexican Bioclon Institute). Cross-reactivities were observed and are reported among the various venoms and anti-venoms used. Lung, heart, liver and pancreas pathological modifications were observed on tissues of intoxicated mice. It seems that there are important variations on the venom compositions of the various samples studied and reported here

  14. Mass fingerprinting of the venom and transcriptome of venom gland of scorpion Centruroides tecomanus.

    PubMed

    Valdez-Velázquez, Laura L; Quintero-Hernández, Verónica; Romero-Gutiérrez, Maria Teresa; Coronas, Fredy I V; Possani, Lourival D

    2013-01-01

    Centruroides tecomanus is a Mexican scorpion endemic of the State of Colima, that causes human fatalities. This communication describes a proteome analysis obtained from milked venom and a transcriptome analysis from a cDNA library constructed from two pairs of venom glands of this scorpion. High perfomance liquid chromatography separation of soluble venom produced 80 fractions, from which at least 104 individual components were identified by mass spectrometry analysis, showing to contain molecular masses from 259 to 44,392 Da. Most of these components are within the expected molecular masses for Na(+)- and K(+)-channel specific toxic peptides, supporting the clinical findings of intoxication, when humans are stung by this scorpion. From the cDNA library 162 clones were randomly chosen, from which 130 sequences of good quality were identified and were clustered in 28 contigs containing, each, two or more expressed sequence tags (EST) and 49 singlets with only one EST. Deduced amino acid sequence analysis from 53% of the total ESTs showed that 81% (24 sequences) are similar to known toxic peptides that affect Na(+)-channel activity, and 19% (7 unique sequences) are similar to K(+)-channel especific toxins. Out of the 31 sequences, at least 8 peptides were confirmed by direct Edman degradation, using components isolated directly from the venom. The remaining 19%, 4%, 4%, 15% and 5% of the ESTs correspond respectively to proteins involved in cellular processes, antimicrobial peptides, venom components, proteins without defined function and sequences without similarity in databases. Among the cloned genes are those similar to metalloproteinases. PMID:23840487

  15. Mass Fingerprinting of the Venom and Transcriptome of Venom Gland of Scorpion Centruroides tecomanus

    PubMed Central

    Valdez-Velázquez, Laura L.; Quintero-Hernández, Verónica; Romero-Gutiérrez, Maria Teresa; Coronas, Fredy I. V.; Possani, Lourival D.

    2013-01-01

    Centruroides tecomanus is a Mexican scorpion endemic of the State of Colima, that causes human fatalities. This communication describes a proteome analysis obtained from milked venom and a transcriptome analysis from a cDNA library constructed from two pairs of venom glands of this scorpion. High perfomance liquid chromatography separation of soluble venom produced 80 fractions, from which at least 104 individual components were identified by mass spectrometry analysis, showing to contain molecular masses from 259 to 44,392 Da. Most of these components are within the expected molecular masses for Na+- and K+-channel specific toxic peptides, supporting the clinical findings of intoxication, when humans are stung by this scorpion. From the cDNA library 162 clones were randomly chosen, from which 130 sequences of good quality were identified and were clustered in 28 contigs containing, each, two or more expressed sequence tags (EST) and 49 singlets with only one EST. Deduced amino acid sequence analysis from 53% of the total ESTs showed that 81% (24 sequences) are similar to known toxic peptides that affect Na+-channel activity, and 19% (7 unique sequences) are similar to K+-channel especific toxins. Out of the 31 sequences, at least 8 peptides were confirmed by direct Edman degradation, using components isolated directly from the venom. The remaining 19%, 4%, 4%, 15% and 5% of the ESTs correspond respectively to proteins involved in cellular processes, antimicrobial peptides, venom components, proteins without defined function and sequences without similarity in databases. Among the cloned genes are those similar to metalloproteinases. PMID:23840487

  16. Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus ().

    PubMed

    Martin-Eauclaire, Marie-France; Pimenta, Adriano M C; Bougis, Pierre E; De Lima, Maria-Elena

    2016-09-01

    Potassium (K(+)) channels are trans-membrane proteins, which play a key role in cellular excitability and signal transduction pathways. Scorpion toxins blocking the ion-conducting pore from the external side have been invaluable probes to elucidate the structural, functional, and physio-pathological characteristics of these ion channels. This review will focus on the interaction between K(+) channels and their peptide blockers isolated from the venom of the scorpion Tityus serrulatus, which is considered as the most dangerous scorpion in Brazil, in particular in Minas-Gerais State, where many casualties are described each year. The primary mechanisms of action of these K(+) blockers will be discussed in correlation with their structure, very often non-canonical compared to those of other well known K(+) channels blockers purified from other scorpion venoms. Also, special attention will be brought to the most recent data obtained by proteomic and transcriptomic analyses on Tityus serrulatus venoms and venom glands. PMID:27349167

  17. Physiological resistance of grasshopper mice (Onychomys spp.) to Arizona bark scorpion (Centruroides exilicauda) venom.

    PubMed

    Rowe, Ashlee H; Rowe, Matthew P

    2008-10-01

    Predators feeding on toxic prey may evolve physiological resistance to the preys' toxins. Grasshopper mice (Onychomys spp.) are voracious predators of scorpions in North American deserts. Two species of grasshopper mice (Onychomys torridus and Onychomys arenicola) are broadly sympatric with two species of potentially lethal bark scorpion (Centruroides exilicauda and Centruroides vittatus) in the Sonoran and Chihuahuan deserts, respectively. Bark scorpions produce toxins that selectively bind sodium (Na(+)) and potassium (K(+)) ion channels in vertebrate nerve and muscle tissue. We previously reported that grasshopper mice showed no effects of bark scorpion envenomation following natural stings. Here we conducted a series of toxicity tests to determine whether grasshopper mice have evolved resistance to bark scorpion neurotoxins. Five populations of grasshopper mice, either sympatric with or allopatric to bark scorpions, were injected with bark scorpion venom; LD50s were estimated for each population. All five populations of grasshopper mice demonstrated levels of venom resistance greater than that reported for non-resistant Mus musculus. Moreover, venom resistance in the mice showed intra- and interspecific variability that covaried with bark scorpion sympatry and allopatry, patterns consistent with the hypothesis that venom resistance in grasshopper mice is an adaptive response to feeding on their neurotoxic prey. PMID:18687353

  18. Camelid antivenom development and potential in vivo neutralization of Hottentotta saulcyi scorpion venom.

    PubMed

    Darvish, Maryam; Ebrahimi, Soltan Ahmad; Shahbazzadeh, Delavar; Bagheri, Kamran-Pooshang; Behdani, Mahdi; Shokrgozar, Mohammad Ali

    2016-04-01

    Scorpion envenoming is a serious health problem which can cause a variety of clinical toxic effects. Of the many scorpion species native to Iran, Hottentotta saulcyi is important because its venom can produce toxic effects in man. Nowadays, antivenom derived from hyper immune horses is the only effective treatment for sever scorpion stings. Current limitations of immunotherapy urgently require an efficient alternative with high safety, target affinity and more promising venom neutralizing capability. Recently, heavy chain-only antibodies (HC-Abs) found naturally in camelid serum met the above mentioned advantages. In this study, immuno-reactivities of polyclonal antibodies were tested after successful immunization of camel using H. saulcyi scorpion crude venom. The lethal potency of scorpion venom in C57BL/6 mice injected intraperitoneally was determined to be 2.7 mg/kg. These results were followed by the efficient neutralization of lethal activity of H. saulcyi scorpion venom by injection of antivenom and purified IgG fractions into mice intraperitonelly or intravenously, respectively. HC-Ab camelid antivenom could be considered as a useful serotherapeutics instead of present treatment for scorpion envenomation. PMID:26809016

  19. Intraspecific variation in the Egyptian scorpion Scorpio maurus palmatus venom collected from different biotopes.

    PubMed

    Abdel-Rahman, Mohamed A; Omran, Mohamed Alaa A; Abdel-Nabi, Ismail M; Ueda, Hitoshi; McVean, Alistair

    2009-03-01

    The present study was conducted to explore the following hypotheses: (i) do scorpions (Scorpio maurus palmatus) from different biotopes exhibit intraspecific diversity in their venom? (ii) if so, is this variation associated with ecological or genetic factors, geographical distance, and/or multiple interrelated parameters? To address these questions, scorpions were collected from four geographically isolated localities in Egypt. Three of these locations are from mutually isolated pockets in the arid biotope of Southern Sinai (Wadi Sahab, El-Agramia and Rahaba plains). The fourth population was sampled from the semiarid biotope of Western Mediterranean Costal Desert (WMCD). Using reducing gel electrophoresis (SDS-PAGE), we have shown biotope-specific variation in the expression of peptides from scorpions collected from these distinct areas. WMCD sourced venom samples contain higher molecular weight protein components (219, 200, 170, 139, 116 kDa) than Southern Sinai scorpion venom samples. The Southern Sinai venom is characterized by the presence of 11 protein bands (93-0.58 kDa) that are not mirrored in the individual venom samples of WMCD. Bands of 33 and 3.4 kDa were characteristics of all individual venom samples of the scorpion populations. Even within Southern Sinai area, Sahab venom contains five fractions that are not detected in both El-Agramia and Rahaba venom samples. Moreover, male and female venom analysis revealed some sex-related proteomic similarities and differences between scorpion populations. Female venom appears to be more complicated than the male venom. Female venom samples showed bands of 219, 200, 77.5, 55.5, 45, 39, 37, 24 and 16 kDa which were absent in the male venom. The random amplified polymorphic DNA (RAPD) technique was used to estimate the genetic distance between the four scorpion populations. The RAPD data confirmed the genetic diversity at molecular level among the sampled populations. More than 77 RAPD bands (ranging in size

  20. SdPI, The First Functionally Characterized Kunitz-Type Trypsin Inhibitor from Scorpion Venom

    PubMed Central

    Li, Tian; He, Yawen; Ma, Yibao; Chen, Zongyun; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

    2011-01-01

    Background Kunitz-type venom peptides have been isolated from a wide variety of venomous animals. They usually have protease inhibitory activity or potassium channel blocking activity, which by virtue of the effects on predator animals are essential for the survival of venomous animals. However, no Kunitz-type peptides from scorpion venom have been functionally characterized. Principal Findings A new Kunitz-type venom peptide gene precursor, SdPI, was cloned and characterized from a venom gland cDNA library of the scorpion Lychas mucronatus. It codes for a signal peptide of 21 residues and a mature peptide of 59 residues. The mature SdPI peptide possesses a unique cysteine framework reticulated by three disulfide bridges, different from all reported Kunitz-type proteins. The recombinant SdPI peptide was functionally expressed. It showed trypsin inhibitory activity with high potency (Ki = 1.6×10−7 M) and thermostability. Conclusions The results illustrated that SdPI is a potent and stable serine protease inhibitor. Further mutagenesis and molecular dynamics simulation revealed that SdPI possesses a serine protease inhibitory active site similar to other Kunitz-type venom peptides. To our knowledge, SdPI is the first functionally characterized Kunitz-type trypsin inhibitor derived from scorpion venom, and it represents a new class of Kunitz-type venom peptides. PMID:22087336

  1. Peripheral and central effects of intracerebroventricular microinjection of Hottentotta gentili (Pallary, 1924) (Scorpiones, Buthidae) venom.

    PubMed

    El Hidan, Moulay Abdelmonaim; Touloun, Oulaid; El Hiba, Omar; Laadraoui, Jawad; Ferehan, Hind; Boumezzough, Ali

    2016-03-01

    Central effects of scorpion venom toxins have been neglected, due both to the common belief that scorpion venoms act by targeting peripheral organs and also to the misunderstanding that these peptides do not cross the brain-blood barrier (BBB). Determining whether scorpion neurotoxicity is restricted to peripheral actions or whether a central mechanism may be partly responsible for systemic manifestations could be crucial in clinical therapy trends. The present study therefore aims to assess histopathological damages in some organs (heart, kidney, liver, and lungs) and the related biochemical impairments, together with a neurobehavioral investigation following an intracerebroventricular (i.c.v) micro-injection of Hottentotta gentili (Scorpiones, Buthidae) venom (0.47 μg/kg). I.c.v. injection of venom produced focal fragmentation of myocardial fibers, while lungs showed rupture of the alveolar structure. Concurrently, there was a significant rise in the serum enzymes levels of ASAT, ALAT, CPK and LDH. Meanwhile, we observed behavioral alterations such as a hypoactivity, and in addition the venom seems to have a marked anxiogenic-like effect. The present investigation has brought new experimental evidence of a peripheral impact of central administration of H. gentili venom, such impact was manifested by physiological and behavioral disturbances, the last of these appearing to reflect profound neuro-modulatory action of H. gentili venom. PMID:26718260

  2. First venom gland transcriptomic analysis of Iranian yellow scorpion "Odonthubuthus doriae" with some new findings.

    PubMed

    NaderiSoorki, Maryam; Galehdari, Hamid; Baradaran, Masomeh; Jalali, Amir

    2016-09-15

    Scorpion venom contains mixture of biologic molecules including selective toxins with medical capability. Odonthubuthus doriae (O. doriae) belonged to Buthidae family of scorpions and gained more interest among Iranian dangerous scorpion since 2005. We constructed the first cDNA library to explore the transcriptomic composition of this Iranian scorpiontelson. Then by used of bioinformatic software each expression sequence taq (EST) from the library analyzed and its quiddity was clear. Analysis showed that toxins (42%) had more venom transcript than other component such as antimicrobial peptides, venom peptides and cell proteins. Over 16% of transcripts didn't have any open reading frames (ORF), however their sequences showed similarity by other scorpion sequences. One EST didn't have any similarity by known scorpion peptides. For the first time; we report a comprehensive study of an Iranian scorpion with interesting and novel findings. We characterized a new putative sodium channel modifier in scorpions by some bioinformatics software, and then predicted its structure and function. PMID:27426055

  3. Resistance of cervical adenocarcinoma cells (HeLa) to venom from the scorpion Centruroides limpidus limpidus

    PubMed Central

    2013-01-01

    Background The venom of Centruroides limpidus limpidus (Cll) is a mixture of pharmacologically active principles. The most important of these are toxic proteins that interact both selectively and specifically with different cellular targets such as ion channels. Recently, anticancer properties of the venom from other scorpion species have been described. Studies in vitro have shown that scorpion venom induces cell death, inhibits proliferation and triggers the apoptotic pathway in different cancer cell lines. Herein, after treating human cervical adenocarcinoma (HeLa) cells with Cll crude venom, their cytotoxic activity and apoptosis induction were assessed. Results Cll crude venom induced cell death in normal macrophages in a dose-dependent manner. However, through viability assays, HeLa cells showed high survival rates after exposure to Cll venom. Also, Cll venom did not induce apoptosis after performing ethidium bromide/acridine orange assays, nor was there any evidence of chromatin condensation or DNA fragmentation. Conclusions Crude Cll venom exposure was not detrimental to HeLa cell cultures. This may be partially attributable to the absence of specific HeLa cell membrane targets for molecules present in the venom of Centruroides limpidus limpidus. Although these results might discourage additional studies exploring the potential of Cll venom to treat human papilloma cervical cancer, further research is required to explore positive effects of crude Cll venom on other cancer cell lines. PMID:24004568

  4. Central effects of Tityus serrulatus and Tityus bahiensis scorpion venoms after intraperitoneal injection in rats.

    PubMed

    Nencioni, Ana Leonor A; Lourenço, Geane Antiques; Lebrun, Ivo; Florio, Jorge Camilo; Dorce, Valquiria A C

    2009-10-01

    A great number of studies on scorpion venoms associate their effects to the autonomic nervous system, and few data are available about their action on the central nervous system (CNS). The aim of this work was to evaluate some central effects after intraperitoneal injection of Tityus serrulatus or T. bahiensis scorpion venoms. The hippocampal concentration of some neurotransmitters and their metabolites were determined. Electroencephalographic and behavioral observations were performed, and all brains were removed for histopathological analysis of hippocampal areas. Both venoms induced electrographic and behavioral alterations despite T. bahiensis venom affects less the electrographic activity than T. serrulatus venom. Neurochemical analysis demonstrated no alteration in the extracellular levels of almost all the neurotransmitters evaluated, at least in the hippocampus, and no neuronal loss in this area was observed. Meanwhile, extracellular concentration of HVA increased up to 10 times in approximately 1/3 of the animals of both groups. Scorpion venoms seem to exert a small but important central effect. More studies in this field are necessary because they may be useful in developing new strategies to reduce the damage caused by scorpion stings. PMID:19664683

  5. Differences in venom toxicity and antigenicity between females and males Tityus nororientalis (Buthidae) scorpions

    PubMed Central

    De Sousa, Leonardo; Borges, Adolfo; Vásquez-Suárez, Aleikar; Op den Camp, Huub JM; Chadee-Burgos, Rosa I; Romero-Bellorín, Mirna; Espinoza, Jorge; De Sousa-Insana, Leonardo; Pino-García, Oscar

    2010-01-01

    Venom from male and female specimens of the medically important Venezuelan scorpion Tityus nororientalis have been compared. Males showed a significantly higher venom yield (2.39mg/individual) compared to female scorpions (0.98mg/individual). Female venom was significantly more toxic than that of males, with a median lethal dose (LD50) in C57BL/6 mice of 9.46 μg venom protein/gm body weight [95% confidence interval (8.91-9.94)] whereas LD50 for males was 13.36(12.58-14.03) μg/gm. Mass spectral analyses by MALDI-TOF revealed differences in venom composition between males and females. From a clinical standpoint, the time course of toxicity course indicated a tendency, in the case of the female venom, to elicit the earlier occurrence of severe signs such as sialorrhea, dyspnea (bradypnea/apnea) and exophthalmus particularly in the late toxicity phase. Female venom was significantly less efficient than male venom to inhibit the binding of anti-T. discrepans antibodies to immobilized T. discrepans venom in ELISA assays, suggesting sex-related differences in the bioactive surfaces of T. nororientalis toxins. These results indicate that males and females of T. nororientalis produce venoms with different composition and activity which may have epidemiological implications. PMID:21544184

  6. A new venomous scorpion responsible for severe envenomation in Argentina: Tityus confluens.

    PubMed

    de Roodt, Adolfo R; Lago, Néstor R; Salomón, Oscar D; Laskowicz, Rodrigo D; Neder de Román, Lilia E; López, Raúl A; Montero, Teresa E; Vega, Valeria Del V

    2009-01-01

    In Argentina the scorpions of medical importance belong to the genus Tityus (T.), particularly the species T. trivittatus, the only scorpion whose sting is recognized to be associated with severe human envenoming and death. This genus is distributed from the north of the Patagonian region to the center and some provinces in the north of the country. During the period 2003-2006 four children died following scorpion stings, of which one was certainly and three were probably by T. confluens. In 2006, in the province of Tucumán, a girl died by scorpion envenoming and the scorpion responsible for the death, found in her shoe, was T. confluens. We thus studied the toxicity of venom gland homogenates from T. confluens from the provinces of Jujuy and Catamarca, and of crude venom from specimens from Catamarca and the province of La Rioja. The lethal potencies of the telson homogenates were 7.0 and 18.6microg/g for Jujuy and Catamarca, respectively, while the lethal potency of the crude venom was 0.7microg/g. Injected mice showed generalized congestion and hepatic lesions. Pancreatic damage was observed in some animals. Lungs showed congestion and foci of hemorrhage and mild edema. The heart showed injury in the muscular fibers. The venom showed high reactivity against anti-T. trivittatus antivenom and against two anti-T. serrulatus antivenoms. The anti-T. trivittatus antivenom neutralized the lethal activity of T. confluens venom. In addition, the venom reacted very slightly against an anti-Centruroides antivenom. Therefore, the stings of this scorpion must be considered of risk for humans to the same degree as the stings of T. trivittatus. PMID:18983868

  7. A first exploration of the venom of the Buthus occitanus scorpion found in southern France

    PubMed Central

    Martin-Eauclaire, Marie-France; Bosmans, Frank; Céard, Brigitte; Diochot, Sylvie; Bougis, Pierre E.

    2014-01-01

    Even though Buthus occitanus scorpions are found throughout the Mediterranean region, a lack of distinctive characteristics has hampered their classification into different subspecies. Yet, stings from this particular scorpion family are reported each year to result in pain followed by various toxic symptoms. In order to determine the toxicity origin of the rare French Buthus occitanus Amoreux scorpion, we collected several specimens and studied their venom composition using a nano ultra high performance liquid chromatography and matrix assisted laser desorption/ionisation time-of-flight mass spectrometry (nano UHPLC/MALDI-TOF-MS) automated workflow combined with an enzyme-linked immunosorbent assay (ELISA) approach. Moreover, we compared this dataset to that obtained from highly lethal Androctonus australis and Androctonus mauretanicus scorpions collected in North Africa. As a result, we found that the Buthus occitanus Amoreux venom is toxic to mice, an observation that is most likely caused by venom components that inhibit voltage-gated sodium channel inactivation. Moreover, we identified similarities in venom composition between Buthus occitanus scorpions living in the South of France and other Buthidae collected in Morocco and Algeria. As such, the results of this study should be taken into consideration when treating stings from the Buthus occitanus species living in the South of France. PMID:24418174

  8. Investigating the chemical profile of regenerated scorpion (Parabuthus transvaalicus) venom in relation to metabolic cost and toxicity.

    PubMed

    Nisani, Zia; Boskovic, Danilo S; Dunbar, Stephen G; Kelln, Wayne; Hayes, William K

    2012-09-01

    We investigated the biochemical profile of regenerated venom of the scorpion Parabuthus transvaalicus in relation to its metabolic cost and toxicity. Using a closed-system respirometer, we compared oxygen consumption between milked and unmilked scorpions to determine the metabolic costs associated with the first 192 h of subsequent venom synthesis. Milked scorpions had a substantially (21%) higher mean metabolic rate than unmilked scorpions, with the largest increases in oxygen consumption occurring at approximately 120 h, 162 h, and 186 h post-milking. Lethality tests in crickets indicated that toxicity of the regenerated venom returned to normal levels within 4 d after milking. However, the chemical profile of the regenerated venom, as evaluated by FPLC and MALDI-TOF mass spectrometry, suggested that regeneration of different venom components was asynchronous. Some peptides regenerated quickly, particularly those associated with the scorpion's "prevenom," whereas others required much or all of this time period for regeneration. This asynchrony could explain the different spikes detected in oxygen consumption of milked scorpions as various peptides and other venom components were resynthesized. These observations confirm the relatively high metabolic cost of venom regeneration and suggest that greater venom complexity can be associated with higher costs of venom production. PMID:22564718

  9. Kalium: a database of potassium channel toxins from scorpion venom.

    PubMed

    Kuzmenkov, Alexey I; Krylov, Nikolay A; Chugunov, Anton O; Grishin, Eugene V; Vassilevski, Alexander A

    2016-01-01

    Kalium (http://kaliumdb.org/) is a manually curated database that accumulates data on potassium channel toxins purified from scorpion venom (KTx). This database is an open-access resource, and provides easy access to pages of other databases of interest, such as UniProt, PDB, NCBI Taxonomy Browser, and PubMed. General achievements of Kalium are a strict and easy regulation of KTx classification based on the unified nomenclature supported by researchers in the field, removal of peptides with partial sequence and entries supported by transcriptomic information only, classification of β-family toxins, and addition of a novel λ-family. Molecules presented in the database can be processed by the Clustal Omega server using a one-click option. Molecular masses of mature peptides are calculated and available activity data are compiled for all KTx. We believe that Kalium is not only of high interest to professional toxinologists, but also of general utility to the scientific community.Database URL:http://kaliumdb.org/. PMID:27087309

  10. Kalium: a database of potassium channel toxins from scorpion venom

    PubMed Central

    Kuzmenkov, Alexey I.; Krylov, Nikolay A.; Chugunov, Anton O.; Grishin, Eugene V.; Vassilevski, Alexander A.

    2016-01-01

    Kalium (http://kaliumdb.org/) is a manually curated database that accumulates data on potassium channel toxins purified from scorpion venom (KTx). This database is an open-access resource, and provides easy access to pages of other databases of interest, such as UniProt, PDB, NCBI Taxonomy Browser, and PubMed. General achievements of Kalium are a strict and easy regulation of KTx classification based on the unified nomenclature supported by researchers in the field, removal of peptides with partial sequence and entries supported by transcriptomic information only, classification of β-family toxins, and addition of a novel λ-family. Molecules presented in the database can be processed by the Clustal Omega server using a one-click option. Molecular masses of mature peptides are calculated and available activity data are compiled for all KTx. We believe that Kalium is not only of high interest to professional toxinologists, but also of general utility to the scientific community. Database URL: http://kaliumdb.org/ PMID:27087309

  11. Action of New World scorpion venom and its neurotoxins in secretion.

    PubMed

    Fletcher, P L; Fletcher, M; Fainter, L K; Terrian, D M

    1996-01-01

    New World scorpion venom contains protein toxins specific for ion channels in the plasmalemma of excitable cells. The effects were examined of whole venoms from Tityus serrulatus, T. bahiensis and T. stigmurus, and some purified toxins in isolated nerve endings (synaptosomes) and pancreatic acinar cells. Both systems initiated exocytosis in a dose-dependent response to the venom or its bioactive protein toxins. Actions differed, however, such that pancreatic acinar cells required Ca2+ while cerebrocortical synaptosomes responded by a Ca(2+)-dependent mechanism, except in the case of one toxin, IV-5, that elicited a Ca(2+)-independent response. Membrane depolarization caused by scorpion venom toxins was measured via radioisotopic discharge of tetra[3H]phenylphosphonium bromide. The role of protein kinase C in second-messenger coupling in pancreatic acinar cells is favored over ion-exclusive routes characteristic of synaptosomes. PMID:9027997

  12. Evidence for a new class of scorpion toxins active against K+ channels.

    PubMed

    Legros, C; Céard, B; Bougis, P E; Martin-Eauclaire, M F

    1998-07-24

    cDNAs encoding novel long-chain scorpion toxins (64 amino acid residues, including only six cysteines) were isolated from cDNA libraries produced from the venom glands of the scorpions Androctonus australis from Old World and Tityus serrulatus from New World. The encoded peptides were very similar to a recently identified toxin from T. serrulatus, which is active against the voltage-sensitive 'delayed-rectifier' potassium channel, but they were completely different from the long-chain and short-chain scorpion toxins already characterised. However, there was some sequence similarity (42%) between these new toxins, Aa TX Kbeta and Ts TX Kbeta, and scorpion defensins purified from the hemolymph of Buthidae scorpions Leiurus quinquestriatus and A. australis. Thus, according to a multiple sequence alignment using CLUSTAL, these new toxins seem to be related to the scorpion defensins. PMID:9714546

  13. Biochemical and molecular characterization of the venom from the Cuban scorpion Rhopalurus junceus.

    PubMed

    García-Gómez, B I; Coronas, F I V; Restano-Cassulini, R; Rodríguez, R R; Possani, L D

    2011-07-01

    This communication describes the first general biochemical, molecular and functional characterization of the venom from the Cuban blue scorpion Rhopalurus junceus, which is often used as a natural product for anti-cancer therapy in Cuba. The soluble venom of this arachnid is not toxic to mice, injected intraperitoneally at doses up to 200 μg/20 g body weight, but it is deadly to insects at doses of 10 μg per animal. The venom causes typical alpha and beta-effects on Na+ channels, when assayed using patch-clamp techniques in neuroblastoma cells in vitro. It also affects K+ currents conducted by ERG (ether-a-go-go related gene) channels. The soluble venom was shown to display phospholipase, hyaluronidase and anti-microbial activities. High performance liquid chromatography of the soluble venom can separate at least 50 components, among which are peptides lethal to crickets. Four such peptides were isolated to homogeneity and their molecular masses and N-terminal amino acid sequence were determined. The major component (RjAa12f) was fully sequenced by Edman degradation. It contains 64 amino acid residues and four disulfide bridges, similar to other known scorpion toxins. A cDNA library prepared from the venomous glands of one scorpion allowed cloning 18 genes that code for peptides of the venom, including RjA12f and eleven other closely related genes. Sequence analyses and phylogenetic reconstruction of the amino acid sequences deduced from the cloned genes showed that this scorpion contains sodium channel like toxin sequences clearly segregated into two monophyletic clusters. Considering the complex set of effects on Na+ currents verified here, this venom certainly warrant further investigation. PMID:21605585

  14. Venom-spraying behavior of the scorpion Parabuthus transvaalicus (Arachnida: Buthidae).

    PubMed

    Nisani, Zia; Hayes, William K

    2015-06-01

    Many animals use chemical squirting or spraying behavior as a defensive response. Some members of the scorpion genus Parabuthus (family Buthidae) can spray their venom. We examined the stimulus control and characteristics of venom spraying by Parabuthus transvaalicus to better understand the behavioral context for its use. Venom spraying occurred mostly, but not always, when the metasoma (tail) was contacted (usually grasped by forceps), and was absent during stinging-like thrusts of the metasoma apart from contact. Scorpions were significantly more likely to spray when contact was also accompanied by airborne stimuli. Sprays happened almost instantaneously following grasping by forceps (median=0.23s) as a brief (0.07-0.30s, mean=0.18s), fine stream (<5° arc) that was not directed toward the stimulus source; however, rapid independent movements of the metasoma and/or telson (stinger) often created a more diffuse spray, increasing the possibility of venom contact with the sensitive eyes of potential scorpion predators. Successive venom sprays varied considerably in duration and velocity. Collectively, these results suggest that venom spraying might be useful as an antipredator function and can be modulated based on threat. PMID:25748565

  15. Variability in venom volume, flow rate and duration in defensive stings of five scorpion species.

    PubMed

    van der Meijden, Arie; Coelho, Pedro; Rasko, Mykola

    2015-06-15

    Scorpions have been shown to control their venom usage in defensive encounters, depending on the perceived threat. Potentially, the venom amount that is injected could be controlled by reducing the flow speed, the flow duration, or both. We here investigated these variables by allowing scorpions to sting into an oil-filled chamber, and recording the accreting venom droplets with high-speed video. The size of the spherical droplets on the video can then be used to calculate their volume. We recorded defensive stings of 20 specimens representing 5 species. Significant differences in the flow rate and total expelled volume were found between species. These differences are likely due to differences in overall size between the species. Large variation in both venom flow speed and duration are described between stinging events of single individuals. Both venom flow rate and flow duration correlate highly with the total expelled volume, indicating that scorpions may control both variables in order to achieve a desired end volume of venom during a sting. PMID:25911958

  16. Screening of plants acting against Heterometrus laoticus scorpion venom activity on fibroblast cell lysis.

    PubMed

    Uawonggul, Nunthawun; Chaveerach, Arunrat; Thammasirirak, Sompong; Arkaravichien, Tarinee; Chuachan, Chattong; Daduang, Sakda

    2006-01-16

    The aqueous extracts of 64 plant species, listed as animal- or insect-bite antidotes in old Thai drug recipes were screened for their activity against fibroblast cell lysis after Heterometrus laoticus scorpion venom treatment. The venom was preincubated with plant extract for 30 min and furthered treated to confluent fibroblast cells for 30 min. More than 40% efficiency (test/control) was obtained from cell treatment with venom preincubated with extracts of Andrographis paniculata Nees (Acanthaceae), Barringtonia acutangula (L.) Gaertn. (Lecythidaceae), Calamus sp. (Palmae), Clinacanthus nutans Lindau (Acanthaceae), Euphorbia neriifolia L. (Euphorbiaceae), Ipomoea aquatica Forssk (Convolvulaceae), Mesua ferrea L. (Guttiferae), Passiflora laurifolia L. (Passifloraceae), Plectranthus amboinicus (Lour.) Spreng. (Labiatae), Ricinus communis L. (Euphorbiaceae), Rumex sp. (Polygonaceae) and Sapindus rarak DC. (Sapindaceae), indicating that they had a tendency to be scorpion venom antidotes. However, only Andrographis paniculata and Barringtonia acutangula extracts provided around 50% viable cells from extract treatments without venom preincubation. These two plant extracts are expected to be scorpion venom antidotes with low cytotoxicity. PMID:16169172

  17. Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells.

    PubMed

    Zargan, Jamil; Sajad, Mir; Umar, Sadiq; Naime, M; Ali, Shakir; Khan, Haider A

    2011-02-01

    Scorpion and its organs have been used to cure epilepsy, rheumatism, and male impotency since medieval times. Scorpion venom which contains different compounds like enzyme and non-enzyme proteins, ions, free amino acids, and other organic inorganic substances have been reported to posses antiproliferative, cytotoxic, apoptogenic, and immunosuppressive properties. We for the first time report the apoptotic and antiproliferative effects of scorpion venom (Odontobuthus doriae) in human neuroblastoma cells. After exposure of cells to medium containing varying concentrations of venom (10, 25, 50, 100, and 200 μg/ml), cell viability decreased to 90.75, 75.53, 55.52, 37.85, and 14.30%, respectively, after 24 h. Cells expressed morphological changes like swelling, inhibition of neurite outgrowth, irregular shape, aggregation, rupture of membrane, and release of cytosolic contents after treatment with venom. Lactate dehydrogenase (LDH) level increased in 50 and 100 μg/ml as compared to control, but there was no significant increase in LDH level at a dose of 10 and 20 μg/ml. Two concentrations viz. 50 and 100 μ/ml were selected because of the profound effect of these concentrations on the cellular health and population. Treatment with these two concentrations induced reactive nitrogen intermediates and depolarization in mitochondria. While caspase-3 activity increased in a concentration-dependent manner, only 50 μg/ml was able to fragment DNA. It was interesting to note that at higher dose, i.e., 100 μg/ml, the cells were killed, supposedly by acute necrosis. DNA synthesis evidenced by bromodeoxyuridine (BrdU) incorporation was inhibited in a concentration-dependent manner. The cells without treatment incorporated BrdU with high affinity confirming their cancerous nature whereas very less incorporation was noticed in treated cells. Our results show apoptotic and antiproliferative potential of scorpion venom (O. doriae) in human neuroblastoma cells. These properties

  18. Behavioural and electroencephalographic effects of Tityus serrulatus scorpion venom in rats.

    PubMed

    Sandoval, M R; Dorce, V A

    1993-02-01

    This study was designed to investigate the convulsant effects of T. serrulatus scorpion venom in rats. Pretreatment of rats with venom increased the minimum convulsant dose of picrotoxin, impaired convulsion generalization and displaced to the left the dose-response curve for picrotoxin. It also decreased the intensity but prolonged the duration of seizures caused by pentylenetetrazol injection. Microinjection of the venom into the dorsal hippocampus induced behavioural alterations and epileptiform waves in the EEG. Venom also altered the threshold for, and intensity of, convulsions induced in different experimental models of epilepsy. Different fractions of the venom may be responsible for these different effects. Therefore, purification of venom toxins is necessary for the complete understanding of the present results. PMID:8456448

  19. Antigenic cross-reactivity among the venoms from several species of Brazilian scorpions.

    PubMed

    Nishikawa, A K; Caricati, C P; Lima, M L; Dos Santos, M C; Kipnis, T L; Eickstedt, V R; Knysak, I; Da Silva, M H; Higashi, H G; Da Silva, W D

    1994-08-01

    The venoms of seven species of scorpions living in different regions of Brazil were analysed with regard to their lethality, antigenic cross-reactivity and ability to induce antibody production. In mice, the tested scorpion venoms can be grouped as: (a) highly toxic: Tityus stigmurus Thorell (LD50 = 0.773 mg/kg), Tityus bahiensis (Perty) (LD50 = 1.062 mg/kg), Tityus serrulatus Lutz and Mello (LD50 = 1.160 mg/kg), and Tityus costatus (Karsch) (LD50 = 1.590 mg/kg); (b) moderately toxic: Tityus cambridgei Pocock (LD50 = 12.136 mg/kg); and (c) practically nontoxic: Rhopalurus agamemnon (Koch) (LD50 = 36.363 mg/kg), and Brotheas amazonicus Lourenço (LD50 = 90.909 mg/kg). On electrophoresis the venoms showed many protein bands displayed along the chromatogram, most of them cross-reacting in immunoelectrophoresis and immunoblotting using horse anti-T. serrulatus, anti-T. bahiensis or anti-T. serrulatus+T. bahiensis sera as probes. The antibodies present in these antivenoms combine with venom components as measured in vitro by the ELISA assay, and neutralize their lethal effects in vivo. These results indicate that horse anti-venoms against a mixture of T. serrulatus and T. bahiensis venoms or only against T. serrulatus venom yield an antibody population able to neutralize the toxic effects found in all venoms studied. PMID:7985203

  20. Characterization of unique amphipathic antimicrobial peptides from venom of the scorpion Pandinus imperator.

    PubMed Central

    Corzo, G; Escoubas, P; Villegas, E; Barnham, K J; He, W; Norton, R S; Nakajima, T

    2001-01-01

    Two novel antimicrobial peptides have been identified and characterized from venom of the African scorpion Pandinus imperator. The peptides, designated pandinin 1 and 2, are alpha-helical polycationic peptides, with pandinin 1 belonging to the group of antibacterial peptides previously described from scorpions, frogs and insects, and pandinin 2 to the group of short magainin-type helical peptides from frogs. Both peptides demonstrated high antimicrobial activity against a range of Gram-positive bacteria (2.4-5.2 microM), but were less active against Gram-negative bacteria (2.4-38.2 microM), and only pandinin 2 affected the yeast Candida albicans. Pandinin 2 also demonstrated strong haemolytic activity (11.1-44.5 microM) against sheep erythrocytes, in contrast with pandinin 1, which was not haemolytic. CD studies and a high-resolution structure of pandinin 2 determined by NMR, showed that the two peptides are both essentially helical, but differ in their overall structure. Pandinin 2 is composed of a single alpha-helix with a predominantly hydrophobic N-terminal sequence, whereas pandinin 1 consists of two distinct alpha-helices separated by a coil region of higher flexibility. This is the first report of magainin-type polycationic antimicrobial peptides in scorpion venom. Their presence brings new insights into the mode of action of scorpion venom and also opens new avenues for the discovery of novel antibiotic molecules from arthropod venoms. PMID:11563967

  1. Teratogenicity in the rat of the venom from the scorpion Androctonus amoreuxi (Aud. & Sav.).

    PubMed

    Ismail, M; Ellison, A C; Tilmisany, A K

    1983-01-01

    A. amoreuxi venom caused a high foetal resorption rate in rats, particularly when injected on days 9-11 of gestation. Vertebral and ossification defects and foetal weight loss were observed in many of the viable foetuses obtained from mothers treated with scorpion venom. Treatment of the rats with phentolamine in addition to the venom significantly reduced the venom-induced hyperglycemia. It also conferred some protection against foetal resorption but had only a slight effect on chondrification or foetal weight loss. This shows that hyperglycemia might be responsible for foetal mortality, but alone is not a decisive factor in the effect of the venom on the chondrification process. Treatment of the rats with triamterene reduced the foetal resorption rate and significantly decreased the effects of the venom on chondrification. However, marked stippling was observed in the long bones and was ascribed to marked mobilization of ionized calcium in the foetus. Foetuses removed from rats treated with phentolamine or triamterene in addition to the venom, however, showed flattened and depressed skulls, possibly from a missing 1st cervical vertebra or failure of the occipital fontanel to close. Treatment of the rats with the scorpion venom over a longer period of time and starting at an earlier time of gestation (days 7-14) caused total foetal resorption, which may be due to inhibition of histamine formation by the venom. The teratogenic effect of the venom appears to be the result of its metabolic effect and action on body electrolytes of the maternal animal, rather than to a direct effect on the foetuses. This was evidenced from experiments with labelled venom, where only a small fraction (0.08-0.33%) was detected in foetuses or placenta. PMID:6344336

  2. Evidence for a direct action of Tityus serrulatus scorpion venom on the cardiac muscle.

    PubMed

    Teixeira, A L; Fontoura, B F; Freire-Maia, L; Machado, C R; Camargos, E R; Teixeira, M M

    2001-05-01

    The ability of toxins to activate the cardiovascular system plays an important role in the morbidity and lethality of the Tityus serrulatus scorpion envenoming. Most of the actions of the scorpion toxins are indirect and due to the release of adrenergic and cholinergic neurotransmitters. Accordingly, treatment following envenoming is targeted towards inhibition of adrenergic and cholinergic receptors. Here, we have sought evidence for a direct action of T. serrulatus venom on the isolated rat heart (Langendorff's method). We show that the bradycardia induced by T. serrulatus venom was completely blocked by atropine, a muscarinic receptor antagonist. Similarly, the increase in heart rate that follows the venom-induced bradycardia was totally inhibited by a beta(1)-adrenoceptor antagonist or by chemical sympathetic denervation with 6-hydroxydopamine. In contrast to these findings, the venom-induced increase in contractile force was not modified by beta(1)-adrenoceptor blockade or by chemical sympathetic denervation. The results clearly demonstrate that the chronotropic effects of T. serrulatus are dependent on neurotransmitter release, but the inotropic effects are not. The neurotransmitter-independent increase in contractility seems to be a direct action of the venom on cardiomyocytes. We suggest that this direct effect on cardiac fibers may play a role in the development of cardiac arrhythmias and contractility defects following envenoming with T. serrulatus scorpion. PMID:11072050

  3. Mild reproductive effects of the Tityus bahiensis scorpion venom in rats

    PubMed Central

    2014-01-01

    Background Scorpion envenoming is a public health problem in Brazil, where Tityus serrulatus and T. bahiensis are considered the most dangerous scorpions. They are well adapted to urbanized environments, and there is an increasing probability of human exposure to these venoms, including during pregnancy. Not much is known about the effects of prenatal exposure to the venom, and no information is available to aid in the rational treatment of victims stung during pregnancy. Thus, this study aimed to investigate whether venom from the scorpion T. bahiensis administered once to pregnant female rats at a dose that causes a moderate envenomation may lead to deleterious effects on the reproductive performance of the dams and on the development of their offspring. This is the first work demonstrating that T. bahiensis venom, when administered experimentally to rats, alters maternal reproductive performance and the morphological development of fetuses. The venom was given to dams on the 5th (GD5) or on the 10th (GD10) gestational day. After laparotomy, on GD21, fetuses and placentas were counted, weighed and externally analyzed. The corpora lutea were counted. The sex and vitality of fetuses were evaluated, and each litter was then randomly divided for visceral or skeletal analyses. Data were analyzed by ANOVA followed by the Tukey-Kramer test and Fisher’s exact test. The significance level for all tests was set at p < 0.05. Results GD5 group presented an increased number of pre-implantation losses. Weight gains in fetuses and placentas were observed in the GD5 and GD10 groups. Weights of the heart and lungs were elevated in GD5 and GD10 and liver weight in GD10. Conclusions Moderate envenomation by T. bahiensis scorpion venom alters maternal reproductive performance and fetal development. However, these are preliminary results whose causes should be investigated more carefully in future studies. PMID:24521392

  4. Overview of the Knottin scorpion toxin-like peptides in scorpion venoms: Insights on their classification and evolution.

    PubMed

    Santibáñez-López, Carlos E; Possani, Lourival D

    2015-12-01

    Scorpion venoms include several compounds with different pharmacological activities. Within these compounds, toxins affecting ion channels are among the most studied. They are all peptides that have been classified based on their 3D structure, chain size and function. Usually, they show a spatial arrangement characterized by the presence of a cysteine-stabilized alpha beta motif; most of them affect Na(+) and K(+) ion-channels. These features have been revised in several occasions before, but a complete phylogenetic analysis of the disulfide containing peptides is not been done. In the present contribution, two databases (Pfam and InterPro) including more than 800 toxins from different scorpions were analyzed. Pfam database included toxins from several organisms other than scorpions such as insects and plants, while InterPro included only scorpion toxins. Our results suggest that Na(+) toxins have evolved independently from those of K(+) toxins no matter the length of the peptidic chains. These preliminary results suggest that current classification needs a more detailed revision, in order to have better characterized toxin families, so the new peptides obtained from transcriptomic analyses would be properly classified. PMID:26187850

  5. Isolation and characterization of an anti-insect β-toxin from the venom of the scorpion Isometrus maculatus.

    PubMed

    Kawachi, Tomoyuki; Miyashita, Masahiro; Nakagawa, Yoshiaki; Miyagawa, Hisashi

    2013-01-01

    Im-3 was isolated from the venom of the scorpion Isometrus maculatus through several steps of HPLC fractionation based on the insect paralytic activity. Injecting Im-3 into crickets induced paralysis, but no toxicity was apparent in mice after an intracerebroventricular injection. Im-3 shares sequence similarity to scorpion β-toxins that specifically affect insect sodium channels. PMID:23291760

  6. Pulmonary oedema produced by scorpion venom augments a phenyldiguanide-induced reflex response in anaesthetized rats

    PubMed Central

    Deshpande, S B; Bagchi, S; Rai, O P; Aryya, N C

    1999-01-01

    The involvement of pulmonary oedema produced by scorpion venom in augmenting a phenyldiguanide (PDG)-induced reflex response was evaluated in urethane-anaesthetized rats. PDG-induced bradycardiac, hypotensive and apnoeic responses, expressed as time–response area, exhibited similarities before or after venom treatment. Hence, the time–response area of bradycardia was taken as a reflex parameter. Pulmonary oedema was determined by physical evaporation and histological methods. Exposure to Indian red scorpion (Buthus tamulus, BT; i.v.) venom for 30 min increased the pulmonary water content (P < 0.05; Student's t test) and augmented the PDG-induced bradycardiac reflex response by more than 2 times (P < 0.001). The increase of pulmonary water content was maximal with 100 μg kg−1 of venom and the augmentation was maximal with 10 μg kg−1. In a separate series of experiments, the venom (100 μg kg−1)-induced pulmonary oedema was confirmed by histological and physical methods. In this group also, the venom augmented the reflex to the same magnitude. Pulmonary oedema (physical and histological) and augmentation of the bradycardiac reflex response after BT venom (100 μg kg−1; i.v.) were absent in animals pretreated with aprotinin, a kallikrein-kinin inhibitor (6000 KIU; i.v.). Ondansetron (10 μg kg−1; i.v.), a 5-HT3 receptor antagonist, failed to block the venom-induced pulmonary oedema (physical and histological) but blocked the venom-induced augmentation of the reflex. The results of this study indicate that the venom-induced augmentation of the PDG reflex is associated with pulmonary oedema involving kinins utilizing 5-HT3 receptors. PMID:10581322

  7. ELISA for the detection of toxic antigens in experimental and clinical envenoming by Tityus serrulatus scorpion venom.

    PubMed

    Chávez-Olórtegui, C; Fonseca, S C; Campolina, D; Amaral, C F; Diniz, C R

    1994-12-01

    An ELISA was developed for identification of circulating toxic antigens from Tityus serrulatus scorpion venom. The toxic fraction from the scorpion venom was purified by Sephadex G-50 chromatography and immunoaffinity techniques were used for identifying antibodies that reacted with this fraction. These antibodies were used to develop a sandwich-type ELISA. The specificity of the assay was demonstrated by its capacity for identifying mice that were experimentally inoculated with T. serrulatus venom from those inoculated with Phoneutria nigriventer spider venom, Apis mellifera bee venom and Bothrops atrox, Crotalus durissus terrificus, Lachesis muta muta and Micrurus frontalis snake venoms. Measurable absorbance signals were obtained with 0.1 ng of venom per assay. The ELISA also detected antigens in the sera of patients systemically envenomed by T. serrulatus. Therefore, this ELISA could be a valuable tool for clinicians and epidemiologists, owing to its sensitivity and specificity. PMID:7725332

  8. Unique diversity of the venom peptides from the scorpion Androctonus bicolor revealed by transcriptomic and proteomic analysis.

    PubMed

    Zhang, Lei; Shi, Wanxia; Zeng, Xian-Chun; Ge, Feng; Yang, Mingkun; Nie, Yao; Bao, Aorigele; Wu, Shifen; E, Guoji

    2015-10-14

    Androctonus bicolor is one of the most poisonous scorpion species in the world. However, little has been known about the venom composition of the scorpion. To better understand the molecular diversity and medical significance of the venom from the scorpion, we systematically analyzed the venom components by combining transcriptomic and proteomic surveys. Random sequencing of 1000 clones from a cDNA library prepared from the venom glands of the scorpion revealed that 70% of the total transcripts code for venom peptide precursors. Our efforts led to a discovery of 103 novel putative venom peptides. These peptides include NaTx-like, KTx-like and CaTx-like peptides, putative antimicrobial peptides, defensin-like peptides, BPP-like peptides, BmKa2-like peptides, Kunitz-type toxins and some new-type venom peptides without disulfide bridges, as well as many new-type venom peptides that are cross-linked with one, two, three, five or six disulfide bridges, respectively. We also identified three peptides that are identical to known toxins from scorpions. The venom was also analyzed using a proteomic technique. The presence of a total of 16 different venom peptides was confirmed by LC-MS/MS analysis. The discovery of a wide range of new and new-type venom peptides highlights the unique diversity of the venom peptides from A. bicolor. These data also provide a series of novel templates for the development of therapeutic drugs for treating ion channel-associated diseases and infections caused by antibiotic-resistant pathogens, and offer molecular probes for the exploration of structures and functions of various ion channels. PMID:26254009

  9. Neurotoxic effects of fractions isolated from Tityus bahiensis scorpion venom (Perty, 1834).

    PubMed

    Lourenço, Geane Antiques; Lebrun, Ivo; Dorce, Valquiria A Coronado

    2002-02-01

    Tityus serrulatus and Tityus bahiensis are considered to be the most venomous scorpions in Brazil and are responsible for most of the accidents that occur in our country. The main toxic agents in scorpion venoms are small basic polypeptides that act as neurotoxins. They cause a derangement of ion channels that result in abnormal release of neurotransmitters. In the present study we fractionated the venom of Tityus bahiensis and studied the effects of fractions P2, P3, P4, P5, P6 and P7, on the mammalian central nervous system. Intravenous injection of P5, P6 and P7 in rats induced spontaneous convulsion, intrahippocampal injection caused behavioural seizures, and P5 and P6 induced electrographic seizures. P5 caused neuronal damage in the CA1 area and P6 in the CA1, CA3 areas and hilus of the dentate gyrus (DG) of the hippocampus. Injection of P3 in the hippocampus did not induce convulsions or lesions. However, when injected intravenously in mice, this fraction reduced behavioural activity in an open field test. Unilateral injection of P4 in the hippocampus caused neuronal damage in the contralateral CA3, but not in the ipsilateral hippocampus. These results suggest that scorpion toxins present in the venom are able to act directly on the central nervous system promoting behavioural and histopathological effects. PMID:11689236

  10. In vitro analysis of the anticancer properties of scorpion venom in colorectal and breast cancer cell lines

    PubMed Central

    AL-ASMARI, ABDULRAHMAN KHAZIM; ISLAM, MOZAFFARUL; AL-ZAHRANI, ALI MATER

    2016-01-01

    Scorpion venom contains various types of proteins and peptides that are able to act as inhibitors of neurotransmitter molecules. This is achieved primarily via the inhibition of ion channels. In addition, scorpion venom has been demonstrated to exhibit anticancer properties in prostate and breast cancer, as well as leukemia. The anticancer properties of scorpion venom are due to its inhibitory effect on matrix metalloproteinase (MMP) activity, which leads to reduced motility and invasion in tumor cells. The inhibitory effects of venom on MMPs additionally lead to a reduction in the metastatic potential of malignant tumors. In the present study, the effect of venom obtained from a local serpentarium facility was examined in colorectal and breast cancer cell lines. Cell motility and clonogenic survival assays revealed a significant decrease (60–90%) in cell motility and colony formation, two significant hallmarks of cancer survival, following treatment with various concentrations of venom. These results were in agreement with previous studies demonstrating the anticancer activity of scorpion venom. In conclusion, the venom utilized at the Research Center of Prince Sultan Military Medical City Hospital (Riyadh, Saudi Arabia) possesses significant anticancer potential against colorectal and breast cancer cell lines. PMID:26893728

  11. Effects of prenatal exposure to Tityus bahiensis scorpion venom on rat offspring development.

    PubMed

    Dorce, Ana Leticia Coronado; Bellot, Rogério Gentil; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2009-11-01

    Scorpion envenoming is a public health problem. In Brazil, the scorpion Tityus serrulatus is considered the most dangerous, but a large number of exposures also occur with Tityus bahiensis. There are quite a few studies in literature about the toxic effects of this venom but it is not known if the venom causes malformations or behavioral defects to the offspring of mothers exposed to the venom during pregnancy. The objective of this work was to determine, in rats, the possible toxic effects of T. bahiensis venom on offspring when injected into rats during different periods of fetal development. Rats were assigned to one of three groups: one control group and two experimental groups that were subcutaneously injected with venom (2.5mg/kg) on the 10th (GD10) or on 16th day (GD16) of gestation. Pups were evaluated for changes in physical and behavioral development. GD10 treatment group offspring showed an increase in body weight gain, earlier ear unfolding, incisor tooth eruption and vaginal opening. A decrease in the time of palmar grasp and surface-righting reflexes was observed only for males. In GD16 treatment group, earlier ear unfolding, incisor tooth eruption, and delay in eye opening were observed in the offspring. In female pups a decrease in weight gain and in time for palmar grasp reflex, and an increase in time for negative geotaxis were observed. In male pups a delay in the testis descent, decrease in the time of palmar grasp, increase in the time of negative geotaxis reflex and in the general and locomotor activities could be noticed. Therefore, we concluded that a moderate dose of scorpion venom administered to pregnant rats was able to elicit alterations in physical and behavioral development in the offspring during the postnatal period. PMID:19383539

  12. Profiling the resting venom gland of the scorpion Tityus stigmurus through a transcriptomic survey

    PubMed Central

    2012-01-01

    Background The scorpion Tityus stigmurus is widely distributed in Northeastern Brazil and known to cause severe human envenoming, inducing pain, hyposthesia, edema, erythema, paresthesia, headaches and vomiting. The present study uses a transcriptomic approach to characterize the gene expression profile from the non-stimulated venom gland of Tityus stigmurus scorpion. Results A cDNA library was constructed and 540 clones were sequenced and grouped into 153 clusters, with one or more ESTs (expressed sequence tags). Forty-one percent of ESTs belong to recognized toxin-coding sequences, with transcripts encoding antimicrobial toxins (AMP-like) being the most abundant, followed by alfa KTx- like, beta KTx-like, beta NaTx-like and alfa NaTx-like. Our analysis indicated that 34% of the transcripts encode “other possible venom molecules”, which correspond to anionic peptides, hypothetical secreted peptides, metalloproteinases, cystein-rich peptides and lectins. Fifteen percent of ESTs are similar to cellular transcripts. Sequences without good matches corresponded to 11%. Conclusions This investigation provides the first global view of gene expression of the venom gland from Tityus stigmurus under resting conditions. This approach enables characterization of a large number of venom gland component molecules, which belong either to known or non yet described types of venom peptides and proteins from the Buthidae family. PMID:22853446

  13. Effect of Androctonus bicolor scorpion venom on serum electrolytes in rats: A 24-h time-course study.

    PubMed

    Al-Asmari, A; Khan, H A; Manthiri, R A

    2016-03-01

    Black fat-tailed scorpion (Androctonus bicolor) belongs to the family Buthidae and is one of the most venomous scorpions in the world. The effects of A. bicolor venom on serum electrolytes were not known and therefore investigated in this study. Adult male Wistar rats were randomly divided into seven groups with five animals in each group. One of the groups served as control and received vehicle only. The animals in the remaining groups received a single subcutaneous injection of crude A. bicolor venom (200 μg/kg bodyweight) and were killed at different time intervals including 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h after venom injection. The results showed that scorpion venom caused significant increase in serum sodium levels within 30 min after injection which slightly subsided after 1 h and then persisted over 24 h. Serum potassium levels continued to significantly increase until 4 h and then slightly subsided. There were significant decreases in serum magnesium (Mg(+)) levels following scorpion venom injection, at all the time points during the course of study. Serum calcium levels were significantly increased during the entire course of study, whereas serum chloride was significantly decreased. In conclusion, A. bicolor envenomation in rats caused severe and persistent hypomagnesemia with accompanied hypernatremia, hyperkalemia, and hypercalcemia. It is important to measure serum Mg(+) levels in victims of scorpion envenomation, and patients with severe Mg(+) deficiency should be treated accordingly. PMID:25964378

  14. Scorpion Venom Heat-Resistant Peptide Protects Transgenic Caenorhabditis elegans from β-Amyloid Toxicity

    PubMed Central

    Zhang, Xiao-Gang; Wang, Xi; Zhou, Ting-Ting; Wu, Xue-Fei; Peng, Yan; Zhang, Wan-Qin; Li, Shao; Zhao, Jie

    2016-01-01

    Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Our previous studies found SVHRP could enhance neurogenesis and inhibit microglia-mediated neuroinflammation in vivo. Here, we use the transgenic CL4176, CL2006, and CL2355 strains of Caenorhabditis elegans which express the human Aβ1-42 to investigate the effects and the possible mechanisms of SVHRP mediated protection against Aβ toxicity in vivo. The results showed that SVHRP-fed worms displayed remarkably decreased paralysis, less abundant toxic Aβ oligomers, reduced Aβ plaque deposition with respect to untreated animals. SVHRP also suppressed neuronal Aβ expression-induced defects in chemotaxis behavior and attenuated levels of ROS in the transgenic C. elegans. Taken together, these results suggest SVHRP could protect against Aβ-induced toxicity in C. elegans. Further studies need to be conducted in murine models and humans to analyze the effectiveness of the peptide. PMID:27507947

  15. Scorpion Venom Heat-Resistant Peptide Protects Transgenic Caenorhabditis elegans from β-Amyloid Toxicity.

    PubMed

    Zhang, Xiao-Gang; Wang, Xi; Zhou, Ting-Ting; Wu, Xue-Fei; Peng, Yan; Zhang, Wan-Qin; Li, Shao; Zhao, Jie

    2016-01-01

    Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Our previous studies found SVHRP could enhance neurogenesis and inhibit microglia-mediated neuroinflammation in vivo. Here, we use the transgenic CL4176, CL2006, and CL2355 strains of Caenorhabditis elegans which express the human Aβ1-42 to investigate the effects and the possible mechanisms of SVHRP mediated protection against Aβ toxicity in vivo. The results showed that SVHRP-fed worms displayed remarkably decreased paralysis, less abundant toxic Aβ oligomers, reduced Aβ plaque deposition with respect to untreated animals. SVHRP also suppressed neuronal Aβ expression-induced defects in chemotaxis behavior and attenuated levels of ROS in the transgenic C. elegans. Taken together, these results suggest SVHRP could protect against Aβ-induced toxicity in C. elegans. Further studies need to be conducted in murine models and humans to analyze the effectiveness of the peptide. PMID:27507947

  16. Developmental effects of Tityus serrulatus scorpion venom on the rat offspring.

    PubMed

    Barão, Aline Aparecida Saltão; Bellot, Rogerio Gentil; Dorce, Valquiria Abrão Coronado

    2008-07-30

    Scorpion envenomation is a public health problem. Extensive research has been conducted to describe the systemic effects of scorpion venoms and their toxins, however, few reports are available about their effects on pre- and post-natal periods. Whole venom of the Tityus serrulatus scorpion was administered to rats on the 10th and 16th days of pregnancy to determine the effect on physical, reflexive and behavioral development of offspring. Thirty female Wistar rats were mated and distributed into three groups with one control group (C) and two experimental groups that were injected with venom (1mg/kg) on the 10th (GD10) or the 16th day (GD16) of pregnancy. After birth, the litter was standardized (eight pups for dam) and the rat pups were submitted to physical and behavioral analysis. A greater weight gain was observed on the 20th day of life (PN20) in the female and male pups of the two experimental groups compared to controls. In the GD16 group, a delay in ear opening and acceleration in ear unfolding were observed. In relation to reflexive development, an increased time for palmar grasp reflex was observed on PN8 in GD16. For this group, there was a decrease in the time of righting reflex on PN4 and PN6, and of negative geotaxis on PN6, PN8 and PN10. In conclusion, scorpion venom administered to pregnant rats on specific gestational days and at a dose that simulates a small accident, results in alterations in some reflex and physical parameters in their offspring. PMID:18534258

  17. BmKn-2 scorpion venom peptide for killing oral cancer cells by apoptosis.

    PubMed

    Tong-ngam, Pirut; Roytrakul, Sittiruk; Sritanaudomchai, Hathaitip

    2015-01-01

    Scorpion venom peptides recently have attracted attention as alternative chemotherapeutic agents that may overcome the limitations of current drugs, providing specific cytotoxicity for cancer cells with an ability to bypass multidrug-resistance mechanisms, additive effects in combination therapy and safety. In the present study, BmKn-2 scorpion venom peptide and its derivatives were chosen for assessment of anticancer activities. BmKn-2 was identified as the most effective against human oral squamous cells carcinoma cell line (HSC-4) by screening assays with an IC50 value of 29 μg/ml. The BmKn-2 peptide killed HSC-4 cells through induction of apoptosis, as confirmed by phase contrast microscopy and RT-PCR techniques. Typical morphological features of apoptosis including cell shrinkage and rounding characteristics were observed in treated HSC-4 cells. The results were further confirmed by increased expression of pro-apoptotic genes such as caspase-3, -7, and -9 but decrease mRNA level of anti-apoptotic BCL-2 in BmKn-2 treated cells, as determined by RT-PCR assay. In summary, the BmKn-2 scorpion venom peptide demonstrates specific membrane binding, growth inhibition and apoptogenic activity against human oral cancer cells. PMID:25854366

  18. A rare complication of scorpion venom: atrial fibrillation.

    PubMed

    Duman, Ali; Turkdogan, Kenan Ahmet; Akoz, Ayhan; Avcil, Mucahit; Dagli, Bekir; Canakci, Selcuk Eren

    2016-05-01

    Although the clinical findings of scorpion stings are often mild, they may lead to multiorgan failure and even cardiogenic shock. The toxin has both local and systemic effects. Local effects include edema, bruising(ecchymosis), and burning pain,whereas systemic effects include nausea,vomiting, hypotension or hypertension, cardiovascular toxicity, renal failure,and hemorrhage at different areas. The toxins have been implicated in a number of cardiac arrhythmias, including torsade de pointes, long QT syndrome, and atrial fibrillation. Here, we present a 90-year-old woman with no history of drug use or complaints due to dysrhythmias who developed atrial fibrillation after being stung by a scorpion. PMID:26508584

  19. Induction of IL-12 from human monocytes after stimulation with Androctonus crassicauda scorpion venom.

    PubMed

    Saadi, Samahir; Assarehzadegan, Mohammad-Ali; Pipelzadeh, Mohammad Hassan; Hadaddezfuli, Reza

    2015-11-01

    The objective of this study was to evaluate the capacity of venom from Androctonus crassicauda to induce expression/production of interleukin (IL)-12 by isolated human monocytes. For this purpose, isolated human monocytes were exposed to different concentrations of the venom (0.16-20 μg/ml) for varying periods (6, 12, and 24 h). Apart from measures of venom cytotoxicity (i.e., lactase dehydrogenase activity [LDH] release), measures of IL-12 p40 mRNA (by Real-time PCR) of IL-12 release (by ELISA) were performed. The results showed that the venom produced significant concentration- and duration of incubation-dependent cytotoxicity. Expression of IL-12 p40 mRNA was significantly increased at all exposure timepoints relative to that in unexposed cells, but was maximal after 6 h of exposure. At that timepoint, the effect from a dose of 2.5 μg venom/ml provided the maximal increase among all doses tested. At the level of the protein itself, IL-12 production remained almost consistently elevated (vs. unexposed control values) across all exposure timepoints, with the greatest formation again occurring after 6 h of incubation at a dose of 2.5 μg venom/ml. The findings from this study demonstrated that venom from the A. crassicauda scorpion contained active constituents that could induce a sustained activation of human monocytes that was manifested, in part, as promotion of the expression/production of IL-12. PMID:26415903

  20. Upregulation of PTEN involved in scorpion venom-induced apoptosis in a lymphoma cell line.

    PubMed

    Gao, Fang; Li, Hao; Chen, Ya-Dong; Yu, Xiao-Ning; Wang, Ran; Chen, Xue-Liang

    2009-04-01

    We investigated whether the venom of the scorpion Buthus martensii Karsch (BmK) inhibited growth of human lymphoma cells by inducing apoptosis, and studied possible signal pathways involved in this cell death. BmK venom selectively reduced the viability of Raji and Jurkat cells, and had low toxicity to human peripheral blood lymphocytes. Flow cytometry showed that BmK venom-induced apoptosis and G(0)/G(1) cell cycle arrest in Raji and Jurkat cells. In Raji cells, BmK venom upregulated the expression of PTEN accompanied by decreased levels of Akt and Bad phosphorylation. Treatment with BmK venom and LY294002 (an inhibitor of Akt) synergistically enhanced apoptosis. The expression of p27 was increased in both PTEN-positive Raji and PTEN-negative Jurkat cells exposed to BmK venom. The results indicate that key regulators in BmK venom-induced apoptosis are PTEN, acting through downregulation of the PI3K/Akt signal pathway, in Raji cells and p27 in Jurkat cells. PMID:19373662

  1. Neurological effects of venomous bites and stings: snakes, spiders, and scorpions.

    PubMed

    Del Brutto, Oscar H

    2013-01-01

    Snake and spider bites, as well as scorpion sting envenoming, are neglected diseases affecting millions of people all over the world. Neurological complications vary according to the offending animal, and are often directly related to toxic effects of the venom, affecting the central nervous system, the neuromuscular transmission, the cardiovascular system, or the coagulation cascade. Snake bite envenoming may result in stroke or muscle paralysis. Metalloproteinases and other substances (common in vipers and colubrids) have anticoagulant or procoagulant activity, and may induce ischemic or hemorrhagic strokes. The venom of elapids is rich in neurotoxins affecting the neuromuscular transmission at either presynaptic or postsynaptic levels. The clinical picture of scorpion sting envenoming is dominated by muscle weakness associated with arterial hypertension, cardiac arrythmias, myocarditis, or pulmonary edema. These manifestations occur as the result of release of catecholamines into the bloodstream or due to direct cardiac toxicity of the venom. Cerebrovascular complications have been reported after the sting of the Indian red scorpion. Intracranial hemorrhages occur in the setting of acute increases in arterial blood pressure related to sympathetic overstimulation, and cerebral infarctions are related to either cerebral hypoperfusion, consumption coagulopathy, vasculitis, or cardiogenic brain embolism. Three main syndromes result from spider bite envenoming: latrodectism, loxoscelism, and funnel-web spider envenoming. Latrodectism is related to neurotoxins present in the venom of widow spiders. Most cases present with headache, lethargy, irritability, myalgia, tremor, fasciculation, or ataxia. Loxoscelism is caused by envenoming by spiders of the family Sicariidae. It may present with a stroke due to a severe coagulopathy. The venom of funnel-web spiders also has neurotoxins that stimulate neurotransmitter release, resulting in sensory disturbances and muscle

  2. Pharmacological investigation of the nociceptive response and edema induced by venom of the scorpion Tityus serrulatus.

    PubMed

    Nascimento, Elias B; Costa, Karina A; Bertollo, Caryne M; Oliveira, Antônio Carlos P; Rocha, Leonardo T S; Souza, Adriano L S; Glória, Maria Beatriz A; Moraes-Santos, Tasso; Coelho, Márcio M

    2005-04-01

    In this study we characterized the nociceptive response and edema induced by the venom of the scorpion Tityus serrulatus in rats and mice and carried out a preliminary pharmacological investigation of the mechanisms involved in these responses. Intraplantar injection of the venom (1 or 10mug) induced edema and a marked ipsilateral nociceptive response, characterized by thermal and mechanical allodynia and paw licking behaviour. The nociceptive response was inhibited by previous intraperitoneal administration of indomethacin (4mg/kg), dipyrone (200mg/kg), cyproheptadine (10mg/kg) or morphine (5 or 10mg/kg), but not by dexamethasone (1 or 4mg/kg) or promethazine (1 or 5mg/kg). The edema was inhibited by previous treatment with promethazine (5 or 10mg/kg) or cyproheptadine (5 or 10mg/kg), but not by indomethacin (2 or 4mg/kg), dexamethasone (1 or 4mg/kg) or cromolyn (40 or 80mg/kg). Some bioactive amines, including histamine and 5-hydroxytryptamine, were found in the venom in low concentrations. In conclusion, the nociceptive response and edema induced by the venom of T. serrulatus may result from the action of multiple mediators including eicosanoids, histamine and 5-hydroxytryptamine. These results may lead to a better understanding of the host response to potent animal toxins and also give insights into a more rational pharmacological approach to alleviate the intense pain associated with the scorpion envenomation. PMID:15777954

  3. Effects of Tityus stigmurus (Thorell 1876) (Scorpiones: Buthidae) venom in isolated perfused rat kidneys.

    PubMed

    Silva, Nathalia A; Albuquerque, Cleide M R; Marinho, Aline D; Jorge, Roberta J B; Silva, Antonio G; Monteiro, Helena S A; Silva, Túlio D; Silva, Márcia V; Correia, Maria Tereza S; Pereira, Ticiana P; Martins, Alice M C; Menezes, Dalgimar B; Ximenes, Rafael M; Martins, René D

    2016-01-01

    Scorpions belonging to the Tityus genus are of medical interest in Brazil. Among them, Tityus stigmurus is the main scorpion responsible for stings in the Northeast region. After a sting, the scorpion venom distributes rapidly to the organs, reaching the kidneys quickly. However, there are few studies concerning the renal pathophysiology of scorpion poisoning. In this study, we evaluated the effects of T. stigmurus venom (TsV) on renal parameters in isolated rat kidneys. Wistar rats (n = 6), weighing 250-300 g, were perfused with Krebs-Henseleit solution containing 6 g/100 mL bovine serum albumin. TsV at 0.3 and 1.0 μg/mL was tested, and the effects on perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and electrolyte excretion were analyzed. Effects were observed only at TsV concentration of 1.0 μg/mL, which increased PP (controlPP40' = 92.7 ± 1.95; TsVPP40' = 182.0 ± 4.70* mmHg, *p < 0.05), RVR (controlRVR40' = 3.28 ± 0.23 mmHg; TstRVR40' = 6.76 ± 0.45* mmHg, *p < 0.05), UF (controlUF50' = 0.16 ± 0.04; TstUF50' = 0.60 ± 0.10* mL/g/min,*p < 0.05), GFR and electrolyte excretion, with histological changes that indicate renal tubular injury. In conclusion, T. stigmurus venom induces a transient increase in PP with tubular injury, both of which lead to an augmented electrolyte excretion. PMID:27142547

  4. Evaluation of the lethal potency of scorpion and snake venoms and comparison between intraperitoneal and intravenous injection routes.

    PubMed

    Oukkache, Naoual; El Jaoudi, Rachid; Ghalim, Noreddine; Chgoury, Fatima; Bouhaouala, Balkiss; Mdaghri, Naima El; Sabatier, Jean-Marc

    2014-06-01

    Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD₅₀) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD₅₀ values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD₅₀ values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD₅₀ values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the

  5. Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

    PubMed Central

    Oukkache, Naoual; Jaoudi, Rachid El; Ghalim, Noreddine; Chgoury, Fatima; Bouhaouala, Balkiss; Mdaghri, Naima El; Sabatier, Jean-Marc

    2014-01-01

    Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins

  6. Characterization of Tityus scorpion venoms using synaptosome binding assays and reactivity towards Venezuelan and Brazilian antivenoms.

    PubMed

    Borges, Adolfo; De Sousa, Leonardo; Espinoza, Jorge; Melo, Marilia Martins; Santos, Raquel G; Kalapothakis, Evanguedes; Valadares, Diogo; Chávez-Olórtegui, Carlos

    2008-01-01

    Venoms from Tityus species inhabiting five endemic regions of scorpionism in Venezuela (Andean, Perijá range, north-central, northeastern, and Guayana) and also southeast Brazil (T. serrulatus and T. bahiensis) were characterized immunologically in ELISA experiments using mouse- and rabbit-derived antibodies to evaluate their cross-reactivity and also functionally, utilizing synaptosome binding assays. While Brazilian and Venezuelan antivenoms cross-reacted poorly, T. discrepans (north-central Venezuela) and T. zulianus (Andean) venoms shared a greater immunological relatedness than with T. perijanensis (Perijá range). Anti-T. breweri (Guayana) antibodies fully cross-reacted with T. discrepans. Native PAGE indicated species-specific fingerprints for all venoms and revealed differences between two populations (Anzoátegui and Monagas States) of T. nororientalis (northeastern Venezuela). Components antigenically related to T. serrulatus beta-toxin TsVII were also detected in T. breweri, T. nororientalis (Anzoátegui) and T. funestus (Andean). Antibodies against T. serrulatus anatoxin TsNTxP did not cross-react significantly with any Venezuelan venoms indicating lack of TsNTxP homologues. The results suggest that the extent of antigenic reactivity depends on the studied species rather than the geographical distance between their habitats. All venoms, with T. discrepans to a lesser extent, were able to significantly displace [(125)I]-TsVII from its binding site in rat brain synaptosomes. Our data indicate that beta-toxins functionally related to TsVII but differing significantly in their antigenic regions exist in Venezuelan venoms from different endemic regions. Identification of shared epitopes with TsVII, at least for some species, may lead to the design of antibodies based on common epitopes for treating scorpion envenoming in Venezuela and Brazil. PMID:17920649

  7. Pathophysiological and neurobehavioral injuries in mice experimentally envenomed with Androctonus liouvillei (Pallary, 1928) scorpion venom.

    PubMed

    El Hidan, Moulay Abdelmonaim; Touloun, Oulaid; El Hiba, Omar; Boumezzough, Ali

    2016-01-01

    The genus Androctonus is represented by 7 scorpion species in Morocco. All studies conducted on the characterization of Androctonus species venom are limited to Androctonus mauritanicus. However, there is other species which arouses also interest of scientists due to their high toxicity. Thus, we chose to assess the toxic effect of Androctonus liouvillei venom by sublethal injection and the effects on some vital organs, by a histological and a biochemical tools. In addition, we aimed to characterize the neurobehavioral impairments, in Swiss mice, 3h, 6h and 12h following envenomation. The LD50 of A. liouvillei scorpion venom was found to be 0.29mg/kg by subcutaneous injection route. Venom administration induced glomerular destruction and disorganization in the Bowman's spac. Examination of lungs showed a remarkable focal rupture of the alveolar structure and intra-alveolar hemorrhage. Concurrently, there was a significant enhancement in the serum enzymes levels of AST, ALT, CPK and LDH, and a high level of glucose and creatinine. Proteinuria was also observed. Regarding the behavioral effects we noted a hypoactivity and anxiogenic-like effect, manifested by an increased time spent in the open arms in groups tested 30min and 12h after the injection. Concomitantly with an increased immobility time in the tail suspension test. The present finding show an obvious profound neuromodulatory effect of A. liouvillei venom manifested by an impaired neurobehavioral and physiological patterns in mice that may in part explain the toxic effect of the venom in human as one of the potent death agents. PMID:26651916

  8. Effects of in utero exposure to Tityus bahiensis scorpion venom in adult rats.

    PubMed

    Dorce, Ana Leticia Coronado; Dorce, Valquiria Abrão Coronado; Nencioni, Ana Leonor Abrahão

    2010-01-01

    The toxicity of Tityus bahiensis scorpion venom is well known, but there are little data about the damage in offspring of dams that were exposed to the venom during pregnancy. The objective of this work was to determine the toxic effects of venom in adult offspring of Wistar rats exposed to venom in utero. Dams were divided into a control group, subcutaneously injected with saline solution on the 10th (GD10) and 16th (GD16) days, and two experimental groups, subcutaneously injected with venom (2.5mg/kg) on GD10 or GD16, respectively. Adult offspring were evaluated according to behavioral development and neuronal integrity in the hippocampus. Tests performed in the activity box and in the enriched environment demonstrated that males from GD10 had motor decrease. Females from GD10 showed a depressive-like state and were more anxious, as demonstrated by the forced swimming test and social interaction. The plus-maze discriminative avoidance task demonstrated that GD16 males had lower levels of anxiety. The number of neuronal cells was decreased in CA1, CA3 and CA4 hippocampal areas of males and females from GD10 group and in CA1 of females and CA4 of males from GD16 group. Thus, we conclude that venom exposure in pregnant dams causes subtle alteration in the behavioral and neuronal development of offspring in adult life in a gender-dependent manner. PMID:19945531

  9. Scorpion venom components that affect ion-channels function

    PubMed Central

    Quintero-Hernández, V.; Jiménez-Vargas, J.M.; Gurrola, G.B.; Valdivia, H.H.F.; Possani, L.D.

    2014-01-01

    SUMMARY The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na+-, K+- and Ca++-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are now adays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na+-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K+-channels are normally pore blocking agents. The Ryanodine Ca++-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells. PMID:23891887

  10. Scorpion venom-induced neutrophilia is inhibited by a PAF receptor antagonist in the rat.

    PubMed

    Borges, C M; Silveira, M R; Aparecida, M; Beker, C L; Freire-Maia, L; Teixeira, M M

    2000-04-01

    A dramatic blood neutrophilia is an important feature of the severe envenoming caused by the Brazilian scorpion Tityus serrulatus and may contribute to the development of lung injury in children. We examined the effects of an intravenous injection of T. serrulatus scorpion venom (TsV) on the total number of leukocytes and neutrophils in the blood of anesthetized rats. Injection of TsV (250 microg/kg) induces a significant leukocytosis 2 and 3 h after its injection, explained by an increase in the number of neutrophils. The release of catecholamines and action on adrenoceptors is responsible for most of the systemic manifestations of TsV. However, pretreatment with the beta-adrenoceptor antagonists metoprolol and propranolol or the alpha1-adrenoceptor antagonist prazosin (0.25 mg/kg) did not prevent TsV-induced neutrophilia. Blood neutrophilia induced by TsV occurred simultaneously with a significant reduction of mature neutrophils in bone marrow. Pretreatment with the platelet-activating factor (PAF) receptor antagonists UK-74505 or WEB-2086 prevented TsV-induced increase in blood neutrophils and reduction in the number of neutrophils in the bone marrow. It is concluded that scorpion venom induces blood neutrophilia in rats, explained by a PAF receptor-dependent mobilization of neutrophils from the bone marrow. PMID:10770284

  11. Serum production against Tityus serrulatus scorpion venom using cross-linked chitosan nanoparticles as immunoadjuvant.

    PubMed

    Rocha Soares, Karla S; Cardozo Fonseca, José L; Oliveira Bitencourt, Mariana A; Santos, Kátia S C R; Silva, Arnóbio A; Fernandes-Pedrosa, Matheus F

    2012-12-15

    Several species of scorpions are known to cause accidents which can lead to death, most of them belonging to the genus Tityus. Tityus serrulatus is considered the most dangerous scorpion in South America. In Brazil, T. serrulatus is responsible for serious accidents, including deaths, which occur mainly with children and elderly people. Anti-scorpion sera are routinely produced by various institutions, and suitable technologies have been investigated for encapsulation and release recombinant or native proteins capable of inducing antibody production. In this context, biocompatible and biodegradable polymers, such as chitosan, have been employed for this purpose. This study aimed to obtain a protein release system for the peptides or proteins from T. serrulatus, based on cross-linked chitosan nanoparticles (CN) in order to generate a new model of immunization in animals, and consequently a potentially novel polyclonal serum, namely an anti-T. serrulatus venom. CN were successfully obtained by ionic gelation using the polyanion tripolyphosphate (TPP), which demonstrated a suitable particle size of about 200 nm, with maximum encapsulation efficiency (100%) and enhanced antigen-specific antibody titers of 72%. The serum production data revealed that CN were equipotent to aluminum hydroxide, the traditional adjuvant for immunization. This study demonstrates that chitosan nanoparticles are a promising and safe system for peptide/protein delivery for T. serrulatus scorpion. PMID:23006936

  12. Effect of maternal exposure to Tityus bahiensis scorpion venom during lactation on the offspring of rats.

    PubMed

    Martins, Adriana do Nascimento; Nencioni, Ana Leonor Abrahão; Dorce, Ana Leticia Coronado; Paulo, Maria Eliza F V; Frare, Eduardo Osório; Dorce, Valquíria Abrão Coronado

    2016-01-01

    Scorpion stings are a public health problem in Brazil and lactating women may be affected. We aimed to study the effects of Tityus bahiensis venom in the offspring of rats treated during lactation. Mothers received a subcutaneous injection of saline (1.0ml/kg) or venom (2.5mg/kg) or an intraperitoneal injection of LPS (lipopolysaccharide) (100μg/kg) on postnatal (PN) days 2 (PN2), 10 (PN10) or 16 (PN16). The offspring were evaluated during the childhood and adulthood. Pups showed a delay in physical and reflexological development, and a decrease in motor activity. Adults displayed low anxiety. There was an increase in the number of viable neuronal cells in hippocampal areas CA1 and CA4. The levels of IFN-γ (interferon-gamma) increased in the experimental groups. Several of the parameters analyzed showed important differences between the sexes. Thus, the scorpion venom affects the development in the offspring of mothers envenomed during the lactation. PMID:26746106

  13. In vitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines.

    PubMed

    Díaz-García, Alexis; Morier-Díaz, Luis; Frión-Herrera, Yahima; Rodríguez-Sánchez, Hermis; Caballero-Lorenzo, Yamira; Mendoza-Llanes, Dianeya; Riquenes-Garlobo, Yanelis; Fraga-Castro, José A

    2013-01-01

    In Cuba the endemic species of scorpion Rhopalurus junceus has been used in traditional medicine for cancer treatment. However, there is little scientific evidence about its potential in cancer therapy. The effect of a range of scorpion venom concentrations (0.1, 0.25, 0.5, 0.75 and 1mg/ml) against a panel of human tumor cell lines from epithelial (Hela, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, HT-29), hematopoietic origins (U937, K562, Raji) and normal cells (MRC-5, MDCK, Vero) was determined by the MTT assay. Additionally, the effect of venom on tumor cell death was assayed by Fluorescence microscopy, RT-PCR and western blot. Only the epithelial cancer cells showed significant cell viability reduction, with medium cytotoxic concentration (IC50) ranging from 0.6-1mg/ml, in a concentration-dependent manner. There was no effect on either normal or hematopoietic tumor cells. Scorpion venom demonstrated to induce apoptosis in less sensitive tumor cells (Hela) as evidenced by chromatin condensation, over expression of p53 and bax mRNA, down expression of bcl-2 mRNA and increase of activated caspases 3, 8, 9. In most sensitive tumor cells (A549), scorpion venom induced necrosis evidenced by acridine orange/ethidium bromide fluorescent dyes and down-expression of apoptosis-related genes. We concluded the scorpion venom from R. junceus possessed a selective and differential toxicity against epithelial cancer cells. This is the first report related to biological effect of R. junceus venom against a panel of tumor cells lines. All these results make R. junceus venom as a promise natural product for cancer treatment. PMID:23946884

  14. In vitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines

    PubMed Central

    Díaz-García, Alexis; Morier-Díaz, Luis; Frión-Herrera, Yahima; Rodríguez-Sánchez, Hermis; Caballero-Lorenzo, Yamira; Mendoza-Llanes, Dianeya; Riquenes-Garlobo, Yanelis; Fraga-Castro, José A

    2013-01-01

    In Cuba the endemic species of scorpion Rhopalurus junceus has been used in traditional medicine for cancer treatment. However, there is little scientific evidence about its potential in cancer therapy. The effect of a range of scorpion venom concentrations (0.1, 0.25, 0.5, 0.75 and 1mg/ml) against a panel of human tumor cell lines from epithelial (Hela, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, HT-29), hematopoietic origins (U937, K562, Raji) and normal cells (MRC-5, MDCK, Vero) was determined by the MTT assay. Additionally, the effect of venom on tumor cell death was assayed by Fluorescence microscopy, RT-PCR and western blot. Only the epithelial cancer cells showed significant cell viability reduction, with medium cytotoxic concentration (IC50) ranging from 0.6-1mg/ml, in a concentration-dependent manner. There was no effect on either normal or hematopoietic tumor cells. Scorpion venom demonstrated to induce apoptosis in less sensitive tumor cells (Hela) as evidenced by chromatin condensation, over expression of p53 and bax mRNA, down expression of bcl-2 mRNA and increase of activated caspases 3, 8, 9. In most sensitive tumor cells (A549), scorpion venom induced necrosis evidenced by acridine orange/ethidium bromide fluorescent dyes and down-expression of apoptosis-related genes. We concluded the scorpion venom from R. junceus possessed a selective and differential toxicity against epithelial cancer cells. This is the first report related to biological effect of R. junceus venom against a panel of tumor cells lines. All these results make R. junceus venom as a promise natural product for cancer treatment. PMID:23946884

  15. Comparative proteomic analysis of male and female venoms from the Cuban scorpion Rhopalurus junceus.

    PubMed

    Rodríguez-Ravelo, Rodolfo; Batista, Cesar V F; Coronas, Fredy I V; Zamudio, Fernando Z; Hernández-Orihuela, Lorena; Espinosa-López, Georgina; Ruiz-Urquiola, Ariel; Possani, Lourival D

    2015-12-01

    A complete mass spectrometry analysis of venom components from male and female scorpions of the species Rhophalurus junceus of Cuba is reported. In the order of 200 individual molecular masses were identified in both venoms, from which 63 are identical in male and females genders. It means that a significant difference of venom components exists between individuals of different sexes, but the most abundant components are present in both sexes. The relative abundance of identical components is different among the genders. Three well defined groups of different peptides were separated and identified. The first group corresponds to peptides with molecular masses of 1000-2000 Da; the second to peptides with 3500-4500 Da molecular weight, and the third with 6500-8000 Da molecular weights. A total of 86 peptides rich in disulfide bridges were found in the venoms, 27 with three disulfide bridges and 59 with four disulfide bridges. LC-MS/MS analysis allowed the identification and amino acid sequence determination of 31 novel peptides in male venom. Two new putative K(+)-channel peptides were sequences by Edman degradation. They contain 37 amino acid residues, packed by three disulfide bridges and were assigned the systematic numbers: α-KTx 1.18 and α-KTx 2.15. PMID:26169670

  16. Immunopathologic effects of scorpion venom on hepato-renal tissues: Involvement of lipid derived inflammatory mediators.

    PubMed

    Lamraoui, Amal; Adi-Bessalem, Sonia; Laraba-Djebari, Fatima

    2015-10-01

    Scorpion venoms are known to cause different inflammatory disorders through complex mechanisms in various tissues. In the study here, the involvement of phospholipase A2 (PLA2) and cyclo-oxygenase (COX)-derived metabolites in hepatic and renal inflammation responses were examined. Mice were envenomed with Androctonus australis hector scorpion venom in the absence or presence of inhibitors that can interfere with lipid inflammatory mediator synthesis, i.e., dexamethasone (PLA2 inhibitor), indomethacin (non-selective COX-1/COX-2 inhibitor), or celecoxib (selective COX-2 inhibitor). The inflammatory response was assessed by evaluating vascular permeability changes, inflammatory cell infiltration, oxidative/nitrosative stress marker levels, and by histologic and functional analyses of the liver and kidney. Results revealed that the venom alone induced an inflammatory response in this tissues marked by increased microvascular permeability and inflammatory cell infiltration, increases in levels of nitric oxide and lipid peroxidation, and decreases in antioxidant defense. Moreover, significant alterations in the histological architecture of these organs were associated with increased serum levels of some metabolic enzymes, as well as urea and uric acid. Pre-treatment of mice with dexamethasone led to significant decreases of the inflammatory disorders in the hepatic parenchyma; celecoxib pre-treatment seemed to be more effective against renal inflammation. Indomethacin pre-treatment only slightly reduced the inflammatory disorders in the tissues. These results suggest that the induced inflammation response in liver was mediated mainly by PLA2 activation, while the renal inflammatory process was mediated by prostaglandin formation by COX-2. These findings provide additional insight toward the understanding of activated pathways and related mechanisms involved in scorpion envenoming syndrome. PMID:26231296

  17. Peptide T, a novel bradykinin potentiator isolated from Tityus serrulatus scorpion venom.

    PubMed

    Ferreira, L A; Alves, E W; Henriques, O B

    1993-08-01

    A bradykinin-potentiating peptide was isolated and characterized from venom of the scorpion Tityus serrulatus by chromatographic techniques followed by biological assays. The complete amino acid sequence (13 residues) of peptide is presented. The peptide potentiated the contractile activity of bradykinin on the isolated guinea-pig ileum, and inhibited the hydrolysis of bradykinin by angiotensin-converting enzyme from B. jararaca plasma and the conversion of angiotensin I to angiotensin II by kininase II from guinea-pig ileum tissue. The peptide also increased the depressor effect of bradykinin on arterial blood pressure in the anaesthetized rat. PMID:8212046

  18. Scorpine, an anti-malaria and anti-bacterial agent purified from scorpion venom.

    PubMed

    Conde, R; Zamudio, F Z; Rodríguez, M H; Possani, L D

    2000-04-14

    A novel peptide, scorpine, was isolated from the venom of the scorpion Pandinus imperator, with anti-bacterial activity and a potent inhibitory effect on the ookinete (ED(50) 0.7 microM) and gamete (ED(50) 10 microM) stages of Plasmodium berghei development. It has 75 amino acids, three disulfide bridges with a molecular mass of 8350 Da. Scorpine has a unique amino acid sequence, similar only to some cecropins in its N-terminal segment and to some defensins in its C-terminal region. Its gene was cloned from a cDNA library. PMID:10767415

  19. Histopathological changes induced by Hemiscorpius lepturus scorpion venom in mice.

    PubMed

    Heidarpour, Mojgan; Ennaifer, Emna; Ahari, Hamed; Srairi-Abid, Najet; Borchani, Lamia; Khalili, Ghader; Amini, Hossein; Anvar, Amir Ali; Boubaker, Samir; El-Ayeb, Mohamed; Shahbazzadeh, Delavar

    2012-03-01

    Envenomation by Hemiscorpius lepturus (H. lepturus) is associated with local necrosis, followed by systemic manifestations. In this work the LD₅₀ of H. lepturus venom were determined by subcutaneous (SC) injection in white Balb/c mice (5 mg/kg). Histopathological alterations in organs such as kidney, heart, liver, lungs, stomach and intestine were determined in 3, 6, 12 and 24 h following experimental (SC) envenoming injection of one LD ₅₀ of the venom in Balb/c mice. Histological studies showed degenerative changes in the kidney with disorganized glomeruli and necrotic tubular in 3 h and reached to its climax in 6 h. Myocardium showed massive myocytolysis with interstitial necrosis in 3 h and reached to its peak after 6 h past envenoming. Bowels showed edema of lamina propria and slight villous necrosis. The enzymatic activities of creatine kinase (CK) and lactate dehydrogenase (LDH) were significantly increased in the serum in 9 h. No necrotic lesion observed in lungs and liver. The results indicate that the venom of H. lepturus is a highly cytotoxic, and induces massive tissue damages in specific organs, starting from the heart and kidney as the first target in 3 h and ends to the bowels in 6 h post envenomation. PMID:22230352

  20. Potentiation of bradykinin action on smooth muscle by a scorpion venom extract.

    PubMed

    Araujo, R L; Gomez, M V

    1976-08-01

    Gel filtration of the water extract of the venom of the scorpion T. serrulatus showed four peaks; the first peak (P1) is devoid of toxic activity but increases the bradykinin-induced contraction of isolated rat uterus and guinea-pig ileum. The stepwise fractionation of the pooled P1 peak was performed in a DEAE-cellulose column and the bradykinin potentiating activity was found in the second protein peak. Finger-printing of this material showed that the bradykinin potentiating material migrates to the anode, giving two spots when submitted to chromatography, the activity being found in the spot that presents the greatest Rf. The potentiator is destroyed by heating at 97 degrees C, is not dialysable and is destroyed by incubation with pronase. Some of these properties differentiate it from the BPF's from snake venoms. PMID:976731

  1. General characterization of Tityus fasciolatus scorpion venom. Molecular identification of toxins and localization of linear B-cell epitopes.

    PubMed

    Mendes, T M; Guimarães-Okamoto, P T C; Machado-de-Avila, R A; Oliveira, D; Melo, M M; Lobato, Z I; Kalapothakis, E; Chávez-Olórtegui, C

    2015-06-01

    This communication describes the general characteristics of the venom from the Brazilian scorpion Tityus fasciolatus, which is an endemic species found in the central Brazil (States of Goiás and Minas Gerais), being responsible for sting accidents in this area. The soluble venom obtained from this scorpion is toxic to mice being the LD50 is 2.984 mg/kg (subcutaneally). SDS-PAGE of the soluble venom resulted in 10 fractions ranged in size from 6 to 10-80 kDa. Sheep were employed for anti-T. fasciolatus venom serum production. Western blotting analysis showed that most of these venom proteins are immunogenic. T. fasciolatus anti-venom revealed consistent cross-reactivity with venom antigens from Tityus serrulatus. Using known primers for T. serrulatus toxins, we have identified three toxins sequences from T. fasciolatus venom. Linear epitopes of these toxins were localized and fifty-five overlapping pentadecapeptides covering complete amino acid sequence of the three toxins were synthesized in cellulose membrane (spot-synthesis technique). The epitopes were located on the 3D structures and some important residues for structure/function were identified. PMID:25817000

  2. In vivo protection against Tityus serrulatus scorpion venom by antibodies raised against a discontinuous synthetic epitope.

    PubMed

    Duarte, Clara Guerra; Alvarenga, Larissa Magalhães; Dias-Lopes, Camila; Machado-de-Avila, Ricardo Andrés; Nguyen, Christophe; Molina, Frank; Granier, Claude; Chávez-Olórtegui, Carlos

    2010-02-01

    Scorpion stings cause human fatalities in numerous countries. Serotherapy is the only specific means to try to circumvent the noxious effects of venom toxins. TsNTxP is a natural anatoxin from the venom of the scorpion Tityus serrulatus that may be useful to raise therapeutic anti-venom sera. Linear epitopes recognized by anti-TsNTxP antibodies have previously been mapped. Here, we attempted to identify discontinuous epitopes in TsNTxP since neutralizing epitopes are often associated with such complex entities. One hundred and fifty-three octadecapeptides with the general formula (P1)-(Gly-Gly)-(P2) were synthesized by the Spot method on cellulose membranes. P1 and P2 were octapeptides from the TsNTxP N-terminal and C-terminal sections, respectively. Each sequence of eight amino acids was frameshifted in turn by three residues, in order to cover TsNTxP entire sequence. Binding of neutralizing anti-TsNTxP rabbit antibodies to spotted peptides revealed GREGYPADGGGLPDSVKI as the more reactive peptide sequence. This epitope was made from the first eight residues of the protein (GREGYPAD) and from residues 47 to 54 (GLPDSVKI) of the C-terminal part of TsNTxP. BALB/c mice were immunized with synthetic GREGYPADGGGLPDSVKI peptide conjugated to ovalbumin. One week after the last immunization, in vivo protection assays showed that immunized mice could resist a challenge by an amount of T.serrulatus whole venom equivalent to 1.75 LD(100), a dose that killed all control non-immune mice. Based on molecular models of TsNTxP and related Tityus toxins, we found that the above peptide matches with a discontinuous epitope, well exposed at the toxin molecular surface which contains residues known to be important for the bioactivity of toxins. PMID:19948263

  3. Positive inotropic effects of Tityus cambridgei and T. serrulatus scorpion venoms on skeletal muscle.

    PubMed

    Borja-Oliveira, C R; Pertinhez, T A; Rodrigues-Simioni, L; Spisni, A

    2009-04-01

    Toxins that block voltage-dependent K+ channels and those that modify Na+ channel gating exhibit positive inotropic effect on skeletal muscle. We compared the effect of the venom of Tityus cambridgei (Tc) and Tityus serrulatus (Ts) scorpions on mouse diaphragm force, in vitro. In indirect and direct (using D-tubocurarine 7.3 microM) stimulation, Tc, 10microg/mL, increased the contractile force, an effect prevented by tetrodotoxin (TTX) while Ts, 0.5 microg/mL, potentiated only indirectly stimulated diaphragm, thus indicating its activity is mainly mediated through acetylcholine release from nerve terminal. This effect is prevented by TTX and attenuated by the K+ channel opener cromakalim. In conclusion, our data show that while the positive inotropic effect of both venoms appears associated to the activity of Na+ and K+ channels, only Tc venom acts also directly on skeletal muscle. This finding call for further studies on Tc venom to identify the toxin responsible for its direct inotropic activity as it may have clinical applications. PMID:18926933

  4. Efficacy of antivenom therapy for neutralizing circulating venom antigens in patients stung by Tityus serrulatus scorpions.

    PubMed

    De Rezende, N A; Dias, M B; Campolina, D; Chavez-Olortegui, C; Diniz, C R; Amaral, C F

    1995-03-01

    Enzyme-linked immunosorbent assays for detection of Tityus serrulatus venom antigen and of horse anti-T. serrulatus venom antibodies were carried out before antivenom treatment and at 1, 6, 12, and 24 hr after antivenom therapy in 18 patients with systemic manifestations following T. serrulatus scorpion sting. Increased levels of circulating venom antigens were detected in the patients before antivenom treatment, but were no longer detected 1 hr after specific antivenom therapy. High titers of antivenom persisted for at least 24 hr after treatment with antivenom. The evolution of clinical and laboratory manifestations of envenoming showed that vomiting and local pain decreased within 1 hr and hyperglycemia was no longer detected 12 hr after antivenom therapy. The cardiorespiratory manifestations disappeared 6-24 hr after the administration of antivenom and all patients recovered completely. This study demonstrates the efficacy of antivenom therapy in neutralizing circulating venom antigens and supports the prompt administration of a potent antivenom to patients with systemic manifestations of envenoming. PMID:7694971

  5. Clinicopathological investigations on mice envenomed with scorpion venom (Androctonus amoreuxi).

    PubMed

    Hamedy, A F; Kilany, Omnia E; Mohallal, Mahmoud E; Soliman, Belal A; Shoukry, Nahla M; Khaled, Howayda S

    2012-12-01

    The present study assessed the toxicity of Androctonus amoreuxi crude venom on blood and biochemical serum parameters of mice. Adult male Albino mice were divided into three groups, in the control group mice were injected S.C. with saline solution. The second group and the third were injected with the venom S.C. in mice in the following doses 1/4 and 1/2 dose of LD50 respectively. Blood and serum samples were taken after 3 hours, 6 hours, 9 hours, 12 hours, 4 days and 7 days. Hematocrit (Ht), red blood cells (RBC) count, hemoglobin, MCV, MCH & MCHC were performed. Serum biochemical parameters, the levels of total proteins, albumin, globulin, glucose, cholesterol, triglycerides, ALT, AST, ALP, creatinine, uric acid and urea were measured. RBCs, Hob, PCV, MCV, MCH & MCHC showed significant increase, and increase in total protein, albumin and globulin within the experiment. Glucose and cholesterol levels were significantly increase from the beginning. Triglycerides showed significant decrease after 6 hours. Liver enzymes and kidney functions revealed significant changes post-injection. PMID:23469627

  6. Neutralizing effects of Mimosa tenuiflora extracts against inflammation caused by Tityus serrulatus scorpion venom.

    PubMed

    Bitencourt, Mariana Angélica Oliveira; de Souza Lima, Maira Conceição Jerônimo; Torres-Rêgo, Manoela; Fernandes, Júlia Morais; da Silva-Júnior, Arnóbio Antônio; Tambourgi, Denise Vilarinho; Zucolotto, Silvana Maria; de Freitas Fernandes-Pedrosa, Matheus

    2014-01-01

    Scorpion bite represents a significant and serious public health problem in certain regions of Brazil, as well as in other parts of the world. Inflammatory mediators are thought to be involved in the systemic and local immune response induced by Tityus serrulatus scorpion envenomation. The aim of this study was to evaluate the effect of extracts of Mimosa tenuiflora on model envenomation. In mice, the envenomation model is induced by Tityus serrulatus venom. Previous treatment of mice with fractions from M. tenuiflora was able to suppress the cell migration to the peritoneal cavity. The treatment of mice with M. tenuiflora extracts also decreased the levels of IL-6, IL-12, and IL-1β. We concluded that the administration of the extract and fractions resulted in a reduction in cell migration and showed a reduction in the level of proinflammatory cytokines. This study demonstrates, for the first time, the anti-inflammatory effect of aqueous extract from the Mimosa tenuiflora plant on T. serrulatus venom. PMID:25013776

  7. Neutralizing Effects of Mimosa tenuiflora Extracts against Inflammation Caused by Tityus serrulatus Scorpion Venom

    PubMed Central

    Bitencourt, Mariana Angélica Oliveira; Lima, Maira Conceição Jerônimo de Souza; Torres-Rêgo, Manoela; da Silva-Júnior, Arnóbio Antônio; Tambourgi, Denise Vilarinho; Zucolotto, Silvana Maria

    2014-01-01

    Scorpion bite represents a significant and serious public health problem in certain regions of Brazil, as well as in other parts of the world. Inflammatory mediators are thought to be involved in the systemic and local immune response induced by Tityus serrulatus scorpion envenomation. The aim of this study was to evaluate the effect of extracts of Mimosa tenuiflora on model envenomation. In mice, the envenomation model is induced by Tityus serrulatus venom. Previous treatment of mice with fractions from M. tenuiflora was able to suppress the cell migration to the peritoneal cavity. The treatment of mice with M. tenuiflora extracts also decreased the levels of IL-6, IL-12, and IL-1β. We concluded that the administration of the extract and fractions resulted in a reduction in cell migration and showed a reduction in the level of proinflammatory cytokines. This study demonstrates, for the first time, the anti-inflammatory effect of aqueous extract from the Mimosa tenuiflora plant on T. serrulatus venom. PMID:25013776

  8. BmK-YA, an Enkephalin-Like Peptide in Scorpion Venom

    PubMed Central

    Wang, Zhiwei; Zhang, Xiuli; Liang, Xinmiao; Civelli, Olivier

    2012-01-01

    By screening extracts of venom from the Asian scorpion Buthus martensii Karsch (BmK) for their abilities to activate opioid receptors, we have identified BmK-YA, an amidated peptide containing an enkephalin-like sequence. BmK-YA is encoded by a precursor that displays a signal sequence and contains four copies of BmK-YA sequences and four of His4-BmK-YA, all flanked by single amino acid residues. BmK-YA and His4-BmK-YA are amidated and thus fulfill the characteristics expected of bioactive peptides. BmK-YA can activate mammalian opioid receptors with selectivity for the δ subtype while His4-BmK-YA is inactive at opioid receptors. The discovery of BmK-YA suggests that scorpion venom may represent a novel source of bioactive molecules targeting G protein-coupled receptors (GPCRs) and reveal additional insights on the evolution of the opioid precursors. PMID:22792309

  9. Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest.

    PubMed

    Zargan, Jamil; Sajad, Mir; Umar, Sadiq; Naime, Mohammad; Ali, Shakir; Khan, Haider A

    2011-08-01

    The purpose of study was to examine the cytotoxic and anti-cancer properties along with addressing the plausible pathway followed by scorpion venom to reduce cell viability in SH-SY5Y and MCF-7 cells. Following exposure of cells with scorpion venom, cytotoxicity was estimated using MTT and lactate dehydrogenase assays. Apoptotic effects were measured by assessment of mitochondrial membrane potential, reactive nitrogen species, DNA fragmentation, and caspase-3 activity whereas antiproliferative effect was assayed using BrdU incorporation. Our results indicate that scorpion venom causes suppression of proliferation by arresting S-phase and induction of apoptosis through increased nitric oxide production, caspase-3 activity and depolarization of mitochondrial membrane. Induction of apoptosis and arrest of DNA synthesis are critical determinant factors for development of anti cancer drugs. These properties may lead to isolation of effective molecule(s) with potential anticancer activity from scorpion venom of Androctonus crassicauda. PMID:21536027

  10. Variability of Potassium Channel Blockers in Mesobuthus eupeus Scorpion Venom with Focus on Kv1.1

    PubMed Central

    Kuzmenkov, Alexey I.; Vassilevski, Alexander A.; Kudryashova, Kseniya S.; Nekrasova, Oksana V.; Peigneur, Steve; Tytgat, Jan; Feofanov, Alexey V.; Kirpichnikov, Mikhail P.; Grishin, Eugene V.

    2015-01-01

    The lesser Asian scorpion Mesobuthus eupeus (Buthidae) is one of the most widely spread and dispersed species of the Mesobuthus genus, and its venom is actively studied. Nevertheless, a considerable amount of active compounds is still under-investigated due to the high complexity of this venom. Here, we report a comprehensive analysis of putative potassium channel toxins (KTxs) from the cDNA library of M. eupeus venom glands, and we compare the deduced KTx structures with peptides purified from the venom. For the transcriptome analysis, we used conventional tools as well as a search for structural motifs characteristic of scorpion venom components in the form of regular expressions. We found 59 candidate KTxs distributed in 30 subfamilies and presenting the cysteine-stabilized α/β and inhibitor cystine knot types of fold. M. eupeus venom was then separated to individual components by multistage chromatography. A facile fluorescent system based on the expression of the KcsA-Kv1.1 hybrid channels in Escherichia coli and utilization of a labeled scorpion toxin was elaborated and applied to follow Kv1.1 pore binding activity during venom separation. As a result, eight high affinity Kv1.1 channel blockers were identified, including five novel peptides, which extend the panel of potential pharmacologically important Kv1 ligands. Activity of the new peptides against rat Kv1.1 channel was confirmed (IC50 in the range of 1–780 nm) by the two-electrode voltage clamp technique using a standard Xenopus oocyte system. Our integrated approach is of general utility and efficiency to mine natural venoms for KTxs. PMID:25792741

  11. Venom from Opisthacanthus elatus scorpion of Colombia, could be more hemolytic and less neurotoxic than thought.

    PubMed

    Estrada-Gómez, Sebastián; Vargas Muñoz, Leidy Johana; Saldarriaga-Córdoba, Mónica; Quintana Castillo, Juan Carlos

    2016-01-01

    We report the first biochemical, biological, pharmacological and partial proteomic characterization studies of the Opisthancanthus elatus venom (Gervais, 1844) from Colombia. The Reverse Phase High-Performance Liquid Chromatography venom profile showed 28 main well-defined peaks, most eluting between 20 and 45min (18-30% of acetonitrile, respectively). High-resolution mass analysis indicates the presence of 106 components ranging from 806.59742Da to 16849.4139Da. O. elatus venom showed hemolytic activity and hydrolyzed the specific substrate BapNa suggesting the presence of proteins with serine-protease activity. Collected RP-HPLC fractions eluting at 52.6, 55.5, 55.8, 56.2, and 63.9min (PLA2 region between 33 and 40% of acetonitrile), showed hemolytic activity and hydrolyzed the synthetic substrate 4-nitro-3-octanoyloxy-benzoic acid, indicating the presence of compounds with phospholipases A2 activity. These RP-HPLC fractions, showed molecular masses values up to 13978.19546Da, corroborating the possible presence of the mentioned enzymes. Tryptic digestion and MS/MS analysis showed the presence of a phospholipase like fragment, similar to on described in other Opisthacanthus genus studies. No coagulant activity was observed. No larvicidal or antimicrobial activity was observed at concentrations evaluated. Lethal and toxic activity is expected at doses above 100mg/kg, no neurotoxic effects were detected at lower doses. In conclusion, O. elatus exhibits a venom with a predominant phospholipase A2 activity than thought; mammal's neurotoxic activity is expected above the 100mg/kg, which is very high compared to the venom from other neurotoxic scorpions. PMID:26477848

  12. Biochemical profile of dogs experimentally envenomed with Tityus serrulatus scorpion venom.

    PubMed

    Ribeiro, E L; Pinto, M C L; Labarrère, C R; Paes, P R O; Paes-Leme, F O; Chávez-Olórtegui, C; Melo, M M

    2010-06-01

    The aim of this study was to evaluate the canine blood and urinary profiles after envenomation by Tityus serrulatus venom. Twelve dogs were randomly distributed into two equal groups. Control group animals received 0.5 mL phosphate buffered saline (PBS) injected subcutaneously into the internal portion of the left thigh, whilst dogs in the envenomed group were injected with scorpion venom (250 microg/kg in 0.5 mL PBS). No significant alterations were detected in the urine of envenomed dogs. Levels of plasma glucose and serum urea, creatinine, total protein, potassium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), and amylase were determined. Semi-quantitative analysis of serum cardiac troponin I (cTnI) was performed using an immunochromatographic test. The concentrations of cortisol and insulin were determined using commercial radioimmunoassay kits. Increases in serum cortisol levels in experimental group animals coincided with hyperglycaemia and was probably a response to pain. Increased insulin levels were observed during the hyperglycaemic peaks. Envenomed dogs presented discreet increases in ALT, AST and CK, but no alterations in LDH, amylase, cTnI, urea, creatinine and potassium levels were observed. It was concluded that the venom of T. serrulatus induces blood and urinary biochemical changes in dogs. PMID:20060404

  13. A hyaluronidase from Tityus serrulatus scorpion venom: isolation, characterization and inhibition by flavonoids.

    PubMed

    Pessini, A C; Takao, T T; Cavalheiro, E C; Vichnewski, W; Sampaio, S V; Giglio, J R; Arantes, E C

    2001-10-01

    The purification procedure of a hyaluronidase from Tityus serrulatus scorpion venom is described. It involves basically an ion-exchange chromatography on CM-cellulose at pH 7.8 followed by a rechromatography of the active fraction on the same column at pH 4.7. The optima pH and temperature for maximum activity of the isolated enzyme was 6.0 and 40 degrees C, respectively. Its K(M) was 69.7 microg/ml at 37 degrees C and its specific activity was 19,900+/-1,730 turbidity reducing units (TRU)/mg against 845+/-88TRU/mg for the whole desiccated venom, representing a 23- to 24-fold purification range. The hyaluronidase activity of the purified protein (51kDa) was inhibited by some flavonoid compounds. This article also showed that T. serrulatus hyaluronidase affected on the activity of the venom's major toxin, tityustoxin-I (TsTX-I or Ts1), as reflected by alterations in the serum levels of creatine kinase (CK), lactate dehydrogenase (LD) and aspartate aminotransferase (AST) following injection of TsTX-I, in the presence or absence of hyaluronidase. PMID:11478957

  14. The effects of a chactoid scorpion venom and its purified toxins on rat blood pressure and mast cells histamine release.

    PubMed

    Ettinger, Keren; Cohen, Gadi; Momic, Tatjana; Lazarovici, Philip

    2013-08-01

    The effect of the venom of the Chactoid family of scorpions on blood pressure was scantly investigated and was addressed in the present study using the venom of the Israeli scorpion, Scorpio maurus palmatus. Blood pressure in rats was monitored via cannulated femoral artery, while venom and toxins were introduced into femoral vein. Venom injection elicited a biphasic effect, expressed first by a fast and transient hypotensive response, which lasted up to 10 min, followed by a hypertensive response, which lasted up to one hour. It was found that these effects resulted from different venom components. Phospholipase A₂ produced the hypotensive effect, while a non-enzymatic neurotoxic polypeptide fraction produced the hypertensive effect. Surprisingly, the main neurotoxic polypeptide to mice had no effect on blood pressure. In vitro experiments indicated that the hypertensive factors caused histamine release from the peritoneal mast cells, but this effect is assumed to be not relevant to their in vivo effect. In spite of the cytotoxic activity of phospholipase A₂, it did not release histamine. These findings suggest that the effects of venom and isolated fractions on blood pressure parameters are mediated by different mechanisms, which deserve further pharmacological investigation. PMID:23899970

  15. The Effects of a Chactoid Scorpion Venom and Its Purified Toxins on Rat Blood Pressure and Mast Cells Histamine Release

    PubMed Central

    Ettinger, Keren; Cohen, Gadi; Momic, Tatjana; Lazarovici, Philip

    2013-01-01

    The effect of the venom of the Chactoid family of scorpions on blood pressure was scantly investigated and was addressed in the present study using the venom of the Israeli scorpion, Scorpio maurus palmatus. Blood pressure in rats was monitored via cannulated femoral artery, while venom and toxins were introduced into femoral vein. Venom injection elicited a biphasic effect, expressed first by a fast and transient hypotensive response, which lasted up to 10 min, followed by a hypertensive response, which lasted up to one hour. It was found that these effects resulted from different venom components. Phospholipase A2 produced the hypotensive effect, while a non-enzymatic neurotoxic polypeptide fraction produced the hypertensive effect. Surprisingly, the main neurotoxic polypeptide to mice had no effect on blood pressure. In vitro experiments indicated that the hypertensive factors caused histamine release from the peritoneal mast cells, but this effect is assumed to be not relevant to their in vivo effect. In spite of the cytotoxic activity of phospholipase A2, it did not release histamine. These findings suggest that the effects of venom and isolated fractions on blood pressure parameters are mediated by different mechanisms, which deserve further pharmacological investigation. PMID:23899970

  16. Scorpion Venom Heat-Resistant Peptide Attenuates Glial Fibrillary Acidic Protein Expression via c-Jun/AP-1.

    PubMed

    Cao, Zhen; Wu, Xue-Fei; Peng, Yan; Zhang, Rui; Li, Na; Yang, Jin-Yi; Zhang, Shu-Qin; Zhang, Wan-Qin; Zhao, Jie; Li, Shao

    2015-11-01

    Scorpion venom has been used in the Orient to treat central nervous system diseases for many years, and the protein/peptide toxins in Buthus martensii Karsch (BmK) venom are believed to be the effective components. Scorpion venom heat-resistant peptide (SVHRP) is an active component of the scorpion venom extracted from BmK. In a previous study, we found that SVHRP could inhibit the formation of a glial scar, which is characterized by enhanced glial fibrillary acidic protein (GFAP) expression, in the epileptic hippocampus. However, the cellular and molecular mechanisms underlying this process remain to be clarified. The results of the present study indicate that endogenous GFAP expression in primary rat astrocytes was attenuated by SVHRP. We further demonstrate that the suppression of GFAP was primarily mediated by inhibiting both c-Jun expression and its binding with AP-1 DNA binding site and other factors at the GFAP promoter. These results support that SVHRP contributes to reducing GFAP at least in part by decreasing the activity of the transcription factor AP-1. In conclusion, the effects of SVHRP on astrocytes with respect to the c-Jun/AP-1 signaling pathway in vitro provide a practical basis for studying astrocyte activation and inhibition and a scientific basis for further studies of traditional medicine. PMID:26134308

  17. Apoptogenic peptides from Tityus discrepans scorpion venom acting against the SKBR3 breast cancer cell line.

    PubMed

    D'Suze, Gina; Rosales, Arnaldo; Salazar, Víctor; Sevcik, Carlos

    2010-12-01

    Two novel peptides named neopladine 1 and neopladine 2 were purified from Tityus discrepans scorpion venom and found to be active on human breast carcinoma SKBR3 cells. Mass spectrometry molecular masses of neopladine 1 and 2 were 29918 and 30388 Da, respectively. Their N-terminal sequences were determined by Edman degradation. The peptides induced apoptosis of SKBR3 cells but had a negligible effect on non-malignant MA104 monkey kidney cells. Neopladine 1 and 2 induced 6.3 and 4.1% of SKBR3 apoptosis, respectively, in 5 h of exposure; the effect was larger with more prolonged exposures. Inmunohistochemistry showed that neopladines bind to SKBR3 cell surface inducing FasL and BcL-2 expression. PMID:20888852

  18. [Chlorotoxin and related peptides are short insect toxins from scorpion venom].

    PubMed

    Arzamasov, A A; Vasilevskiĭ, A A; Grishin, E V

    2014-01-01

    Scorpion venom is a complex multicomponent mixture of biologically active substances, some of which possess very interesting properties and are used in quite unexpected fields. The family of chlorotoxin (CTX)-like peptides serves a good example. These toxins exhibit insecticidal activity, however, their molecular mechanism of action on insect organism remains elusive. Nevertheless, CTX-like peptides attracted considerable research effort due to their ability to specifically interact with cells of brain tumors, i.e. gliomas. In the future these compounds may considerably aid anticancer therapy. This review summarizes the results obtained during the past 40 years of CTX-like peptides investigation. Both biological function aspects and the applied field related to gliomas are considered. PMID:25898748

  19. Moving pieces in a proteomic puzzle: mass fingerprinting of toxic fractions from the venom of Tityus serrulatus (Scorpiones, Buthidae).

    PubMed

    Pimenta, A M; Stöcklin, R; Favreau, P; Bougis, P E; Martin-Eauclaire, M F

    2001-01-01

    Scorpion venoms are very complex mixtures of molecules, most of which are peptides that display different kinds of biological activity. These venoms have been studied in the light of their pharmacological targets and their constituents are able to bind specifically to a variety of ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins that modulate Na(+), K(+), Ca(++) and Cl(-) currents have been described in scorpion venoms. Mass spectrometry was employed to analyze toxic fractions from the venom of the Brazilian scorpion Tityus serrulatus in order to shed light on the molecular composition of this venom and to facilitate the search for novel pharmacologically active compounds. T. serrulatus venom was first subjected to gel filtration to separate its constituents according to their molecular size. The resultant fractions II and III, which account for 90 and 10% respectively of the whole venom toxic effect, were further analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), on-line liquid chromatography/electrospray mass spectrometry (LC/ESMS) and off-line LC/MALDI-TOFMS in order to establish their mass fingerprints. The molecular masses in fraction II were predominantly between 6500 and 7500 Da. This corresponds to long-chain toxins that mainly act on voltage-gated Na(+) channels. Fraction III is more complex and predominantly contained molecules with masses between 2500 and 5000 Da. This corresponds to the short-chain toxin family, most of which act on K(+) channels, and other unknown peptides. Finally, we were able to measure the molecular masses of 380 different compounds present in the two fractions investigated. To our knowledge, this is the largest number of components ever detected in the venom of a single animal species. Some of the toxins described previously from T. serrulatus venom could be detected by virtue of their molecular masses. The interpretation of this large set of data

  20. Histopathological changes in liver of mice after experimental envenomation with Androctonus amoreuxi scorpion venom.

    PubMed

    Fetaih, Hamdy A; Shoukry, Nahla M; Soliman, Belal A; Mohallal, Mahmoud E; Khaled, Howayda S

    2013-08-01

    A total of 78 adult male Albino mice were divided into thirteen groups (6 mice in each). One served as a control group and the other twelve groups were venom treated groups. The mice of treated groups were injected with 0.1 ml saline solution in which a particular amount of scorpion venom. The first 6 groups were subcutaneously injected with 1/2 LD50 (0.05 microg/g body weight), while the other 6 groups were injected with 1/4 LD 50 (0.025 microg/g body weight) by the same route. The animals from each group were anesthetized with ethyl ether and sacrificed at different time intervals (3, 6, 9, 12 hrs, 4 & 7days post toxin administration). The microscopic examination of liver tissue obtained from envenomed animals showed variable histopathological changes being severely increased with the time interval of envenoming. The most obvious changes in the liver were acute cellular swelling, hydropic degeneration, congestion of central veins and portal blood vessels. Besides, extramedullary hematopoiesis and invaginations in nuclei of hepatic cells, with formation of intranuclear cytoplasmic inclusions were observed. PMID:24260823

  1. Isolation and characterization of a hyaluronidase from the venom of Chinese red scorpion Buthus martensi.

    PubMed

    Feng, Luo; Gao, Rong; Gopalakrishnakone, Ponnampalam

    2008-09-01

    A hyaluronidase, named BmHYA1, was purified from the venom of Chinese red scorpion (Buthus martensi), using successive chromatography. The homogeneity of BmHYA1 was confirmed by SDS-PAGE and MALDI-TOF mass spectrometry. The molecular mass of BmHYA1 was 48,696 Da determined by MALDI-TOF MS. The optimal temperature and pH of BmHYA1 were 50 degrees C and pH 4.5, respectively. It could be inhibited by DTT, Cu(2+), Fe(3+) or heparin, but not Mg(2+), Ca(2+), reduced glutathione, l-cysteine or EDTA. The sequence of thirty N-terminal amino acids of BmHYA1 was obtained by Edman degradation, as TSADF KVVWE VPSIM CSKKF KICVT DLLTS; but no similarity was found to other venom hyaluronidases. Further, BmHYA1 can hydrolyze hyaluronan into relatively smaller oligosaccharides and modulate the expression of CD44 variant in the breast cancer cell line MDA-MB-231. PMID:18611448

  2. Scorpion venom component III inhibits cell proliferation by modulating NF-κB activation in human leukemia cells

    PubMed Central

    SONG, XIANGFENG; ZHANG, GUOJUN; SUN, AIPING; GUO, JIQIANG; TIAN, ZHONGWEI; WANG, HUI; LIU, YUFENG

    2012-01-01

    Scorpion venom contains various groups of compounds that exhibit anticancer activity against a variety of malignancies through a poorly understood mechanism. While the aberrant activation of nuclear factor κB (NF-κB) has been linked with hematopoietic malignancies, we hypothesized that scorpion venom mediates its effects by modulating the NF-κB signaling pathway. In the present study, we examined the effects of scorpion venom component III (SVCIII) on the human leukemia cell lines THP-1 and Jurkat and focused on the NF-κB signaling pathway. Our results showed that SVCIII inhibited cell proliferation, caused cell cycle arrest at G1 phase and inhibited the expression of cell cycle regulatory protein cyclin D1 in a dose-dependent manner in THP-1 and Jurkat cells. SVCIII also suppressed the constitutive NF-κB activation through inhibition of the phosphorylation and degradation of IκBα. NF-κB luciferase reporter activity was also inhibited by SVCIII. Our data suggest that SVCIII, a natural compound, may exert its antiproliferative effects by inhibiting the activation of NF-κB and, thus, has potential use in the treatment of hematopoietic malignancies, alone or in combination with other agents. PMID:23060939

  3. Proteomic analysis of the venom from the scorpion Tityus stigmurus: biochemical and physiological comparison with other Tityus species.

    PubMed

    Batista, C V F; Román-González, S A; Salas-Castillo, S P; Zamudio, F Z; Gómez-Lagunas, F; Possani, L D

    2007-01-01

    The venom from the Brazilian scorpion Tityus stigmurus was fractionated by high performance liquid chromatography (HPLC) and the corresponding components were used for molecular mass determination using electrospray ion trap mass spectrometry. One hundred distinct components were clearly assigned showing molecular masses from 216.5 to 44,800.0 Da. Fifteen new components were isolated and sequenced, four of them to completion: Tst-3 (similar to Na(+) channel specific scorpion toxins), Tst-17 (a K(+) channel blocking peptide similar to Tc1), Tst beta KTx (a peptide with identical sequence as that of TsTX-K beta toxin earlier described to exist in T. serrulatus venom) and finally a novel proline-rich peptide of unknown function. Among the eleven components partially sequenced were two enzymes: hyaluronidase and lysozyme. The first enzyme has a molecular mass of 44,800.0 Da. This enzyme showed high activity against the substrate hyaluronan in vitro. Amino acid sequence of the second enzyme showed that it is similar to other known lysozymes, with similar molecular mass and sequence to that of bona fide lysozymes reported in public protein data banks. Finally, this communication reports a correlation among HPLC retention times and molecular masses of folded scorpion toxins as well as a comparative structural and physiological analysis of components from the venom of several species of the genus Tityus. PMID:17270501

  4. Toxin gamma from Tityus serrulatus scorpion venom plays an essential role in immunomodulation of macrophages.

    PubMed

    Petricevich, Vera L; Hernández Cruz, Anselmo; Coronas, Fredy I V; Possani, Lourival D

    2007-10-01

    Fraction number II obtained from Sephadex G-50 gel filtration of the soluble venom from the Brazilian scorpion Tityus serrulatus (TSV) stimulates macrophage function in vitro. The aim of this study was to identify which one of the several components of this fraction was responsible for the main stimulatory activity on macrophages. This component was identified as sub-fraction II-11, also known by the name of gamma toxin or simply abbreviated Ts1, which stands for toxin 1 of T. serrulatus venom. The effect of Ts1 was analyzed by detection of inflammatory mediators. Several functional bioassays were performed: TNF activity was assayed by measuring its cytotoxicity on L929 cells, whereas IL-1, IL-6, IFN-gamma and IL-10 were assayed by enzyme-linked immunosorbent assay. The levels of NO were evaluated by Griess colorimetric reactions in supernatants of macrophages in culture exposed to Ts1 and compared with FII. Macrophages exposed to Ts1 increase the production of mediators. With respect to the pro-inflammatory cytokines, an increment of IL-1alpha, IL-1beta was observed after 12 h; the maximum levels of IL-6 and TNF were observed after 24 h; the highest levels of IFN-gamma and NO were observed after 72 h. In contrast, the highest levels of anti-inflammatory cytokines such as IL-10 were observed after 120 h. With respect to the balance of pro- and anti-inflammatory cytokines, IL-1alpha/IL-10 and IL-6/IL-10 ratios appear incremented between 12 and 48 h in macrophages exposed to Ts1. IL-1beta/IL-10 and TNF/IL-10 ratios were increased in macrophages exposed to Ts1 for 12 h. IFN-gamma/IL-10 ratios increased up to 48 h, decaying thereafter. Elevated IL-6/TNF ratios were observed up to 24 h. These ratios may possibly reflect the inflammatory status during exposition to the venom. In conclusion, these data indicate that Ts1 has an important immunomodulatory effect on macrophages, and add important knowledge for understanding scorpion envenomation. It also opens the field for

  5. In vitro and in vivo antitumor effects of the Egyptian scorpion Androctonus amoreuxi venom in an Ehrlich ascites tumor model.

    PubMed

    Salem, Mohamed L; Shoukry, Nahla M; Teleb, Wafaa K; Abdel-Daim, Mohamed M; Abdel-Rahman, Mohamed A

    2016-01-01

    Scorpion venom is a highly complex mixture of about 100-700 different components, where peptides are the major constituents with various biological and pharmacological properties including anticancer activities. In this study, anticancer efficacy of the venom of the Egyptian scorpion Androctonus amoreuxi has been evaluated. In vitro, the human breast cancer MCF-7 cell line was treated with the venom and the IC50 was estimated. In vivo studies, Ehrlich ascites carcinoma (EAC) cells were inoculated into CD-1 mice intraperitoneally to form liquid tumor or subcutaneously to form solid tumor and then treated with intraperitoneal injection with venom (0.22 mg/kg) every other day. The total tumor cells in the ascitic fluid and the size of the solid tumor were assessed after 14 and 30 days, respectively. In addition, the mean survival time (MST), body weight, tumor volume, PCV, viability of tumor cells, CBC, AST, ALP, creatinine, oxidative stress biomarkers (GSH, MDA, PCC), tumor marker Ki67, growth factor VEGF and caspase-3 were measured in normal control, EAC control and venom-treated groups (n = 6). Treatment with venom induced anti-tumor effects against liquid and in solid tumors as indicated by a significant (P < 0.05) reduction in tumor volume/size, count of viable EAC cells, expression of Ki67 and VEGF as well as by remarkable increases in MST and caspase-3 expression as compared to non-treated group. Interestingly, the venom restored the altered hematological and biochemical parameters of tumor-bearing animals and significantly increased their life span. These data indicate to (1) the cytotoxic potential effects of A. amoreuxi on tumor cells via anti-proliferative, apoptotic and anti-angiogenic activities; (2) opening a new avenue for further studies on the anti-cancer effects of this agent. PMID:27247867

  6. Venom conjugated polylactide applied as biocompatible material for passive and active immunotherapy against scorpion envenomation.

    PubMed

    Ayari-Riabi, Sana; Trimaille, Thomas; Mabrouk, Kamel; Bertin, Denis; Gigmes, Didier; Benlasfar, Zakaria; Zaghmi, Ahlem; Bouhaouala-Zahar, Balkiss; Elayeb, Mohamed

    2016-04-01

    Scorpion envenoming represents a public health issue in subtropical regions of the world. Treatment and prevention need to promote antitoxin immunity. Preserving antigenic presentation while removing toxin effect remains a major challenge in toxin vaccine development. Among particulate adjuvant, particles prepared with poly (D,L-lactide) polymer are the most extensively investigated due to their excellent biocompatibility and biodegradability. The aim of this study is to develop surfactant-free PLA nanoparticles that safely deliver venom toxic fraction to enhance specific immune response. PLA nanoparticles are coated with AahG50 (AahG50/PLA) and BotG50 (BotG50/PLA): a toxic fraction purified from Androctonus australis hector and Buthus occitanus tunetanus venoms, respectively. Residual toxicities are evaluated following injections of PLA-containing high doses of AahG50 (or BotG50). Immunization trials are performed with the detoxified fraction administered alone without adjuvant. A comparative study of the effect of Freund is also included. The neutralizing capacity of sera is determined in naive mice. Six months later, immunized mice are challenged subcutaneously with increased doses of AahG50. Subcutaneous lethal dose 50 (LD50) of AahG50 and BotG50 is of 575 μg/kg and 1300 μg/kg respectively. By comparison, BotG50/PLA is totally innocuous while 50% of tested mice survive 2875 μg AahG50/kg. Alhydrogel and Freund are not able to detoxify such a high dose. Cross-antigenicity between particulate and soluble fraction is also, ensured. AahG50/PLA and BotG50/PLA induce high antibody levels in mice serum. The neutralizing capacity per mL of anti-venom was 258 μg/mL and 186 μg/mL calculated for anti-AahG50/PLA and anti-BotG50/PLA sera, respectively. Animals immunized with AahG50/PLA are protected against AahG50 injected dose of 3162 μg/kg as opposed all non-immunized mice died at this dose. We find that the detoxification approach based PLA nanoparticles, benefit

  7. Two Biological Active Fractions Isolated from Buthotus schach (BS)Scorpion Venom Examined on Striated Muscle Preparation, In-vitro

    PubMed Central

    Vatanpour, Hossein; Ahmadi, Farhad; Zare Mirakabadi, Abbas; Jalali, Amir

    2012-01-01

    Buthotus schach is one of the most dangerous scorpions in tropical part of Iran. The effects of its crude venom at 1, 3, 10 μg/mL and its obtained fractions by gel filtrations were investigated on neuromuscular transmission. CBC and MHD indirectly and directly stimulated preparations techniques were used to study their possible pre or post junctional activities. At 3 and 10 μg/mL (not at 1 μg/mL), BS venom caused initiall increase in twitch height followed by blockage due to large contraction that responded gradually at the same time. Contracture responses to exogenous Ach (1-2 mM, 30 sec) and Carb (30-40 μM, 60 sec) in the presence of the venom were not increased which does show no anticholinstrease effects. Furthermore Contracture response to KCl (20-40 mM, 30 sec) does changed exposure to venom in CBC preparations. On the other hand the effects of the venom in response to directly stimulated preparations was shallower than in indirect stimulated preparations. So in agreement with KCL response BS venom affects mostly prejunctionally to facilitate the neurotransmitter release rather than postjunctionally effects. To access bioactive components, seven fractions were collected by gel filtrations techniques. Among the fractions F6, LD50=21 μg < F4, LD50= 35.5 μg < Venom LD50= 84 μg per mice were more toxic respectively. Both fractions show the same effects but stronger than venom on twitch height responses in indirectly stimulated CBC preparations. Finally, according to our results venom as well as fractions F4 and F6 act mostly prejunctionally on Ach release. More attempt is carrying out to study their effects on ion channel activities. PMID:24250518

  8. Human bronchial epithelial cells injury and cytokine production induced by Tityus serrulatus scorpion venom: An in vitro study.

    PubMed

    Rigoni, Vera Lucia Silva; Kwasniewski, Fabio H; Vieira, Rodolfo Paula; Linhares, Ingrid Sestrem; da Silva, Joelmir Lucena Veiga; Nogueira-Pedro, Amanda; Zamuner, Stella Regina

    2016-09-15

    Tityus serrulatus is the scorpion specie responsible for the majority of scorpion sting accidents in Brazil. Symptoms of envenomation by Tityus serrulatus range from local pain to severe systemic reactions such as cardiac dysfunction and pulmonary edema. Thus, this study has evaluated the participation of bronchial epithelial cells in the pulmonary effects of Tityus serrulatus scorpion venom (Tsv). Human bronchial epithelial cell line BEAS-2B were utilized as a model target and were incubated with Tsv (10 or 50 μg/mL) for 1, 3, 6 and 24 h. Effects on cellular response of venom-induce cytotoxicity were examined including cell viability, cell integrity, cell morphology, apoptosis/necrosis as well as cell activation through the release of pro-inflammatory cytokines IL-1β, IL-6 and IL-8. Tsv caused a decrease in cell viability at 10 and 50 μg/mL, which was confirmed by lactate dehydrogenase (LDH) measurement. Flow cytometry analyses revealed necrosis as the main cell death pathway caused by Tsv. Furthermore, Tsv induced the release of IL-1β, IL-6 and IL-8. Altogether, these results demonstrate that Tsv induces cytotoxic effects on bronchial epithelial cells, involving necrosis and release of pro-inflammatory cytokines, suggesting that bronchial epithelial cells may play a role in the pulmonary injury caused by Tsv. PMID:27452928

  9. Isolation and characterization of toxic proteins from the venom of the Brazilian scorpion Tityus serrulatus.

    PubMed

    Sampaio, S V; Laure, C J; Giglio, J R

    1983-01-01

    Through gel filtration on Sephadex G-25 and chromatography on CM-cellulose-52 five toxic proteins, electrophoretically pure, were isolated from the venom of the Brazilian scorpion Tityus serrulatus and partially characterized, as follows: 1. Toxin T1 VIII, with 61 amino acid residues, mol. wt 6675 and amino terminal sequence Lys-Glx-Gly-Tyr-Leu-Met-Asx-His-Glx-Gly-Cys-Lys-; 2. Toxin T1VI with amino acid residues, mol. wt. 7549 and amino terminal sequence Gly-His-Phe-Gly-Lys; 3. Toxin T2III(I), with 63 amino acid residues, mol. wt. 7216 and amino terminal sequence Lys-Lys-Asx-Gly-Tyr-Pro-Val-Cys-Cys-Ser-; 4. Toxin T2IV, which is apparently identical to toxin T1VIII above, since it showed the same elution volume in chromatography on CM-cellulose-52, the same N-terminal Lys and the same electrophoretic mobility as T1VIII; 5. Toxin T1IV, a not previously described toxin from the venom of T. serrulatus, with 45 amino acid residues, mol. wt. 5188 and amino terminal sequence Lys-Glx-Gly-Tyr-Leu-, identical to the first five residues of T1VIII, although with a lower molecular weight. The pharmacological study of T1VIII in guinea pig vas deferens showed a pre-junctional sensitizing action, evidenced by a decrease of the dose-response curves to adrenaline and acetylcholine, with no increase of the maximum. This effect may be due to the liberation of noradrenaline. PMID:6857710

  10. Targeting the Ion Channel Kv1.3 with Scorpion Venom Peptides Engineered for Potency, Selectivity, and Half-life

    PubMed Central

    Edwards, Wilson; Fung-Leung, Wai-Ping; Huang, Chichi; Chi, Ellen; Wu, Nancy; Liu, Yi; Maher, Michael P.; Bonesteel, Rachelle; Connor, Judith; Fellows, Ross; Garcia, Elena; Lee, Jerry; Lu, Lu; Ngo, Karen; Scott, Brian; Zhou, Hong; Swanson, Ronald V.; Wickenden, Alan D.

    2014-01-01

    Ion channels are an attractive class of drug targets, but progress in developing inhibitors for therapeutic use has been limited largely due to challenges in identifying subtype selective small molecules. Animal venoms provide an alternative source of ion channel modulators, and the venoms of several species, such as scorpions, spiders and snails, are known to be rich sources of ion channel modulating peptides. Importantly, these peptides often bind to hyper-variable extracellular loops, creating the potential for subtype selectivity rarely achieved with small molecules. We have engineered scorpion venom peptides and incorporated them in fusion proteins to generate highly potent and selective Kv1.3 inhibitors with long in vivo half-lives. Kv1.3 has been reported to play a role in human T cell activation, and therefore, these Kv1.3 inhibitor fusion proteins may have potential for the treatment of autoimmune diseases. Our results support an emerging approach to generating subtype selective therapeutic ion channel inhibitors. PMID:24939846

  11. Characterization of Am IT, an anti-insect β-toxin isolated from the venom of scorpion Androctonus mauretanicus.

    PubMed

    Oukkache, Naoual; ElJaoudi, Rachid; Chgoury, Fatima; Rocha, Marisa Teixeira; Sabatier, Jean-Marc

    2015-06-25

    In the present study, a 'novel' toxin, called Am IT from the venom of scorpion Androctonus mauretanicus is isolated and characterized. A detailed analysis of the action of Am IT on insect axonal sodium currents is reported. Am IT was purified through gel filtration followed by C18 reversed-phase HPLC. Toxicity of Am IT in vivo was assessed on male German cockroach (Blattella germanica) larvae and C57/BL6 mice. Cross-reactivity of Am IT with two β-toxins was evidenced using (125)I-iodinated toxin-based radioimmunoassays with synaptosomal preparations from rat brain. The complete amino acid sequence of Am IT was finally determined by Edman sequencing. Am IT was observed to compete with AaH IT4 purified from the venom of scorpion Androctonus australis in binding assays. It was recognized by an antibody raised against a β-type toxin, which indicated some structural similarity with β-toxins (or related toxin family). The 'novel' toxin exhibited dual activity since it competed with anti-mammal toxins in binding assays as well as showed contracting activity to insect. The toxin competed with radio-labeled β-toxin Css IV by binding to Na(+) channels of rat brain synaptosomes. Analysis of toxin amino acid sequences showed that Am IT shares high structural identity (92%) with AaH IT4. In conclusion, Am IT not only reveals an anti-insect compound properties secreted by 'Old World' scorpions, paralyzing insect larvae by binding to Na(+) channels on larvae's nerve-cell membranes, but also exerts toxic activity in mice, which is similar to anti-mammal toxins from 'New World' scorpions (North and South Americas). Therefore, Am IT appears to be structurally and functionally similar to AaH IT4. PMID:26109302

  12. Characterizing Tityus discrepans scorpion venom from a fractal perspective: Venom complexity, effects of captivity, sexual dimorphism, differences among species.

    PubMed

    D'Suze, Gina; Sandoval, Moisés; Sevcik, Carlos

    2015-12-15

    A characteristic of venom elution patterns, shared with many other complex systems, is that many their features cannot be properly described with statistical or euclidean concepts. The understanding of such systems became possible with Mandelbrot's fractal analysis. Venom elution patterns were produced using the reversed phase high performance liquid chromatography (HPLC) with 1 mg of venom. One reason for the lack of quantitative analyses of the sources of venom variability is parametrizing the venom chromatograms' complexity. We quantize this complexity by means of an algorithm which estimates the contortedness (Q) of a waveform. Fractal analysis was used to compare venoms and to measure inter- and intra-specific venom variability. We studied variations in venom complexity derived from gender, seasonal and environmental factors, duration of captivity in the laboratory, technique used to milk venom. PMID:26415902

  13. Scorpions: A Presentation

    PubMed Central

    Goyffon, Max; Tournier, Jean-Nicolas

    2014-01-01

    Scorpions, at least the species of the family Buthidæ whose venoms are better known, appear as animals that have evolved very little over time. The composition of their venoms is relatively simple as most toxins have a common structural motif that is found in other venoms from primitive species. Moreover, all the scorpion venom toxins principally act on membrane ionic channels of excitable cells. The results of recent works lead to the conclusion that in scorpions there is a close relationship between venomous function and innate immune function both remarkably efficient. PMID:25133517

  14. Isolation of toxin TsTX-VI from Tityus serrulatus scorpion venom. Effects on the release of neurotransmitters from synaptosomes.

    PubMed

    Sampaio, S V; Coutinho-Netto, J; Arantes, E C; Marangoni, S; Oliveira, B; Giglio, J R

    1996-07-01

    A detailed procedure for the purification of Tityustoxin-VI, TsTX-VI, from Tityus serrulatus scorpion venom is described. For comparative purposes, a second toxin, CM-VI, obtained from the same fractionation procedure, was analyzed in parallel. Typical biochemical parameters, such as electrophoretic migration, mol.weight, amino acid composition and N-terminal sequence (first 42 amino acid residues out of a total of approx. 60) were determined for both. Our data showed that CM-VI is identical or extremely homologous to gamma-toxin (TsTX-I), the highly toxic major toxin from T. serrulatus venom. TsTX-VI was less toxic, although still effective at inducing an allergic reaction, lacrymation and contraction of the hind legs of mice. Both toxins produced a dose dependent release of the neurotransmitters glutamic acid and gamma aminobutyric acid from rat brain synaptosomes, this effect being blocked by tetrodotoxin. PMID:8843341

  15. An in vitro comparative study upon the toxic properties of the venoms from Hemiscorpius lepturus, Androctonus crassicauda and Mesobuthus eupeus scorpions.

    PubMed

    Khodadadi, Ali; Pipelzadeh, Mohammad Hassan; Vazirianzadeh, Babak; Pipelzadeh, Mahsa; Sharifat, Mossa

    2012-09-01

    The aim of the present study was to compare the toxic effects of the venoms from Hemiscorpius lepturus (H. lepturus), Androctonus crassicauda (A. crassicauda) and Mesobuthus eupeus (M. eupeus). For this purpose, three in vitro models were employed to compare the toxic effects of various concentrations of the venoms from these three scorpions, namely: hemolytic potential using human RBCs, phospholipase activity using Saubouraud's dextrose agar (SDA) supplemented with 2% egg yolk and lactate dehydrogenase (LDH) enzyme releasing effect using K562 leukemia cell line. In addition, the neutralizing effectiveness of the antivenom against these toxic properties was assessed. The results showed that, unlike the venoms from A. crassicauda and M. eupeus, the venom from H. lepturus produced dose-dependent lysis of human RBCs and showed phospholipase activity. However, all the tested venoms showed variable degrees of LDH releasing properties. The venom from H. lepturus had highest and the venom from M. eupeus had the lowest LDH releasing effect. The antivenom effectively inhibited all the tested toxicities. In conclusion, these results suggest that the venoms from the studied scorpions have variable toxic properties, which may explain the underlying reason for the differences in their clinical manifestations. In addition, the antivenom was effective in neutralizing all the tested toxic effects. PMID:22569320

  16. Comprehensive analysis of venom from the scorpion Centruroides tecomanus reveals compounds with antimicrobial, cytotoxic, and insecticidal activities.

    PubMed

    Valdez-Velazquéz, L L; Romero-Gutierrez, M T; Delgado-Enciso, I; Dobrovinskaya, O; Melnikov, V; Quintero-Hernández, V; Ceballos-Magaña, S G; Gaitan-Hinojosa, M A; Coronas, F I; Puebla-Perez, A M; Zamudio, F; De la Cruz-García, I; Vázquez-Vuelvas, O F; Soriano-Hernandez, A D; Possani, L D

    2016-08-01

    Centruroides tecomanus is a medically important scorpion of the state of Colima (Mexico). This communication reports the identification of venom components of this scorpion with biological activity over insects/crickets (Acheta domestica), crustaceans/fresh water shrimps (Cambarellus montezumae), and mammalians/mice (Mus musculus, strain CD1). It also describes the pharmacological effects on cell lines in culture (L5178Y cells, HeLa cells, HuTu cells and Jurkat E6-1 cells), as well as on several types of bacteria (see below). The soluble venom of this scorpion was fractionated by high-performance liquid chromatography (HPLC) and collected separately in twelve independent fractions collected over 60 min run (5 min time apart each other). The HPLC components of fraction VII were lethal to all three species used for assay. The IVth fraction had a toxic effect on freshwater shrimps. In this species, fractions VI, VII and VIII were all lethal. For crickets, fractions V and VI were toxic and fraction VII was lethal. In mouse, the lethal components were found in fraction VII, whereas fraction VIII was toxic, but not lethal, at the doses assayed. The molecular weight of peptides from the various group of fractions were identified by mass spectrometry determination. Components lethal to mice showed molecular weights from 7013 to 7487 Da. Two peptides were obtained in homogeneous form and shown to be lethal to the three species of animal used for assay. The soluble venom tested on L5178Y cell line survival was shown to be cytotoxic, at 10-100 μg/mL concentration, when compared to control murine splenocytes (p = 0.007). The soluble venom applied to Hela, Hutu and Jurkat cell lines did not show cytotoxic effects at these concentrations. On the contrary, it seems to have a proliferative effect. However the HPLC fractions I, III, VI and XII do have a cytotoxic effect on Jurkat E06-1 cells in culture at 200 μg/mL concentration. The antimicrobial activity of the venom

  17. Tityus perijanensis González-Sponga (Scorpiones, Buthidae): molecular assessment of its geographical distribution and venom lethality of Venezuelan populations.

    PubMed

    Borges, Adolfo; Rojas-Runjaic, Fernando J M

    2007-12-01

    An extensive field survey allowed us to expand the geographical distribution of the scorpion Tityus perijanensis in the Perijá range, western Zulia State, Venezuela, including areas where adult cases of severe scorpionism have been reported. 16S ribosomal RNA (rRNA) gene sequencing, DL(50) determination, and native PAGE suggest low genetic and venom proteomic divergence across the distribution range. The results also indicate phylogenetic divergence between T. perijanensis and T. discrepans, the species prevalent in northcentral Venezuela. T. perijanensis venom lethality (0.91-0.94 mg/kg) is comparable to that of the Brazilian T. serrulatus and ranks highest among toxic Venezuelan Tityus studied so far. The data indicate that the Perijá range should be included amongst the endemic areas of scorpionism of Venezuela and Colombia. PMID:17868753

  18. A bradykinin-potentiating peptide (peptide K12) isolated from the venom of Egyptian scorpion Buthus occitanus.

    PubMed

    Meki, A R; Nassar, A Y; Rochat, H

    1995-01-01

    A nontoxic peptide with bradykinin-potentiating activity was isolated from the dialyzed venom of the scorpion Buthus occitanus by reverse-phase high performance liquid chromatography (RP-HPLC). The pharmacological activity of the peptide was bioassayed by its ability to potentiate added bradykinin (BK) on the isolated guinea pig ileum as well as the isolated rat uterus for contraction. Moreover, the peptide potentiates in vivo the depressor effect of BK on arterial blood pressure in the normotensive anesthetized rat. Chemical characterization of the peptide was also performed. The amino acid composition of the peptide showed 21 amino acid residues per molecule including three proline residues. The amino acid sequence of the purified peptide was confirmed by mass spectrometry. Either N- or C-terminal ends were free. The sequence does not show a homology with bradykinin-potentiating peptides isolated from either scorpion or snake venoms. Furthermore, we did not find a significant sequence homology between the sequence of the isolated peptide and any of proteins or peptides in GenPro or NBRF data banks. The peptide also inhibited angiotensin-converting enzyme (ACE), and could not serve as substrate for the enzyme. It could be concluded that the mechanism of bradykinin-potentiating peptide (BPP) activity may be due to ACE inhibition. PMID:8745044

  19. Vietnamese Heterometrus laoticus scorpion venom: evidence for analgesic and anti-inflammatory activity and isolation of new polypeptide toxin acting on Kv1.3 potassium channel.

    PubMed

    Hoang, Anh N; Vo, Hoang D M; Vo, Nguyen P; Kudryashova, Kseniya S; Nekrasova, Oksana V; Feofanov, Alexey V; Kirpichnikov, Mikhail P; Andreeva, Tatyana V; Serebryakova, Marina V; Tsetlin, Victor I; Utkin, Yuri N

    2014-01-01

    The scorpion Heterometrus laoticus (Scorpionidae) inhabits Indochinese peninsula and is widely distributed in South-West Vietnam. Since no human fatalities caused by H. laoticus stings were reported, no systematic characterization of the venom was earlier done. In this study we report on biological activity of the venom from H. laoticus caught in Vietnamese province An Giang. The venom manifested a very low acute toxicity with LD50 of about 190 mg/kg body weight in mice at subcutaneous (s.c.) injection and 12 mg/kg at intravenous injection. The venom analgesic effects using tail immersion and writhing tests as well as anti-inflammatory effect using carrageenan test were analyzed at doses of 9.5 and 19 mg/kg at s.c. injections. It was found that at two doses tested H. laoticus venom showed both anti-nociceptive and anti-inflammatory activity. The venom was fractionated by means of gel-filtration and reversed-phase HPLC. As a result several polypeptide toxins were isolated and new toxin hetlaxin was identified. Its amino acid sequence was determined and binding to the extracellular vestibule of the K⁺-conducting pore of Kv1.1 and Kv1.3 potassium channels was studied. Hetlaxin belongs to the scorpion alpha-toxin family and is the first toxin isolated from H. laoticus venom which possesses high affinity (K(i) 59 nM) to Kv1.3 potassium channel. PMID:24189292

  20. Individual variability in Tityus serrulatus (Scorpiones, Buthidae) venom elicited by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    PubMed

    Pimenta, Adriano M C; De Marco Almeida, Flavia; de Lima, Maria Elena; Martin-Eauclaire, Marie France; Bougis, Pierre E

    2003-01-01

    Venom variability in specimens of Tityus serrulatus scorpion was assessed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) analyses. An expanded time lag venom extraction protocol was carried out using ten scorpions to study individual variations that might occur due to different rates in protein expression and/or processing. The first extraction of venom was made from the animals after 20 days of starvation, which allowed the venom gland to be filled up. The second extraction event was carried out 24 hours after the first one. The third was 8 days after the first extraction. By means of MALDI-TOF analyses, important variations were observed in venoms of a single specimen extracted at different times, especially in latter extraction events. These variations are most probably related to dynamics in cell gland production. Since T. serrulatus is a parthenogenetic species, sexual variations are naturally excluded and we did not expect intra-specific variations, which was confirmed. Knowledge of individual venom variability is extremely important to avoid misunderstandings in the use of venom proteomic analysis as a taxonomic tool. PMID:12590389

  1. Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of mitochondria and reduces S-phase population in human breast cancer cells (MCF-7).

    PubMed

    Zargan, Jamil; Umar, Sadiq; Sajad, Mir; Naime, M; Ali, Shakir; Khan, Haider A

    2011-12-01

    Venom of some species of scorpions induces apoptosis and arrests proliferation in cancer cells. This is an important property that can be harnessed and can lead to isolation of compounds of therapeutic importance in cancer research. Cytotoxicity was investigated using MTT reduction and confirmed with lactate dehydrogenase release following venom exposure. Apoptosis was evaluated with determination of mitochondrial membrane potential, reactive nitrogen species assay, measurement of Caspase-3 activity and DNA fragmentation analysis. To confirm that venom can inhibit DNA synthesis in proliferating breast cancer cells, immunocytochemical detection of BrdU incorporation was done. Our results demonstrated that venom of Odontobuthus doriae not only induced apoptosis but lead to the inhibition of DNA synthesis in human breast cancer cells (MCF-7). Cell viability decreased with parallel increment of LDH release in dose dependent manner after treatment with varying concentrations of venom. Moreover, venom depleted cellular antioxidants evidenced by depression of GSH and Catalases and concomitantly increased reactive nitrogen intermediates (RNI). These events were related to the depolarization of mitochondria and associated Caspase-3 activation following venom treatment in a concentration dependent manner. Finally, fragmentation of nuclear DNA following venom treatment confirmed the apoptotic property of the said venom. These results suggest that venom of O. doriae can be potential source for the isolation of effective anti-proliferative and apoptotic molecules. PMID:21945044

  2. Influence of post-starvation extraction time and prey-specific diet in Tityus serrulatus scorpion venom composition and hyaluronidase activity.

    PubMed

    Pucca, Manuela Berto; Amorim, Fernanda Gobbi; Cerni, Felipe Augusto; Bordon, Karla de Castro Figueiredo; Cardoso, Iara Aimê; Anjolette, Fernando Antonio Pino; Arantes, Eliane Candiani

    2014-11-01

    The role of diet in venom composition has been a topic of intense research interest. This work presents evidence that the variation in the venom composition from the scorpion Tityus serrulatus (Ts) is closely associated with post-starvation extraction time and prey-specific diet. The scorpions were fed with cockroach, cricket, peanut beetle or giant Tenebrio. The venoms demonstrated a pronounced difference in the total protein and toxins composition, which was evaluated by electrophoresis, reversed-phase chromatography, densitometry, hyaluronidase activity and N-terminal sequencing. Indeed, many toxins and peptides, such as Ts1, Ts2, Ts4, Ts5, Ts6, Ts15, Ts19 frag. II, hypotensins 1 and 3, PAPE peptide and peptide 9797 (first described in Ts venom), were all identified in different proportions in the analyzed Ts venoms. This study is pioneer on assessing the influence of the starvation time and the prey diet on hyaluronidase activity as well as to describe a modification of Tricine-gel-electrophoresis to evaluate this enzyme activity. Altogether, this study reveal a large contribution of the extraction time and diet on Ts venom variability as well as present a background to recommend the cockroach diet to obtain higher protein content and the cricket diet to obtain higher hyaluronidase specific activity. PMID:25199494

  3. In vitro studies with renal proximal tubule cells show direct cytotoxicity of Androctonus australis hector scorpion venom triggered by oxidative stress, caspase activation and apoptosis.

    PubMed

    Saidani, Chanez; Hammoudi-Triki, Djelila; Laraba-Djebari, Fatima; Taub, Mary

    2016-09-15

    Scorpion envenomation injures a number of organs, including the kidney. Mechanisms proposed to explain the renal tubule injury include direct effects of venom on tubule epithelial cells, as well as indirect effects of the autonomic nervous system, and inflammation. Here, we report direct effects of Androctonus australis hector (Aah) scorpion venom on the viability of Renal Proximal Tubule (RPT) cells in vitro, unlike distal tubule and collecting duct cells. Extensive NucGreen nuclear staining was observed in immortalized rabbit RPT cells following treatment with Aah venom, consistent with cytotoxicity. The involvement of oxidative stress is supported by the observations that 1) anti-oxidants mitigated the Aah venom-induced decrease in the number of viable RPT cells, and 2) Aah venom-treated RPT cells were intensively stained with the CellROX(®) Deep Red reagent, an indicator of Reactive Oxygen Species (ROS). Relevance to normal RPT cells is supported by the red fluorescence observed in Aah venom treated primary rabbit RPT cell cultures following their incubation with the Flica reagent (indicative of caspase activation and apoptosis), and the green fluorescence of Sytox Green (indicative of dead cells). PMID:27470530

  4. Molecular systematics of the neotropical scorpion genus Tityus (Buthidae): the historical biogeography and venom antigenic diversity of toxic Venezuelan species.

    PubMed

    Borges, Adolfo; Bermingham, Eldredge; Herrera, Nimiadina; Alfonzo, Marcelo J; Sanjur, Oris I

    2010-01-01

    We provide a mitochondrial DNA-based phylogenetic hypothesis for 21 Tityus species collected in Venezuela, Trinidad, Brazil and Panama, including 12 taxa known to be toxic to humans. Our phylogenetic reconstruction is based on 850 nucleotides of the combined cytochrome oxidase subunit I and 16S rRNA genes for most species, and centered on Venezuelan scorpions owing to the detailed taxonomic and biogeographic information available for Tityus in this region. The principal phylogenetic result was the strong support for mtDNA clades representing geographical groupings associated with the Perijá mountain range, the Mérida Andes, or the central and eastern coastal ranges in Venezuela, suggesting that vicariance has been a potent force in the diversification of local scorpions. Venezuelan Tityus species have been organized by González-Sponga into three artificial morphological groups, "androcottoides", "discrepans", and "nematochirus", based on the array of ventral carinae in metasomal segments II-IV. We also incorporated a fourth morphological group ("Tityus clathratus"), recently documented in Venezuela. Our results do not support the clustering of the species in the "androcottoides" and "discrepans" morphological groups, which include the majority of taxa of medical importance, but provided support for the "nematochirus" species group. T. clathratus was found to cluster with the Brazilian T. serrulatus and T. bahiensis. Divergence times of most clades are consistent with major events in the geological history of northern Venezuela and suggest that many Venezuelan Tityus species formed in the late Miocene and the Pliocene. In turn, we used the Tityus mtDNA phylogeny to determine the potential utility of phylogenetic systematics to predict Tityus venom antigenic reactivity by testing the recognition of T. nororientalis, T. discrepans, T. zulianus, T. perijanensis, and T. clathratus venoms by anti-T. discrepans horse antibodies. Cross-reactivity was significantly

  5. Standardization of an enzyme linked immunosorbent assay (ELISA) for detecting circulating toxic venom antigens in patients stung by the scorpion Tityus serrulatus.

    PubMed

    de Rezende, N A; Dias, M B; Campolina, D; Chavéz-Olortegui, C; Amaral, C F

    1995-01-01

    The sensitivity and specificity of an enzyme-linked immunosorbent assay (ELISA) for the detection of circulating antigens from toxic components of Tityus serrulatus scorpion venom was determined in patients stung by T. serrulatus before antivenom administration. Thirty-seven patients were classified as mild cases and 19 as moderate or severe cases. The control absorbance in the venom assay was provided by serum samples from 100 individuals of same socioeconomic group and geographical area who had never been stung by scorpions or treated with horse antisera. The negative cutoff value (mean + 2 SD) corresponded to a venom concentration of 4.8 ng/ml. Three out of the 100 normal sera were positive, resulting in a specificity of 97%. The sensitivity of the ELISA when all cases of scorpion sting were included was 39.3%. When mild cases were excluded, the sensitivity increased to 94.7%. This study showed that this ELISA can be used for the detection of circulating venom toxic antigens in patients with systemic manifestations following. T. serrulatus sting but cannot be used for clinical studies in mild cases of envenoming since the test does not discriminate mild cases from control patients. PMID:7569644

  6. Effects of tachykinin NK1 or PAF receptor blockade on the lung injury induced by scorpion venom in rats.

    PubMed

    Matos, I M; Souza, D G; Seabra, D G; Freire-Maia, L; Teixeira, M M

    1999-07-01

    In cases of severe human scorpion envenoming, lung injury is a common finding and frequently the cause of death. In the rat, two distinct mechanisms account for oedema following the intravenous injection of the venom -- acute left ventricular failure resulting from a massive release of catecholamines and an increase in pulmonary vascular permeability. In the present work, we investigated the effects of a tachykinin NK1 receptor antagonist (CP96,345, the dihydrochloride salt of (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)methyl)-1-az abicycol[2.2.2]octan-3-amine) and its 2 R-3 R inactive enantiomer (CP96,344) on the acute lung injury induced by the i.v. injection of Tityus serrulatus venom in rats. Lung injury was assessed by evaluating the extravasation of Evans blue dye in the bronchoalveolar lavage fluid and in the lung of venom-treated and control animals. The effects of the platelet-activating factor (PAF) receptor antagonist WEB2170 (2-methyl-1-phenylimidazol[4,5c]pyridine) were evaluated for comparison. The i.v. injection of the venom induced the extravasation of Evans blue in the bronchoalveolar lavage fluid and into the left lung. Pretreament with the tachykinin NK1 receptor antagonist CP96,345, but not CP96,344, inhibited Evans blue dye extravasation in the bronchoalveolar lavage fluid and in the lung by 96% and 86%, respectively. The PAF receptor antagonist WEB2170 inhibited the increase in vascular permeability in the bronchoalveolar lavage fluid by 60% and had no effect on the extravasation to the lung parenchyma of venom-injected animals. In addition to abrogating lung injury, pretreatment of rats with CP96,345, but not CP96,344 or WEB2170, decreased by 70% the mortality induced by the venom. This is the first study to show the relevance of the tachykinin NK1 receptor in mediating lung injury and mortality in animals injected with the neurotoxic T. serrulatus venom. Blockade of the tachykinin NK1 receptor may represent an important strategy in

  7. Structural characterization of a novel peptide with antimicrobial activity from the venom gland of the scorpion Tityus stigmurus: Stigmurin.

    PubMed

    de Melo, Edinara Targino; Estrela, Andréia Bergamo; Santos, Elizabeth Cristina Gomes; Machado, Paula Renata Lima; Farias, Kleber Juvenal Silva; Torres, Taffarel Melo; Carvalho, Enéas; Lima, João Paulo Matos Santos; Silva-Júnior, Arnóbio Antonio; Barbosa, Euzébio Guimarães; Fernandes-Pedrosa, Matheus de Freitas

    2015-06-01

    A new antimicrobial peptide, herein named Stigmurin, was selected based on a transcriptomic analysis of the Brazilian yellow scorpion Tityus stigmurus venom gland, an underexplored source for toxic peptides with possible biotechnological applications. Stigmurin was investigated in silico, by circular dichroism (CD) spectroscopy, and in vitro. The CD spectra suggested that this peptide interacts with membranes, changing its conformation in the presence of an amphipathic environment, with predominance of random coil and beta-sheet structures. Stigmurin exhibited antibacterial and antifungal activity, with minimal inhibitory concentrations ranging from 8.7 to 69.5μM. It was also showed that Stigmurin is toxic against SiHa and Vero E6 cell lines. The results suggest that Stigmurin can be considered a potential anti-infective drug. PMID:25805002

  8. Neuroprotection by scorpion venom heat resistant peptide in 6-hydroxydopamine rat model of early-stage Parkinson's disease.

    PubMed

    Yin, Sheng-Ming; Zhao, Dan; Yu, De-Qin; Li, Sheng-Long; An, Dong; Peng, Yan; Xu, Hong; Sun, Yi-Ping; Wang, Dong-Mei; Zhao, Jie; Zhang, Wan-Qin

    2014-12-25

    Neuroprotective effect of scorpion venom on Parkinson's disease (PD) has already been reported. The present study was aimed to investigate whether scorpion venom heat resistant peptide (SVHRP) could attenuate ultrastructural abnormalities in mitochondria and oxidative stress in midbrain neurons of early-stage PD model. The early-stage PD model was established by injecting 6-hydroxydopamine (6-OHDA) (20 μg/3 μL normal saline with 0.1% ascorbic acid) into the striatum of Sprague Dawley (SD) rats unilaterally. The rats were intraperitoneally administered with SVHRP (0.05 mg/kg per day) or vehicle (saline) for 1 week. Two weeks after 6-OHDA treatment, the rats received behavior tests for validation of model. Three weeks after 6-OHDA injection, the immunoreactivity of dopaminergic neurons were detected by immunohistochemistry staining, and the ultrastructure of neuronal mitochondria in midbrain was observed by electron microscope. In the meantime, the activities of monoamine oxidase-B (MAO-B), superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the mitochondria of the midbrain neurons, as well as the inhibitory ability of hydroxyl free radical and the antioxidant ability in the serum, were measured by corresponding kits. The results showed that 6-OHDA reduced the optical density of dopaminergic neurons, induced damage of mitochondrial ultrastructure of midbrain neurons, decreased SOD activity, increased MAO-B activity and MDA content, and reduced the antioxidant ability of the serum. SVHRP significantly reversed the previous harmful effects of 6-OHDA in early-stage PD model. These findings indicate that SVHRP may contribute to neuroprotection by preventing biochemical and ultrastructure damage changes which occur during early-stage PD. PMID:25516514

  9. Cloning and characterization of BmK86, a novel K{sup +}-channel blocker from scorpion venom

    SciTech Connect

    Mao, Xin; Cao, Zhijian; Yin, Shijin; Ma, Yibao; Wu, Yingliang; Li, Wenxin . E-mail: liwxlab@whu.edu.cn

    2007-09-07

    Scorpion venom represents a tremendous hitherto unexplored resource for understanding ion channels. BmK86 is a novel K{sup +}-channel toxin gene isolated from a cDNA library of Mesobuthus martensii Karsch, which encodes a signal peptide of 22 amino acid residues and a mature toxin of 35 residues with three disulfide bridges. The genomic sequence of BmK86 consists of two exons disrupted by an intron of 72 bp. Comparison with the other scorpion toxins BmK86 shows low sequence similarity. The GST-BmK86 fusion protein was successfully expressed in Escherichia coli. The fusion protein was cleaved by enterokinase and the recombinant BmK86 was purified by HPLC. Using whole-cell patch-clamp recording, the recombinant BmK86 was found to inhibit the potassium current of mKv1.3 channel expressed in COS7 cells. These results indicated that BmK86 belongs to a representative member of a novel subfamily of {alpha}-KTxs. The systematic number assigned to BmK86 is {alpha}-KTx26.1.

  10. Effects of Tityus serrulatus scorpion venom and its toxin TsTX-V on neurotransmitter uptake in vitro

    SciTech Connect

    Cecchini, Alessandra L.; Vasconcelos, Flavio; Giglio, Jose Roberto; Arantes, Eliane Candiani . E-mail: ecabraga@fcfrp.usp.br

    2006-12-01

    Scorpion neurotoxins targeting the Na{sub v} channel can be classified into two classes: {alpha}- and {beta}-neurotoxins and are reported as highly active in mammalian brain. In this work, we evaluate the effects of Tityus serrulatus venom (Ts venom) and its {alpha}-neurotoxin TsTX-V on {gamma}-aminobutyric acid (GABA), dopamine (DA) and glutamate (Glu) uptake in isolated rat brain synaptosomes. TsTX-V was isolated from Ts venom by ion exchange chromatography followed by reverse-phase (C18) high-performance liquid chromatography. Neither Ts venom nor TsTX-V was able to affect {sup 3}H-Glu uptake. On the other hand, Ts venom (0.13 {mu}g/mg) significantly inhibited both {sup 3}H-GABA and {sup 3}H-DA uptake ({approx} 50%). TsTX-V showed IC{sub 5} values of 9.37 {mu}M and 22.2 {mu}M for the inhibition of {sup 3}H-GABA and {sup 3}H-DA uptake, respectively. These effects were abolished by pre-treatment with tetrodotoxin (TTX, 1 {mu}M), indicating the involvement of voltage-gated Na{sup +} channels in this process. In the absence of Ca{sup 2+}, and at low Ts venom concentrations, the reduction of {sup 3}H-GABA uptake was not as marked as in the presence of Ca{sup 2+}. TsTX-V did not reduce {sup 3}H-GABA uptake in COS-7 cells expressing the GABA transporters GAT-1 and GAT-3, suggesting that this toxin indirectly reduces the transport. The reduced {sup 3}H-GABA uptake by synaptosomes might be due to rapid cell depolarization as revealed by confocal microscopy of C6 glioma cells. Thus, TsTX-V causes a reduction of {sup 3}H-GABA and {sup 3}H-DA uptake in a Ca{sup 2+}-dependent manner, not directly affecting GABA transporters, but, in consequence of depolarization, involving voltage-gated Na{sup +} channels.

  11. The anti-proliferative effects and mechanisms of low molecular weight scorpion BmK venom peptides on human hepatoma and cervical carcinoma cells in vitro.

    PubMed

    Li, Weiling; Xin, Yi; Chen, Yang; Li, Xinli; Zhang, Cuili; Bai, Jing; Yuan, Jieli

    2014-10-01

    Peptides from scorpion venom have been previously studied for use in the prevention and treatment of various types of cancer in folk medicine. The present study investigated the anti-proliferative effects and mechanisms of the low molecular weight (~3 kDa) BmK scorpion venom peptides (LMWSVP) on human hepatoma (SMMC 7721) and cervical carcinoma (HeLa) cells. The data indicated that LMWSVP inhibited the growth of SMMC 7721 cells, but had no effect on the growth of HeLa cells. SMMC 7721 cells were more sensitive, with a higher affinity, to LMWSVP as compared with HeLa cells. In addition, LMWSVP induced apoptosis of SMMC 7721 cells by upregulating the expression of caspase-3 and downregulating the expression of Bcl-2. These data provide an experimental basis for further purification and application of LMWSVP for use as an anti-tumor drug in clinical trials. PMID:25202371

  12. Characterization of the venom from the Australian scorpion Urodacus yaschenkoi: Molecular mass analysis of components, cDNA sequences and peptides with antimicrobial activity.

    PubMed

    Luna-Ramírez, Karen; Quintero-Hernández, Veronica; Vargas-Jaimes, Leonel; Batista, Cesar V F; Winkel, Kenneth D; Possani, Lourival D

    2013-03-01

    The Urodacidae scorpions are the most widely distributed of the four families in Australia and represent half of the species in the continent, yet their venoms remain largely unstudied. This communication reports the first results of a proteome analysis of the venom of the scorpion Urodacus yaschenkoi performed by mass fingerprinting, after high performance liquid chromatography (HPLC) separation. A total of 74 fractions were obtained by HPLC separation allowing the identification of approximately 274 different molecular masses with molecular weights varying from 287 to 43,437 Da. The most abundant peptides were those from 1 K Da and 4-5 K Da representing antimicrobial peptides and putative potassium channel toxins, respectively. Three such peptides were chemically synthesized and tested against Gram-positive and Gram-negative bacteria showing minimum inhibitory concentration in the low micromolar range, but with moderate hemolytic activity. It also reports a transcriptome analysis of the venom glands of the same scorpion species, undertaken by constructing a cDNA library and conducting random sequencing screening of the transcripts. From the resultant cDNA library 172 expressed sequence tags (ESTs) were analyzed. These transcripts were further clustered into 120 unique sequences (23 contigs and 97 singlets). The identified putative proteins can be assorted in several groups, such as those implicated in common cellular processes, putative neurotoxins and antimicrobial peptides. The scorpion U. yaschenkoi is not known to be dangerous to humans and its venom contains peptides similar to those of Opisthacanthus cayaporum (antibacterial), Scorpio maurus palmatus (maurocalcin), Opistophthalmus carinatus (opistoporines) and Hadrurus gerstchi (scorpine-like molecules), amongst others. PMID:23182832

  13. Scorpion venom heat-resistant peptide (SVHRP) enhances neurogenesis and neurite outgrowth of immature neurons in adult mice by up-regulating brain-derived neurotrophic factor (BDNF).

    PubMed

    Wang, Tao; Wang, Shi-Wei; Zhang, Yue; Wu, Xue-Fei; Peng, Yan; Cao, Zhen; Ge, Bi-Ying; Wang, Xi; Wu, Qiong; Lin, Jin-Tao; Zhang, Wan-Qin; Li, Shao; Zhao, Jie

    2014-01-01

    Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2'-dexoxyuridine (BrdU)-positive cells, BrdU-positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of SVHRP

  14. Scorpion Venom Heat-Resistant Peptide (SVHRP) Enhances Neurogenesis and Neurite Outgrowth of Immature Neurons in Adult Mice by Up-Regulating Brain-Derived Neurotrophic Factor (BDNF)

    PubMed Central

    Zhang, Yue; Wu, Xue-Fei; Peng, Yan; Cao, Zhen; Ge, Bi-Ying; Wang, Xi; Wu, Qiong; Lin, Jin-Tao; Zhang, Wan-Qin; Li, Shao; Zhao, Jie

    2014-01-01

    Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2’-dexoxyuridine (BrdU)-positive cells, BrdU- positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of

  15. Effects of Buthus martensii (Karsch) scorpion venom on sodium currents in rat anterior pituitary (GH3/B6) cells.

    PubMed

    Bauer, C K; Krylov, B; Zhou, P A; Schwarz, J R

    1992-01-01

    The effects of two fractions (II, containing anti-insect toxins, and III, containing eight anti-mammal toxins) isolated from the venom of the Old World scorpion Buthus martensii (Karsch) on Na+ currents of rat anterior pituitary cells (GH3/B6 cells) were investigated using the whole-cell configuration of the patch clamp technique. Fraction II induced a temporary, and fraction III a permanent increase of the Na+ current amplitude. Application of each of the venom fractions resulted in a flattening of the curve relating steady state Na+ inactivation to membrane potential. In addition, the two fractions had specific effects. Fraction II shifted the voltage dependence of Na+ current activation by -42 mV, and the voltage dependence of Na+ inactivation by -25 mV in the absence of a conditioning depolarizing pre-pulse. Slowing of Na+ inactivation was most prominent at negative membrane potentials, resulting in a steady Na+ inward current at the holding potential of -80 mV. Fraction III induced a pronounced slowing of Na+ inactivation leading to an increase of peak Na+ currents and to incomplete steady state Na+ inactivation even at positive membrane potentials. PMID:1325686

  16. StCT2, a new antibacterial peptide characterized from the venom of the scorpion Scorpiops tibetanus.

    PubMed

    Cao, Luyang; Li, Zhongjie; Zhang, Ruhong; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

    2012-08-01

    Bacterial infection poses an increasing threat to global public health and new types of antibacterial agents are urgently needed to respond to the threat. Scorpion venom contains series of bioactive peptides, among which antibacterial peptide is an important part. Herein, a new antimicrobial peptide StCT2 was characterized from the venomous gland cDNA library of the Scorpiops tibetanus. The full-length cDNA of StCT2 is 369 nucleotides encoding the precursor that contains a putative 24 residues signal peptide, a presumed 14 residues mature peptide, and a putative 37 residues acidic propeptide at the C-terminus. The minimal inhibition concentrations (MICs) of StCT2 for Staphylococcus aureus were 6.25-25μg/ml, including antibiotic-resistant strains such as methicillin resistant S. aureus (MRSA). StCT2 was further found to show high in vivo antimicrobial activity by an S. aureus infection mouse model. StCT2 exerted its antimicrobial activity via a rapid bactericidal mechanism. Taken together, these results demonstrate the efficacy and general mechanism of StCT2 antimicrobial action and the therapeutic potential of StCT2 as a new antimicrobial peptide. PMID:22542475

  17. Modular Organization of α-Toxins from Scorpion Venom Mirrors Domain Structure of Their Targets, Sodium Channels*

    PubMed Central

    Chugunov, Anton O.; Koromyslova, Anna D.; Berkut, Antonina A.; Peigneur, Steve; Tytgat, Jan; Polyansky, Anton A.; Pentkovsky, Vladimir M.; Vassilevski, Alexander A.; Grishin, Eugene V.; Efremov, Roman G.

    2013-01-01

    To gain success in the evolutionary “arms race,” venomous animals such as scorpions produce diverse neurotoxins selected to hit targets in the nervous system of prey. Scorpion α-toxins affect insect and/or mammalian voltage-gated sodium channels (Navs) and thereby modify the excitability of muscle and nerve cells. Although more than 100 α-toxins are known and a number of them have been studied into detail, the molecular mechanism of their interaction with Navs is still poorly understood. Here, we employ extensive molecular dynamics simulations and spatial mapping of hydrophobic/hydrophilic properties distributed over the molecular surface of α-toxins. It is revealed that despite the small size and relatively rigid structure, these toxins possess modular organization from structural, functional, and evolutionary perspectives. The more conserved and rigid “core module” is supplemented with the “specificity module” (SM) that is comparatively flexible and variable and determines the taxon (mammal versus insect) specificity of α-toxin activity. We further show that SMs in mammal toxins are more flexible and hydrophilic than in insect toxins. Concomitant sequence-based analysis of the extracellular loops of Navs suggests that α-toxins recognize the channels using both modules. We propose that the core module binds to the voltage-sensing domain IV, whereas the more versatile SM interacts with the pore domain in repeat I of Navs. These findings corroborate and expand the hypothesis on different functional epitopes of toxins that has been reported previously. In effect, we propose that the modular structure in toxins evolved to match the domain architecture of Navs. PMID:23637230

  18. A scorpion venom peptide fraction induced prostaglandin biosynthesis in guinea pig kidneys: incorporation of 14C-linoleic acid.

    PubMed

    el-Saadani, Muhammad A

    2004-01-01

    A peptide fraction isolated from the venom of the Egyptian scorpion Buthus occitanus was proved to have a bradykinin- potentiating activity. In vivo and in vitro modes of action of the isolated bradykinin-potentiating peptide (BPP) on kidneys of guinea pigs were investigated. Animals received five successive i.p. doses of the scorpion BPP (1 microg/g body weight) at one-week intervals. The control animals were i.p. injected with saline solution only. In vivo experiments showed a significant increase in renal tissue PGE(2) content and lipid peroxides of the treated guinea pigs compared to the control animals (p < 0.05). Nonsignificant changes were detected in the levels of tissue c-AMP and 5-nucleotidase activity (p > 0.05) of the treated animals, while the changes in c-GMP and c-AMP/c-GMP ratio were both significant (p < 0.05). In vitro experiments demonstrated enhanced capacity of guinea pig-renal tissue to convert (14)C-linoleic acid to its metabolites, 6-keto-PGF(1)alpha, PGF(2)alpha, PGE(2), TxB(2), PGD(2), and arachidonic acid, in response to the added PBP (1 microg/ml) and bradykinin (1 microg/ml). This enhanced response was abolished upon the addition of 1 microg/ml of BK-inhibitor (D-Arg- [Hyp(3), Thi(5,6), Phe(7)]). The capacity for labeled metabolites recovery in BPP treated renal tissue was 19.78%, while it was 13.00% in the basal control. The total increase that evoked by BPP was 62.78%. The results clearly indicate that the isolated BPP induced prostaglandin biosynthesis, which may trigger enhanced glomerular filtration in guinea pigs. PMID:14999016

  19. Study of severe scorpion envenoming following subcutaneous venom injection into dogs: Hemodynamic and concentration/effect analysis.

    PubMed

    Elatrous, Souheil; Ouanes-Besbes, Lamia; Ben Sik-Ali, Habiba; Hamouda, Zineb; BenAbdallah, Saoussen; Tilouche, Nejla; Jalloul, Faten; Fkih-Hassen, Mohamed; Dachraoui, Fahmi; Ouanes, Islem; Abroug, Fekri

    2015-09-15

    To evaluate the dose-effects of Androctonus australis hector (Aah) venom injected subcutaneously on hemodynamics and neurohormonal secretions, 10 anesthetized and ventilated mongrel dogs, were split in two groups (n = 5/group). Subcutaneous injection was done with either 0.2 mg/kg or 0.125 mg/kg of the purified G50 scorpion toxic fraction. Hemodynamic parameters using right heart catheter were recorded and plasma concentrations of catecholamine, troponin, and serum toxic fraction were measured sequentially from baseline to 120 min. We identified the dose of toxic fraction evoking characteristic hemodynamic perturbation of severe envenomation, the time-lapse to envenomation, and the associated plasma level. The injection of 0.125 mg/kg toxic fraction was not associated with significant variations in hemodynamic parameters, whereas the 0.2 mg/kg dose caused envenomation characterized by significant increase in plasma catecholamines, increased pulmonary artery occluded pressure, mean arterial pressure, and systemic vascular resistance (p < 0.05), in association with sustained decline in cardiac output (p < 0.001). Envenomation occurred by the 30th minute, and the corresponding concentration of toxic fraction was 1.14 ng/ml. The current experiment allowed the identification of the sub-lethal dose (0.2 mg/kg) of the toxic fraction of Aah administered by the subcutaneous route. Two parameters with potential clinical relevance were also uncovered: the time-lapse to envenomation and the corresponding concentration of toxic fraction. PMID:26166304

  20. Opposing roles of LTB4 and PGE2 in regulating the inflammasome-dependent scorpion venom-induced mortality.

    PubMed

    Zoccal, Karina F; Sorgi, Carlos A; Hori, Juliana I; Paula-Silva, Francisco W G; Arantes, Eliane C; Serezani, Carlos H; Zamboni, Dario S; Faccioli, Lúcia H

    2016-01-01

    Tityus serrulatus sting causes thousands of deaths annually worldwide. T. serrulatus-envenomed victims exhibit local or systemic reaction that culminates in pulmonary oedema, potentially leading to death. However, the molecular mechanisms underlying T. serrulatus venom (TsV) activity remain unknown. Here we show that TsV triggers NLRP3 inflammasome activation via K(+) efflux. Mechanistically, TsV triggers lung-resident cells to release PGE2, which induces IL-1β production via E prostanoid receptor 2/4-cAMP-PKA-NFκB-dependent mechanisms. IL-1β/IL-1R actions account for oedema and neutrophil recruitment to the lungs, leading to TsV-induced mortality. Inflammasome activation triggers LTB4 production and further PGE2 via IL-1β/IL-1R signalling. Activation of LTB4-BLT1/2 pathway decreases cAMP generation, controlling TsV-induced inflammation. Exogenous administration confirms LTB4 anti-inflammatory activity and abrogates TsV-induced mortality. These results suggest that the balance between LTB4 and PGE2 determines the amount of IL-1β inflammasome-dependent release and the outcome of envenomation. We suggest COX1/2 inhibition as an effective therapeutic intervention for scorpion envenomation. PMID:26907476

  1. Scorpion venom activates natural killer cells in hepatocellular carcinoma via the NKG2D-MICA pathway.

    PubMed

    Chen, Han; Zhidan, Wang; Xia, Ren; Zhaoxia, Wang; Qing, Jia; Qiang, Guo; Haipeng, Yin; Hengxiao, Wang

    2016-06-01

    Previous studies have demonstrated that polypeptides extracted from scorpion venom (PESV) inhibited cell proliferation in several tumors, however, the effect on dysfunctional and exhausted natural killer cells which contribute to tumor escape from immune surveillance remain to be elucidated. In this study, we determined the effect of PESV on NK infiltration into H22 cells orthotopic transplantation tumors and on the expression of MHC class I chain-related proteins A (MICA) in HepG2 cells. We found that tumor growth in mice was significantly inhibited by PESV and the survival time of tumor-bearing mice treated with PESV was significantly prolonged. Moreover, levels of tumor-infiltrating NK cells, NKG2D protein, perforin and granzyme B mRNA were significantly increased in the group treated with PESV compared with the tumor-bearing control group. In addition, In addition, up-regulation of MICA by PESV enhances the susceptibility of HepG2 cells to NK lysis in vitro. These results indicate that the inhibitory effects of PESV on hepatic carcinoma are likely mediated by up-regulation of NK cell activity via the MICA-NKG2D pathway. PMID:27089390

  2. Effects of Scorpion venom peptide B5 on hematopoietic recovery in irradiated mice and the primary mechanisms.

    PubMed

    Wang, Caixia; Zhou, Meixun; Li, Ting; Wang, Yan; Xing, Baiqian; Kong, Tianhan; Dong, Weihua

    2015-01-01

    Scorpion venom peptide B5 (SVP-B5) stimulates recovery of hematopoiesis after exposure to radiation. However, its radioprotective effects and mechanisms are still unclear. The aim of this study was to investigate the effects of SVP-B5 on hematopoietic recovery in mice after total body irradiation (TBI) at a dose of 7.5 Gy and 6 Gy and to explore the possible primary mechanisms. SVP-B5 at a dose of 2.63 μg/kg significantly reduced the mortality rate of mice after TBI (p < 0.05). It showed markedly protective effects against radiation injury. SVP-B5 also significantly increased the number of bone marrow nucleated cells (BMNCs) and increased the colony forming unit (CFU) number in irradiated mice, accelerated the post-irradiation recovery of peripheral blood leukocytes and platelets in mice. SVP-B5 treatment markedly reduced the Reactive Oxygen Species (ROS) levels in BMNCs after TBI, reduced γH2AX levels, and decreased the relative expression levels of p16 and p21 mRNA at day 14 (d14) after irradiation. Our study indicated that SVP-B5 could partially mitigate radiation-induced DNA damage, enhance the post-radiation hematopoietic recovery, and improve the survival rate probably through the ROS-p16/p21 pathway. PMID:26482294

  3. Effects of Scorpion venom peptide B5 on hematopoietic recovery in irradiated mice and the primary mechanisms

    PubMed Central

    Wang, Caixia; Zhou, Meixun; Li, Ting; Wang, Yan; Xing, Baiqian; Kong, Tianhan; Dong, Weihua

    2015-01-01

    Scorpion venom peptide B5 (SVP-B5) stimulates recovery of hematopoiesis after exposure to radiation. However, its radioprotective effects and mechanisms are still unclear. The aim of this study was to investigate the effects of SVP-B5 on hematopoietic recovery in mice after total body irradiation (TBI) at a dose of 7.5Gy and 6Gy and to explore the possible primary mechanisms. SVP-B5 at a dose of 2.63 μg/kg significantly reduced the mortality rate of mice after TBI (p < 0.05). It showed markedly protective effects against radiation injury. SVP-B5 also significantly increased the number of bone marrow nucleated cells (BMNCs) and increased the colony forming unit (CFU) number in irradiated mice, accelerated the post-irradiation recovery of peripheral blood leukocytes and platelets in mice. SVP-B5 treatment markedly reduced the Reactive Oxygen Species (ROS) levels in BMNCs after TBI, reduced γH2AX levels, and decreased the relative expression levels of p16 and p21 mRNA at day14 (d14) after irradiation. Our study indicated that SVP-B5 could partially mitigate radiation-induced DNA damage, enhance the post-radiation hematopoietic recovery, and improve the survival rate probably through the ROS-p16/p21 pathway. PMID:26482294

  4. Opposing roles of LTB4 and PGE2 in regulating the inflammasome-dependent scorpion venom-induced mortality

    PubMed Central

    Zoccal, Karina F.; Sorgi, Carlos A.; Hori, Juliana I.; Paula-Silva, Francisco W. G.; Arantes, Eliane C.; Serezani, Carlos H.; Zamboni, Dario S.; Faccioli, Lúcia H.

    2016-01-01

    Tityus serrulatus sting causes thousands of deaths annually worldwide. T. serrulatus-envenomed victims exhibit local or systemic reaction that culminates in pulmonary oedema, potentially leading to death. However, the molecular mechanisms underlying T. serrulatus venom (TsV) activity remain unknown. Here we show that TsV triggers NLRP3 inflammasome activation via K+ efflux. Mechanistically, TsV triggers lung-resident cells to release PGE2, which induces IL-1β production via E prostanoid receptor 2/4-cAMP-PKA-NFκB-dependent mechanisms. IL-1β/IL-1R actions account for oedema and neutrophil recruitment to the lungs, leading to TsV-induced mortality. Inflammasome activation triggers LTB4 production and further PGE2 via IL-1β/IL-1R signalling. Activation of LTB4-BLT1/2 pathway decreases cAMP generation, controlling TsV-induced inflammation. Exogenous administration confirms LTB4 anti-inflammatory activity and abrogates TsV-induced mortality. These results suggest that the balance between LTB4 and PGE2 determines the amount of IL-1β inflammasome-dependent release and the outcome of envenomation. We suggest COX1/2 inhibition as an effective therapeutic intervention for scorpion envenomation. PMID:26907476

  5. Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion.

    PubMed

    Dardevet, Lucie; Rani, Dipti; Aziz, Tarek Abd El; Bazin, Ingrid; Sabatier, Jean-Marc; Fadl, Mahmoud; Brambilla, Elisabeth; De Waard, Michel

    2015-04-01

    Chlorotoxin is a small 36 amino-acid peptide identified from the venom of the scorpion Leiurus quinquestriatus. Initially, chlorotoxin was used as a pharmacological tool to characterize chloride channels. While studying glioma-specific chloride currents, it was soon discovered that chlorotoxin possesses targeting properties towards cancer cells including glioma, melanoma, small cell lung carcinoma, neuroblastoma and medulloblastoma. The investigation of the mechanism of action of chlorotoxin has been challenging because its cell surface receptor target remains under questioning since two other receptors have been claimed besides chloride channels. Efforts on chlorotoxin-based applications focused on producing analogues helpful for glioma diagnosis, imaging and treatment. These efforts are welcome since gliomas are very aggressive brain cancers, close to impossible to cure with the current therapeutic arsenal. Among all the chlorotoxin-based strategies, the most promising one to enhance patient mean survival time appears to be the use of chlorotoxin as a targeting agent for the delivery of anti-tumor agents. Finally, the discovery of chlorotoxin has led to the screening of other scorpion venoms to identify chlorotoxin-like peptides. So far several new candidates have been identified. Only detailed research and clinical investigations will tell us if they share the same anti-tumor potential as chlorotoxin. PMID:25826056

  6. Chlorotoxin: A Helpful Natural Scorpion Peptide to Diagnose Glioma and Fight Tumor Invasion

    PubMed Central

    Dardevet, Lucie; Rani, Dipti; Abd El Aziz, Tarek; Bazin, Ingrid; Sabatier, Jean-Marc; Fadl, Mahmoud; Brambilla, Elisabeth; De Waard, Michel

    2015-01-01

    Chlorotoxin is a small 36 amino-acid peptide identified from the venom of the scorpion Leiurus quinquestriatus. Initially, chlorotoxin was used as a pharmacological tool to characterize chloride channels. While studying glioma-specific chloride currents, it was soon discovered that chlorotoxin possesses targeting properties towards cancer cells including glioma, melanoma, small cell lung carcinoma, neuroblastoma and medulloblastoma. The investigation of the mechanism of action of chlorotoxin has been challenging because its cell surface receptor target remains under questioning since two other receptors have been claimed besides chloride channels. Efforts on chlorotoxin-based applications focused on producing analogues helpful for glioma diagnosis, imaging and treatment. These efforts are welcome since gliomas are very aggressive brain cancers, close to impossible to cure with the current therapeutic arsenal. Among all the chlorotoxin-based strategies, the most promising one to enhance patient mean survival time appears to be the use of chlorotoxin as a targeting agent for the delivery of anti-tumor agents. Finally, the discovery of chlorotoxin has led to the screening of other scorpion venoms to identify chlorotoxin-like peptides. So far several new candidates have been identified. Only detailed research and clinical investigations will tell us if they share the same anti-tumor potential as chlorotoxin. PMID:25826056

  7. Antimicrobial/cytolytic peptides from the venom of the North African scorpion, Androctonus amoreuxi: biochemical and functional characterization of natural peptides and a single site-substituted analog.

    PubMed

    Almaaytah, Ammar; Zhou, Mei; Wang, Lei; Chen, Tianbao; Walker, Brian; Shaw, Chris

    2012-06-01

    The venoms of scorpions are complex cocktails of polypeptide toxins that fall into two structural categories: those that contain cysteinyl residues with associated disulfide bridges and those that do not. As the majority of lethal toxins acting upon ion channels fall into the first category, most research has been focused there. Here we report the identification and structural characterization of two novel 18-mer antimicrobial peptides from the venom of the North African scorpion, Androctonus amoreuxi. Named AamAP1 and AamAP2, both peptides are C-terminally amidated and differ in primary structure at just two sites: Leu-->Pro at position 2 and Phe-->Ile at position 17. Synthetic replicates of both peptides exhibited a broad-spectrum of antimicrobial activity against a Gram-positive bacterium (Staphylococcus aureus), a Gram-negative bacterium (Escherichia coli) and a yeast (Candida albicans), at concentrations ranging between 20 μM and 150 μM. In this concentration range, both peptides produced significant degrees of hemolysis. A synthetic replicate of AamAP1 containing a single substitution (His-->Lys) at position 8, generated a peptide (AamAP-S1) with enhanced antimicrobial potency (3-5 μM) against the three test organisms and within this concentration range, hemolytic effects were negligible. In addition, this His-->Lys variant exhibited potent growth inhibitory activity (ID(50) 25-40 μm) against several human cancer cell lines and endothelial cells that was absent in both natural peptides. Natural bioactive peptide libraries, such as those that occur in scorpion venoms, thus constitute a unique source of novel lead compounds with drug development potential whose biological properties can be readily manipulated by simple synthetic chemical means. PMID:22484288

  8. Scorpion sting nephropathy

    PubMed Central

    Prabhu, Chaitanya

    2011-01-01

    Scorpion envenomations are ubiquitous, but nephropathy is a rare manifestation, reported mainly from the Middle East and North Africa. Rapid venom redistribution from blood, delayed excretion from the kidneys, direct toxicity of venom enzymes, cytokine release and afferent arteriolar constriction have been seen in experimental animals. Haemoglobinuria, acute tubular necrosis, interstitial nephritis and haemolytic–uraemic syndrome have been documented in human victims of scorpion envenomation. Epidemiology, venom components and toxins, effects on the laboratory mammals especially the kidneys and reports of renal failure in humans are reviewed in this article. PMID:25984198

  9. Effects of Tityus serrulatus scorpion venom on lung mechanics and inflammation in mice.

    PubMed

    Paneque Peres, Ana Claudia; Nonaka, Paula Naomi; de Carvalho, Paulo de Tarso Camillo; Toyama, Marcos Hikari; Silva, Cesar Augusto Melo e; Vieira, Rodolfo de Paula; Dolhnikoff, Marisa; Zamuner, Stella Regina; de Oliveira, Luis Vicente Franco

    2009-06-01

    The present study evaluated the effects of an intramuscular injection of Tityus serrulatus venom (TsV) (0.67 miocrog/g) on lung mechanics and lung inflammation at 15, 30, 60 and 180 min after inoculation. TsV inoculation resulted in increased lung elastance when compared with the control group (p < 0.001); these values were significantly higher at 60 min than at 15 and 180 min (p < 0.05). Resistive pressure (DeltaP1) values decreased significantly at 30, 60 and 180 min after TsV injection (p < 0.001). TsV inoculation resulted in increased lung inflammation, characterised by an increased density of mononuclear cells at 15, 30, 60 and 180 min after TsV injection when compared with the control group (p < 0.001). TsV inoculation also resulted in an increased pulmonary density of polymorphonuclear cells at 15, 30 and 60 min following injection when compared to the control group (p < 0.001). In conclusion, T. serrulatus venom leads to acute lung injury, characterised by altered lung mechanics and increased pulmonary inflammation. PMID:19470319

  10. Cationicity-enhanced analogues of the antimicrobial peptides, AcrAP1 and AcrAP2, from the venom of the scorpion, Androctonus crassicauda, display potent growth modulation effects on human cancer cell lines.

    PubMed

    Du, Qiang; Hou, Xiaojuan; Ge, Lilin; Li, Renjie; Zhou, Mei; Wang, Hui; Wang, Lei; Wei, Minjie; Chen, Tianbao; Shaw, Chris

    2014-01-01

    The non disulphide-bridged peptides (NDBPs) of scorpion venoms are attracting increased interest due to their structural heterogeneity and broad spectrum of biological activities. Here, two novel peptides, named AcrAP1 and AcrAP2, have been identified in the lyophilised venom of the Arabian scorpion, Androctonus crassicauda, through "shotgun" molecular cloning of their biosynthetic precursor-encoding cDNAs. The respective mature peptides, predicted from these cloned cDNAs, were subsequently isolated from the same venom sample using reverse phase HPLC and their identities were confirmed by use of mass spectrometric techniques. Both were found to belong to a family of highly-conserved scorpion venom antimicrobial peptides - a finding confirmed through the biological investigation of synthetic replicates. Analogues of both peptides designed for enhanced cationicity, displayed enhanced potency and spectra of antimicrobial activity but, unlike the native peptides, these also displayed potent growth modulation effects on a range of human cancer cell lines. Thus natural peptide templates from venom peptidomes can provide the basis for rational analogue design to improve both biological potency and spectrum of action. The diversity of such templates from such natural sources undoubtedly provides the pharmaceutical industry with unique lead compounds for drug discovery. PMID:25332684

  11. Subtype-selective activation of K(v)7 channels by AaTXKβ₂₋₆₄, a novel toxin variant from the Androctonus australis scorpion venom.

    PubMed

    Landoulsi, Zied; Miceli, Francesco; Palmese, Angelo; Amoresano, Angela; Marino, Gennaro; El Ayeb, Mohamed; Taglialatela, Maurizio; Benkhalifa, Rym

    2013-11-01

    K(v)7.4 channel subunits are expressed in central auditory pathways and in inner ear sensory hair cells and skeletal and smooth muscle cells. Openers of K(v)7.4 channels have been suggested to improve hearing loss, systemic or pulmonary arterial hypertension, urinary incontinence, gastrointestinal and neuropsychiatric diseases, and skeletal muscle disorders. Scorpion venoms are a large source of peptides active on K⁺ channels. Therefore, we have optimized a combined purification/screening procedure to identify specific modulator(s) of K(v)7.4 channels from the venom of the North African scorpion Androctonus australis (Aa). We report the isolation and functional characterization of AaTXKβ₂₋₆₄, a novel variant of AaTXKβ₁₋₆₄, in a high-performance liquid chromatography fraction from Aa venom (named P8), which acts as the first peptide activator of K(v)7.4 channels. In particular, in both Xenopus oocytes and mammalian Chinese hamster ovary cells, AaTXKβ₂₋₆₄, but not AaTXKβ₁₋₆₄, hyperpolarized the threshold voltage of current activation and increased the maximal currents of heterologously expressed K(v)7.4 channels. AaTXKβ₂₋₆₄ also activated K(v)7.3, K(v)7.2/3, and K(v)7.5/3 channels, whereas homomeric K(v)1.1, K(v)7.1, and K(v)7.2 channels were unaffected. We anticipate that these results may prove useful in unraveling the novel biologic roles of AaTXKβ₂₋₆₄-sensitive K(v)7 channels and developing novel pharmacologic tools that allow subtype-selective targeting of K(v)7 channels. PMID:24019223

  12. Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus).

    PubMed

    Alves, Renata S; Ximenes, Rafael M; Jorge, Antonio R C; Nascimento, Nilberto R F; Martins, René D; Rabello, Marcelo M; Hernandes, Marcelo Z; Toyama, Daniela O; Toyama, Marcos H; Martins, Alice M C; Havt, Alexandre; Monteiro, Helena S A

    2013-11-01

    Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityus serrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64 Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1 μg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60 min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1 μg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C. PMID:23911732

  13. Apoptosis induction in human leukemic cells by a novel protein Bengalin, isolated from Indian black scorpion venom: through mitochondrial pathway and inhibition of heat shock proteins.

    PubMed

    Gupta, Shubho Das; Gomes, Antony; Debnath, Anindita; Saha, Archita; Gomes, Aparna

    2010-01-27

    Scorpion venom possesses protein toxins having numerous biological activities, some of which are potentially anticancerous. Previously we had reported antiproliferative activity of the venom of Indian black scorpion, Heterometrus bengalensis Koch. Here we have isolated and purified a novel protein named Bengalin (72kDa) from the venom, responsible for antiproliferative and apoptogenic activities against human leukemic cells U937 (histiocytic lymphoma) and K562 (chronic myelogenous leukemia). N-terminal sequence of first 20 amino acids of Bengalin was G-P-L-T-I-L-H-I-N-D-V-H-A-A/R-F-E-Q/G-F/G-N-T. Bengalin induced cell growth inhibition at IC(50) values of 3.7 and 4.1 microg/ml for U937 and K562 cells respectively did not significantly affect normal human lymphocytes. Inhibition of U937 and K562 cell proliferation occurred by apoptosis as evidenced from damaged nuclei, cell cycle arrest at sub G1 phase, increase of early apoptotic cells, augmentation of DNA fragmentation and also a reduction of telomerase activity. Further insights revealed that Bax:Bcl2 ratio was elevated after Bengalin treatment. Moreover Bengalin elicited loss of mitochondrial membrane potential (MMP) which commenced cytochrome c release in cytosol, decreased heat shock protein (HSP) 70 and 90 expression, activated caspase-9, caspase-3 and induced poly(ADP-ribose) polymerase (PARP) cleavage. We have also determined that HSP70 and 90 inhibitions correlated with Bengalin induced antiproliferation, caspase-3 upregulation, apoptogenesis and increased DNA fragmentation. These results hypothesize that Bengalin might provide a putative molecular mechanism for their anticancer effect on human leukemic cells which might be mediated by mitochondrial death cascade. Inhibition of HSPs might also play a crucial role in induction of apoptosis. PMID:19913524

  14. Molecular basis for the cross-reactivity of antibodies elicited by a natural anatoxin with alpha- and beta-toxins from the venom of Tityus serrulatus scorpion.

    PubMed

    Chavez-Olortegui, Carlos; Molina, Franck; Granier, Claude

    2002-03-01

    A non-toxic protein (TsNTxP) isolated from the venom of the noxious scorpion Tityus serrulatus (Ts) induces polyclonal antibodies cross-reactive with several toxins from the venom, in sharp contrast to anti-toxin antibodies which are toxin specific. To try to uncover the molecular basis for these unusual properties, peptide scanning experiments were performed and indicated that the N- and C-terminal parts of TsNTxP enclose continuous epitopes (residues 1-15 and 47-61). Antibodies raised against peptides corresponding to these two regions were found to have neutralizing properties against a mixture of all toxic proteins from the T. serrulatus venom, indicating that residues 1-15 and 47-61 correspond to neutralizing epitopes. The identification of key antigenic residues within these two epitopes revealed that several of them are well conserved in the amino-acid sequences of the three main toxins (Ts II, Ts IV and Ts VII) from the venom: Glu 3, Tyr 5, Asp 8, Asp 50, Trp 55 and Lys 61. A single key-residue (Glu 58) is unique to TsNTxP. By using homology modeling, a model of the three-dimensional structure of TsNTxP was obtained. The antigenically important residues from TsNTxP were found to be surface exposed, with five of them clustered on the facet of the protein reported to enclose the active site of toxins. Residues equivalent to the seven key-residues of the anatoxin were also found to be exposed in the active toxins from T. serrulatus venom. These results show that antibodies elicited by the non-toxic protein TsNTxP recognized, within the N- and C-terminal parts of toxins of T. serrulatus, conserved and surface exposed residues which might also be involved in the toxic action of the proteins. PMID:11922945

  15. Purification and N-terminal sequence of a serine proteinase-like protein (BMK-CBP) from the venom of the Chinese scorpion (Buthus martensii Karsch).

    PubMed

    Gao, Rong; Zhang, Yong; Gopalakrishnakone, Ponnampalam

    2008-08-01

    A serine proteinase-like protein was isolated from the venom of Chinese red scorpion (Buthus martensii Karsch) by combination of gel filtration, ion-exchange and reveres-phase chromatography and named BMK-CBP. The apparent molecular weight of BMK-CBP was identified as 33 kDa by SDS-PAGE under non-reducing condition. The sequence of N-terminal 40 amino acids was obtained by Edman degradation. The sequence shows highest similarity to proteinase from insect source. When tested with commonly used substrates of proteinase, no significant hydrolytic activity was observed for BMK-CBP. The purified BMK-CBP was found to bind to the cancer cell line MCF-7 and the cell binding ability was dose-dependent. PMID:18625260

  16. Isolation, chemical and functional characterization of several new K(+)-channel blocking peptides from the venom of the scorpion Centruroides tecomanus.

    PubMed

    Olamendi-Portugal, Timoteo; Bartok, Adam; Zamudio-Zuñiga, Fernando; Balajthy, Andras; Becerril, Baltazar; Panyi, Gyorgy; Possani, Lourival D

    2016-06-01

    Six new peptides were isolated from the venom of the Mexican scorpion Centruroides tecomanus; their primary structures were determined and the effects on ion channels were verified by patch-clamp experiments. Four are K(+)-channel blockers of the α-KTx family, containing 32 to 39 amino acid residues, cross-linked by three disulfide bonds. They all block Kv1.2 in nanomolar concentrations and show various degree of selectivity over Kv1.1, Kv1.3, Shaker and KCa3.1 channels. One peptide has 42 amino acids cross-linked by four disulfides; it blocks ERG-channels and belongs to the γ-KTx family. The sixth peptide has only 32 amino acid residues, three disulfide bonds and has no effect on the ion-channels assayed. It also does not have antimicrobial activity. Systematic numbers were assigned (time of elution on HPLC): α-KTx 10.4 (time 24.1); α-KTx 2.15 (time 26.2); α-KTx 2.16 (time 23.8); α-KTx 2.17 (time 26.7) and γ-KTx 1.9 (elution time 29.6). A partial proteomic analysis of the short chain basic peptides of this venom, which elutes on carboxy-methyl-cellulose column fractionation, is included. The pharmacological properties of the peptides described in this study may provide valuable tools for understanding the structure-function relationship of K(+) channel blocking scorpion toxins. PMID:26921461

  17. Evaluation of separation properties of a modified strong cation exchange material named MEX and its application in 2D-MEX × C18 system to separate peptides from scorpion venom.

    PubMed

    Chen, Bo; Xu, Junyan; Fu, Qing; Dong, Xuefang; Guo, Zhimou; Jin, Yu; Liang, Xinmiao

    2015-07-01

    Peptides from scorpion venom represent one of the most promising drug sources for drug discovery for some specific diseases. Current challenges in their separation include high complexity, high homologies and the huge range of peptides. In this paper, a modified strong cation exchange material, named MEX, was utilised for the two-dimensional separation of peptides from complex scorpion venom. The silica-based MEX column was bonded with two functional groups; benzenesulfonic acid and cyanopropyl. To better understand its separation mechanisms, seven standard peptides with different properties were employed in an evaluation study, the results of which showed that two interactions were involved in the MEX column: electrostatic interactions based on benzenesulfonic acid groups dominated the separation of peptides; weak hydrophobic interactions introduced by cyanopropyl groups increased the column's selectivity for peptides with the same charge. This characteristic allowed the MEX column to overcome some of the drawbacks of traditional strong cation exchange (SCX) columns. Furthermore, the study showed the great effects of the acetonitrile (ACN) content, the sodium perchlorate (NaClO4) concentration and the buffer pH in the mobile phase on the peptides' retention and separation selectivity on the MEX column. Subsequently, the MEX column was combined with a C18 column to establish an off-line 2D-MEX × C18 system to separate peptides from scorpion Buthus martensi Karsch (BmK) venom. Due to complementary separation mechanisms in each dimension, a high orthogonality of 47.62% was achieved. Moreover, a good loading capacity, excellent stability and repeatability were exhibited by the MEX column, which are beneficial for its use in future preparation experiments. Therefore, the MEX column could be an alternative to the traditional SCX columns for the separation of peptides from scorpion venom. PMID:25996445

  18. A study on the experimental envenomation in mice with the venom of Tityus trivitattus Kraepelin 1898 (Scorpiones, Buthidae) captured in Argentina.

    PubMed

    de Roodt, A R; Gimeno, E; Portiansky, E; Varni, L; Dolab, J A; Segre, L; Litwin, S; Vidal, J C

    2001-05-01

    Although Tityus trivitattus is the only scorpion species reported to cause severe human envenomation in Argentina, no previous studies on its venom have been done. Telson homogenates from T. trivitattus specimens collected in Santiago del Estero, Cordoba, and Buenos Aires were employed to study their protein composition and toxicity to mice. Regardless of the site of collection, electrophoretic analysis showed bands at 205, 150, 100, 40, 32, and 13 kDa or smaller. FPLC gel filtration showed three major peaks and 6-8 minor peaks with similar elution volumes. One of the minor peaks from FPLC containing a component of approximately 8 kDa was lethal to mice. Mice injected intravenously with different doses of homogenates presented severe autonomic signs like tachypnea, tachycardia, sialorrhea, lacrimation, profuse sweating, diarrhea, dyspnea, and death. Pathology studies of lungs showed severe congestion of alveolar capillaries, pulmonary edema, and hemorrhagic areas. The kidneys showed glomerular as well as tubular lesions and exocrine glands showed areas of necrosis. The calculated LD50 was 0.38 +/- 0.08 telsons per 20 g mouse, which suggests a lethal potency similar to that of T. serrulatus venom. The lethal potency of 5.0 LD50 of T. trivitattus telson homogenate was neutralized by both an anti-T. trivitattus and a heterologous anti Tityus with ED50 values of 41 +/- 19 and 170 +/- 42 microl, respectively. PMID:11405281

  19. Neutralizing capacity of antibodies elicited by a non-toxic protein purified from the venom of the scorpion Tityus serrulatus.

    PubMed

    Chávez-Olórtegui, C; Kalapothakis, E; Ferreira, A M; Ferreira, A P; Diniz, C R

    1997-02-01

    Polyclonal rabbit antibodies raised against a non-toxic protein (TsNTxP) purified from the toxic fraction of the crude venom of Tityus serrulatus can neutralize the effects of the venom. The antigenic specificities of anti-TsNTxP were compared by an indirect enzyme-linked immunosorbent assay using TsNTxP, TstFG50 (toxic fraction of venom that represents most of the toxicity of the crude venom), and crude venoms from T. serrulatus, T. bahiensis, T. cambridgei, T. stigmurus, Androctonus australis Hector and Centruroides sculpturatus to coat microtitration plates. The anti-TsNTxP antibodies had a comparable high cross-reactivity with the toxic fraction and crude venom of T. serrulatus, moderate binding capacity for T. bahiensis, T. cambridgei, T. stigmurus and were unable to recognize the venoms of A. australis Hector and C. sculpturatus. Quantities of venom equivalent to 20 LD50 were effectively neutralized by 1 ml of the anti-TsNTxP serum. This result shows that this protein may be of interest in the production of antivenoms for clinical use. PMID:9080578

  20. Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities.

    PubMed

    Guo, Xiaoxiao; Ma, Chengbang; Du, Qiang; Wei, Ran; Wang, Lei; Zhou, Mei; Chen, Tianbao; Shaw, Chris

    2013-09-01

    Here we report two novel 17-mer amidated linear peptides (TsAP-1 and TsAP-2) whose structures were deduced from cDNAs cloned from a venom-derived cDNA library of the Brazilian yellow scorpion, Tityus serrulatus. Both mature peptides were structurally-characterised following their location in chromatographic fractions of venom and synthetic replicates of each were subjected to a range of biological assays. The peptides were each active against model test micro-organisms but with different potencies. TsAP-1 was of low potency against all three test organisms (MICs 120-160 μM), whereas TsAP-2 was of high potency against the Gram-positive bacterium, Staphylococcus aureus (MIC 5 μM) and the yeast, Candida albicans (10 μM). Haemolytic activity of TsAP-1 was low (4% at 160 μM) and in contrast, that of TsAP-2 was considerably higher (18% at 20 μM). Substitution of four neutral amino acid residues with Lys residues in each peptide had dramatic effects on their antimicrobial potencies and haemolytic activities, particularly those of TsAP-1. The MICs of the enhanced cationic analogue (TsAP-S1) were 2.5 μM for S. aureus/C. albicans and 5 μM for E. coli but with an associated large increase in haemolytic activity (30% at 5 μM). The same Lys residue substitutions in TsAP-2 produced a dramatic effect on its MIC for E. coli lowering this from >320 μM to 5 μM. TsAP-1 was ineffective against three of the five human cancer cell lines tested while TsAP-2 inhibited the growth of all five. Lys residue substitution of both peptides enhanced their potency against all five cell lines with TsAp-S2 being the most potent with IC50 values ranging between 0.83 and 2.0 μM. TsAP-1 and TsAP-2 are novel scorpion venom peptides with broad spectrum antimicrobial and anticancer cell activities the potencies of which can be significantly enhanced by increasing their cationicity. PMID:23770440

  1. Overview of Scorpion Species from China and Their Toxins

    PubMed Central

    Cao, Zhijian; Di, Zhiyong; Wu, Yingliang; Li, Wenxin

    2014-01-01

    Scorpions are one of the most ancient groups of terrestrial animals. They have maintained a steady morphology over more than 400 million years of evolution. Their venom arsenals for capturing prey and defending against predators may play a critical role in their ancient and conservative appearance. In the current review, we present the scorpion fauna of China: 53 species covering five families and 12 genera. We also systematically list toxins or genes from Chinese scorpion species, involving eight species covering four families. Furthermore, we review the diverse functions of typical toxins from Chinese scorpion species, involving Na+ channel modulators, K+ channel blockers, antimicrobial peptides and protease inhibitors. Using scorpion species and their toxins from China as an example, we build the bridge between scorpion species and their toxins, which helps us to understand the molecular and functional diversity of scorpion venom arsenal, the dynamic and functional evolution of scorpion toxins, and the potential relationships of scorpion species and their toxins. PMID:24577583

  2. Antepartum fetal death following a yellow scorpion sting.

    PubMed

    Leibenson, Lilach; Leibenson, M; Silberstein, T

    2010-02-01

    Scorpion envenomation in pregnant victims has been scarcely studied. We would like to suggest an association between yellow scorpion sting during the third trimester of pregnancy and adverse fetal outcome. The particular deleterious mechanism of scorpion venom has not been elucidated yet. PMID:19466438

  3. Sj7170, a Unique Dual-function Peptide with a Specific α-Chymotrypsin Inhibitory Activity and a Potent Tumor-activating Effect from Scorpion Venom*

    PubMed Central

    Song, Yu; Gong, Ke; Yan, Hong; Hong, Wei; Wang, Le; Wu, Yingliang; Li, Wenhua; Li, Wenxin; Cao, Zhijian

    2014-01-01

    A new peptide precursor, termed Sj7170, was characterized from the venomous gland cDNA library of the scorpion Scorpiops jendeki. Sj7170 was deduced to be a 62-amino acid peptide cross-linked by five disulfide bridges. The recombinant Sj7170 peptide (rSj7170) with chromatographic purity was produced by a prokaryotic expression system. Enzyme inhibition assay in vitro and in vivo showed that rSj7170 specifically inhibited the activity of α-chymotrypsin at micromole concentrations. In addition, Sj7170 not only promoted cell proliferation and colony formation by up-regulating the expression of cyclin D1 in vitro but also enhanced tumor growth in nude mice. Finally, Sj7170 accelerated cellular migration and invasion by increasing the expression of the transcription factor Snail and then inducing the epithelial-mesenchymal transition. Moreover, Sj7170 changed cell morphology and cytoskeleton of U87 cells by the GTPase pathway. Taken together, Sj7170 is a unique dual-function peptide, i.e. a specific α-chymotrypsin inhibitor and a potent tumorigenesis/metastasis activator. Our work not only opens an avenue of developing new modulators of tumorigenesis/metastasis from serine protease inhibitors but also strengthens the functional link between protease inhibitors and tumor activators. PMID:24584937

  4. Diversity of long-chain toxins in Tityus zulianus and Tityus discrepans venoms (Scorpiones, Buthidae): molecular, immunological, and mass spectral analyses.

    PubMed

    Borges, Adolfo; García, Carmen C; Lugo, Elizabeth; Alfonzo, Marcelo J; Jowers, Michael J; Op den Camp, Huub J M

    2006-01-01

    In Venezuela, stings by Tityus zulianus scorpions produce cardiorespiratory arrest, whereas envenoming by Tityus discrepans involves gastrointestinal/pancreatic complications, suggesting structural and/or functional differences. We sought to compare their toxin repertoires through immunological, molecular, and mass spectral analyses. First, in vivo tests showed that neutralization of T. zulianus venom toxicity by the anti-T. discrepans antivenom was not complete. To compare T. discrepans and T. zulianus long-chain (sodium channel-active) toxins, their most toxic Sephadex G-50 fractions, TdII and TzII, were subjected to acid-urea PAGE, which showed differences in composition. Amplification of toxin-encoding mRNAs using a leader peptide-based oligonucleotide rendered cDNAs representing twelve T. discrepans and two T. zulianus distinct toxin transcripts, including only one shared component, indicating divergence between T. zulianus and T. discrepans 5' region-encoded, toxin signal peptides. A 3'-UTR polymorphism was also noticed among the transcripts encoding shared components Tz1 and Td4. MALDI-TOF MS profiling of TdII and TzII produced species-specific spectra, with seven of the individual masses matching those predicted by cDNA sequencing. Phylogenetic analysis showed that the unique T. zulianus transcript-encoded sequence, Tz2, is structurally related to Tityus serrulatus and Centruroides toxins. Together with previous reports, this work indicates that T. zulianus and T. discrepans toxin repertoires differ structurally and functionally. PMID:16356783

  5. Sj7170, a unique dual-function peptide with a specific α-chymotrypsin inhibitory activity and a potent tumor-activating effect from scorpion venom.

    PubMed

    Song, Yu; Gong, Ke; Yan, Hong; Hong, Wei; Wang, Le; Wu, Yingliang; Li, Wenhua; Li, Wenxin; Cao, Zhijian

    2014-04-25

    A new peptide precursor, termed Sj7170, was characterized from the venomous gland cDNA library of the scorpion Scorpiops jendeki. Sj7170 was deduced to be a 62-amino acid peptide cross-linked by five disulfide bridges. The recombinant Sj7170 peptide (rSj7170) with chromatographic purity was produced by a prokaryotic expression system. Enzyme inhibition assay in vitro and in vivo showed that rSj7170 specifically inhibited the activity of α-chymotrypsin at micromole concentrations. In addition, Sj7170 not only promoted cell proliferation and colony formation by up-regulating the expression of cyclin D1 in vitro but also enhanced tumor growth in nude mice. Finally, Sj7170 accelerated cellular migration and invasion by increasing the expression of the transcription factor Snail and then inducing the epithelial-mesenchymal transition. Moreover, Sj7170 changed cell morphology and cytoskeleton of U87 cells by the GTPase pathway. Taken together, Sj7170 is a unique dual-function peptide, i.e. a specific α-chymotrypsin inhibitor and a potent tumorigenesis/metastasis activator. Our work not only opens an avenue of developing new modulators of tumorigenesis/metastasis from serine protease inhibitors but also strengthens the functional link between protease inhibitors and tumor activators. PMID:24584937

  6. Involvement of Kallikrein-Kinin System on Cardiopulmonary Alterations and Inflammatory Response Induced by Purified Aah I Toxin from Scorpion Venom.

    PubMed

    Medjadba, Wafa; Martin-Eauclaire, Marie-France; Laraba-Djebari, Fatima

    2016-02-01

    Bradykinins are released from kininogen by kallikrein. They increase capillary lung permeability after their binding to β1 and especially β2 receptors before being metabolized by kininase enzyme. This study was performed to evaluate cardiopulmonary damages and inflammatory response on injected rats with Aah I toxin of scorpion venom and the involvement of Kallikrein-Kinin system in this pathogenesis. Obtained results revealed that Aah I toxin induces inflammatory cell infiltration accompanied by cellular peroxidase activities, a release of cytokine levels, pulmonary and myocardial damage, with altered metabolic activities and imbalanced redox status. Administration of aprotinin (bradykinin inhibitor) and especially icatibant (bradykinin β2 receptor antagonist) seemed to be able to protect animals against the toxicity of Aah I; nevertheless, the use of captopril (kininase II inhibitor) reduced partially some cardiac disorders. These findings indicate that the kallikrein-kinin system may contribute to the physiopathological effect and lung edema formation induced by toxin, which suggests a potential use of drugs with significant anti-kinin properties. PMID:26361946

  7. Purification and characterization of a scorpion defensin, a 4kDa antibacterial peptide presenting structural similarities with insect defensins and scorpion toxins.

    PubMed

    Cociancich, S; Goyffon, M; Bontems, F; Bulet, P; Bouet, F; Menez, A; Hoffmann, J

    1993-07-15

    Insect defensins are a group of inducible small-sized antibacterial peptides with three intramolecular disulfide bridges. NMR studies have recently shown that they share striking structural similarities with scorpion toxins. We have investigated in a scorpion species, Leiurus quinquestriatus, the potential presence of antibacterial molecules and report the isolation and structural characterization of a novel insect defensin homologue, which we refer to as scorpion defensin. This peptide shows a remarkably high degree of sequence homology with a defensin recently characterized in a species belonging to the ancient insect order of the Odonata with which it defines a novel ancient subclass of defensins. The scorpion defensin has in common with the scorpion toxins a consensus sequence Cys-[...]-Cys-Xaa-Xaa-Xaa-Cys-[...]-Gly-Xaa-Cys-[...]-Cys-Xaa-Cys present in all scorpion toxins characterized so far. PMID:8333834

  8. High performance liquid chromatography purification and amino acid sequence of toxins from the muscarinic fraction of Tityus discrepans scorpion venom.

    PubMed

    D'Suze, G; Corona, F; Possani, L D; Sevcik, C

    1996-05-01

    Tityus discrepans venom was fractionated by gel filtration on Sephadex G-50 column. The peptides in fraction II from Sephadex were further purified by high performance liquid chromatography, through a C4 reverse-phase column. Lethality of purified peptides was determined by injection into mice and crabs, and their effects were verified electrophysiologically on frog (Hyla crepitans) sartorius neuromuscular junction. Toxins having retention times between 39.6 and 40.7 min depolarized the muscle membrane and caused acetylcholine release at the endplate. The toxin eluted at 42.67 min increased the frequency of miniature endplate potentials without depolarizing muscle fibres. The four most active toxins were reduced, carboxymethylated and sequenced by automatic Edman degradation and named TdII-1 to II-4. Toxin gamma from Tityus serrulatus venom and the toxins from T. discrepans venom were found to be structurally distinct. TdII-1 to II-4 lack the pancreatic effects of T. serrulatus' toxin gamma; yet, the five toxins act on Na+ channels. PMID:8783453

  9. Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels.

    PubMed Central

    Jouirou, Besma; Mosbah, Amor; Visan, Violeta; Grissmer, Stephan; M'Barek, Sarrah; Fajloun, Ziad; Van Rietschoten, Jurphaas; Devaux, Christiane; Rochat, Hervé; Lippens, Guy; El Ayeb, Mohamed; De Waard, Michel; Mabrouk, Kamel; Sabatier, Jean-Marc

    2004-01-01

    CoTX1 (cobatoxin 1) is a 32-residue toxin with three disulphide bridges that has been isolated from the venom of the Mexican scorpion Centruroides noxius Hoffmann. Here we report the chemical synthesis, disulphide bridge organization, 3-D (three-dimensional) solution structure determination, pharmacology on K+ channel subtypes (voltage-gated and Ca2+-activated) and docking-simulation experiments. An enzyme-based cleavage of the synthetic folded/oxidized CoTX1 indicated half-cystine pairs between Cys3-Cys22, Cys8-Cys27 and Cys12-Cys29. The 3-D structure of CoTX1 (solved by 1H-NMR) showed that it folds according to the common alpha/beta scaffold of scorpion toxins. In vivo, CoTX1 was lethal after intracerebroventricular injection to mice (LD50 value of 0.5 microg/mouse). In vitro, CoTX1 tested on cells expressing various voltage-gated or Ca2+-activated (IKCa1) K+ channels showed potent inhibition of currents from rat K(v)1.2 ( K(d) value of 27 nM). CoTX1 also weakly competed with 125I-labelled apamin for binding to SKCa channels (small-conductance Ca2+-activated K+ channels) on rat brain synaptosomes (IC50 value of 7.2 microM). The 3-D structure of CoTX1 was used in docking experiments which suggests a key role of Arg6 or Lys10, Arg14, Arg18, Lys21 (dyad), Ile23, Asn24, Lys28 and Tyr30 (dyad) residues of CoTX1 in its interaction with the rat K(v)1.2 channel. In addition, a [Pro7,Gln9]-CoTX1 analogue (ACoTX1) was synthesized. The two residue replacements were selected aiming to restore the RPCQ motif in order to increase peptide affinity towards SKCa channels, and to alter the CoTX1 dipole moment such that it is expected to decrease peptide activity on K(v) channels. Unexpectedly, ACoTX1 exhibited an activity similar to that of CoTX1 towards SKCa channels, while it was markedly more potent on IKCa1 and several voltage-gated K+ channels. PMID:14498829

  10. Two neurotoxins (BmK I and BmK II) from the venom of the scorpion Buthus martensi Karsch: purification, amino acid sequences and assessment of specific activity.

    PubMed

    Ji, Y H; Mansuelle, P; Terakawa, S; Kopeyan, C; Yanaihara, N; Hsu, K; Rochat, H

    1996-09-01

    Two neurotoxins, BmK I and BmK II, were purified from the venom of the Chinese scorpion Buthus martensi Karsch. The complete amino acid sequences of both toxins, each containing 64 amino acid residues, were determined by the automatic sequencing of reduced and S-carboxymethylated toxins and their peptides, obtained after cleavage with TPCK-treated trypsin and Staphylococcus aureus V8 protease, respectively. Toxicity as minimum lethal dose tested by i.c.v. injection in mice showed that BmK I was six times more potent than BmK II. Only two amino acid replacements were found: at position 59 Val in BmK I was replaced by Ile in BmK II, and at position 62 a basic Lys residue in BmK I was substituted by a neutral Asn residue in BmK II. These features suggest that the positively charged residue (Lys or Arg) in the C-terminal position 62 (or 61 or 63) may also play an important role in facilitating the interaction between scorpion neurotoxins and the receptor on sodium channels. The effects of BmK I on nerve excitability were examined with the crayfish axon using intracellular recording and voltage-clamp conditions. The results indicate that BmK I preferentially blocks the sodium channel inactivation process. Thus, functional and structural similarities suggest that BmK I and BmK II belong to group 3 of scorpion alpha-type toxins. PMID:8896191

  11. Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese scorpion for human gliomas.

    PubMed

    Fu, Yue-Jun; Yin, Li-Tian; Liang, Ai-Hua; Zhang, Chao-Feng; Wang, Wei; Chai, Bao-Feng; Yang, Jian-Yi; Fan, Xiao-Jun

    2007-01-22

    Chlorotoxin, one of the key toxins in scorpion Leiurus quinquestriatus venom, has been shown to bind specifically to glioma cell surface as a specific chloride channel blocker. In this study, a purified, recombinant chlorotoxin-like peptide from the scorpion Buthus martensii Karsch (named rBmK CTa) was characterized by in vivo and in vitro studies. The results from cell proliferation assay with human glioma (SHG-44) cells showed that rBmK CTa inhibits the growth of glioma cells in a dose-dependent manner, with an IC(50) value of approximately 0.28microM. Under the same conditions, the IC(50) value for normal astrocytes increased to 8microM. This clearly indicated that rBmK CTa had specific toxicity against glioma cells but not astrocytes. Results from whole-cell patch-clamp recording showed that chloride current in SHG-44 was inhibited by rBmK CTa in a voltage-dependent manner and percent inhibitions for the blocking action of rBmK CTa (0.07 and 0.14microM) on I(Cl) was 17.64+/-3.06% and 55.86+/-2.83%, respectively. Histological analysis of rBmK CTa treated mice showed that brain, leg muscle and cardiac muscle were the target organs of this toxin. These results suggest that rBmK CTa may have potential therapeutic application in clinical treatment of human glioma. It represents an approach for developing a novel therapeutic agent. PMID:17166663

  12. Tityus serrulatus scorpion venom improves survival and lung inflammation in lethal sepsis induced by CLP in mice.

    PubMed

    Maciel, Márcia C G; Fialho, Eder M S; Guerra, Rosane N M; Borges, Valéria M; Kwasniewski, Fábio H; Nascimento, Flávia R F

    2014-10-01

    Tityus serrulatus venom (Tsv) modifies the behavior of immune cells and induces the production of inflammatory and anti-inflammatory cytokines; such action may interfere with physiological or pathological states. Because sepsis is characterized as an inflammatory disorder, the aim of present study was to investigate the effect of a non-lethal dose of Tsv in mice submitted to a polymicrobial infection by cecal ligation and puncture (CLP) model. The parameters evaluated were survival index, cellularity on lymphoid organs, peritoneal cavity and brochoalveolar space, production of IL-10, IL-12, IL-6, TNF-α, IFN-γ and MCP-1, pulmonary inflammation and oxidative burst. The results demonstrated that in sharp contrast to CLP group in which sepsis was lethal in a 24 h period all mice pretreated with Tsv survived even 60 h after CLP. Lung inflammation, another hallmark of CLP group, was also dramatically down regulated in Tsv/CLP group. Despite pretreatment with Tsv did not reduce the inflammatory serum cytokines when compared to CLP group; there was an increase in IL-10. In conclusion, subcutaneous Tsv administration 6 h before CLP was able to control the harmful effects of sepsis (lethality and lung inflammation). We suggest that both systemic IL-10 and oxidative burst are involved in this effect. PMID:24976596

  13. Are ticks venomous animals?

    PubMed Central

    2014-01-01

    Introduction As an ecological adaptation venoms have evolved independently in several species of Metazoa. As haematophagous arthropods ticks are mainly considered as ectoparasites due to directly feeding on the skin of animal hosts. Ticks are of major importance since they serve as vectors for several diseases affecting humans and livestock animals. Ticks are rarely considered as venomous animals despite that tick saliva contains several protein families present in venomous taxa and that many Ixodida genera can induce paralysis and other types of toxicoses. Tick saliva was previously proposed as a special kind of venom since tick venom is used for blood feeding that counteracts host defense mechanisms. As a result, the present study provides evidence to reconsider the venomous properties of tick saliva. Results Based on our extensive literature mining and in silico research, we demonstrate that ticks share several similarities with other venomous taxa. Many tick salivary protein families and their previously described functions are homologous to proteins found in scorpion, spider, snake, platypus and bee venoms. This infers that there is a structural and functional convergence between several molecular components in tick saliva and the venoms from other recognized venomous taxa. We also highlight the fact that the immune response against tick saliva and venoms (from recognized venomous taxa) are both dominated by an allergic immunity background. Furthermore, by comparing the major molecular components of human saliva, as an example of a non-venomous animal, with that of ticks we find evidence that ticks resemble more venomous than non-venomous animals. Finally, we introduce our considerations regarding the evolution of venoms in Arachnida. Conclusions Taking into account the composition of tick saliva, the venomous functions that ticks have while interacting with their hosts, and the distinguishable differences between human (non-venomous) and tick salivary

  14. Natural infestation of Pimeliaphilus joshuae on scorpion species from Egypt.

    PubMed

    Ibrahim, Mohamed M; Abdel-Rahman, Mohamed A

    2011-09-01

    The main goal of this study was to study the acarine parasite, Pimeliaphilus joshuae (Prostigmata: Pterygosomatidae) on various scorpion species from Egypt to determine its prevalence, abundance and intensity in relation to host species, size and sex. A total of 95 Leiurus quinquestriatus, 98 Androctonus australis, 40 A. amoreuxi, 30 Scorpio maurus palmatus and 46 Orthochirus scrobicuosus were examined during August 2009. Prevalence and mean abundance of P. joshuae varied significantly in relation to host species, host size and sex. In L. quinquestriatus, A. australis, and A. amoreuxi, the prevalence was 76.8, 13.3, and 50.0%, whereas the mean abundance was 47.6, 6.7 and 14.3%, respectively. Prevalence and mean abundance of P. joshuae were both positively correlated with host size in L. quinquestriatus and A. australis. We conclude that P. joshuae is found in a wide range of scorpion species exhibiting a low degree of host specificity. Controlled laboratory infection experiments are required to explain why S. m. palmatus and O. scrobicuosus are not susceptible to infestation by P. joshuae. PMID:21465333

  15. Biological assays on the effects of Acra3 peptide from Turkish scorpion Androctonus crassicauda venom on a mouse brain tumor cell line (BC3H1) and production of specific monoclonal antibodies.

    PubMed

    Caliskan, Figen; Ergene, Emel; Sogut, Ibrahim; Hatipoglu, Ibrahim; Basalp, Aynur; Sivas, Hulya; Kanbak, Gungor

    2013-12-15

    Constitutes of the venom scorpion are a rich source of low molecular mass peptides which are toxic to various organisms, including man. Androctonus crassicauda is one of the scorpions from the Southeastern Anatolia of Turkey with public health importance. This work is focused on the investigation of biological effects of Acra3 peptide from Androctonus crassicauda. For this purpose, Acra3 isolated from crude venoms was tested for its cytotoxicity on BC3H1 mouse brain tumor cells using tetrazolium salt cleavage and lactate dehydrogenase activity assays. To determine whether the cytotoxic effects of Acra3 was related to the induction of apoptosis, the morphology of the cells and the nuclear fragmentation was examined by using Acridin Orange staining and DNA fragmentation assay, respectively. Caspase 3 and caspase 9 activities were measured spectrophotometrically and flow cytometric assay was performed using Annexin-V FITC and Propidium Iodide staining. Furthermore toxic peptide Acra3 was used as an antigen for immunological studies. Results showed that Acra3 exerted very strong cytotoxic effect on BC3H1 cells with an IC50 value of 5 μg/ml. Exposure of the cells to 0.1 and 0.5 μg/ml was resulted in very strong appearance of the apoptotic morphology in a dose dependent manner. On the other side, not any DNA fragmentation was observed after treatment of the cells. Caspase 3 and 9 activities were slightly decreased with Acra3. Results from flow cytometry and lactate dehydrogenase activity assays indicate that Acra3 exerts its effects by inducing a stronger necrosis than apoptosis in BC3H1 cells. To evaluate its immunogenicity, monoclonal antibody (MAb) specific for Acra3 antigen (5B9) was developed by hybridoma technology using spleen and lymph nodes of mice and immunoglobulin type of antibody was found to be IgM. We suggest that Acra3 may exert its effects by inducing both necrotic and apoptotic pathway in some way on mouse brain tumor cells. These findings will be

  16. Clinical update on scorpion envenoming.

    PubMed

    Cupo, Palmira

    2015-01-01

    Scorpion stings are currently the leading cause of venom-related injury to humans in Brazil and are a significant public health problem globally. Only scorpions of the Tityus genus are of medical importance in Brazil, and Tityus serrulatus is responsible for the most serious envenomations and deaths. The toxic effects of scorpion envenomation are due to a massive release of sympathetic and parasympathetic neurotransmitters; the severity is related to cardiac and hemodynamic changes, with cardiogenic shock and pulmonary edema contributing to the main causes of death. The pathophysiology of cardiac involvement has been discussed for decades and has been attributed to adrenergic discharge and a possible toxic effect of venom on the myocardium, while acute pulmonary edema may have a cardiogenic and/or non-cardiogenic origin. Currently, the clinical data point to catecholamine excess as the cause for reversible scorpion cardiomyopathy . These data include electrocardiographic changes, profiling of cardiac enzymes and troponin I, echocardiographic data with global or regional left ventricle dysfunction, and myocardial perfusion alterations compatible with spasm in the coronary microcirculation. Furthermore, recent data on cardiac magnetic resonance imaging findings, which are similar to those observed for stress-induced cardiomyopathy, have also been linked to catecholamine excess. The efficiency of antivenom serum treatment is controversial in the literature. Our experience in Brazil is that the management of patients with systemic manifestations of scorpion stings is based on three approaches, all of which are extremely important. These include symptomatic treatment, antivenom serum, and cardiorespiratory support. PMID:26676487

  17. Toxins and genes isolated from scorpions of the genus Tityus.

    PubMed

    Becerril, B; Marangoni, S; Possani, L D

    1997-06-01

    Scorpion venoms contain a variety of low mol. wt peptides toxic to different organisms. These peptides have been intensively studied because they represent excellent models for investigating structure-function relationships and they are also fine probes for studying ionic channel functions. This review deals with the biological and chemical aspects of toxic peptides that affect Na+ or K+ channels and the cloning of the cDNAs and genes encoding the main alpha and beta neurotoxins present in the venom of the three most dangerous species of Brazilian scorpion, Tityus bahiensis, Tityus stigmurus and Tityus serrulatus, and the Venezuelan scorpion Tityus discrepans. At least 16 different peptides specific for Na+ channels and five affecting K+ channels were isolated and characterized from the venom of these scorpions. The isolation of cDNAs and genes encoding four distinct toxins has permitted the elucidation of their nucleotide sequences as well as their genomic organization. Venoms and isolated toxins from scorpions of the genus Tityus were shown to enhance the secretory activity of the pancreas. Antisera obtained against venom of T. serrulatus show cross-reactivity with other species of the Brazilian scorpions. PMID:9241777

  18. Quo vadis venomics? A roadmap to neglected venomous invertebrates.

    PubMed

    von Reumont, Bjoern Marcus; Campbell, Lahcen I; Jenner, Ronald A

    2014-01-01

    Venomics research is being revolutionized by the increased use of sensitive -omics techniques to identify venom toxins and their transcripts in both well studied and neglected venomous taxa. The study of neglected venomous taxa is necessary both for understanding the full diversity of venom systems that have evolved in the animal kingdom, and to robustly answer fundamental questions about the biology and evolution of venoms without the distorting effect that can result from the current bias introduced by some heavily studied taxa. In this review we draw the outlines of a roadmap into the diversity of poorly studied and understood venomous and putatively venomous invertebrates, which together represent tens of thousands of unique venoms. The main groups we discuss are crustaceans, flies, centipedes, non-spider and non-scorpion arachnids, annelids, molluscs, platyhelminths, nemerteans, and echinoderms. We review what is known about the morphology of the venom systems in these groups, the composition of their venoms, and the bioactivities of the venoms to provide researchers with an entry into a large and scattered literature. We conclude with a short discussion of some important methodological aspects that have come to light with the recent use of new -omics techniques in the study of venoms. PMID:25533518

  19. Quo Vadis Venomics? A Roadmap to Neglected Venomous Invertebrates

    PubMed Central

    von Reumont, Bjoern Marcus; Campbell, Lahcen I.; Jenner, Ronald A.

    2014-01-01

    Venomics research is being revolutionized by the increased use of sensitive -omics techniques to identify venom toxins and their transcripts in both well studied and neglected venomous taxa. The study of neglected venomous taxa is necessary both for understanding the full diversity of venom systems that have evolved in the animal kingdom, and to robustly answer fundamental questions about the biology and evolution of venoms without the distorting effect that can result from the current bias introduced by some heavily studied taxa. In this review we draw the outlines of a roadmap into the diversity of poorly studied and understood venomous and putatively venomous invertebrates, which together represent tens of thousands of unique venoms. The main groups we discuss are crustaceans, flies, centipedes, non-spider and non-scorpion arachnids, annelids, molluscs, platyhelminths, nemerteans, and echinoderms. We review what is known about the morphology of the venom systems in these groups, the composition of their venoms, and the bioactivities of the venoms to provide researchers with an entry into a large and scattered literature. We conclude with a short discussion of some important methodological aspects that have come to light with the recent use of new -omics techniques in the study of venoms. PMID:25533518

  20. Biochemical and physiological characterization of a new Na(+)-channel specific peptide from the venom of the Argentinean scorpion Tityus trivittatus.

    PubMed

    Coronas, Fredy I V; Diego-García, Elia; Restano-Cassulini, Rita; de Roodt, Adolfo R; Possani, Lourival D

    2015-06-01

    A new peptide with 61 amino acids cross-linked by 4 disulfide bridges, with molecular weight of 6938.12Da, and an amidated C-terminal amino acid residue was purified and characterized. The primary structure was obtained by direct Edman degradation and sequencing its gene. The peptide is lethal to mammals and was shown to be similar (95% identity) to toxin Ts1 (gamma toxin) from the Brazilian scorpion Tityus serrulatus; it was named Tt1g (from T. trivittatus toxin 1 gamma-like). Tt1g was assayed on several sub-types of Na(+)-channels showing displacement of the currents to more negative voltages, being the hNav1.3 the most affected channel. This toxin displays characteristics typical to the β-type sodium scorpion toxins. Lethality tests and physiological assays indicate that this peptide is probably the most important toxic component of this species of scorpion, known for causing human fatalities in the South American continent. PMID:24862827

  1. The unfulfilled promises of scorpion insectotoxins.

    PubMed

    Ortiz, Ernesto; Possani, Lourival D

    2015-01-01

    Since the description and biochemical characterization of the first insect-specific neurotoxins from scorpion venoms, almost all contributions have highlighted their potential application as leads for the development of potent bioinsecticides. Their practical use, however, has been hindered by different factors, some of which are intrinsically related to the toxins and other external determinants. Recent developments in the understanding of the action mechanisms of the scorpion insectotoxins and their bioactive surfaces, coupled with the exploration of novel bioinsecticide delivery systems have renewed the expectations that the scorpion insectotoxins could find their way into commercial applications in agriculture, as part of integrated pest control strategies. Herein, we review the current arsenal of available scorpion neurotoxins with a degree of specificity for insects, the progress made with alternative delivery methods, and the drawbacks that still preclude their practical use. PMID:26085828

  2. Purification and primary structure determination of Tf4, the first bioactive peptide isolated from the venom of the Brazilian scorpion Tityus fasciolatus.

    PubMed

    Wagner, Simone; Castro, Mariana S; Barbosa, João Alexandre R G; Fontes, Wagner; Schwartz, Elisabeth N F; Sebben, Antonio; Rodrigues Pires, Osmindo; Sousa, Marcelo V; Schwartz, Carlos Alberto

    2003-06-01

    In the present study Tityus fasciolatus crude venom toxicity was evaluated and we also report the purification and characterization of a 6.6 kDa neurotoxin isolated from T. fasciolatus venom. This new toxin, named Tf4, has a molecular mass of 6614Da and its primary structure is homologous to TbIT-I from T. bahiensis and TsTX-VI and TsNTxP from T. serrulatus. Tf4 delays frog sodium channel inactivation reversibly, but it is non-toxic to mammals or crustaceans. An attempt to identify the residues responsible for the partial loss of toxicity in Tf4 was carried out based on homology modeling and sequence comparison. PMID:12782073

  3. A novel cysteine-free venom peptide with strong antimicrobial activity against antibiotics-resistant pathogens from the scorpion Opistophthalmus glabrifrons.

    PubMed

    Bao, Aorigele; Zhong, Jie; Zeng, Xian-Chun; Nie, Yao; Zhang, Lei; Peng, Zhao Feng

    2015-10-01

    Antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, pose serious threat to human health. The outbreak of antibiotic-resistant pathogens in recent years emphasizes once again the urgent need for the development of new antimicrobial agents. Here, we discovered a novel antimicrobial peptide from the scorpion Opistophthalmus glabrifrons, which was referred to as Opisin. Opisin consists of 19 amino acid residues without disulfide bridges. It is a cationic, amphipathic, and α-helical molecule. Protein sequence homology search revealed that Opisin shares 42.1-5.3% sequence identities to the 17/18-mer antimicrobial peptides from scorpions. Antimicrobial assay showed that Opisin is able to potently inhibit the growth of the tested Gram-positive bacteria with the minimal inhibitory concentration (MIC) values of 4.0-10.0 μM; in contrast, it possesses much lower activity against the tested Gram-negative bacteria and a fungus. It is interesting to see that Opisin is able to strongly inhibit the growth of methicillin- and vancomycin-resistant pathogens with the MICs ranging from 2.0 to 4.0 μM and from 4.0 to 6.0 μM, respectively. We found that at a concentration of 5 × MIC, Opisin completely killed all the cultured methicillin-resistant Staphylococcus aureus. These results suggest that Opisin is a promising therapeutic candidate for the treatment of the antibiotic-resistant bacterial infections. PMID:26251012

  4. Polypyrazolylborates: Scorpionates

    ERIC Educational Resources Information Center

    Trofimenko, Swiatoslaw

    2005-01-01

    Scorpionate-type ligands and the original polypyrazolylborates are easy to synthesize, have good stability, and are quite user-friendly. Their thallium(I) salts are readily soluble in organic solvents that permits their use in organic media, or in two-phase aquo-organic solvent mixtures.

  5. AaeAP1 and AaeAP2: novel antimicrobial peptides from the venom of the scorpion, Androctonus aeneas: structural characterisation, molecular cloning of biosynthetic precursor-encoding cDNAs and engineering of analogues with enhanced antimicrobial and anticancer activities.

    PubMed

    Du, Qiang; Hou, Xiaojuan; Wang, Lei; Zhang, Yingqi; Xi, Xinping; Wang, Hui; Zhou, Mei; Duan, Jinao; Wei, Minjie; Chen, Tianbao; Shaw, Chris

    2015-02-01

    The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3'- and 5'-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation. PMID:25626077

  6. AaeAP1 and AaeAP2: Novel Antimicrobial Peptides from the Venom of the Scorpion, Androctonus aeneas: Structural Characterisation, Molecular Cloning of Biosynthetic Precursor-Encoding cDNAs and Engineering of Analogues with Enhanced Antimicrobial and Anticancer Activities

    PubMed Central

    Du, Qiang; Hou, Xiaojuan; Wang, Lei; Zhang, Yingqi; Xi, Xinping; Wang, Hui; Zhou, Mei; Duan, Jinao; Wei, Minjie; Chen, Tianbao; Shaw, Chris

    2015-01-01

    The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3'- and 5'-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation. PMID:25626077

  7. Mass landscapes of seven scorpion species: The first analyses of Australian species with 1,5-DAN matrix

    PubMed Central

    Smith, Jennifer J; Jones, Alun; Alewood, Paul F

    2012-01-01

    Scorpion venoms have been studied for over fifty years; however, the majority of research has focussed primarily on medically important Buthidae species. Additionally, venoms of the estimated 200 species of scorpion native to Australia have received very little attention. The first venom mass profiles of six non-buthid and one buthid scorpion species are presented herein, four of which are endemic to Australia. While masses under 5 kDa dominated the venoms of all species, the buthid venom contained considerably more masses between 7 and 8 kDa than those of the non-buthids, corroborating the emergent trend that buthids are richer in long-chain neurotoxins than non-buthids. The Australian scorpion venom fractions were also analysed with the relatively new MALDI-ToF matrix 1,5-DAN. Over forty partial sequences were obtained, the majority of which are homologous to scorpion antimicrobials such as opistoporin and IsCT2. Overall, this study is the single most comprehensive mass spectrometric analysis of scorpion venom landscapes to date and provides an insight into untapped Australian species. PMID:23236582

  8. Target-Driven Evolution of Scorpion Toxins.

    PubMed

    Zhang, Shangfei; Gao, Bin; Zhu, Shunyi

    2015-01-01

    It is long known that peptide neurotoxins derived from a diversity of venomous animals evolve by positive selection following gene duplication, yet a force that drives their adaptive evolution remains a mystery. By using maximum-likelihood models of codon substitution, we analyzed molecular adaptation in scorpion sodium channel toxins from a specific species and found ten positively selected sites, six of which are located at the core-domain of scorpion α-toxins, a region known to interact with two adjacent loops in the voltage-sensor domain (DIV) of sodium channels, as validated by our newly constructed computational model of toxin-channel complex. Despite the lack of positive selection signals in these two loops, they accumulated extensive sequence variations by relaxed purifying selection in prey and predators of scorpions. The evolutionary variability in the toxin-bound regions of sodium channels indicates that accelerated substitutions in the multigene family of scorpion toxins is a consequence of dealing with the target diversity. This work presents an example of atypical co-evolution between animal toxins and their molecular targets, in which toxins suffered from more prominent selective pressure from the channels of their competitors. Our discovery helps explain the evolutionary rationality of gene duplication of toxins in a specific venomous species. PMID:26444071

  9. Global Transcriptome Analysis of the Scorpion Centruroides noxius: New Toxin Families and Evolutionary Insights from an Ancestral Scorpion Species

    PubMed Central

    Rendón-Anaya, Martha; Delaye, Luis; Possani, Lourival D.; Herrera-Estrella, Alfredo

    2012-01-01

    Scorpion venoms have been studied for decades, leading to the identification of hundreds of different toxins with medical and pharmacological implications. However, little emphasis has been given to the description of these arthropods from cellular and evolutionary perspectives. In this report, we describe a transcriptomic analysis of the Mexican scorpion Centruroides noxius Hoffmann, performed with a pyrosequencing platform. Three independent sequencing experiments were carried out, each including three different cDNA libraries constructed from RNA extracted from the whole body of the scorpion after telson removal, and from the venom gland before and after venom extraction. Over three million reads were obtained and assembled in almost 19000 isogroups. Within the telson-specific sequences, 72 isogroups (0.4% of total unique transcripts) were found to be similar to toxins previously reported in other scorpion species, spiders and sea anemones. The annotation pipeline also revealed the presence of important elements of the small non-coding RNA processing machinery, as well as microRNA candidates. A phylogenomic analysis of concatenated essential genes evidenced differential evolution rates in this species, particularly in ribosomal proteins and proteasome components. Additionally, statistical comparison of transcript abundance before and after venom extraction showed that 3% and 2% of the assembled isogroups had higher expression levels in the active and replenishing gland, respectively. Thus, our sequencing and annotation strategies provide a general view of the cellular and molecular processes that take place in these arthropods, allowed the discovery of new pharmacological and biotechnological targets and uncovered several regulatory and metabolic responses behind the assembly of the scorpion venom. The results obtained in this report represent the first high-throughput study that thoroughly describes the universe of genes that are expressed in the scorpion

  10. Highly efficient anti-cancer therapy using scorpion 'NanoVenin'.

    PubMed

    Misra, Santosh K; Ye, Mao; Kim, Sumin; Pan, Dipanjan

    2014-11-11

    Host defence peptidotoxins from animal venoms have been identified to possess substantial anticancer properties. Towards a safer, translatable approach, we have developed a viable chemical methodology based on a well-defined, self-assembled polymeric nano-architecture for controlled delivery of toxins derived from scorpion venom. PMID:25061638

  11. Biotechnological Trends in Spider and Scorpion Antivenom Development.

    PubMed

    Laustsen, Andreas Hougaard; Solà, Mireia; Jappe, Emma Christine; Oscoz, Saioa; Lauridsen, Line Præst; Engmark, Mikael

    2016-01-01

    Spiders and scorpions are notorious for their fearful dispositions and their ability to inject venom into prey and predators, causing symptoms such as necrosis, paralysis, and excruciating pain. Information on venom composition and the toxins present in these species is growing due to an interest in using bioactive toxins from spiders and scorpions for drug discovery purposes and for solving crystal structures of membrane-embedded receptors. Additionally, the identification and isolation of a myriad of spider and scorpion toxins has allowed research within next generation antivenoms to progress at an increasingly faster pace. In this review, the current knowledge of spider and scorpion venoms is presented, followed by a discussion of all published biotechnological efforts within development of spider and scorpion antitoxins based on small molecules, antibodies and fragments thereof, and next generation immunization strategies. The increasing number of discovery and development efforts within this field may point towards an upcoming transition from serum-based antivenoms towards therapeutic solutions based on modern biotechnology. PMID:27455327

  12. Biotechnological Trends in Spider and Scorpion Antivenom Development

    PubMed Central

    Laustsen, Andreas Hougaard; Solà, Mireia; Jappe, Emma Christine; Oscoz, Saioa; Lauridsen, Line Præst; Engmark, Mikael

    2016-01-01

    Spiders and scorpions are notorious for their fearful dispositions and their ability to inject venom into prey and predators, causing symptoms such as necrosis, paralysis, and excruciating pain. Information on venom composition and the toxins present in these species is growing due to an interest in using bioactive toxins from spiders and scorpions for drug discovery purposes and for solving crystal structures of membrane-embedded receptors. Additionally, the identification and isolation of a myriad of spider and scorpion toxins has allowed research within next generation antivenoms to progress at an increasingly faster pace. In this review, the current knowledge of spider and scorpion venoms is presented, followed by a discussion of all published biotechnological efforts within development of spider and scorpion antitoxins based on small molecules, antibodies and fragments thereof, and next generation immunization strategies. The increasing number of discovery and development efforts within this field may point towards an upcoming transition from serum-based antivenoms towards therapeutic solutions based on modern biotechnology. PMID:27455327

  13. Antigenic Cross-Reactivity Anti-Birtoxin Antibody against Androctonus crassicauda Venom

    PubMed Central

    Van Zoelen, Suhandan Adigüzel; Ozkan, Ozcan; Inceoglu, Bora

    2015-01-01

    Background: Antivenom is still widely used in the treatment of envenomation as there are no vaccines or other effective agents available against animal venoms. Recently, neurotoxins named birtoxin family have been described from Parabuthus transvaalicus and Androctonus crassicauda. The aim of the present study was to test the anti-birtoxin antibodies for their ability to neutralize the lethal effects of A. crassicauda scorpion venom. Methods: SDS-PAGE and Western blotting used the presence of components from A. crassicauda and P. transvaalicus scorpion venoms and to determine the degree of cross-reactivity. The Minimum Lethal Dose (MLD) of venom was assessed by subcutaneously (sc) injections in mice. Results: The MLD of the A. crassicauda venom was 35 μg/ 20g mouse by sc injection route. Western blotting showed the presence of components from A. crassicauda and P. transvaalicus scorpion venoms strongly cross react with the A. crassicauda antivenom. However, Western blotting of the A. crassicauda scorpion venom using the Refik Saydam Public Health Agency (RSPHA) generated antibody showed that not all the venom components cross reacted with the anti-birtoxin antibody. The antibodies only cross reacted with components falling under the 19 kDa protein size of A. crassicauda venom. Conclusion: The bioassays and Western blotting of A. crassicauda venom with the anti-birtoxin antibodies produced against a synthetic peptide showed that these antibodies cross reacted but did not neutralize the venom of A. crassicauda. PMID:26623429

  14. Scorpion envenomation-induced acute thrombotic inferior myocardial infarction.

    PubMed

    Baykan, Ahmet Oytun; Gür, Mustafa; Acele, Armağan; Şeker, Taner; Çaylı, Murat

    2016-01-01

    The occurrence of a serious cardiac emergency following scorpion envenomation has rarely been reported and, when so, mostly presented as non-ST segment elevation myocardial infarction, cardiogenic shock, or myocarditis. Possible mechanisms include imbalance in blood pressure and coronary vasospasm caused by the combination of sympathetic excitation, scorpion venom-induced release of catecholamines, and the direct effect of the toxin on the myocardium. We report a case of a 55-year-old man who presented with acute inferior wall myocardial infarction (MI) within 2 h of being stung by a scorpion. Coronary angiogram revealed total thrombotic occlusion of the left circumflex artery, which was treated successfully with glycoprotein IIb/IIIa inhibitor, thrombus aspiration, antivenom serum, and supportive therapy. Therefore, life-threatening MI can complicate the clinical course during some types of scorpion envenomation and should be managed as an acute coronary syndrome. PMID:26875137

  15. Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds

    PubMed Central

    Sunagar, Kartik; Undheim, Eivind A. B.; Chan, Angelo H. C.; Koludarov, Ivan; Muñoz-Gómez, Sergio A.; Antunes, Agostinho; Fry, Bryan G.

    2013-01-01

    The episodic nature of natural selection and the accumulation of extreme sequence divergence in venom-encoding genes over long periods of evolutionary time can obscure the signature of positive Darwinian selection. Recognition of the true biocomplexity is further hampered by the limited taxon selection, with easy to obtain or medically important species typically being the subject of intense venom research, relative to the actual taxonomical diversity in nature. This holds true for scorpions, which are one of the most ancient terrestrial venomous animal lineages. The family Buthidae that includes all the medically significant species has been intensely investigated around the globe, while almost completely ignoring the remaining non-buthid families. Australian scorpion lineages, for instance, have been completely neglected, with only a single scorpion species (Urodacus yaschenkoi) having its venom transcriptome sequenced. Hence, the lack of venom composition and toxin sequence information from an entire continent’s worth of scorpions has impeded our understanding of the molecular evolution of scorpion venom. The molecular origin, phylogenetic relationships and evolutionary histories of most scorpion toxin scaffolds remain enigmatic. In this study, we have sequenced venom gland transcriptomes of a wide taxonomical diversity of scorpions from Australia, including buthid and non-buthid representatives. Using state-of-art molecular evolutionary analyses, we show that a majority of CSα/β toxin scaffolds have experienced episodic influence of positive selection, while most non-CSα/β linear toxins evolve under the extreme influence of negative selection. For the first time, we have unraveled the molecular origin of the major scorpion toxin scaffolds, such as scorpion venom single von Willebrand factor C-domain peptides (SV-SVC), inhibitor cystine knot (ICK), disulphide-directed beta-hairpin (DDH), bradykinin potentiating peptides (BPP), linear non-disulphide bridged

  16. Scorpion fish sting

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002849.htm Scorpion fish sting To use the sharing features on this page, please enable JavaScript. Scorpion fish are members of the family Scorpaenidae, which includes ...

  17. Insects and Scorpions

    MedlinePlus

    ... gov . Workplace Safety and Health Topics Insects & Scorpions Bees, Wasps, and Hornets Fire Ants Scorpions Additional Resources ... to outdoor workers. Stinging or biting insects include bees, wasps, hornets, and fire ants. The health effects ...

  18. Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel

    PubMed Central

    Hakim, Md Abdul; Jiang, Wenbin; Luo, Lei; Li, Bowen; Yang, Shilong; Song, Yuzhu; Lai, Ren

    2015-01-01

    The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation. PMID:26389953

  19. Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel.

    PubMed

    Hakim, Md Abdul; Jiang, Wenbin; Luo, Lei; Li, Bowen; Yang, Shilong; Song, Yuzhu; Lai, Ren

    2015-09-01

    The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation. PMID:26389953

  20. Transcriptome Analysis of Scorpion Species Belonging to the Vaejovis Genus

    PubMed Central

    Quintero-Hernández, Verónica; Ramírez-Carreto, Santos; Romero-Gutiérrez, María Teresa; Valdez-Velázquez, Laura L.; Becerril, Baltazar; Possani, Lourival D.; Ortiz, Ernesto

    2015-01-01

    Scorpions belonging to the Buthidae family have traditionally drawn much of the biochemist’s attention due to the strong toxicity of their venoms. Scorpions not toxic to mammals, however, also have complex venoms. They have been shown to be an important source of bioactive peptides, some of them identified as potential drug candidates for the treatment of several emerging diseases and conditions. It is therefore important to characterize the large diversity of components found in the non-Buthidae venoms. As a contribution to this goal, this manuscript reports the construction and characterization of cDNA libraries from four scorpion species belonging to the Vaejovis genus of the Vaejovidae family: Vaejovis mexicanus, V. intrepidus, V. subcristatus and V. punctatus. Some sequences coding for channel-acting toxins were found, as expected, but the main transcribed genes in the glands actively producing venom were those coding for non disulfide-bridged peptides. The ESTs coding for putative channel-acting toxins, corresponded to sodium channel β toxins, to members of the potassium channel-acting α or κ families, and to calcium channel-acting toxins of the calcin family. Transcripts for scorpine-like peptides of two different lengths were found, with some of the species coding for the two kinds. One sequence coding for La1-like peptides, of yet unknown function, was found for each species. Finally, the most abundant transcripts corresponded to peptides belonging to the long chain multifunctional NDBP-2 family and to the short antimicrobials of the NDBP-4 family. This apparent venom composition is in correspondence with the data obtained to date for other non-Buthidae species. Our study constitutes the first approach to the characterization of the venom gland transcriptome for scorpion species belonging to the Vaejovidae family. PMID:25659089

  1. Transcriptome analysis of scorpion species belonging to the Vaejovis genus.

    PubMed

    Quintero-Hernández, Verónica; Ramírez-Carreto, Santos; Romero-Gutiérrez, María Teresa; Valdez-Velázquez, Laura L; Becerril, Baltazar; Possani, Lourival D; Ortiz, Ernesto

    2015-01-01

    Scorpions belonging to the Buthidae family have traditionally drawn much of the biochemist's attention due to the strong toxicity of their venoms. Scorpions not toxic to mammals, however, also have complex venoms. They have been shown to be an important source of bioactive peptides, some of them identified as potential drug candidates for the treatment of several emerging diseases and conditions. It is therefore important to characterize the large diversity of components found in the non-Buthidae venoms. As a contribution to this goal, this manuscript reports the construction and characterization of cDNA libraries from four scorpion species belonging to the Vaejovis genus of the Vaejovidae family: Vaejovis mexicanus, V. intrepidus, V. subcristatus and V. punctatus. Some sequences coding for channel-acting toxins were found, as expected, but the main transcribed genes in the glands actively producing venom were those coding for non disulfide-bridged peptides. The ESTs coding for putative channel-acting toxins, corresponded to sodium channel β toxins, to members of the potassium channel-acting α or κ families, and to calcium channel-acting toxins of the calcin family. Transcripts for scorpine-like peptides of two different lengths were found, with some of the species coding for the two kinds. One sequence coding for La1-like peptides, of yet unknown function, was found for each species. Finally, the most abundant transcripts corresponded to peptides belonging to the long chain multifunctional NDBP-2 family and to the short antimicrobials of the NDBP-4 family. This apparent venom composition is in correspondence with the data obtained to date for other non-Buthidae species. Our study constitutes the first approach to the characterization of the venom gland transcriptome for scorpion species belonging to the Vaejovidae family. PMID:25659089

  2. Scorpion sting: eclampsia.

    PubMed

    Zengin, Suat; Al, Behçet; Oktay, Mehmet Murat; Kilic, Hasan

    2012-01-01

    Scorpion stings are common in many regions of the world, particularly in rural areas. While most of the stings are harmless and tend to be milder, some stings rarely have severe clinical course, including neurological, cardiovascular and respiratory system complications. Although there are many studies in the literature related to the scorpion sting, data on effects of scorpion stings in pregnant woman are very little. The authors have not come across any case report of eclampsia as a complication of scorpion sting. With this study, the authors aimed to discuss a scorpion sting lead to an unexpected complication, eclampsia. PMID:22962387

  3. Assessment of immunogenic characteristics of Hemiscorpius lepturus venom and its cross-reactivity with venoms from Androctonus crassicauda and Mesobuthus eupeus.

    PubMed

    Khanbashi, Shahin; Khodadadi, Ali; Assarehzadegan, Mohammad-Ali; Pipelzadeh, Mohammad Hassan; Vazirianzadeh, Babak; Hosseinzadeh, Mohsen; Rahmani, Ali Hassan; Asmar, Akbar

    2015-01-01

    Hemiscorpius lepturus (H. lepturus), one of the most venomous scorpions in tropical and sub-tropical areas, belongs to the Hemiscorpiidae family. Studies of antibodies in sera against the protein component of the venom from this organism can be of great use for the development of engineered variants of proteins for eventual use in the diagnosis/treatment of, and prevention of reactions to, stings. In the present in vitro study, the proteins of H. lepturus venom, which could specifically activate the production of immunoglobulin G (IgG) in victims accidently exposed to the venom from this scorpion, were evaluated and their cross-reactivity with venoms from two other important scorpion species including Androctonus crassicauda and Mesobuthus eupeus assessed. H. lepturus venom was analyzed with respect to its protein composition and its antigenic properties against antibodies found in sera collected from victims exposed to the venom of this scorpion within a previous 2-month period. The cross-reactivity of the H. lepturus venom with those from A. crassicauda and M. eupeus was assessed using ELISA and immunoblotting. Electrophoretic analysis of the venom of H. lepturus revealed several protein bands with weights of 8-116 KDa. The most frequent IgG-reactive bands in the test sera had weights of 34, 50, and 116 kDa. A weak cross-reactivity H. lepturus of venom with venoms from A. crassicauda and M. eupeus was detected. The results of immunoblotting and ELISA experiments revealed that H. lepturus venom activated the host immune response, leading to the production of a high titer of antibodies. Clearly, a determination of the major immunogenic components of H. lepturus venom could be valuable for future studies and ultimately of great importance for the potential production of recombinant or hypo-venom variants of these proteins. PMID:24946724

  4. Scorpion sting prevention and treatment in ancient Iran

    PubMed Central

    Dehghani, Rouhullah; Arani, Mohammad Ghannaee

    2015-01-01

    Due to the medical and therapeutic importance of scorpions in Iranian traditional medicine, this review was conducted on the treatment of scorpion sting as performed by traditional healers in order to realize complications, clinical manifestations, diversities, and deficiencies in the prevention, control, and treatment as mentioned in the pertained literatures. This study tried to make known and investigate attitudes of the Iranian national and traditional medicine towards controlling these venomous animals. Keywords and articles were searched through relevant sites on the Internet. We investigated different journals and references for the Iranian traditional medicine. Based on the articles and books found, we tried to find suitable solutions to problems from the viewpoint of traditional medicine. Scorpion sting dates back to ancient Iran and has been widely reflected in the resources of Iranian traditional medicine. The traditional medicine offers various guidelines that can be beneficial in this respect. New attitude towards scorpion sting with regard to traditional medicine resources can enhance control and prevention of scorpion stings. Consequently, this attitude leads authorities and researchers to a decreased level of scorpion stings or related consequences. PMID:26151015

  5. Scorpion Toxin Polyptides as Therapeutic Agents: An Overview.

    PubMed

    Bhavya, Janardhan; Francois, Niyonzima N; More, Veena S; More, Sunil S

    2016-01-01

    Scorpions are distributed throughout the world and numerous biological molecules are found in their venom most importantly peptide toxins. These toxins modulate the ion channels either by blocking the pore of the channel or by altering the voltage gating. Molecules which block the pores have been useful in deciphering the structure of the ion channels. Many scorpion toxins have already been used for probing the voltage gated sodium channels and studying their activation and inactivation processes. The specialty of scorpion toxins is to discriminate between vertebrate and invertebrate channels which have led them to applications as pharmacological tools. Most of the scorpion toxin polypeptides were isolated, characterized and were shown to possess vital properties useful in the field of medicine. For instance, they show therapeutic properties such as antimicrobial activity, anticancer activity, used to treat autoimmune diseases and cardiovascular effects. Although the scorpion toxins exhibited good therapeutic effects in vitro and in vivo, no one has reached the market with success up to date. In this mini-review, the scorpion polypeptides, their interactions with ion channels and their uses as therapeutic agents are discussed. PMID:27397476

  6. Scorpion sting prevention and treatment in ancient Iran.

    PubMed

    Dehghani, Rouhullah; Arani, Mohammad Ghannaee

    2015-04-01

    Due to the medical and therapeutic importance of scorpions in Iranian traditional medicine, this review was conducted on the treatment of scorpion sting as performed by traditional healers in order to realize complications, clinical manifestations, diversities, and deficiencies in the prevention, control, and treatment as mentioned in the pertained literatures. This study tried to make known and investigate attitudes of the Iranian national and traditional medicine towards controlling these venomous animals. Keywords and articles were searched through relevant sites on the Internet. We investigated different journals and references for the Iranian traditional medicine. Based on the articles and books found, we tried to find suitable solutions to problems from the viewpoint of traditional medicine. Scorpion sting dates back to ancient Iran and has been widely reflected in the resources of Iranian traditional medicine. The traditional medicine offers various guidelines that can be beneficial in this respect. New attitude towards scorpion sting with regard to traditional medicine resources can enhance control and prevention of scorpion stings. Consequently, this attitude leads authorities and researchers to a decreased level of scorpion stings or related consequences. PMID:26151015

  7. Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution

    PubMed Central

    Barlow, Axel; Pook, Catharine E.; Harrison, Robert A.; Wüster, Wolfgang

    2009-01-01

    The processes that drive the evolution of snake venom variability, particularly the role of diet, have been a topic of intense recent research interest. Here, we test whether extensive variation in venom composition in the medically important viper genus Echis is associated with shifts in diet. Examination of stomach and hindgut contents revealed extreme variation between the major clades of Echis in the proportion of arthropod prey consumed. The toxicity (median lethal dose, LD50) of representative Echis venoms to a natural scorpion prey species was found to be strongly associated with the degree of arthropod feeding. Mapping the results onto a novel Echis phylogeny generated from nuclear and mitochondrial sequence data revealed two independent instances of coevolution of venom toxicity and diet. Unlike venom LD50, the speed with which venoms incapacitated and killed scorpions was not associated with the degree of arthropod feeding. The prey-specific venom toxicity of arthropod-feeding Echis may thus be adaptive primarily by reducing venom expenditure. Overall, our results provide strong evidence that variation in snake venom composition results from adaptive evolution driven by natural selection for different diets, and underscores the need for a multi-faceted, integrative approach to the study of the causes of venom evolution. PMID:19364745

  8. Tityus serrulatus venom peptidomics: assessing venom peptide diversity.

    PubMed

    Rates, Breno; Ferraz, Karla K F; Borges, Márcia H; Richardson, Michael; De Lima, Maria Elena; Pimenta, Adriano M C

    2008-10-01

    MALDI-TOF-TOF and de novo sequencing were employed to assess the Tityus serrulatus venom peptide diversity. Previous works has shown the cornucopia of molecular masses, ranging from 800 to 3000Da, present in the venom from this and other scorpions species. This work reports the identification/sequencing of several of these peptides. The majority of the peptides found were fragments of larger venom toxins. For instance, 28 peptides could be identified as fragments from Pape proteins, 10 peptides corresponded to N-terminal fragments of the TsK beta (scorpine-like) toxin and fragments of potassium channel toxins (other than the k-beta) were sequenced as well. N-terminal fragments from the T. serrulatus hypotensins-I and II and a novel hypotensin-like peptide could also be found. This work also reports the sequencing of novel peptides without sequence similarities to other known molecules. PMID:18718845

  9. Acute myocardial infarction following scorpion sting in a case with obstructive coronary artery disease.

    PubMed

    Patra, Soumya; Satish, K; Singla, Vivek; Ravindranath, K S

    2013-01-01

    The occurrence of an acute myocardial infarction (MI) following a scorpion sting has been very rarely reported in the previous literature. Possible pathogenetic mechanisms include severe hypotension due to hypovolaemic shock and coronary spasm with subsequent thrombosis of coronary vessels developed after the release of vasoactive, inflammatory and thrombogenic substances contained in the scorpion venom. All of the previously reported cases had normal coronary angiogram. We report a case of a 65-year-old woman who presented with severe scorpion sting and was treated with prazosin. But a few hours later, she developed acute anterior wall MI. Coronary angiogram revealed the presence of significant stenosis in coronary arteries. As acute MI owing to significant coronary artery disease can be evident after severe scorpion envenomation, so every case of acute coronary syndrome following scorpion sting needs early diagnosis, thorough cardiovascular evaluation and appropriate treatment. PMID:23715842

  10. Scorpion image segmentation system

    NASA Astrophysics Data System (ADS)

    Joseph, E.; Aibinu, A. M.; Sadiq, B. A.; Bello Salau, H.; Salami, M. J. E.

    2013-12-01

    Death as a result of scorpion sting has been a major public health problem in developing countries. Despite the high rate of death as a result of scorpion sting, little report exists in literature of intelligent device and system for automatic detection of scorpion. This paper proposed a digital image processing approach based on the floresencing characteristics of Scorpion under Ultra-violet (UV) light for automatic detection and identification of scorpion. The acquired UV-based images undergo pre-processing to equalize uneven illumination and colour space channel separation. The extracted channels are then segmented into two non-overlapping classes. It has been observed that simple thresholding of the green channel of the acquired RGB UV-based image is sufficient for segmenting Scorpion from other background components in the acquired image. Two approaches to image segmentation have also been proposed in this work, namely, the simple average segmentation technique and K-means image segmentation. The proposed algorithm has been tested on over 40 UV scorpion images obtained from different part of the world and results obtained show an average accuracy of 97.7% in correctly classifying the pixel into two non-overlapping clusters. The proposed 1system will eliminate the problem associated with some of the existing manual approaches presently in use for scorpion detection.

  11. The First Venomous Crustacean Revealed by Transcriptomics and Functional Morphology: Remipede Venom Glands Express a Unique Toxin Cocktail Dominated by Enzymes and a Neurotoxin

    PubMed Central

    von Reumont, Björn M.; Blanke, Alexander; Richter, Sandy; Alvarez, Fernando; Bleidorn, Christoph; Jenner, Ronald A.

    2014-01-01

    Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, and Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes, and hymenopterans. Surprisingly, despite their great diversity of body plans, there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind, and cave-dwelling remipede crustaceans are venomous and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a nontoxin paralog of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin and underlines the importance of incorporating data derived from nonvenom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions, and spiders and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species. PMID:24132120

  12. Scorpion Envenomation in Pregnancy.

    PubMed

    Shah, Noor; Martens, Mark G

    2016-06-01

    Scorpion envenomation affects more than 1 million people every year and represents an important public health problem worldwide. The effects of envenomation range from localized pain and paresthesias to overactivation of the sympathetic nervous system, leading to neurotoxicity and even death. Of the individuals affected by scorpion envenomation, certain populations, such as young children and older adults, are at high risk for severe disease. Substantial literature exists on the management of envenomation in children; however, scant literature exists that addresses the same phenomenon in pregnant women. This review serves to identify the effects of scorpion envenomation on pregnant women and the treatment options available to them. After thorough review of the treatment modalities that are used to treat scorpion envenomation, we developed a treatment algorithm that may help guide the management of pregnant women who present with scorpion envenomation. PMID:27255088

  13. Some biological effects of scorpion envenomation in late pregnant rats.

    PubMed

    Ben Nasr, Hmed; Serria, Hammami; Chaker, Selma; Riadh, Badraoui; Zouheir, Sahnoun; Kamel, Jamoussi; Tarek, Rebai; Khaled, Zeghal

    2009-11-01

    Scorpion envenoming is less studied during gestation; however, it may induce various biological disturbances in maternal organism and hypothetical ones on their fetuses. The scope of this report was to elucidate some biological effects of such poisoning in late pregnant rats. Hence, TBARS levels in maternal lung, placental and fetal pulmonary and hepatic tissues and dam's biochemical blood parameters (glucose, creatinine, 17-beta estradiol, progesterone, blood nitrogen urea, sodium and potassium maternal plasma concentrations) had been evaluated after saline (G1), and scorpion venom (G2: 30 min and G3: 60 min) injections in 22nd day pregnant rats. Histological microscopic examination of these tissues was also carried out in HE-stained paraffin sections. In addition, the mean arterial blood pressure following the envenomation variations was measured in three rats from the same pool. Our results showed that Buthus occitanus tunetanus crude venom induced significant increase in maternal, placental and fetal tissues lipid peroxidation, concomitant with blood pressure elevation. Maternal plasma creatinine, estradiol and progesterone concentrations levelled up significantly after 30 min or later (60 min) after the venom injection. Except for a probable pronounced oedema and few congestions in maternal lungs and degenerative aspects of trophoblast cells, all examined tissues showed a conserved structure. These results suggest that scorpion envenomation may induce gestation process disturbances and threatens both mother's and fetus' well-being. PMID:19185478

  14. A review of venomous animal bites and stings in pregnant patients.

    PubMed

    Langley, Ricky Lee

    2004-01-01

    This is a review of Medline and PubMed articles on venomous animal bites and stings during pregnancy reported in English literature from 1966 to 2002. Eighty-five venomous snakebites were reported in pregnant women. Although there are frequent anecdotal reports of scorpion stings in pregnant women, few case reports are documented. Other venomous animal bites or stings to pregnant women that have been reported include spiders, jellyfish, and insects, and these are described. Adverse reproductive and teratogenic effects of venoms on gravid animals are also briefly reviewed. Although uncommon, venomous bites and stings during pregnancy may have significant adverse effects on the fetus and the mother. PMID:15473462

  15. Preliminary spectroscopic characterization of six toxins from Latin American scorpions.

    PubMed

    Possani, L; Steinmetz, W E; Dent, M A; Alagón, A C; Wüthrich, K

    1981-07-28

    This paper reports on spectroscopic studies of six toxins from the Latin American scorpions Centruroides noxius Hoffmann, Centruroides elegans Thorell and Tityus serrulatus Lutz and Mello. The isolation and purification of five of these toxins was described previously. The preparation of toxin II.9.2.2 from the venom of C. noxius is first described here. Circular dichroism and nuclear magnetic resonance spectra indicate similarities and differences between these scorpion toxins and previously characterized snake toxins. While there is evidence that the toxins from scorpions and snakes both contain extended beta-sheet secondary structures, the spectral properties of the scorpion toxins are overall of a different type from those of snake toxins. Among the six scorpion toxins those from T. serrulatus have spectral properties markedly different from those of the Centruroides species. Furthermore, thermal denaturation and amide proton exchange measurements showed that the globular structures of the Tityus toxins were markedly less stable and less rigid than those of the Centruroides toxins. PMID:7284435

  16. Voltage-Gated Sodium Channel in Grasshopper Mice Defends Against Bark Scorpion Toxin

    PubMed Central

    Rowe, Matthew P.; Cummins, Theodore R.; Zakon, Harold H.

    2014-01-01

    Painful venoms are used to deter predators. Pain itself, however, can signal damage and thus serves an important adaptive function. Evolution to reduce general pain responses, although valuable for preying on venomous species, is rare, likely because it comes with the risk of reduced response to tissue damage. Bark scorpions capitalize on the protective pain pathway of predators by inflicting intensely painful stings. However, grasshopper mice regularly attack and consume bark scorpions, grooming only briefly when stung. Bark scorpion venom induces pain in many mammals (house mice, rats, humans) by activating the voltage-gated Na+ channel Nav1.7, but has no effect on Nav1.8. Grasshopper mice Nav1.8 has amino acid variants that bind bark scorpion toxins and inhibit Na+ currents, blocking action potential propagation and inducing analgesia. Thus, grasshopper mice have solved the predator-pain problem by using a toxin bound to a nontarget channel to block transmission of the pain signals the venom itself is initiating. PMID:24159039

  17. Centipede venoms and their components: resources for potential therapeutic applications.

    PubMed

    Hakim, Md Abdul; Yang, Shilong; Lai, Ren

    2015-11-01

    Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components. PMID:26593947

  18. Centipede Venoms and Their Components: Resources for Potential Therapeutic Applications

    PubMed Central

    Hakim, Md Abdul; Yang, Shilong; Lai, Ren

    2015-01-01

    Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components. PMID:26593947

  19. Neurotoxic and cytotoxic effects of venom from different populations of the Egyptian Scorpio maurus palmatus.

    PubMed

    Abdel-Rahman, Mohamed A; Omran, Mohamed Alaa A; Abdel-Nabi, Ismail M; Nassier, Omimah A; Schemerhorn, Brandon J

    2010-01-01

    Neurotoxic and cytotoxic effects of venoms from Scorpio maurus palmatus taken from different populations were assessed for geographic based variability in toxicity, and to evaluate their insecticidal potency. Scorpions were collected from four regions. Three locations were mutually isolated pockets in the arid area of Southern Sinai. The fourth sample was collected from a population inhabiting the semi-arid environment of Western Mediterranean Coastal Desert. The neurotoxic (paralytic) effect of the venom from each population was assayed by its ability to induce permanent disability in adult cockroaches within 3h. Venom was applied using microinjection techniques through an intersegmental membrane. Probit analysis was used to calculate the Paralytic Effective Dose (PED(50), ng/100mg). Levels of glutathione, lipid peroxidation, protein carbonyl content and nitric oxide, as well as the activities of superoxide dismutase, catalase and cholinesterase, were measured to assess the cytotoxicity of the venom. The results show that the injected venom from each population induced obvious spasticity, followed by flaccid paralysis. All the tested biochemical parameters, except glutathione content, revealed significant differences in toxicity in venom taken from the different scorpion populations. We conclude that (i) the venom of this scorpion has significant neurotoxic and cytotoxic effects on insect cells, (ii) its efficacy, as assessed by the PED(50) unit, exhibited variation across its geographic range, and (iii) components in the venom may have the potential for being developed into effective and environmentally friendly bioinsecticides. PMID:19682484

  20. Tityus serrulatus venom--A lethal cocktail.

    PubMed

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

    2015-12-15

    Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). PMID:26522893

  1. Plectreurys tristis venome: A proteomic and transcriptomic analysis

    PubMed Central

    Zobel-Thropp, Pamela A; Thomas, Emily Z; David, Cynthia L; Breci, Linda A; Binford, Greta J

    2014-01-01

    Spider venoms are complex cocktails rich in peptides, proteins and organic molecules that collectively act to immobilize prey. Venoms of the primitive hunting spider, Plectreurys tristis, have numerous neurotoxic peptides called “plectoxins” (PLTX), a unique acylpolyamine called bis(agmatine)oxalamide, and larger unidentified protein components. These spiders also have unconventional multi-lobed venom glands. Inspired by these unusual characteristics and their phylogenetic position as Haplogynes, we have partially characterized the venome of P. tristis using combined transcriptomic and proteomic methods. With these analyses we found known venom neurotoxins U1-PLTX-Pt1a, U3-PLTX-Pt1a, and we discovered new groups of potential neurotoxins, expanding the U1- and ω-PLTX families and adding U4-through U9-PLTX as six new groups. The venom also contains proteins that are homologs of astacin metalloproteases that, combined with venom peptides, make up 94% of components detected in crude venom, while the remaining 6% is a single undescribed protein with unknown function. Other proteins detected in the transcriptome were found to be members of conserved gene families and make up 20% of the transcripts. These include cDNA sequences that match venom proteins from Mesobuthus and Hottentotta scorpions, Loxosceles and Dysdera spiders, and also salivary and secreted peptide sequences from Ixodes, Amblyomma and Rhipicephalus ticks. Finally, we show that crude venom has neurotoxic effects and an effective paralytic dose on crickets of 3.3µg/gm. PMID:25400903

  2. Purification of the Immunogenic Fractions and Determination of Toxicity in Mesobuthus eupeus (Scorpionida: Buthidae) Venom

    PubMed Central

    Khoobdel, Mehdi; Zahraei-Salehi, Taghi; Nayeri-Fasaei, Bahar; Khosravi, Mohammad; Omidian, Zahra; Motedayen, Mohammad Hassan; Akbari, Abolfazal

    2013-01-01

    Background: Scorpions stings are a health problem in many parts of the world. Mesobuthus eupeus (Buthidae) is the most prevalent species in the Middle East and Central Asia. Definition of toxicogenic and immunogenic characteristics of the venom is necessary to produce antidote. In this study, the noted properties of M. eupeus venom were evaluated. Methods: Venom was obtained by milking M. eupeus scorpions for lyophilization. Toxicity was determined after injecting the venom to albino mice and calculating LD50. Polyclonal antibodies against M. eupeus venom were obtained from immunized rabbits. The CH-Sepharose 4B column was used for isolating the specific antibodies. 10 mg of the affinity-purified antibodies were conjugated with a CH-Sepharose 4B column and M. eupeus venom was applied to the column. The bound fragments were eluted using hydrogen chloride (pH: 2.5). Crude venom and affinity-purified fractions of the venom were analyzed by SDS-PAGE technique. Results: Lethal dose (LD) was 8.75, 11.5 and 4.5 mg/kg for IP, SC and IV respectively. The LD50 of M. eupeus venom was 6.95 mg/kg. The crude venom had 12 detectable bands with molecular weights of 140, 70, 50, 33, 30, 27, 22, 18, 14, 10 kDa and two bands less than 5 kDa. The affinity-purified venom presented eight bands. The 27 kDa band was clearly sharper than other bands but 70, 18, 10 and one of the less than 5 kDa bands were not observed. Conclusions: Contrary to popular belief, which know scorpion venom as non-immunogenic composition, the current study was shown that the most fractions of the M. eupeus are immunogenic. PMID:24409439

  3. Scorpion Sheds ‘Tail’ to Escape: Consequences and Implications of Autotomy in Scorpions (Buthidae: Ananteris)

    PubMed Central

    Mattoni, Camilo I.; García-Hernández, Solimary; Botero-Trujillo, Ricardo; Ochoa, José A.; Ojanguren-Affilastro, Andrés A.; Pinto-da-Rocha, Ricardo; Prendini, Lorenzo

    2015-01-01

    Autotomy, the voluntary shedding or detachment of a body part at a determined cleavage plane, is a common anti-predation defense mechanism in several animal taxa, including arthropods. Among arachnids, autotomy has been observed in harvestmen, mites, and spiders, always involving the loss of legs. Autotomy of the opisthosoma (abdomen) was recently reported in a single species of the Neotropical buthid scorpion genus Ananteris Thorell, 1891, but few details were revealed. Based on observations in the field and laboratory, examination of material in museum collections, and scanning electron microscopy, we document autotomy of the metasoma (the hind part of the opisthosoma, or ‘tail’) in fourteen species of Ananteris. Autotomy is more common in males than females, and has not been observed in juveniles. When the scorpion is held by the metasoma, it is voluntarily severed at the joints between metasomal segments I and II, II and III, or III and IV, allowing the scorpion to escape. After detachment, the severed metasoma moves (twitches) automatically, much like the severed tail of a lizard or the severed leg of a spider, and reacts to contact, even attempting to sting. The severed surface heals rapidly, scar tissue forming in five days. The lost metasomal segments and telson cannot be regenerated. Autotomy of the metasoma and telson results in permanent loss of the posterior part of the scorpion’s digestive system (the anus is situated posteriorly on metasomal segment V) and the ability to inject venom by stinging. After autotomy, scorpions do not defecate and can only capture small prey items. However, males can survive and mate successfully for up to eight months in the laboratory. In spite of diminished predation ability after autotomy, survival allows males to reproduce. Autotomy in Ananteris therefore appears to be an effective, adaptive, anti-predation escape mechanism. PMID:25629529

  4. Development of protective agent against Hottentotta saulcyi venom using camelid single-domain antibody.

    PubMed

    Darvish, Maryam; Behdani, Mahdi; Shokrgozar, Mohammad Ali; Pooshang-Bagheri, Kamran; Shahbazzadeh, Delavar

    2015-12-01

    Hottentotta saulcyi, medically important scorpion species, causes some of harmful toxic exposure in Iran. Administrated, conventional antivenom-based immunotherapy is still limited and hardly meet ideal characteristic of effective treatment for scorpion envenomation. In this study we aimed to develop a neutralizing agent directed against scorpion venom based on VHH, variable domain of the Camelidae heavy chain antibody or Nanobody. This promising biomolecule is well-established as an advantageous tool for therapeutic purposes due to its small size, stability, monomeric performance and less immunogenicity. In this study, a large Nb library was constructed and phage displayed after successful camel immunization using H. saulcyi scorpion crude venom. After a series of biopanning rounds on Sephadex G50 purified venom fraction and screening by monoclonal phage ELISA, the best reactive Nb was retrieved and designated Nb12. The selected Nb was then expressed as soluble protein in Escherichia coli, purified and confirmed by SDS-PAGE analysis and western blotting. The lead candidate Nb12 bound scorpion venom with Kaff value of 5×10(7)M(-1). Nb12 was shown to be capable of neutralizing 2 LD50 of whole venom of scorpion toxin when injected in the ratio of the Nb/toxin of 1.4:1 into C57BL/6 mice. In challenge experiment, Nb succeeded to rescue all i.p. lethal dose injected mice even when administrated i.v., 20min after envenoming. These results with ease of production and superior neutralizing activity make Nb a suitable anti-toxin candidate for treatment of scorpion envenoming. PMID:26468036

  5. Clinical pathology alterations in pregnant and non-pregnant rats following scorpion envenomation.

    PubMed

    Nasr, Hmed Ben; Bolon, Brad; Hammami, Serria Turky; Sahnoun, Zouhier; Jamoussi, Kamel; Lahyani, Amina; Zeghal, Khaled Mounir

    2009-10-01

    Scorpion envenomation is a growing problem in many countries, especially among women and children. Existing diagnostic criteria are not sufficiently specific to allow antivenin administration in the absence of a confirmed scorpion sting. This study was performed to evaluate conventional haematological and serum chemical measurements as potential indices of scorpion envenomation. Adult, cycling nulliparous and near-term primiparous, white Wistar rats received a single subcutaneous injection of crude venom (600 µg/kg) from the Buthidae scorpion (Buthus occitanus tunetanus). All envenomed rats were observed for external signs and symptoms of toxicity until necropsy, which entailed terminal blood collection at either 0.5, 1, 2, or 4 hr after venom administration (n = 6 per reproductive state per time-point) for evaluation of selected clinical chemistry and haematological analytes. Control cohorts (matched for age and reproductive state) received saline injections subcutaneously and were necropsied at 0.5 hr. Almost all envenomed rats but no control animals displayed physical symptoms of intoxication, including agitation, mastication with hypersalivation, and/or vocalizing. Reproducible alterations in clinical pathology parameters were lacking in venom-treated rats regardless of reproductive status, although modest but significant Rho correlations suggested that mild haemoconcentration, haemolysis, renal function deficits and possibly coagulation difficulties developed over time. PMID:19663823

  6. Insights into Antimicrobial Peptides from Spiders and Scorpions.

    PubMed

    Wang, Xiuqing; Wang, Guangshun

    2016-01-01

    The venoms of spiders and scorpions contain a variety of chemical compounds. Antimicrobial peptides (AMPs) from these organisms were first discovered in the 1990s. As of May 2015, there were 42 spider's and 63 scorpion's AMPs in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). These peptides have demonstrated broad or narrow-spectrum activities against bacteria, fungi, viruses, and parasites. In addition, they can be toxic to cancer cells, insects and erythrocytes. To provide insight into such an activity spectrum, this article discusses the discovery, classification, structure and activity relationships, bioinformatics analysis, and potential applications of spider and scorpion AMPs. Our analysis reveals that, in the case of linear peptides, spiders use both glycine-rich and helical peptide models for defense, whereas scorpions use two distinct helical peptide models with different amino acid compositions to exert the observed antimicrobial activities and hemolytic toxicity. Our structural bioinformatics study improves the knowledge in the field and can be used to design more selective peptides to combat tumors, parasites, and viruses. PMID:27165405

  7. Emerging options for the management of scorpion stings

    PubMed Central

    Chippaux, Jean-Philippe

    2012-01-01

    Scorpion stings are common in many tropical countries. Although most scorpion stings cause only localized pain without life-threatening envenoming, about one third of stings cause systemic envenoming which can result in death. Children are particularly sensitive to scorpion envenoming. The severity of scorpion stings is related to the presence of neurotoxins in the venom that cause a sudden release of neurotransmitters from the autonomic nervous system, predominantly sympathetic. There is also a strong inflammatory response that worsens symptoms, including those of a respiratory nature. Several vital functions may be directly affected, including the cardiovascular, respiratory, and neuromuscular systems. Hypertension is constant at the beginning of systemic envenoming and sometimes has a severe cardiac and respiratory impact. Although controversial, immunotherapy is the only etiological treatment. Administered early, it prevents many complications and improves the outcome. New antivenoms are highly purified immunoglobulin fragments, the efficacy and safety of which are excellent. As a consequence, adverse reactions to antivenoms are now very rare and usually mild, which should limit any reluctance regarding their routine use. Symptomatic treatment is still necessary to support immunotherapy, especially in cases of delayed arrival at hospital. A combination of both approaches should be considered, based on local resources and constraints. PMID:22826633

  8. Broadening the neutralizing capacity of a family of antibody fragments against different toxins from Mexican scorpions.

    PubMed

    Rodríguez-Rodríguez, Everardo Remi; Olamendi-Portugal, Timoteo; Serrano-Posada, Hugo; Arredondo-López, Jonathan Noé; Gómez-Ramírez, Ilse; Fernández-Taboada, Guillermo; Possani, Lourival D; Anguiano-Vega, Gerardo Alfonso; Riaño-Umbarila, Lidia; Becerril, Baltazar

    2016-09-01

    New approaches aimed at neutralizing the primary toxic components present in scorpion venoms, represent a promising alternative to the use of antivenoms of equine origin in humans. New potential therapeutics developed by these approaches correspond to neutralizing antibody fragments obtained by selection and maturation processes from libraries of human origin. The high sequence identity shared among scorpion toxins is associated with an important level of cross reactivity exhibited by these antibody fragments. We have exploited the cross reactivity showed by single chain variable antibody fragments (scFvs) of human origin to re-direct the neutralizing capacity toward various other scorpion toxins. As expected, during these evolving processes several variants derived from a parental scFv exhibited the capacity to simultaneously recognize and neutralize different toxins from Centruroides scorpion venoms. A sequence analyses of the cross reacting scFvs revealed that specific mutations are responsible for broadening their neutralizing capacity. In this work, we generated a set of new scFvs that resulted from the combinatorial insertion of these point mutations. These scFvs are potential candidates to be part of a novel recombinant antivenom of human origin that could confer protection against scorpion stings. A remarkable property of one of these new scFvs (ER-5) is its capacity to neutralize at least three different toxins and its complementary capacity to neutralize the whole venom from Centruroides suffusus in combination with a second scFv (LR), which binds to a different epitope shared by Centruroides scorpion toxins. PMID:27212628

  9. Scorpion fauna and epidemiological aspects of scorpionism in southeastern Iran

    PubMed Central

    Nejati, Jalil; Mozafari, Ehsan; Saghafipour, Abedin; Kiyani, Malek

    2014-01-01

    Objective To identify the scorpion fauna and classify the epidemiological aspects of scorpionism in an endemic region, Southeast Iran. Methods Scorpionism data were collected from health centers and hospitals in Sistan-Baluchestan Province during 2010-2011. Specimens were collected at night, using UV light, between May and October 2012. Results In total, 246 scorpions were collected from two families (Buthidae and Scorpionidae). Five species including Odontobuthus odonturus, Hottentotta (Buthotus) jayakari, Compsobuthus matthiesseni, Scorpio maurus and Orthochirus scrobiculosus are reported for the first time from this area. Androctonus crassicauda was the dominant species. In total, 3 638 scorpion sting cases were recorded by health system, the majority of which were females. Stings mostly occurred in July and the age group of 15-24 years presented the highest frequency. Scorpionism decreased during 2011 compared with that in 2010 (68.2%). Conclusions Based on the results, scorpionism is a serious health problem in this area and increasing knowledge of residents regarding the prevention methods of scorpion stings is recommended. Additional research on the scorpion fauna, their ecological and molecular variety in this part of the country is needed as well as the correlation between scorpions' species and the clinical signs and symptoms. PMID:25183084

  10. Behavioral, histopathological and biochemical impairments observed in mice envenomed by the scorpion: Hottentota gentili (Pallary, 1924).

    PubMed

    El Hidan, Moulay Abdelmonaim; Touloun, Oulaid; El Hiba, Omar; Chait, Abderrahman; Eddine Hafid, Jamal; Boumezzough, Ali

    2015-09-01

    Hottentota gentili is a black scorpion which has been considered as dangerous specie by many authors. However there are no data regarding minimal lethal dose and effects of the scorpion venom till now. We therefore aimed, by the present investigation, to assess on the one hand, the LD50 of H. gentili venom by sublethal injection and the effects on some vital organs, by a histological and a biochemical tools. On the other hand, the possible neurobehavioral impairments, in Swiss mice, 3 h, 6 h and 12 h following envenomation. The LD50 of H. gentili scorpion venom was found to be 0.46 mg/kg by subcutaneous injection route. Venom produced focal fragmentation of myocardial fibers, while lungs showed rupture of the alveolar structure. Intestines showed selective histopathological changes. Concomitantly, there was a significant rise in the serum enzymes levels, as well as hyperkalemia and a high level of plasma albumine and creatine. Proteinuria was also observed. The observed behavioral effects were a hypoactivity in the both experiments 30 min and 3 h after injection. The envenomation produced an increased immobility time only 30 min and 3 h post injection in the tail suspension test (TST). PMID:26091876