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Sample records for quinquestriatus scorpion venom

  1. Oxidative stress and some biochemical alterations due to scorpion (Leiurus quinquestriatus) crude venom in rats.

    PubMed

    Salman, Muhammad M A; Hammad, Seddik

    2017-07-01

    Scorpion envenomation is a common medical problem in many countries; it is an important cause of morbidity and mortality. The venom of Leiurus quinquestriatus (LQ) is responsible for a number of deaths in children and adults. It has been stated that specific pathophysiological conditions such as generation of oxygen free radicals may trigger the onset of multiple organ dysfunction; therefore, the present study aimed to assess the oxidative stress mediated by LQ crude venom and its effect on the biochemical parameters in rats. Adult male Albino rats (250±30g body weight) were divided into three groups (n=5). In control group, rats were intraperitoneally (ip) injected with 50μL saline solution. Groups 2 and 3 were ip injected with 0.1mg/kg and 0.2mg/kg body weight of crude venom, respectively. Blood samples and liver tissues were harvested 1, 2 and 4h post-injection. Serum levels of glucose, cholesterol, creatinine, urea, uric acid and malondialdehyde increased significantly in envenomed animals within 1, 2 and 4h post-injection, compared to controls. However, the levels of total serum protein, albumin, globulin and triglycerides as well as catalase, glutathione peroxidase and super oxide dismutase in envenomed rats were significantly decreased compared to controls. We can conclude that LQ crude venom induces oxidative stress via reduction of antioxidant systems and alters some biochemical parameters of envenomed rats. Copyright © 2017. Published by Elsevier Masson SAS.

  2. Elemental analysis of scorpion venoms.

    PubMed

    Al-Asmari, AbdulRahman K; Kunnathodi, Faisal; Al Saadon, Khalid; Idris, Mohammed M

    2016-01-01

    Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the host on envenomation and may also have a therapeutic potential. Scorpion venoms produced by the columnar cells of venom gland are complex mixture of mucopolysaccharides, neurotoxic peptides and other components. This study was aimed at cataloguing the elemental composition of venoms obtained from medically important scorpions found in the Arabian peninsula. The global elemental composition of the crude venom obtained from Androctonus bicolor, Androctonus crassicauda and Leiurus quinquestriatus scorpions were estimated using ICP-MS analyzer. The study catalogued several chemical elements present in the scorpion venom using ICP-MS total quant analysis and quantitation of nine elements exclusively using appropriate standards. Fifteen chemical elements including sodium, potassium and calcium were found abundantly in the scorpion venom at PPM concentrations. Thirty six chemical elements of different mass ranges were detected in the venom at PPB level. Quantitative analysis of the venoms revealed copper to be the most abundant element in Androctonus sp. venom but at lower level in Leiurus quinquestriatus venom; whereas zinc and manganese was found at higher levels in Leiurus sp. venom but at lower level in Androctonus sp. venom. These data and the concentrations of other different elements present in the various venoms are likely to increase our understanding of the mechanisms of venom activity and their pharmacological potentials.

  3. Elemental analysis of scorpion venoms

    PubMed Central

    Al-Asmari, AbdulRahman K; Kunnathodi, Faisal; Al Saadon, Khalid; Idris, Mohammed M

    2016-01-01

    Scorpion venom is a rich source of biomolecules, which can perturb physiological activity of the host on envenomation and may also have a therapeutic potential. Scorpion venoms produced by the columnar cells of venom gland are complex mixture of mucopolysaccharides, neurotoxic peptides and other components. This study was aimed at cataloguing the elemental composition of venoms obtained from medically important scorpions found in the Arabian peninsula. The global elemental composition of the crude venom obtained from Androctonus bicolor, Androctonus crassicauda and Leiurus quinquestriatus scorpions were estimated using ICP-MS analyzer. The study catalogued several chemical elements present in the scorpion venom using ICP-MS total quant analysis and quantitation of nine elements exclusively using appropriate standards. Fifteen chemical elements including sodium, potassium and calcium were found abundantly in the scorpion venom at PPM concentrations. Thirty six chemical elements of different mass ranges were detected in the venom at PPB level. Quantitative analysis of the venoms revealed copper to be the most abundant element in Androctonus sp. venom but at lower level in Leiurus quinquestriatus venom; whereas zinc and manganese was found at higher levels in Leiurus sp. venom but at lower level in Androctonus sp. venom. These data and the concentrations of other different elements present in the various venoms are likely to increase our understanding of the mechanisms of venom activity and their pharmacological potentials. PMID:27826410

  4. Effect of a bradykinin-potentiating factor isolated from scorpion venom (Leiurus quinquestriatus) on some blood indices and lipid profile in irradiated rats.

    PubMed

    Salman, Muhammad M A; Kotb, Ahmed M; Haridy, Mohie A M; Golka, Klaus; Hammad, Seddik

    2017-04-08

    Bradykinin appears to be an important regulator of cardiovascular function. It is also being increasingly noted as a participant in actions of drugs that affect the liver, kidney, and circulation. In our previous studies, bradykinin-potentiating factor (BPF) isolated from scorpion venom (Leiurus quinquestriatus) has been shown to be protective against hepato- and nephrotoxicity as well as healing skin burns by reducing oxidative stress in hyperglycemic conditions. Therefore, we aim to evaluate the ability of BPF in treating irradiated rats. A group of rats was exposed to γ-irradiation and subsequently treated with BPF injections aiming to elucidate the possibility of BPF to rescue γ-irradiation harmful effects. As controls, we used γ-irradiation exposed, BPF-injected, and untreated rats. The data obtained showed that the irradiated animals suffered from marked changes of many important blood parameters including red blood cells, leukocytes, platelets, hemoglobin, packed cell volume, high-density cholesterol, total cholesterol, triglycerides, and low-density cholesterol. Interestingly, BPF was able to rescue the deleterious effects of irradiation in rats and normalized their blood parameters to the basal levels. We conclude that BPF could ameliorate irradiation damaging effects.

  5. Characterization of scorpion alpha-like toxin group using two new toxins from the scorpion Leiurus quinquestriatus hebraeus.

    PubMed

    Hamon, Alain; Gilles, Nicolas; Sautière, Pierre; Martinage, Arlette; Kopeyan, Charles; Ulens, Chris; Tytgat, Jan; Lancelin, Jean-Marc; Gordon, Dalia

    2002-08-01

    Two novel toxins, Lqh6 and Lqh7, isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus, have in their sequence a molecular signature (8Q/KPE10) associated with a recently defined group of alpha-toxins that target Na channels, namely the alpha-like toxins [reviewed in Gordon, D., Savarin, P., Gurevitz, M. & Zinn-Justin, S. (1998) J. Toxicol. Toxin Rev. 17, 131-159]. Lqh6 and Lqh7 are highly toxic to insects and mice, and inhibit the binding of alpha-toxins to cockroach neuronal membranes. Although they kill rodents by intracerebroventricular injection, they do not inhibit the binding of antimammal alpha-toxins (e.g. Lqh2) to rat brain synaptosomes, not even at high concentrations. Furthermore, in voltage-clamp experiments, rat brain Na channels IIA (rNav1.2A) expressed in Xenopus oocytes are not affected by Lqh6 nor by Lqh7 below 3 micro m. In contrast, muscular Na channels (rNav1.4 and hNav1.5) expressed in the same cells respond to nanomolar concentrations of Lqh6 and Lqh7 by slowing of Na current inactivation and a leftward shift of the peak conductance-voltage curve. The structural and pharmacological properties of the new toxins are compared to those of other scorpion alpha-toxins in order to re-examine the hallmarks previously set for the alpha-like toxin group.

  6. 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.

  7. Scorpion venoms in gastric cancer

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Pei-Ying

    2016-01-01

    Venom secretions from snakes, scorpions, spiders and bees, have been widely applied in traditional medicine and current biopharmaceutical research. Possession of anticancer potential is another novel discovery for animal venoms and toxins. An increasing number of studies have shown the anticancer effects of venoms and toxins of snakes, and scorpions in vitro and in vivo, which were achieved mainly through the inhibition of cancer growth, arrest of cell cycle, induction of apoptosis and suppression of cancer metastasis. However, more evidence is needed to support this concept and the mechanisms of anticancer actions are not clearly understood. The present review is focused on the recant updates on anticancer venom research. PMID:27900054

  8. Virocidal activity of Egyptian scorpion venoms against hepatitis C virus.

    PubMed

    El-Bitar, Alaa M H; Sarhan, Moustafa M H; Aoki, Chie; Takahara, Yusuke; Komoto, Mari; Deng, Lin; Moustafa, Mohsen A; Hotta, Hak

    2015-03-24

    Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions. The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities. S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC₅₀) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV. S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.

  9. 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.

  10. Leiurus quinquestriatus venom inhibits different kinds of Ca2+-dependent K+ channels.

    PubMed

    Abia, A; Lobatón, C D; Moreno, A; García-Sancho, J

    1986-04-14

    A minor protein component of Leiurus quinquestriatus venom has been reported to inhibit selectively the apamin-insensitive Ca2+-dependent K+ channels of mammalian skeletal muscle (Miller, C., Moczydlowski, E., Latorre, R. and Phillips, M. (1985) Nature 313, 316-318). We report the effect of the venom on both the apamin-insensitive channels of the human erythrocyte, the Ehrlich cell and the rat thymocyte and the apamin-sensitive channel of the guinea pig hepatocyte. The venom inhibited Ca2+-dependent K+ transport in all the cases with a Ki value within the range of 1 to 10 micrograms/ml, similar to that reported previously in muscle. Valinomycin-induced K+ transport was also antagonized by the venom but its sensitivity was about 1/10 as much as that of the Ca2+-dependent K+ channel.

  11. The histological changes in the liver, lung and kidney after scorpion poisoning (Buthus quinquestriatus).

    PubMed

    Nawar, N N; Shoukri, N A; Hanna, M M

    1979-06-01

    The effect of sublethal doses of Buthus quinquestriatus on the hepatic vascular bed and hepatic parenchyma were studied. The main effect of the venom was primarily on the vascular bed of the liver as manifested by dilatation of branches of the hepatic artery, portal vein together with intravascular thrombi and subcapsular haemorrhages. Apart from mild hydropic degeneration some cells of the hepatic parenchyma showed focal necrosis and Kupffer cells were frequently hypertrophied and contained pigment. In the lung, dilated thrombosed vessels were observed. In the kidney, the vessels showed the smae changes. The epithelial and endothelial cells of the glomeruli appeared normal except for slight swelling with intact basement membrane. The tubular cells were swollen with increased granularity and attenuation of their tubular lumen, a picture compatible with hydropic degeneration. The possible mechanisms in inducing such lesions were discussed.

  12. Genetic mechanisms of scorpion venom peptide diversification.

    PubMed

    Zhijian, Cao; Feng, Luo; Yingliang, Wu; Xin, Mao; Wenxin, Li

    2006-03-01

    The diversity of scorpion venom peptides is well shown by the presence of about 400 such polypeptides with or without disulfide bonds. Scorpion toxins with disulfide bonds present a variety of sequence features and pharmacological functions by affecting different ion channels, while the venom peptides without disulfide bonds represent a new subfamily, having much lower sequence homology among each other and different functions (e.g. bradykinin-potentiating, antimicrobial, molecular cell signal initiating and immune modulating). Interestingly, all scorpion venom peptides with divergent functions may have evolved from a common ancestor gene. Over the lengthy evolutionary time, the diversification of scorpion venom peptides evolved through polymorphism, duplication, trans-splicing, or alternative splicing at the gene level. In order to completely clarify the diversity of scorpion toxins and toxin-like peptides, toxinomics (genomics and proteomics of scorpion toxins and toxin-like peptides) are expected to greatly advance in the near future.

  13. Evaluation of the in vitro antimicrobial activity of selected Saudi scorpion venoms tested against multidrug-resistant micro-organisms.

    PubMed

    Al-Asmari, Abdulrahman K; Alamri, Meshref Ali; Almasoudi, Aqeel Salman; Abbasmanthiri, Rajamohamed; Mahfoud, Maysa

    2017-09-01

    Scorpion venoms are a rich source of bioactive peptides with promising clinical value that may lead to the discovery and development of new drugs. The present study was designed to evaluate the in vitro antimicrobial activities of the venoms extracted from three medically important Saudi scorpions (Androctonus crassicauda, Androctonus bicolor and Leiurus quinquestriatus). Antimicrobial assays were performed using a microplate growth inhibition assay against 10 multidrug-resistant (MDR) micro-organisms (4 Gram-negative bacteria, 2 Gram-positive bacteria and 4 fungi and yeasts) at concentrations ranging from 0 to 20mg/mL of each venom. Following qualitative analysis, dose-response assays were performed for bacterial and fungal killing curves using the MTT colorimetric assay. Among the three tested scorpion venoms, only L. quinquestriatus venom showed significant broad-spectrum antimicrobial activity in a dose-dependent manner from 5 to 20mg/mL. Leiurus quinquestriatus venom inhibited the growth and survival of MDR Escherichia coli (55.2%), Acinetobacter baumannii (50.6%), Klebsiella pneumoniae (35.1%), Pseudomonas aeruginosa (31.3%), Staphylococcus aureus (36.4%), Enterococcus faecalis (47.6%), Candida albicans (31.2%) and Candida glabrata (39.0%), whereas no significant activity against Fusarium oxysporum and Aspergillus flavus was observed. In contrast, the venoms of A. crassicauda and A. bicolor did not show noticeable antimicrobial activity against any of the tested organisms. The findings of the current study demonstrate that L. quinquestriatus venom possesses antimicrobial activity and thus can be used as a template for designing and development of novel antimicrobial drugs. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  14. Neutralizing capacity of murine sera induced by different antigens of scorpion venom.

    PubMed

    Calderon-Aranda, E S; Hozbor, D; Possani, L D

    1993-03-01

    Approximately 700 people die in Mexico each year from scorpion stings. The only useful therapy available is antiserum obtained from horses immunized with macerates of venomous gland from scorpions of the genus Centruroides. We report the results of experiments conducted with mice and rats in order to evaluate the relevant components of the venom from Centruroides noxius in the induction of a protective response against scorpion envenomation, either in vivo or in vitro. Gland macerates of whole telsons (stinger), soluble venom extracted by electrical stimulation, toxic fractions from gel filtration on Sephadex G-50 and highly purified toxin 2 from this scorpion venom were all used to produce hyperimmune mice and rats, which were challenged in vivo with the equivalent of the lethal dose 50% (LD50) of soluble venom, or their sera were prepared for in vitro neutralization experiments using non-immunized animals. The maximum neutralizing capacity (100%) was obtained when soluble venom was used as antigen, while purified toxin 2 produces 80% survival in vivo. The neutralizing capacity of murine antisera evaluated in vitro was: sera antifraction II > antitoxin 2 > antitotal venom > anti-gland macerates of whole telsons. Two additional aspects were further investigated in the present work. One is the demonstration by immunoblotting that proteins corresponding to the electrophoretic mobility of toxins known to block sodium channels are highly immunodominant in this venom. Second, there is a strong cross-reactivity of antisera produced with Centruroides noxius when assayed against venoms from other dangerous species of Centruroides scorpions from Mexico, but not against the Israeli scorpion Leiurus quinquestriatus. Finally, the immunodominance of toxic fractions in the immune response was observed either with immunization using Freund's adjuvant or by means of adsorption to nitrocellulose membranes. This latter vehicle was shown to be an excellent detoxifying agent, without

  15. [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.

  16. Effects of potassium channel toxins from Leiurus quinquestriatus hebraeus venom on responses to cromakalim in rabbit blood vessels.

    PubMed Central

    Strong, P. N.; Weir, S. W.; Beech, D. J.; Hiestand, P.; Kocher, H. P.

    1989-01-01

    1. The effects of fractionated Leiurus quinquestriatus hebraeus venom on cromakalim-induced 86Rb+ efflux in rabbit aortic smooth muscle were examined. 2. Crude venom (0.1-30 micrograms ml-1) produced a concentration-dependent decrease of 1 microM cromakalim-induced 86Rb+ response. The maximum blocking activity attainable was approximately 60%. 3. Fractionation of crude venom by gel permeation chromatography and subsequent chromatography on a cation ion-exchange column, produced two fractions (X and XI), active in the 86Rb+ blocking assay. 4. Fraction XII contained charybdotoxin (approximately 85% pure). After a final high performance liquid chromatography (h.p.l.c.) purification step, the purified toxin failed to inhibit the cromakalim-stimulated 86Rb+ efflux although it was a potent inhibitor of A23187-induced K+ flux in human erythrocytes and the large conductance calcium-activated potassium channel in rabbit portal vein smooth muscle. 5. Subsequent purification of fraction X by h.p.l.c. yielded a minor peak which contained 86Rb+ blocking activity. This subfraction was also capable of inhibiting apamin-sensitive, angiotensin II-stimulated K+ flux in guinea-pig hepatocytes. 6. It is concluded that the potassium channel opened by cromakalim in rabbit aortic smooth muscle is not blocked by charybdotoxin but by another distinct toxin in the venom of Leiurus quinquestriatus hebraeus. PMID:2531622

  17. Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development

    PubMed Central

    Al Asmari, Abdulrahman K; Khan, Abdul Quaiyoom

    2016-01-01

    Cancer is the leading cause of morbidity and mortality all over the world in spite of the advances made in its management. In this study, we investigated the in vivo anti-tumorigenic potential of the venom obtained from a medically important scorpion species Leiurus quinquestriatus on chemically induced skin cancer in mice. Animals were divided into five groups, with 13 animals in each group. All the treatments were given topically on the shaved dorsal surface of the skin. Animals in Group 1 received vehicle only (0.2 mL acetone). Moreover, 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol per mouse) was applied to all the animals in the remaining four groups. After 1 week, different concentrations of venom (17.5 μg, 35 μg, and 52.5 μg per animal) were applied to each animal in the Groups III–V. Thirty minutes after the application of venom, croton oil was applied on the same position where venom was administered to the animals of Groups III–V. Animals in Group II were treated as the positive control (without venom) and received croton oil as in Groups III–V. The findings of this study revealed that venom extract of L. quinquestriatus inhibits DMBA + croton oil-induced mouse skin tumor incidence and tumor multiplicity. Venom treatment also decreased the expression of proinflammatory cytokines. Immunohistochemistry results showed a downregulation of the expression of molecular markers such as Ki-67, nuclear factor kappa-B, cyclooxygenase-2, B-cell lymphoma-2, and vascular endothelial growth factor, in venom-treated animals. Our findings suggest that the venom of L. quinquestriatus possesses in vivo anticancer potential and may be used in the development of anticancer molecules. PMID:27799739

  18. Extreme diversity of scorpion venom peptides and proteins revealed by transcriptomic analysis: implication for proteome evolution of scorpion venom arsenal.

    PubMed

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

    2012-02-16

    Venom is an important genetic development crucial to the survival of scorpions for over 400 million years. We studied the evolution of the scorpion venom arsenal by means of comparative transcriptome analysis of venom glands and phylogenetic analysis of shared types of venom peptides and proteins between buthids and euscorpiids. Fifteen types of venom peptides and proteins were sequenced during the venom gland transcriptome analyses of two Buthidae species (Lychas mucronatus and Isometrus maculatus) and one Euscorpiidae species (Scorpiops margerisonae). Great diversity has been observed in translated amino acid sequences of these transcripts for venom peptides and proteins. Seven types of venom peptides and proteins were shared between buthids and euscorpiids. Molecular phylogenetic analysis revealed that at least five of the seven common types of venom peptides and proteins were likely recruited into the scorpion venom proteome before the lineage split between Buthidae and Euscorpiidae with their corresponding genes undergoing individual or multiple gene duplication events. These are α-KTxs, βKSPNs (β-KTxs and scorpines), anionic peptides, La1-like peptides, and SPSVs (serine proteases from scorpion venom). Multiple types of venom peptides and proteins were demonstrated to be continuously recruited into the venom proteome during the evolution process of individual scorpion lineages. Our results provide an insight into the recruitment pattern of the scorpion venom arsenal for the first time.

  19. Scorpion venom components as potential candidates for drug development.

    PubMed

    Ortiz, Ernesto; Gurrola, Georgina B; Schwartz, Elisabeth Ferroni; Possani, Lourival D

    2015-01-01

    Scorpions are well known for their dangerous stings that can result in severe consequences for human beings, including death. Neurotoxins present in their venoms are responsible for their toxicity. Due to their medical relevance, toxins have been the driving force in the scorpion natural compounds research field. On the other hand, for thousands of years, scorpions and their venoms have been applied in traditional medicine, mainly in Asia and Africa. With the remarkable growth in the number of characterized scorpion venom components, several drug candidates have been found with the potential to tackle many of the emerging global medical threats. Scorpions have become a valuable source of biologically active molecules, from novel antibiotics to potential anticancer therapeutics. Other venom components have drawn attention as useful scaffolds for the development of drugs. This review summarizes the most promising candidates for drug development that have been isolated from scorpion venoms.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. [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.

  5. 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

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

    PubMed

    Luna-Ramírez, Karen; Quintero-Hernández, Verónica; 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

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

    PubMed

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

    2015-12-24

    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.

  8. 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

  9. 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. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  10. Venomous snake bites, scorpions, and spiders.

    PubMed

    Kularatne, S A M; Senanayake, Nimal

    2014-01-01

    Neurologic dysfunction due to natural neurotoxins is an important, but neglected, public health hazard in many parts of the world, particularly in the tropics. These toxins are produced by or found among a variety of live forms that include venomous snakes, arthropods such as scorpions, spiders, centipedes, stinging insects (Hymenoptera), ticks, certain poisonous fish, shellfish, crabs, cone shells, skin secretions of dart-poison frogs, and bacterial poisons such as botulinum toxin. These toxins commonly act on neuromuscular transmission at the neuromuscular junction where acetylcholine is the neurotransmitter, but in certain situations the toxins interfere with neurotransmitters such as GABA, noradrenaline, adrenaline, dopamine, and γ-aminobutyrate. Of the toxins, α-toxins and κ-toxins (e.g., Chinese krait, Bungarus multicinctus) act on the postsynaptic membrane, blocking the receptors, whilst β-toxin (e.g., common krait, B. caeruleus) acts on the presynaptic membrane, causing impairment of acetylcholine release. Conversely, dendrotoxins of the African mamba enhance acetylcholine release. The toxins of scorpions and spiders commonly interfere with voltage-gated ion channels. Clinically, the cardinal manifestation is muscle paralysis. In severe cases respiratory paralysis could be fatal. Effective antivenoms are the mainstay of treatment of envenoming, but their lack of availability is the major concern in the regions of the globe where they are desperately needed. Interestingly, some toxins have proved to be valuable pharmaceutical agents, while some others are widely exploited to study neuromuscular physiology and pathology.

  11. 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

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

    PubMed

    Ruiming, Zhao; Yibao, Ma; Yawen, He; Zhiyong, Di; Yingliang, Wu; Zhijian, Cao; Wenxin, Li

    2010-07-28

    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. 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. 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.

  13. 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

  14. 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

  15. Scorpion venom peptides with no disulfide bridges: a review.

    PubMed

    Almaaytah, Ammar; Albalas, Qosay

    2014-01-01

    Scorpion venoms are rich sources of biologically active peptides that are classified into disulfide-bridged peptides (DBPs) and non-disulfide-bridged peptides (NDBPs). DBPs are the main scorpion venom components responsible for the neurotoxic effects observed during scorpion envenomation as they usually target membrane bound ion channels of excitable and non-excitable cells. Several hundred DBPs have been identified and functionally characterized in the past two decades. The NDBPs represent a novel group of molecules that have gained great interest only recently due to their high diversity both in their primary structures and bioactivities. This review provides an overview of scorpion NDBPs focusing on their therapeutic applications, modes of discovery, mechanisms of NDBPs genetic diversity and structural properties. It also provides a simple classification for NDBPs that could be adopted and applied to other NDBPs identified in future studies.

  16. Scorpion anti-venom activity of botanicals: a pharmacological approach.

    PubMed

    Dey, Abhijit; Dey, Amrita; De, Jitendra Nath

    2013-03-01

    Scorpion bite is considered as one of the common and dangerous phenomenon throughout the world. The clinical manifestations include pulmonary edema, myocardial damage, intracerebral haemorrhage, brachial plexopathy, renal failure etc. which sometimes leads to mortality. The common antivenin therapy includes anti-scorpion venom serum or prazosin. In the vast rural areas of the third world countries phytotherapy is considered as an alternative system of medicine and scorpion sting is treated with the help of medicinal botanicals. As the safety and efficacy are considered as important aspects of anti venin therapy, conventional treatment can be supported by the herbal remedy. The present review compiles a number of medicinal plants pharmacologically evaluated in vitro and/or in vivo for scorpion antivenin properties. Considering the aspects like cost effectiveness, availability, lesser side effects and development of drug resistance, plant based anti venin therapy may be considered as a possible remedy against scorpion envenomation.

  17. Evolution of alternative methodologies of scorpion antivenoms production.

    PubMed

    Carmo, A O; Chatzaki, M; Horta, C C R; Magalhães, B F; Oliveira-Mendes, B B R; Chávez-Olórtegui, C; Kalapothakis, E

    2015-04-01

    Scorpionism represents a serious public health problem resulting in the death of children and debilitated individuals. Scorpion sting treatment employs various strategies including the use of specific medicines such as antiserum, especially for patients with severe symptoms. In 1909 Charles Todd described the production of an antiserum against the venom of the scorpion Buthus quinquestriatus. Based on Todd's work, researchers worldwide began producing antiserum using the same approach i.e., immunization of horses with crude venom as antigen. Despite achieving satisfactory results using this approach, researchers in this field have developed alternative approaches for the production of scorpion antivenom serum. In this review, we describe the work published by experts in toxinology to the development of scorpion venom antiserum. Methods and results describing the use of specific antigens, detoxified venom or toxins, purified toxins and or venom fractions, native toxoids, recombinant toxins, synthetic peptides, monoclonal and recombinant antibodies, and alternative animal models are presented. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Exon Shuffling and Origin of Scorpion Venom Biodiversity

    PubMed Central

    Wang, Xueli; Gao, Bin; Zhu, Shunyi

    2016-01-01

    Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences. PMID:28035955

  19. 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.

  20. In vitro determination of the efficacy of scorpion venoms as anti-cancer agents against colorectal cancer cells: a nano-liposomal delivery approach.

    PubMed

    Al-Asmari, Abdulrahman K; Ullah, Zabih; Al Balowi, Ali; Islam, Mozaffarul

    2017-01-01

    The use of liposomes in biological and medicinal sciences is a relatively new approach. The liposomal strategy greatly depends on the technological advancement in the formation of vesicles of various sizes and properties. In the current study, we encapsulated the venoms obtained from medically important scorpions such as Androctonus bicolor (AB), Androctonus crassicauda (AC), and Leiurus quinquestriatus (LQ). To begin with, our first and foremost aim was to prepare biocompatible and biodegradable nanovesicles. Additionally, we intended to enhance the anti-cancer potential of these encapsulated venoms. The liposomal venoms were prepared by rehydration and dehydration methods. Morphology, particle size, and size distribution of the liposomes were examined by scanning electron microscope (SEM), transmission electron microscope (TEM), and Zetasizer. We found that the prepared liposomes had a smooth surface and a spherical/ovoid shape and existed mainly as single unilamellar vesicles (SUVs). Furthermore, the liposomal formulation of all three venoms exhibited excellent stability and good encapsulation efficiency (EE). Additionally, the anti-cancer potential of the encapsulated venoms was also evaluated on a colorectal cancer cell line (HCT-8). The venom-loaded liposomes showed elevated anti-cancer properties such as low rate of cell survival, higher reactive oxygen species (ROS) generation, and enhancement in the number of apoptotic cells. In addition to this, cell cycle analysis revealed G0/G1 enrichment upon venom treatment. The effect of treatment was more pronounced when venom-liposome was used as compared to free venom on the HCT-8 cell line. Furthermore, we did not observe any interference of liposomal lipids used in these preparations on the progression of cancer cells. Considering these findings, we can conclude that the encapsulated scorpion venoms exhibit better efficacy and act more vigorously as an anti-cancer agent on the colorectal cancer cell line when

  1. Turkish scorpion Buthacus macrocentrus: general characterization of the venom and description of Bu1, a potent mammalian Na⁺-channel α-toxin.

    PubMed

    Caliskan, F; Quintero-Hernández, V; Restano-Cassulini, R; Batista, C V F; Zamudio, F Z; Coronas, F I; Possani, L D

    2012-03-01

    The venom of the scorpion Buthacus macrocentrus of Turkey was fractionated by high performance liquid chromatography (HPLC) and its mass finger print analysis was obtained by spectrometry. More than 70 different fractions were obtained, allowing the determination of the molecular masses of at least 60 peptides ranging between 648 and 44,336 Da. The venom is enriched with peptides containing molecular masses between 3200-4500 Da, and 6000-7500 Da. They very likely correspond to K⁺-channel and Na⁺-channel specific peptides, respectively, as expected from venoms of scorpions of the family Buthidae, already determined for other species. The major component obtained from HPLC was shown to be lethal to mice and was further purified and characterized. It contains 65 amino acid residues maintained closely packed by 4 disulfide bridges, and shows a molecular weight of 7263 Da. Additionally, a cDNA from the venomous glands of this scorpion was used in conjunction with sequence data from Edman degradation and mass spectrometry for cloning the gene that codes for Bu1 as we named this toxin. This gene codes for a 67 amino acid residues peptide, where the two last are eliminated post-translationally for production of an amidated C-terminal arginine. Its sequence is closely related to toxins from the species Leiurus quinquestriatus, as revealed by a phylogenetic tree analysis. Electrophysiological results conducted with Bu1 using patch-clamp techniques indicate that it modifies the Na⁺ currents, in a similar way as other well known α-scorpion toxins. These results support the conclusion that this species of scorpions is dangerous to humans, having an epidemiological interest for the country.

  2. In vitro determination of the efficacy of scorpion venoms as anti-cancer agents against colorectal cancer cells: a nano-liposomal delivery approach

    PubMed Central

    Al-Asmari, Abdulrahman K; Ullah, Zabih; Al Balowi, Ali; Islam, Mozaffarul

    2017-01-01

    The use of liposomes in biological and medicinal sciences is a relatively new approach. The liposomal strategy greatly depends on the technological advancement in the formation of vesicles of various sizes and properties. In the current study, we encapsulated the venoms obtained from medically important scorpions such as Androctonus bicolor (AB), Androctonus crassicauda (AC), and Leiurus quinquestriatus (LQ). To begin with, our first and foremost aim was to prepare biocompatible and biodegradable nanovesicles. Additionally, we intended to enhance the anti-cancer potential of these encapsulated venoms. The liposomal venoms were prepared by rehydration and dehydration methods. Morphology, particle size, and size distribution of the liposomes were examined by scanning electron microscope (SEM), transmission electron microscope (TEM), and Zetasizer. We found that the prepared liposomes had a smooth surface and a spherical/ovoid shape and existed mainly as single unilamellar vesicles (SUVs). Furthermore, the liposomal formulation of all three venoms exhibited excellent stability and good encapsulation efficiency (EE). Additionally, the anti-cancer potential of the encapsulated venoms was also evaluated on a colorectal cancer cell line (HCT-8). The venom-loaded liposomes showed elevated anti-cancer properties such as low rate of cell survival, higher reactive oxygen species (ROS) generation, and enhancement in the number of apoptotic cells. In addition to this, cell cycle analysis revealed G0/G1 enrichment upon venom treatment. The effect of treatment was more pronounced when venom–liposome was used as compared to free venom on the HCT-8 cell line. Furthermore, we did not observe any interference of liposomal lipids used in these preparations on the progression of cancer cells. Considering these findings, we can conclude that the encapsulated scorpion venoms exhibit better efficacy and act more vigorously as an anti-cancer agent on the colorectal cancer cell line when

  3. The first report on transcriptome analysis of the venom gland of Iranian scorpion, Hemiscorpius lepturus.

    PubMed

    Kazemi-Lomedasht, Fatemeh; Khalaj, Vahid; Bagheri, Kamran Pooshang; Behdani, Mahdi; Shahbazzadeh, Delavar

    2017-01-01

    Hemiscorpius lepturus scorpion is one of the most venomous members of the Hemiscorpiidae family. H. lepturus is distributed in Iran, Iraq and Yemen. The prevalence and severity of scorpionism is high and health services are not able to control it. Scorpionism in Iran especially in the southern regions (Khuzestan, Sistan and Baluchestan, Hormozgan, Ilam) is one of the main health challenges. Due to the medical and health importance of scorpionism, the focus of various studies has been on the identification of H. lepturus venom components. Nevertheless, until now, only a few percent of H. lepturus venom components have been identified and there is no complete information about the venom components of H. lepturus. The current study reports transcriptome analysis of the venom gland of H. lepturus scorpion. Illumina Next Generation Sequencing results identified venom components of H. lepturus. When compared with other scorpion's venom, the venom of H. lepturus consists of mixtures of peptides, proteins and enzymes such as; phospholipases, metalloproteases, hyaluronidases, potassium channel toxins, calcium channel toxins, antimicrobial peptides (AMPs), venom proteins, venom toxins, allergens, La1-like peptides, proteases and scorpine-like peptides. Comparison of identified components of H. lepturus venom was carried out with venom components of reported scorpions and various identities and similarities between them were observed. With transcriptome analysis of H. lepturus venom unique sequences, coding venom components were investigated. Moreover, our study confirmed transcript expression of previously reported peptides; Hemitoxin, Hemicalcin and Hemilipin. The gene sequences of venom components were investigated employing transcriptome analysis of venom gland of H. lepturus. In summary, new bioactive molecules identified in this study, provide basis for venomics studies of scorpions of Hemiscorpiidae family and promises development of novel biotherapeutics

  4. Sex Differences in Defensive Behavior and Venom of The Striped Bark Scorpion Centruroides vittatus (Scorpiones: Buthidae).

    PubMed

    Miller, D W; Jones, A D; Goldston, J S; Rowe, M P; Rowe, A H

    2016-11-01

    Studies of venom variability have advanced from describing the mechanisms of action and relative potency of medically important toxins to understanding the ecological and evolutionary causes of the variability itself. While most studies have focused on differences in venoms among taxa, populations, or age-classes, there may be intersexual effects as well. Striped bark scorpions (Centruroides vittatus) provide a good model for examining sex differences in venom composition and efficacy, as this species exhibits dramatic sexual dimorphism in both size and defensive behavior; when threatened by an enemy, larger, slower females stand and fight while smaller, fleeter males prefer to run. We here add evidence suggesting that male and female C. vittatus indeed have different defensive propensities; when threatened via an electrical stimulus, females were more likely to sting than were males. We reasoned that intersexual differences in defensive phenotypes would select for venoms with different functions in the two sexes; female venoms should be effective at predator deterrence, whereas male venoms, less utilized defensively, might be better suited to capturing prey or courting females. This rationale led to our predictions that females would inject more venom and/or possess more painful venom than males. We were wrong. While females do inject more venom than males in a defensive sting, females are also larger; when adjusted for body size, male and female C. vittatus commit equal masses of venom in a sting to a potential enemy. Additionally, house mice (Mus musculus) find an injection of male venom more irritating than an equal amount of female venom, likely because male venom contains more of the toxins that induce pain. Taken together, our results suggest that identifying the ultimate causes of venom variability will, as we move beyond adaptive storytelling, be hard-won.

  5. 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.

  6. Arizona bark scorpion venom resistance in the pallid bat, Antrozous pallidus.

    PubMed

    Hopp, Bradley H; Arvidson, Ryan S; Adams, Michael E; Razak, Khaleel A

    2017-01-01

    The pallid bat (Antrozous pallidus), a gleaning bat found in the western United States and Mexico, hunts a wide variety of ground-dwelling prey, including scorpions. Anecdotal evidence suggests that the pallid bat is resistant to scorpion venom, but no systematic study has been performed. Here we show with behavioral measures and direct injection of venom that the pallid bat is resistant to venom of the Arizona bark scorpion, Centruroides sculpturatus. Our results show that the pallid bat is stung multiple times during a hunt without any noticeable effect on behavior. In addition, direct injection of venom at mouse LD50 concentrations (1.5 mg/kg) has no effect on bat behavior. At the highest concentration tested (10 mg/kg), three out of four bats showed no effects. One of the four bats showed a transient effect suggesting that additional studies are required to identify potential regional variation in venom tolerance. Scorpion venom is a cocktail of toxins, some of which activate voltage-gated sodium ion channels, causing intense pain. Dorsal root ganglia (DRG) contain nociceptive neurons and are principal targets of scorpion venom toxins. To understand if mutations in specific ion channels contribute to venom resistance, a pallid bat DRG transcriptome was generated. As sodium channels are a major target of scorpion venom, we identified amino acid substitutions present in the pallid bat that may lead to venom resistance. Some of these substitutions are similar to corresponding amino acids in sodium channel isoforms responsible for reduced venom binding activity. The substitution found previously in the grasshopper mouse providing venom resistance to the bark scorpion is not present in the pallid bat, indicating a potentially novel mechanism for venom resistance in the bat that remains to be identified. Taken together, these results indicate that the pallid bat is resistant to venom of the bark scorpion and altered sodium ion channel function may partly underlie

  7. Arizona bark scorpion venom resistance in the pallid bat, Antrozous pallidus

    PubMed Central

    Hopp, Bradley H.; Arvidson, Ryan S.; Adams, Michael E.; Razak, Khaleel A.

    2017-01-01

    The pallid bat (Antrozous pallidus), a gleaning bat found in the western United States and Mexico, hunts a wide variety of ground-dwelling prey, including scorpions. Anecdotal evidence suggests that the pallid bat is resistant to scorpion venom, but no systematic study has been performed. Here we show with behavioral measures and direct injection of venom that the pallid bat is resistant to venom of the Arizona bark scorpion, Centruroides sculpturatus. Our results show that the pallid bat is stung multiple times during a hunt without any noticeable effect on behavior. In addition, direct injection of venom at mouse LD50 concentrations (1.5 mg/kg) has no effect on bat behavior. At the highest concentration tested (10 mg/kg), three out of four bats showed no effects. One of the four bats showed a transient effect suggesting that additional studies are required to identify potential regional variation in venom tolerance. Scorpion venom is a cocktail of toxins, some of which activate voltage-gated sodium ion channels, causing intense pain. Dorsal root ganglia (DRG) contain nociceptive neurons and are principal targets of scorpion venom toxins. To understand if mutations in specific ion channels contribute to venom resistance, a pallid bat DRG transcriptome was generated. As sodium channels are a major target of scorpion venom, we identified amino acid substitutions present in the pallid bat that may lead to venom resistance. Some of these substitutions are similar to corresponding amino acids in sodium channel isoforms responsible for reduced venom binding activity. The substitution found previously in the grasshopper mouse providing venom resistance to the bark scorpion is not present in the pallid bat, indicating a potentially novel mechanism for venom resistance in the bat that remains to be identified. Taken together, these results indicate that the pallid bat is resistant to venom of the bark scorpion and altered sodium ion channel function may partly underlie

  8. Venom Gland Transcriptomic and Proteomic Analyses of the Enigmatic Scorpion Superstitionia donensis (Scorpiones: Superstitioniidae), with Insights on the Evolution of Its Venom Components

    PubMed Central

    Santibáñez-López, Carlos E.; Cid-Uribe, Jimena I.; Batista, Cesar V. F.; Ortiz, Ernesto; Possani, Lourival D.

    2016-01-01

    Venom gland transcriptomic and proteomic analyses have improved our knowledge on the diversity of the heterogeneous components present in scorpion venoms. However, most of these studies have focused on species from the family Buthidae. To gain insights into the molecular diversity of the venom components of scorpions belonging to the family Superstitioniidae, one of the neglected scorpion families, we performed a transcriptomic and proteomic analyses for the species Superstitionia donensis. The total mRNA extracted from the venom glands of two specimens was subjected to massive sequencing by the Illumina protocol, and a total of 219,073 transcripts were generated. We annotated 135 transcripts putatively coding for peptides with identity to known venom components available from different protein databases. Fresh venom collected by electrostimulation was analyzed by LC-MS/MS allowing the identification of 26 distinct components with sequences matching counterparts from the transcriptomic analysis. In addition, the phylogenetic affinities of the found putative calcins, scorpines, La1-like peptides and potassium channel κ toxins were analyzed. The first three components are often reported as ubiquitous in the venom of different families of scorpions. Our results suggest that, at least calcins and scorpines, could be used as molecular markers in phylogenetic studies of scorpion venoms. PMID:27941686

  9. Venom Gland Transcriptomic and Proteomic Analyses of the Enigmatic Scorpion Superstitionia donensis (Scorpiones: Superstitioniidae), with Insights on the Evolution of Its Venom Components.

    PubMed

    Santibáñez-López, Carlos E; Cid-Uribe, Jimena I; Batista, Cesar V F; Ortiz, Ernesto; Possani, Lourival D

    2016-12-09

    Venom gland transcriptomic and proteomic analyses have improved our knowledge on the diversity of the heterogeneous components present in scorpion venoms. However, most of these studies have focused on species from the family Buthidae. To gain insights into the molecular diversity of the venom components of scorpions belonging to the family Superstitioniidae, one of the neglected scorpion families, we performed a transcriptomic and proteomic analyses for the species Superstitionia donensis. The total mRNA extracted from the venom glands of two specimens was subjected to massive sequencing by the Illumina protocol, and a total of 219,073 transcripts were generated. We annotated 135 transcripts putatively coding for peptides with identity to known venom components available from different protein databases. Fresh venom collected by electrostimulation was analyzed by LC-MS/MS allowing the identification of 26 distinct components with sequences matching counterparts from the transcriptomic analysis. In addition, the phylogenetic affinities of the found putative calcins, scorpines, La1-like peptides and potassium channel κ toxins were analyzed. The first three components are often reported as ubiquitous in the venom of different families of scorpions. Our results suggest that, at least calcins and scorpines, could be used as molecular markers in phylogenetic studies of scorpion venoms.

  10. Scorpion and spider venom peptides: gene cloning and peptide expression.

    PubMed

    Quintero-Hernández, V; Ortiz, E; Rendón-Anaya, M; Schwartz, E F; Becerril, B; Corzo, G; Possani, L D

    2011-12-01

    This communication reviews most of the important findings related to venom components isolated from scorpions and spiders, mainly by means of gene cloning and expression. Rather than revising results obtained by classical biochemical studies that report structure and function of venom components, here the emphasis is placed on cloning and identification of genes present in the venomous glands of these arachnids. Aspects related to cDNA library construction, specific or random ESTs cloning, transcriptome analysis, high-throughput screening, heterologous expression and folding are briefly discussed, showing some numbers of species and components already identified, but also shortly mentioning limitations and perspectives of research for the future in this field. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Ipomoea asarifolia neutralizes inflammation induced by Tityus serrulatus scorpion venom.

    PubMed

    Lima, Maira Conceição Jerônimo de Souza; Bitencourt, Mariana Angélica Oliveira; Furtado, Allanny Alves; Oliveira Rocha, Hugo Alexandre; Oliveira, Ruth Medeiros; da Silva-Júnior, Arnóbio Antônio; Tabosa do Egito, Eryvaldo Sócrates; Tambourgi, Denise Vilarinho; Zucolotto, Silvana Maria; Fernandes-Pedrosa, Matheus de Freitas

    2014-05-14

    Envenoming caused by scorpion sting is a serious public health problem. In Brazil, 13,038 accidents caused by venomous animals have been reported. Of this total, 53% of the cases and 14 deaths were caused by scorpions. Furthermore, Tityus serrulatus (Buthidae) is the most dangerous scorpion due to the high toxicity of its venom. The treatment is the common supportive therapy and the serum therapy, but some people do not have access to both therapies and seek healing through the use of medical plants. This study evaluated the ability of the crude extract and fractions from the leaves of Ipomoea asarifolia in neutralizing the main biological effects caused by Tityus serrulatus envenoming in mice. BALB/c mice were pretreated (i.v.) with 100 μλ of aqueous extracts and fractions dichloromethane, ethyl acetate, and n-butanol (CH₂Cl₂, EtOAc, and n-BuOH, respectively) of Ipomoea asarifolia, rutin or saline. Then, the animals received 100 μλ (i.p.) of venom of Tityus serrulatus (0.8 mg/kg). After six hours, the peritoneal lavage was performed with PBS and the number cells were determined using a Neubauer chamber. The supernatants were collected for determination of cytokines, such as IL-6, IL-12, and IL-1β. The aqueous extract, fractions and rutin, at all doses, significantly reduced cell migration, which was endorsed by the reduction of the levels of certain cytokines. This is the first study that demonstrated the potential effect of Ipomoea asarifolia against inflammation caused by Tityus serrulatus venom, suggesting that these extracts and/or their bioactive molecules, especially the flavonoid rutin, have potential use in the therapy of this envenomation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Venom gland transcriptomic and venom proteomic analyses of the scorpion Megacormus gertschi Díaz-Najera, 1966 (Scorpiones: Euscorpiidae: Megacorminae).

    PubMed

    Santibáñez-López, Carlos E; Cid-Uribe, Jimena I; Zamudio, Fernando Z; Batista, Cesar V F; Ortiz, Ernesto; Possani, Lourival D

    2017-07-01

    The soluble venom from the Mexican scorpion Megacormus gertschi of the family Euscorpiidae was obtained and its biological effects were tested in several animal models. This venom is not toxic to mice at doses of 100 μg per 20 g of mouse weight, while being lethal to arthropods (insects and crustaceans), at doses of 20 μg (for crickets) and 100 μg (for shrimps) per animal. Samples of the venom were separated by high performance liquid chromatography and circa 80 distinct chromatographic fractions were obtained from which 67 components have had their molecular weights determined by mass spectrometry analysis. The N-terminal amino acid sequence of seven protein/peptides were obtained by Edman degradation and are reported. Among the high molecular weight components there are enzymes with experimentally-confirmed phospholipase activity. A pair of telsons from this scorpion species was dissected, from which total RNA was extracted and used for cDNA library construction. Massive sequencing by the Illumina protocol, followed by de novo assembly, resulted in a total of 110,528 transcripts. From those, we were able to annotate 182, which putatively code for peptides/proteins with sequence similarity to previously-reported venom components available from different protein databases. Transcripts seemingly coding for enzymes showed the richest diversity, with 52 sequences putatively coding for proteases, 20 for phospholipases, 8 for lipases and 5 for hyaluronidases. The number of different transcripts potentially coding for peptides with sequence similarity to those that affect ion channels was 19, for putative antimicrobial peptides 19, and for protease inhibitor-like peptides, 18. Transcripts seemingly coding for other venom components were identified and described. The LC/MS analysis of a trypsin-digested venom aliquot resulted in 23 matches with the translated transcriptome database, which validates the transcriptome. The proteomic and transcriptomic analyses

  13. 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

  14. [Dangerous scorpions from Niger].

    PubMed

    Goyffon, M; Guette, C

    2005-11-01

    Two dangerous scorpion species are responsible for the severe human envenomations in Niger, Leiurus quinquestriatus (H. et E.), the most abundant, and Androctonus aeneas C.L. Koch, less frequent and described in a Sahel country for the first time. Up to now, A. aeneas was known in North Africa only. Its venom is highly toxic for humans, similar to those of the most dangerous species living in Africa, such as L. quinquestriatus and other species belonging to the genus Androctonus, A. australis (L.) and A. mauretanicus (Poc.), for the envenoming treatment of which specific antivenoms are prepared. Taking into account the absence of a specific antivenom for A. aeneas, the paraspecific neutralising effect of these antivenoms should be tested.

  15. Indian scorpions collected in Karnataka: maintenance in captivity, venom extraction and toxicity studies.

    PubMed

    Nagaraj, Santhosh Kambaiah; Dattatreya, Pavana; Boramuthi, Thippeswamy Nayaka

    2015-01-01

    Maintenance of scorpions under laboratory conditions is ideal for long-term venom collection to explore the therapeutic applications of scorpion venom. Collection of venom by electrical stimulation requires a reliable stimulator and effective restrainer. Thus, the present study was conducted to develop a convenient method to maintain scorpions and to extract their venom for toxicity studies via a modified restrainer and stimulator. Four different scorpion species were collected, among which three species were maintained in the laboratory in containers that mimic their natural habitat. Venom was extracted from Hottentotta rugiscutis by electrical stimulation at 8 V for 18 months and LD50 was estimated by the graphic method of Miller and Tainter. A total of 373 scorpions including Hottentotta rugiscutis, Hottentotta tamulus, Lychas tricarinatus and Heterometrus swammerdami were collected, identified and maintained successfully, achieving a 97 % survival rate. Hottentotta rugiscutis yielded 6.0 mL of venom by electrical stimulation. The LD50 of H. rugiscutis venom was estimated to be 3.02 mg/kg of body weight in female Swiss albino mice. Scorpions were successfully maintained for 18 months. Herein we have also documented a simple, cost-effective method of venom extraction by electrical stimulation using a modified restrainer. Furthermore, Hottentotta rugiscutis was reported for the first time in Karnataka.

  16. 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.

  17. Immune cells recruitment and activation by Tityus serrulatus scorpion venom.

    PubMed

    Fialho, Eder M S; Maciel, Márcia C G; Silva, Arlley C B; Reis, Aramys S; Assunção, Anne Karine M; Fortes, Thiare S; Silva, Lucilene A; Guerra, Rosane N M; Kwasniewski, Fabio H; Nascimento, Flávia R F

    2011-11-01

    Despite several studies showed that the Tityus serrulatus scorpion venom (Tsv) induces an inflammatory response, just a few have investigated the effect of the venom on the immune response. Therefore, the aim of this study was to evaluate alterations of venom application on lymphoid organs and on the recruitment and activation of cells and also on the cytokine production. Swiss male mice (2-3 months, 20-25 g) received a non-lethal dose of crude Tsv (200 μg/kg), diluted in sterile PBS by subcutaneous route. Control animals received only sterile PBS. The animals were sacrificed after 30, 120 and 360 min. The inflammatory parameters studied were skin histology at the site of venom application, leukocyte count, and blood cytokine levels (IL-6, IL-10, and TNF-α). Inguinal lymph node, spleen and bone marrow cellularity was determined for evaluation of the Tsv effect on immune system organs. The results showed that Tsv caused no local inflammation, but it induced an increase of blood neutrophils and serum IL-6, TNF-α and IL-10. After 360 min of envenomation there was a reduction in the cells number from peritoneum and spleen, but there was an increase in the cell number from lymph nodes. In conclusion, the Tsv induces systemic alterations characterized by changes in the cell number in lymphoid organs, increase pro and anti-inflammatory cytokines. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Pedipalps and venom vesicle anomalies in two families of scorpions (Scorpiones: Hemiscorpiidae, Buthidae) from Iran.

    PubMed

    Jahanifard, E; Navidpour, Sh; Masihipour, B

    2008-01-15

    The developmental anomalies are reported in this study. The first and second abnormally are presented in right pedipalps of Paraorthochirus and Orthochirus (Buthidae) while Paraorthochirus pedipalp just includes coxa, trochanter and without other parts (femur, patella, movable and fixed finger). The right pedipalp of Orthochirus specimen has abnormally too; it has all parts ofpedipalp except complete fixed finger. In both of scorpions, the left pedipalp is normal. Another case is present in venom vesicle of Hemiscourpius (Hemiscorpiidae). Pictures and morphometric measurements for three specimens are given.

  19. 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

  20. 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

  1. One scorpion, two venoms: Prevenom of Parabuthus transvaalicus acts as an alternative type of venom with distinct mechanism of action

    PubMed Central

    Inceoglu, Bora; Lango, Jozsef; Jing, Jie; Chen, Lili; Doymaz, Fuat; Pessah, Isaac N.; Hammock, Bruce D.

    2003-01-01

    Scorpion venom is a complex mixture of salts, small molecules, peptides, and proteins. Scorpions employ this valuable tool in several sophisticated ways for subduing prey, deterring predators, and possibly during mating. Here, a subtle but clever strategy of venom utilization by scorpions is reported. Scorpions secrete a small quantity of transparent venom when initially stimulated that we propose to name prevenom. If secretion continues, a cloudy and dense venom that is white in color is subsequently released. The prevenom contains a combination of high K+ salt and several peptides including some that block rectifying K+ channels and elicit significant pain and toxicity because of a massive local depolarization. The presence of high extracellular K+ in the prevenom can depolarize cells and also decrease the local electrochemical gradient making it more difficult to reestablish the resting potential. When this positive change to the K+ equilibrium potential is combined with the blockage of rectifying K+ channels, this further delays the recovery of the resting potential, causing a prolonged effect. We propose that the prevenom of scorpions is used as a highly efficacious predator deterrent and for immobilizing small prey while conserving metabolically expensive venom until a certain level of stimuli is reached, after which the venom is secreted. PMID:12552107

  2. 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.

  3. 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

  4. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Partial transcriptomic profiling of toxins from the venom gland of the scorpion Parabuthus stridulus.

    PubMed

    Mille, Bea G; Peigneur, Steve; Diego-García, Elia; Predel, Reinhard; Tytgat, Jan

    2014-06-01

    Since it is an apocrine secretion, scorpion venom is a complex mixture that contains a variety of low-molecular-weight basic proteins (neurotoxins), mucus, salts, as well as a large number of other constituents. Diversity of scorpion venom peptides exists also at the transcript level. Two kinds of venom peptides are typically considered: the neurotoxins and the antimicrobial peptides. We constructed a cDNA library and carried an EST (Expressed Sequence Tag) approach to overview the different peptides in the transcriptome of the telson from Parabuthus stridulus. P. stridulus are psammophilous and highly venomous scorpions endemic to Namibia (Prendini 2004) with medical relevance because of important human envenomation occurrence. We obtained 111 ESTs, 20% of them corresponding to cellular process transcripts, 7% to hypothetical proteins and 17% were sequences without good matches, but the majority of ESTs, 56%, corresponds to transcripts encoding for different venom components, including voltage-gated sodium, potassium and calcium channel toxins, antimicrobial peptides and other venom and cell proteins. To the best of our knowledge this report contains the first transcriptome analysis of genes transcribed by the venomous gland of the scorpion species P. stridulus, belonging to the family of medically important Buthidae scorpions. One hundred and eleven ESTs were analyzed, showing an important number of genes that encode for products similar to known scorpion venom components. In total, 17 unique and novel sequences were indentified. The identification and characterization of these compounds will be a good source of novel pharmacological tools for studying ion channels and the understanding of the physiological effects of toxins in P. stridulus envenomations at a molecular level.

  6. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Proteins, lethality and in vivo effects of Iurus dufoureius asiaticus scorpion venom.

    PubMed

    Ozkan, Ozcan; Ciftci, Gulay; Pekmezci, Gokmen Zafer; Kar, Sirri; Uysal, Hamdi; Karaer, Kadri Zafer

    2007-09-01

    Iurus dufoureius asiaticus, Birula, 1903 scorpions were collected in Mugla province located in the Aegean region, Turkey. There are few number of publications about I.d. asiaticus, and there are no data regarding minimal lethal dose and effects of the scorpion venom till now. This is the first study about toxicity and effects of I.d. asiaticus scorpion venom in mice. Previously, most of the proteins in venom of I.d. asiaticus from Aydin region in Turkey were reported to be between 14 and 205 kDa in size. In this study, we determined the electrophoretic protein pattern of the venom taken from Mugla province to be between 29 and 116 kDa by SDS-PAGE. Intracerebroventricular (i.c.v.) was determined instead of s.c. injection since there were no deaths in any s.c. test groups. The LD(50) of I.d. asiaticus scorpion venom was found to be 47.7 microg/20 g mouse by i.c.v. injection route. After s.c. injection venom, mice were shown any intoxication symptoms. On the other hand, after i.c.v. administration of venom, mice showed symptoms such as excitability, hyper salivation, weakness, paralysis, coma and resulting in death. The possible cause of death could be due to multi-system organ failure depending on the toxic effect of the venom. These both results showed that the venom was not lethal on s.c. injection, but it was lethal on i.c.v. injection. This may imply that the scorpion is of little danger to humans.

  8. 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

  9. Recombinant Expression, Functional Characterization of Two Scorpion Venom Toxins with Three Disulfide Bridges from the Chinese Scorpion Buthus martensii Karsch.

    PubMed

    Lin, Shengguo; Wang, Xuelin; Hu, Xueyao; Zhao, Yongshan; Zhao, Mingyi; Zhang, Jinghai; Cui, Yong

    2017-01-01

    Scorpion venom contains a large variety of biologically active peptides. However, most of these peptides have not been identified and characterized. Peptides with three disulfide bridges, existing in the scorpion venom, have not been studied in detail and have been poorly characterized until now. Here, we report the recombinant expression and functional characterization of two kinds of venom peptides (BmKBTx and BmNaL-3SS2) with three disulfide bridges. This study adopted an effective Escherichia coli system. The genes for BmKBTx and BmNaL-3SS2 were obtained by polymerase chain reaction and cloned to the pSYPU-1b vector. After expression and purification, the two recombinant proteins were subjected to an analgesic activity assay in mice and whole-cell patchclamp recording of hNav1.7-CHO cell lines. Functional tests showed that BmKBTx and BmNaL- 3SS2 have analgesic activity in mice and can interact with the hNav1.7 subtype of the voltage-gated sodium channel (VGSC). Scorpion venom is rich in bioactive proteins, but most of their functions are unknown to us. This study has increased our knowledge of these novel disulfide-bridged peptides (DBPs) and their biological activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. 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

  11. 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.

  12. Simultaneous modifications of sodium channel gating by two scorpion toxins.

    PubMed Central

    Wang, G K; Strichartz, G

    1982-01-01

    The effects of purified scorpion toxins from two different species on the kinetics of sodium currents were evaluated in amphibian myelinated nerves under voltage clamp. A toxin from Leiurus quinquestriatus slowed and prevented sodium channel inactivation, exclusively, and a toxin from Centruroides sculpturatus Ewing reduced transient sodium currents during a maintained depolarization, and induced a novel inward current that appeared following repolarization, as previously reported by Cahalan (1975, J. Physiol. [Lond.]. 244:511-534) for the crude scorpion venom. Both of these effects were observed in fibers treated with both of these toxins, and the kinetics of the induced current were modified in a way that showed that the same sodium channels were modified simultaneously by both toxins. Although the toxins can act on different sites, the time course of the action of C. sculpturatus toxin was accelerated in the presence of the L. quinquestriatus toxin, indicating some form of interaction between the two toxin binding sites. PMID:6293596

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

    PubMed

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

    2014-03-01

    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 B. 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 B. 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 B. 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 B. occitanus species living in the South of France.

  14. 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

  15. 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.

  16. The transcriptome recipe for the venom cocktail of Tityus bahiensis scorpion.

    PubMed

    de Oliveira, Ursula Castro; Candido, Denise Maria; Dorce, Valquíria Abrão Coronado; Junqueira-de-Azevedo, Inácio de Loiola Meirelles

    2015-03-01

    Scorpion venom is a mixture of peptides, including antimicrobial, bradykinin-potentiating and anionic peptides and small to medium proteins, such as ion channel toxins, metalloproteinases and phospholipases that together cause severe clinical manifestation. Tityus bahiensis is the second most medically important scorpion species in Brazil and it is widely distributed in the country with the exception of the North Region. Here we sequenced and analyzed the transcripts from the venom glands of T. bahiensis, aiming at identifying and annotating venom gland expressed genes. A total of 116,027 long reads were generated by pyrosequencing and assembled in 2891 isotigs. An annotation process identified transcripts by similarity to known toxins, revealing that putative venom components represent 7.4% of gene expression. The major toxins identified are potassium and sodium channel toxins, whereas metalloproteinases showed an unexpected high abundance. Phylogenetic analysis of deduced metalloproteinases from T. bahiensis and other scorpions revealed a pattern of ancient and intraspecific gene expansions. Other venom molecules identified include antimicrobial, anionic and bradykinin-potentiating peptides, besides several putative new venom components. This report provides the first attempt to massively identify the venom components of this species and constitutes one of the few transcriptomic efforts on the genus Tityus.

  17. 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

  18. 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.

  19. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. 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.

  1. 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

  2. Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro.

    PubMed Central

    Blaustein, M P

    1975-01-01

    1. 45-Ca uptake by pinched-off nerve terminals (synaptosomes) of rat brain incubated in standard physiological saline (including 132 mM-Na + 5mM-K + 1-2 mM-Ca) at 30 degrees C averages about 0-5 mumole Ca per g protein per minute. This may be equivalent to a Ca influx of about 0-03 p-mole/cm-2 sec. 2. The rate of 45-Ca uptake is increased when the concentration of K in the medium is increased above 15-20 mM, K replacing Na isosmotically. Maximum stimulation, a three- to six-fold increase in the rate of Ca uptake, occurs when [K]o is about 60 mM. The effect of increased [K]o is reversible. 3. The K-stimulated Ca uptake is associated primarily with the nerve terminal fraction of brain homogenates. The entering Ca is not accompanied by extracellular markers such as mannitol or inulin. Replacement of external chloride by methylsulphate or sulphate does not prevent the stimulation by K. 4. The effects of external K are quantitatively mimicked by Rb. Caesium also stimulates Ca uptake, but is only about one fifth as effective as K or Rb; Li is ineffective. 5. Two other depolarizing agents also stimulate Ca uptake by synaptosomes: veratridine (7-5 times 10- minus 6 to 7-5 times 10- minus 5 M) and scorpion (Leirus quinquestriatus) venom (6-7 times 10- minus 7 to 6-7 times 10- minus g/ml.). The stimulatory effects of veratridine and scorpion venom, but not of increased [K] are blocked by 2 times 10- minus 7 M tetrodotoxin. 6. Internal K also influences the rate of 45-Ca uptake by synaptosomes: lowering [K]i reduces the stimulatory effect of external K and veratridine. 7. Replacement of external Na by choline markedly inhibits the response to veratridine, but has a much smaller effect on the response to increased [K]o. 8. The Ca uptake mechanism has an apparent dissociation constant for Ca (KCa) of about 0-8 mM. Increasing [K]o increases the maximal rate of Ca uptake, but has no effect on KCa. The K-induced 45-Ca uptake is competitively inhibited by Mg-2+, Mn-2+ and La-3+. 9

  3. 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.

  4. 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

  5. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Functional evolution of scorpion venom peptides with an inhibitor cystine knot fold.

    PubMed

    Gao, Bin; Harvey, Peta J; Craik, David J; Ronjat, Michel; De Waard, Michel; Zhu, Shunyi

    2013-06-27

    The ICK (inhibitor cystine knot) defines a large superfamily of polypeptides with high structural stability and functional diversity. Here, we describe a new scorpion venom-derived K+ channel toxin (named λ-MeuKTx-1) with an ICK fold through gene cloning, chemical synthesis, nuclear magnetic resonance spectroscopy, Ca2+ release measurements and electrophysiological recordings. λ-MeuKTx-1 was found to adopt an ICK fold that contains a three-strand anti-parallel β-sheet and a 310-helix. Functionally, this peptide selectively inhibits the Drosophila Shaker K+ channel but is not capable of activating skeletal-type Ca2+ release channels/ryanodine receptors, which is remarkably different from the previously known scorpion venom ICK peptides. The removal of two C-terminal residues of λ-MeuKTx-1 led to the loss of the inhibitory activity on the channel, whereas the C-terminal amidation resulted in the emergence of activity on four mammalian K+ channels accompanied by the loss of activity on the Shaker channel. A combination of structural and pharmacological data allows the recognition of three putative functional sites involved in channel blockade of λ-MeuKTx-1. The presence of a functional dyad in λ-MeuKTx-1 supports functional convergence among scorpion venom peptides with different folds. Furthermore, similarities in precursor organization, exon-intron structure, 3D-fold and function suggest that scorpion venom ICK-type K+ channel inhibitors and Ca2+ release channel activators share a common ancestor and their divergence occurs after speciation between buthidae and non-buthids. The structural and functional characterizations of the first scorpion venom ICK toxin with K+ channel-blocking activity sheds light on functionally divergent and convergent evolution of this conserved scaffold of ancient origin.

  7. Production of Recombinant Alpha Neurotoxin of Scorpion Venom Mesobuthus eupeus and Analysis of its Immunogenicity

    PubMed Central

    Eskandari, Ghafar; Jolodar, Abbas; Seyfiabad Shapouri, Masoud Reza; Bahmainmehr, Ardeshir; Navidpour, Shahrokh

    2014-01-01

    Background: Scorpion venom is important and rich source of peptides, most of which have been widely used as pharmacological tools for unraveling structure-function relationship of various ion channels. Naturally occurring toxins can be also considered as lead compounds in the development of novel drugs. Objectives: In this context, the scorpion-derived peptide neurotoxins specific to sodium channels have shown promise as potential therapeutic targets for the treatment of various human diseases. Materials and Methods: A cDNA library from the extracted RNA was constructed using RT-PCR and semi-nested RT-PCR. DNA sequencing followed by phylogenetic analysis was applied to screen the cDNA library clones. For molecular characterization of the BMK gene we used cloning and recombinant protein expression techniques based on E.coli systems. Then we performed mice immunization and Western blot and Immunodot analyses. Results: A novel BMK neurotoxin has been cloned, expressed and characterized from the Iranian scorpion M. eupeus venom. We analyzed the recombinant BMK by immunoblotting with treated antiserum. The result showed that mice antiserum can react also with scorpion crude venom, so is able to recognize native BMK toxin. Conclusion: The newly produced recombinant protein BMK revealed to be immunogenic. Moreover, anti-BMK antibodies produced in mice were able to recognize both the recombinant BMK neurotoxin and the one in M. eupeus crude venome. Taken together, the molecular characterization and recombinant production of the Iranian scorpion M. eupeus venom component can serve as a new probe for further studies of sodium channels function and physiology. This provides a promising perspective for the future design of selective drugs, as well as for research of antivenom production. PMID:24719721

  8. Functional evolution of scorpion venom peptides with an inhibitor cystine knot fold

    PubMed Central

    Gao, Bin; Harvey, Peta J.; Craik, David J.; Ronjat, Michel; De Waard, Michel; Zhu, Shunyi

    2013-01-01

    The ICK (inhibitor cystine knot) defines a large superfamily of polypeptides with high structural stability and functional diversity. Here, we describe a new scorpion venom-derived K+ channel toxin (named λ-MeuKTx-1) with an ICK fold through gene cloning, chemical synthesis, nuclear magnetic resonance spectroscopy, Ca2+ release measurements and electrophysiological recordings. λ-MeuKTx-1 was found to adopt an ICK fold that contains a three-strand anti-parallel β-sheet and a 310-helix. Functionally, this peptide selectively inhibits the Drosophila Shaker K+ channel but is not capable of activating skeletal-type Ca2+ release channels/ryanodine receptors, which is remarkably different from the previously known scorpion venom ICK peptides. The removal of two C-terminal residues of λ-MeuKTx-1 led to the loss of the inhibitory activity on the channel, whereas the C-terminal amidation resulted in the emergence of activity on four mammalian K+ channels accompanied by the loss of activity on the Shaker channel. A combination of structural and pharmacological data allows the recognition of three putative functional sites involved in channel blockade of λ-MeuKTx-1. The presence of a functional dyad in λ-MeuKTx-1 supports functional convergence among scorpion venom peptides with different folds. Furthermore, similarities in precursor organization, exon–intron structure, 3D-fold and function suggest that scorpion venom ICK-type K+ channel inhibitors and Ca2+ release channel activators share a common ancestor and their divergence occurs after speciation between buthidae and non-buthids. The structural and functional characterizations of the first scorpion venom ICK toxin with K+ channel-blocking activity sheds light on functionally divergent and convergent evolution of this conserved scaffold of ancient origin. PMID:23721518

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

    PubMed

    Dorce, Ana Leticia C; Dorce, Valquiria Ac; Nencioni, Ana Leonor A

    2014-02-12

    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. 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. 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.

  10. 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

  11. 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.

  12. Antarease-like Zn-metalloproteases are ubiquitous in the venom of different scorpion genera.

    PubMed

    Ortiz, Ernesto; Rendón-Anaya, Martha; Rego, Solange Cristina; Schwartz, Elisabeth Ferroni; Possani, Lourival Domingos

    2014-06-01

    The venoms of several scorpion species have long been associated with pancreatitis in animal models and humans. Antarease, a Zn-metalloprotease from Tityus serrulatus, is able to penetrate intact pancreatic tissue and disrupts the normal vesicular traffic necessary for secretion, so it could play a relevant role in the onset of acute pancreatitis. The cDNA libraries from five different scorpion species were screened for antarease homologs with specific primers. The amplified PCR products were cloned and sequenced. A structural model was constructed to assess the functionality of the putative metalloproteases. A phylogenetic analysis was performed to identify clustering patterns of these venom components. Antarease-like sequences were amplified from all the screened cDNA libraries. The complete sequence of the antarease from T. serrulatus was obtained. The structural model of the putative antarease from Tityus trivittatus shows that it may adopt a catalytically active conformation, sharing relevant structural elements with previously reported metalloproteases of the ADAM family. The phylogenetic analysis reveals that the reported sequences cluster in groups that correlate with the geographical localization of the respective species. Antareases are ubiquitous to a broad range of scorpion species, where they could be catalytically active enzymes. These molecules can be used to describe the evolution of scorpion venoms under different ecogeographic constrains. For the first time the complete sequence of the antareases is reported. It is demonstrated that antareases are common in the venom of different scorpion species. They are now proposed as targets for antivenom therapies. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Characterization of Leiurus abdullahbayrami (Scorpiones: Buthidae) venom: peptide profile, cytotoxicity and antimicrobial activity.

    PubMed

    Erdeş, Efe; Doğan, Tuğba Somay; Coşar, Ilhan; Danışman, Tarık; Kunt, Kadir Boğaç; Seker, Tamay; Yücel, Meral; Ozen, Can

    2014-01-01

    Scorpion venoms are rich bioactive peptide libraries that offer promising molecules that may lead to the discovery and development of new drugs. Leiurus abdullahbayrami produces one of the most potent venoms among Turkish scorpions that provokes severe symptoms in envenomated victims. In the present study, the peptide profile of the venom was investigated by electrophoretic methods, size-exclusion and reversed-phase chromatography and mass spectroscopy. Cytotoxic and antimicrobial effects were evaluated on a breast cancer cell line (MCF-7) and various bacterial and fungal species. Proteins make up approximately half of the dry weight of L. abdullahbayrami crude venom. Microfluidic capillary electrophoresis indicated the presence of 6 to 7 kDa peptides and proved to be a highly practical peptidomics tool with better resolution when compared to conventional polyacrylamide gel electrophoresis. Mass spectroscopy analysis helped us to identify 45 unique peptide masses between 1 to 7 kDa with a bimodal mass distribution peaking between molecular weights of 1 to 2 kDa (29%) and 3 to 4 kDa (31%). L. abdullahbayrami crude venom had a proliferative effect on MCF-7 cells, which may be explained by the high concentration of polyamines as well as potassium and calcium ions in the arachnid venoms. Antimicrobial effect was stronger on gram-negative bacteria. This work represents the first peptidomic characterization of L. abdullahbayrami venom. Considering the molecular weight-function relationship of previously identified venom peptides, future bioactivity studies may lead to the discovery of novel potassium and chloride ion channel inhibitors as well as new antimicrobial peptides from L. abdullahbayrami venom.

  14. [Partial purification of peptides present in the Tityus macrochirus (Buthidae) scorpion venom and preliminary assessment of their cytotoxicity].

    PubMed

    Rincón-Cortés, Clara Andrea; Reyes-Montaño, Edgar Antonio; Vega-Castro, Nohora Angélica

    2017-06-01

    Scorpion venom contains peptides with neurotoxic action primarily active on ion channels in the nervous system of insects and mammals. They are also characterized as cytolytic and anticancer, biological characteristics that have not yet been reported for the Tityus macrochirus venom. To assess if the total T. macrochirus venom and the fraction of partially purified peptides decrease the viability of various tumor-derived cell lines. The scorpion venom was collected by electrical stimulation and, subsequently, subjected to chromatography, electrophoresis, and ultrafiltration with Amicon Ultra 0.5® membranes for the partial identification and purification of its peptides. The cytotoxic activity of the venom and the peptides fraction trials on tumor-derived cell lines were carried out by the MTT method. The T. macrochirus scorpion venom has peptides with molecular weights ranging between 3 and 10 kDa. They were partially purified using the ultrafiltration technique, and assessed by the RP-HPLC method. Cytotoxicity trials with the whole T. macrochirus venom showed a higher viability decrease on the PC3 cell line compared to the other cell lines assessed, while the partially purified peptides decreased the HeLa cell line viability. Peptides in the T. macrochirus scorpion venom showed cytotoxic activity on some tumorderived cell lines. We observed some degree of selectivity against other cell lines assessed.

  15. 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

  16. [Toxicological and immunological aspects of scorpion venom (Tytius pachyurus): neutralizing capacity of antivenoms produced in Latin America].

    PubMed

    Barona, Jacqueline; Otero, Rafael; Núñez, Vitelbina

    2004-03-01

    The toxicity and immunochemical properties of Tityus pachyurus Pocock scorpion venom was characterized, as well as the neutralization capacity against it by three anti-scorpion antivenoms (Alacramyn, Instituto Bioclón, México; Suero antiescorpiónico, Instituto Butantán, Sao Paulo, Brasil; and Suero antiescorpiónico, Centro de Biotecnología, Universidad Central de Venezuela, Caracas, Venezuela). The venom yield, obtained by manual milking, 680+/-20 microg venom, a 50% lethal dose in mice was 4.8 microg/kg (90 microg for an 18-20 g mouse). The most common symptoms of venom poisoning in mice were sialorrhea, respiratory distress, profuse sweating, ataxia, behavior alterations (restlessness, somnolence) and hyperglycemia at 3 and 24 hours after subcutaneous venom injection (0.5 LD50). The neutralizing capacity of Bioclón (México City) and Butantán (Sao Paulo) antivenoms (for a 50% effective dose) was 330 and 292 microg venom/ml antivenom, respectively. The Biotecnología (Caracas) antivenom did not neutralize the lethal effect of venom. By electrophoresis (SDS-PAGE) was demonstrated that the venom contains proteins from less than 14 kd to 97 kd. The Western blots indicated immunological reactivity of the three antivenoms with most of venom components, including proteins of low molecular mass (<14 kd). The results allow to conclude that T. pachyurus venom is neutralized efficiently by anti-scorpion antivenoms produced in México and Brasil.

  17. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

    PubMed Central

    Akahoshi, Mitsuteru; Song, Chang Ho; Piliponsky, Adrian M.; Metz, Martin; Guzzetta, Andrew; Åbrink, Magnus; Schlenner, Susan M.; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

    2011-01-01

    Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell–derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell–deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function. PMID:21926462

  18. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice.

    PubMed

    Akahoshi, Mitsuteru; Song, Chang Ho; Piliponsky, Adrian M; Metz, Martin; Guzzetta, Andrew; Abrink, Magnus; Schlenner, Susan M; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J

    2011-10-01

    Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell-derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell-deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function.

  19. 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.

  20. 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

  1. Proteomic analysis of the venom of Heterometrus longimanus (Asian black scorpion).

    PubMed

    Bringans, Scott; Eriksen, Soren; Kendrick, Tulene; Gopalakrishnakone, P; Livk, Andreja; Lock, Robert; Lipscombe, Richard

    2008-03-01

    Venoms have evolved over millions of years into potent cocktails of bioactive peptides and proteins. These compounds can be of great value to the pharmaceutical industry for numerous clinical applications. In this study, a novel proteomic - bioinformatic approach was utilised, where chromatography followed by gel electrophoresis was utilised to separate the venom peptides/proteins of Heterometrus longimanus (Asian black scorpion). Purified peptides were analysed by tandem mass spectrometry, de novo sequenced and then homology matched against known peptides in the Swiss-Prot protein database. Numerous potentially biologically active peptide matches were discovered, and a simple scoring system applied to putatively assign functions to the peptides. As a validation of this approach, the functional composition of the experimentally derived proteome is similar to that of other scorpions, and contains a potent mix of toxins, antimicrobials and ionic channel inhibitors.

  2. Vejovine, a new antibiotic from the scorpion venom of Vaejovis mexicanus.

    PubMed

    Hernández-Aponte, Cynthia A; Silva-Sanchez, Jesus; Quintero-Hernández, Verónica; Rodríguez-Romero, Adela; Balderas, Cipriano; Possani, Lourival D; Gurrola, Georgina B

    2011-01-01

    Multidrug resistant bacterial infections are one of the most important health problems in recent years. Resistance to conventional antibiotics limits the therapeutic options causing increase rate in morbid-mortality in hospitals. Therefore, new antibacterial agents with new bacterial targets have been searched and found in many different sources, including scorpion venom and scorpion hemolymph. Here, we report a new anti-microbial peptide named Vejovine. This peptide was isolated from the venom of the Mexican scorpion Vaejovis mexicanus by two steps of reversed phase high performance liquid chromatography (RP-HPLC). It is composed of 47 amino acid residues with no cysteine residues in its sequence, with a molecular weight of 4873 Da. The chemical synthesis of Vejovine was performed by the solid phase method of Merrifield, using fluoren-9-ylmethoxycarbonyl (Fmoc)-amino acids. Both the native and synthetic peptides were shown to have essentially the same activity. Vejovine inhibits growth of clinical isolates of Gram-negative multidrug resistant (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Acinetobacter baumanii) causing nosocomial infections with a minimum inhibitory concentration (MIC) of 4.4 μM up to 50 μM. This peptide has also hemolytic activity against human erythrocytes with a HC(50) value of 100 μM. A cDNA library of the venomous gland of this scorpion provided material for cloning the gene encoding Vejovine. This peptide is a new type of antibiotic, showing less than 50% similarity to other known scorpion peptides. Vejovine is a candidate to be used as a leading compound for future development of an effective peptide against multidrug resistant bacteria. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. 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.

  4. Insights into the Hypertensive Effects of Tityus serrulatus Scorpion Venom: Purification of an Angiotensin-Converting Enzyme-Like Peptidase

    PubMed Central

    Cajado-Carvalho, Daniela; Kuniyoshi, Alexandre Kazuo; Duzzi, Bruno; Iwai, Leo Kei; de Oliveira, Úrsula Castro; Junqueira de Azevedo, Inácio de Loiola Meirelles; Kodama, Roberto Tadashi; Portaro, Fernanda Vieira

    2016-01-01

    The number of cases of envenomation by scorpions has grown significantly in Brazil since 2007, with the most severe cases being caused by the Tityus serrulatus scorpion. Although envenomed patients mostly suffer neurotoxic manifestations, other symptoms, such as hypertension, cannot be exclusively attributed to neurotoxins. Omics analyses have detected plentiful amounts of metalloproteases in T. serrulatus venom. However, the roles played by these enzymes in envenomation are still unclear. Endeavoring to investigate the functions of scorpion venom proteases, we describe here for the first time an Angiotensin I-Converting Enzyme-like peptidase (ACE-like) purified from T. serrulatus venom. The crude venom cleaved natural and fluorescent substrates and these activities were inhibited by captopril. Regarding the serum neutralization, the scorpion antivenom was more effective at blocking the ACE-like activity than arachnid antivenom, although neither completely inhibited the venom cleavage action, even at higher doses. ACE-like was purified from the venom after three chromatographic steps and its identity was confirmed by mass spectrometric and transcriptomic analyses. Bioinformatics analysis showed homology between the ACE-like transcript sequences from Tityus spp. and human testis ACE. These findings advance our understanding of T. serrulatus venom components and may improve treatment of envenomation victims, as ACE-like may contribute to envenomation symptoms, especially the resulting hypertension. PMID:27886129

  5. 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

  6. Neolignans from Aristolochia elegans as antagonists of the neurotropic effect of scorpion venom.

    PubMed

    Zamilpa, Alejandro; Abarca-Vargas, Rodolfo; Ventura-Zapata, Elsa; Osuna-Torres, Lidia; Zavala, Miguel A; Herrera-Ruiz, Maribel; Jiménez-Ferrer, Enrique; González-Cortazar, Manasés

    2014-11-18

    The high frequency of poisoning by sting or bite from venomous animals has begun to be a serious public health problem in Mexico where scorpion sting is the most common. Because of this, there is the need to seek active substances in plant species with an antagonistic effect against neurotropic activity of scorpion venom. The aim of this work was to demonstrate which of the compounds contained in the n-hexane extract from Aristolochia elegans roots display activity against scorpion venom. Antagonist activity displayed by extract, fractions and isolated compounds obtained from Aristolochia elegans was guided by the inhibition of smooth muscle contraction induced by scorpion venom (Centruroides limpidus limpidus) in a model of isolated guinea pig ileum. The neolignans obtained from this extract were isolated and analyzed by chromatographic methods including HPLC. The chemical characterization of these compounds was performed by the analysis of (1)H and (13)C NMR spectra. The bio-guided chromatographic fractionation allowed us to isolate 4 known neolignans: Eupomatenoid-7 (1), licarin A (2), licarin B (3), eupomatenoid-1 (4) and other new neolignan which was characterized as 2-(3'-hydroxy-4'-methoxyphenyl)-3-methyl-5-[(E)-α-propen-γ-al]-7-methoxy-benzo [b] furan (5). This compound was named as eleganal. Compounds 1 and 2 were purified from the most active fraction AeF3 (EC50 of 149.9μg/mL, Emax of 65.66%). A doses-response analysis of eupomatenoid-7(1) and licarin A(2) allowed us to establish EC50 values (65.96μg/mL and 51.96μg/mL) respectively. The antagonistic effect against Centuroides limpidus limpidus scorpion venom displayed by the n-hexane extract from Aristolochia elegans roots is due to the presence of neolignans 1-2 contained in the fraction AeF3. Chemical analysis of fraction AeF2 allowed the isolation of a new compound which was identified as 2-(3'-hydroxy-4'-methoxyphenyl)-3-methyl-5-[(E)-α-propen-γ-al]-7-methoxy-benzo[b]furan (5), denominated as

  7. The depressant scorpion neurotoxin LqqIT2 selectively modulates the insect voltage-gated sodium channel.

    PubMed

    Bosmans, Frank; Martin-Eauclaire, Marie-France; Tytgat, Jan

    2005-03-15

    LqqIT2 is a depressant neurotoxin present in the venom of the Leiurus quinquestriatus quinquestriatus scorpion, one of the world's most dangerous scorpions endemic to dry habitats in Africa and Asia. In order to determine its efficacy, potency and selectivity, LqqIT2 was subjected for the first time to an electrophysiological and pharmacological comparison between two different cloned sodium channels expressed in Xenopus laevis oocytes. Aside from typical beta-toxin effects, LqqIT2 also affected the inactivation process and ion selectivity of the insect voltage-gated sodium channel. The most interesting feature of LqqIT2 is its total insect-selectivity. At a concentration of 1 microM, the insect-voltage-gated sodium channel, para, was profoundly modulated while its mammalian counterpart, the rat brain Na(v)1.2 channel, was not affected. This trait offers excellent prospects for the development of novel insecticides.

  8. Novel potassium channel blocker venom peptides from Mesobuthus gibbosus (Scorpiones: Buthidae).

    PubMed

    Diego-García, Elia; Peigneur, Steve; Debaveye, Sarah; Gheldof, Eveline; Tytgat, Jan; Caliskan, Figen

    2013-01-01

    In the present study, we report for the first time, the molecular, biochemical and electrophysiological characterization of the components present in the soluble venom from Mesobuthus gibbosus (Brullé, 1832). According to the epidemiological and clinical situation of scorpion envenomation cases M. gibbosus scorpion is one of the most important health-threatening species of Turkey. Despite the medical importance reported for M. gibbosus, there is no additional information on toxin peptides and venom components to clarify the toxic effect of the M. gibbosus sting. Biochemical characterization of the venom was performed using different protocols and techniques following a bioassay-guided strategy (HPLC, mass spectrometry and Edman degradation sequencing). Venom fractions were tested in electrophysiological assays on a panel of six K(+) channels (K(v)1.1-1.6) by using the two-electrode voltage clamp technique. Three new α-KTx peptides were found and called MegKTx1, MegKTx2 and MegKTx3 (M. gibbosus, K(+) channel toxin number 1-3). A cDNA library from the telson was constructed and specific screening of transcripts was performed. Biochemical and molecular characterization of MegKTx peptides and transcripts shows a relation with toxins of three different α-KTx subfamilies (α-KTx3.x, α-KTx9.x and α-KTx16.x). Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. 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

    2014-06-12

    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

  10. 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.

  11. 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.

  12. 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.

  13. Effect of clonidine in mice injected with Tityus discrepans scorpion venom.

    PubMed

    Rodríguez, A; Zerpa, H; Ruiz, A; Bermúdez, V; García, F; Silva, A; Gutiérrez, L; Villasmil, S

    2013-03-01

    A study was conducted to assess the effect of clonidine (α(2)-adrenoceptor selective agonist) on glycemia, serum and urine α-amylase, blood urea nitrogen (BUN), serum creatinine, white blood cell count, kidney histology and zymogen granule content in pancreatic acini, in mice under the effect of Tityus discrepans (Td) scorpion venom. BALB/c male mice (20 ± 2 g, n = 7-11) were intraperitoneally (ip) injected with a sublethal dose (1 μg/g) of Td venom, and were treated (ip) with 0.1 μg/g of clonidine (Catapresan(®)) or 0.9% NaCl 30 min after the venom injection, and then every 2 h. Six hours later, mice were anesthetized with diethylether and urine and blood samples were withdrawn by cystocentesis and cardiocentesis, respectively. Tissue samples were obtained and fixed immediately in buffered formalin (2%, pH 7.4) and then processed for stain H&E. Td venom did not cause hyperglycemia by itself. However, clonidine induced hyperglycemia, which was synergized by Td venom. Although the venom did not produce hyperamylasemia, clonidine significantly diminished serum α-amylase activity in envenomed mice. Td venom did not significantly increase urinary α-amylase activity, which was unaffected by clonidine. Morphometric analysis using microphotographs of pancreata from mice injected with Td venom showed a reduced zymogen granule content as judged by the acidophilic bidimensional area of acini. This effect was significantly reduced by clonidine. Kidney samples showed histological changes which were partially affected by the drug. Clonidine reduced the increase in BUN and serum creatinine concentration in envenomed mice. Td venom produced neutrophilia and lymphopenia, which were clonidine-resistant at the assayed dose. These results suggest that α(2)-adrenoceptor selective agonists would be able to reduce some scorpion venom-induced renal and pancreatic disturbances, possibly through the inhibition of neurotransmitter release from presynaptic cholinergic and

  14. Antigenic cross-reactivity between sixteen venoms from scorpions belonging to six genera.

    PubMed

    D'Suze, G; Moncada, S; González, C; Sevcik, C; Alagón, A

    2007-01-01

    Venoms of 15 scorpion species from Venezuela and one from Brazil were compared in their antigenic cross-reactivity with specific F(ab')2 against Tityus discrepans (Td-antibodies), using the method of King and collaborators (1). Our results show that Tityus venoms cross-reactivity (shared epitopes) with the venoms of other species within the genus tended to be less for a greater distance between the habitat of the species. A nonparametric linear regression of free Td-antibody binding to T. discrepans venom immobilized to a solid phase in the presence of other Tityus venoms versus distance showed binding = a + b x log10 (distance) where: median (95% confidence interval) for a = 0.92 (7.43, 9.80) and b = 17.20 (4.15, 22.57) binding/log10(Km); Spearman rS = 0.783 with associated P = 0.006. Our results show that toxins from different Tityus species, targeting mammalian Na+ and K+ channels, are antigenically very similar. Venoms from species from other genera such as Centruroides, Broteas, Diplocentrus, Chactas, and Rhopalurus did not cross-react with Td-antibodies.

  15. 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. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  16. 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

  17. Molecular characterization of a new scorpion venom lipolysis activating peptide: Evidence for disulfide bridge-mediated functional switch of peptides.

    PubMed

    Zhu, S; Gao, B

    2006-12-22

    Venoms from scorpions contain extremely rich bioactive peptides that often carry diverse functions and are presumably needed to achieve synergistic effects for rapidly immobilizing prey and defending themselves. BotLVP1 is a unique heterodimer protein recently found in the scorpion Buthus occitanus tunetanus venom that is structurally related to scorpion toxins affecting sodium channels (NaScTxs) but exhibits adipocyte lipolysis activity. We have isolated and identified two cDNA clones encoding subunits alpha and beta of a BotLVP1-like peptide (named BmLVP1) from the Chinese scorpion Buthus martensii venom gland and determined the first complete gene structure of this subfamily. These results highlight a genetic link between these lipolysis activating peptides and NaScTxs. Comparison of cDNA and genomic sequences combined with protein structural and functional analysis provides evidence supporting the existence of RNA editing mechanism in scorpion venom glands, which could mediate functional switch of BmLVP1 gene, from adipocyte lipolysis to neurotoxicity, by altering the wrapper disulfide bridge (WDB) pattern of the peptides.

  18. Comparative analyses and implications for antivenom serotherapy of four Moroccan scorpion Buthus occitanus venoms: Subspecies tunetanus, paris, malhommei, and mardochei.

    PubMed

    Emerich, Bruna Luiza; De Lima, Maria Elena; Martin-Eauclaire, Marie-France; Bougis, Pierre E

    2017-07-13

    Temporary passive immunity such as serotherapy against venoms requires the full knowledge of all venom's components. Here, four venoms from Moroccan common yellow scorpions belonging to Buthus occitanus, subspecies tunetanus, paris, malhommei, and mardochei, all collected in four different restricted areas, were analysed in deep. They were fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC) and their molecular masse profile determined by off-line MALDI-TOF mass spectrometry. Characterisation of their main components was achieved by enzyme-linked immunosorbent assay (ELISA) using specific antisera against the major lethal scorpion toxins identified so far, i.e. voltage-gated sodium channels (Nav) modulators α- and β-toxins, as well as diverse potassium channel pore blocker toxins. For fractions with identical RP-HPLC retention times, we observe that their relative quantities show large differences. Moreover, identical masses present simultaneously in the four venoms are infrequent. ELISAs show that the majority of the RP-HPLC compounds cross-react with the antiserum against the "α-like" toxin Bot I, which has been previously identified in the Algerian Buthus occitanus tunetanus venom. Moreover, minor fractions were recognised by the antiserum against the highly lethal "classical" α-toxin of reference AaH II from the Androctonus australis venom. As such, our results bring new sights for further improving scorpion venom serotherapy in Morocco. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. 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.

  20. Comparison of the neurotoxic and myotoxic effects of two Moroccan scorpion venoms and their neutralization by experimental polyclonal antivenom.

    PubMed

    Oukkache, Naoual; Ahmad Rusmili, Muhamad Rusdi; Othman, Iekhsan; Ghalim, Noreddine; Chgoury, Fatima; Boussadda, Lofti; Elmdaghri, Naima; Sabatier, Jean-Marc

    2015-03-01

    Scorpion venoms contain complex mixtures of molecules, including peptides. These peptides specifically bind to various targets, in particular ion channels. Toxins modulating Na(+), K(+), Ca(2+) and Cl(-) currents were described from venoms. The Androctonus and Buthus geni of scorpions are widely distributed in Morocco. Their stings can cause pain, inflammation, necrosis, muscle paralysis and death. The myotoxicity is predominantly associated with neurotoxic effects and is a cause of mortality and morbidity. In this study, pharmacological effects of venoms were investigated in vitro on neuromuscular transmission. Effects of Androctonus mauretanicus (Am) and Buthus occitanus (Bo) venoms were investigated using the chick biventer cervicis nerve-muscle preparations. The protective activity of antivenom was also investigated. The antivenom was made from serum of horse that was hyperimmunized with Bo and Androctonus australis hector (Aah) venoms and one venom from Middle East species (Lq). The protective activity of the antivenom was assessed on the neuromuscular system by using stimulated chick nerve-muscle. The results were compared with lethal activity neutralization in mice. Am and Bo venoms contain myotoxins and postsynaptic neurotoxins. In agreement with lethal potencies of these venoms in mice, Am venom displays greater neurotoxicity and myotoxicity. The antivenom prevented lethality caused by Am, Bo and Aah venoms. The antivenom did not prevent toxic effects caused by Am venom whereas it neutralized Bo venom. Am and Bo venoms contain distinct toxins that are responsible for myotoxicity and neurotoxicity. It would be appropriate to add Am venom to produce more efficient antivenom. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. 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

  2. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Comparative proteomic analysis of female and male venoms from the Mexican scorpion Centruroides limpidus: Novel components found.

    PubMed

    Cid Uribe, Jimena Isaias; Jiménez Vargas, Juana Maria; Ferreira Batista, Cesar Vicente; Zamudio Zuñiga, Fernando; Possani, Lourival Domingos

    2017-01-01

    Venom from male and female scorpions of the species Centruroides limpidus were separated by HPLC and their molecular masses determined by mass spectrometry. The relative concentration of components eluting in equivalent retention times from the HPLC column shows some differences. A new peptide with 29 amino acids, cross-linked by three disulfide bonds was found in male scorpions and its structure determined. Another unknown peptide present in female venom, with sequence identity similar to K(+)-channel blocking peptide was isolated. This peptide contains 39 amino acid residues linked by three disulfide bonds. Due to sequence similarities, a systematic number (αKTx2.18) was assigned. Venom from male and female scorpions was separated by Sephadex G-50 gel filtration. Components of fraction I of this chromatogram were analyzed by two-dimensional gel electrophoresis and 41 spots were selected (20 from female and 21 from male). The spots were excised from the gel, enzymatically digested and sequenced by LC-MS/MS. This procedure allowed the identification of several proteins containing similar amino acid sequence of other known proteins registered on UniProt database. Among these proteins the presence of metalloproteinases (proteolytic enzymes), hyaluronidases and phosphatases were experimentally determined and shown to be present in both venom samples. The results shown here should help further work aimed at fully identification of the structure and function of venom components form C. limpidus male and female scorpions.

  4. Characterization of LmTxLP11 and LmVP1.1 transcripts and genomic organizations: alternative splicing contributing to the diversity of scorpion venom peptides.

    PubMed

    Ma, Yibao; Zhao, Ruiming; Li, Songryong; Fan, Shaozhong; Wu, Yingliang; Liu, Hui; Cao, Zhijian; Li, Wenxin

    2009-01-01

    Scorpion venoms are rich resources of bioactive peptides with extreme variability. Multiple molecular mechanisms are involved in the diversity of scorpion venom peptides. However, alternative splicing, which plays a major role in the generation of proteomic and functional diversity in metazoan organisms, hasn't been reported in genes coding for scorpion venom peptides. In the EST analysis of venom peptide transcripts from scorpion Lychas mucronatus, we reported an alternative splicing event. Transcripts of LmTxLP11 and LmVP1.1 share identical 5' region. LmVP1.1 is a novel type of scorpion venom peptides constrained by one disulfide bridge, whereas LmTxLP11 is an extended version of LmVP1.1. By transcript alignment with its genomic sequence, it is found that both transcripts are generated from a single gene by alternative poly A site and terminal exon. The gene encoding LmTxLP11 and LmVP1.1 is the first one harboring three introns ever reported from scorpion venoms. This work demonstrates for the first time that alternative splicing is involved in regulating the diversity of scorpion venom peptides.

  5. 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.

  6. AaTX1, from Androctonus australis scorpion venom: purification, synthesis and characterization in dopaminergic neurons.

    PubMed

    Mlayah-Bellalouna, Saoussen; Dufour, Martial; Mabrouk, Kamel; Mejdoub, Hafedh; Carlier, Edmond; Othman, Houcemeddine; Belghazi, Maya; Tarbe, Marion; Goaillard, Jean Marc; Gigmes, Didier; Seagar, Michael; El Ayeb, Mohamed; Debanne, Dominique; Srairi-Abid, Najet

    2014-12-15

    We have purified the AaTX1 peptide from the Androctonus australis (Aa) scorpion venom, previously cloned and sequenced by Legros and collaborators in a venom gland cDNA library from Aa scorpion. AaTX1 belongs to the α-Ktx15 scorpion toxins family (αKTx15-4). Characterized members of this family share high sequence similarity and were found to block preferentially IA-type voltage-dependent K(+) currents in rat cerebellum granular cells in an irreversible way. In the current work, we studied the effects of native AaTX1 (nAaTX1) using whole-cell patch-clamp recordings of IA current in substantia nigra pars compacta dopaminergic neurons. At 250 nM, AaTX1 induces 90% decrease in IA current amplitude. Its activity was found to be comparable to that of rAmmTX3 (αKTx15-3), which differs by only one conserved (R/K) amino acid in the 19th position suggesting that the difference between R19 and K19 in AaTX1 and AmmTX3, respectively, may not be critical for the toxins' effects. Molecular docking of both toxins with Kv4.3 channel is in agreement with experimental data and suggests the implication of the functional dyade K27-Y36 in toxin-channel interactions. Since AaTX1 is not highly abundant in Aa venom, it was synthesized as well as AmmTX3. Synthetic peptides, native AaTX1 and rAmmTX3 peptides showed qualitatively the same pharmacological activity. Overall, these data identify a new biologically active toxin that belongs to a family of peptides active on Kv4.3 channel. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

    PubMed Central

    Chen, Yaoqing; Cao, Luyang; Zhong, Maohua; Zhang, Yan; Han, Chen; Li, Qiaoli; Yang, Jingyi; Zhou, Dihan; Shi, Wei; He, Benxia; Liu, Fang; Yu, Jie; Sun, Ying; Cao, Yuan; Li, Yaoming; Li, Wenxin; Guo, Deying; Cao, Zhijian; Yan, Huimin

    2012-01-01

    For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1. PMID:22536342

  8. Impact of scorpion venom as an acute stressor on the neuroendocrine-immunological network.

    PubMed

    Santhosh, K N; Pavana, D; Thippeswamy, N B

    2016-11-01

    Although immunomodulatory property and many other pharmaceutical applications of scorpion venom have been addressed before, no studies were reported about its application as a neuroimmunomodulator at therapeutic dose. In this study, we conceptualized the property of scorpion venom, capable of inducing the acute pain and neurotoxicity can cause acute stress resulting in the modulation of immune cells through HPA axis. The whole venom from Hottentotta rugiscutis, a widely seen scorpion in the region of eastern Karnataka, was extracted and injected a single dose of 1 mg/kg b.w. to Swiss albino mice and then erythrocytes and leukogram were measured. Whole brain AChE activity, corticosterone, cytokines and NO levels in plasma were also evaluated at various time points. Hrv didn't show any histopathological changes in the lymphoid organs and at the site of injection. However, lymphocytes and neutrophils did get altered at 2 h post-injection. Plasma corticosterone, cytokine levels such as IL-1β, IL-6, TNF-α and IL-10 and the AChE activity were significantly increased in a time-dependent manner. Based on these results, it may be predicted, Hrv's ability to cause acute stress resulted in the activation of HPA axis, which stimulates the release of glucocorticoid hormones which in turn elicits the immunomodulation of leukocytes by altering the levels of pro and anti-inflammatory cytokines. Thus, we can conclude, the impact of acute stress induced by Hrv can intercommunicate the signals between neuroendocrine-immune systems.

  9. Enzymatic properties of venoms from Brazilian scorpions of Tityus genus and the neutralisation potential of therapeutical antivenoms.

    PubMed

    Venancio, Emerson J; Portaro, Fernanda C V; Kuniyoshi, Alexandre K; Carvalho, Daniela Cajado; Pidde-Queiroz, Giselle; Tambourgi, Denise V

    2013-07-01

    Tityus scorpion stings are an important public health problem in Brazil, where the incidence of such stings exceeds the incidence of the health problems caused by other venomous animals, including snakes. In this study, we have analysed specific enzymatic activities of the venom from the Brazilian scorpions of Tityus genus, i.e., Tityus serrulatus, Tityus bahiensis and Tityus stigmurus. The data presented here revealed that Tityus spp. venoms exhibited significant hyaluronidase activity but no phospholipase activity. All the venom samples exhibited the ability to hydrolyse Abz-FLRRV-EDDnp and dynorphin 1-13 substrates. These activities were inhibited by 1,10-phenanthroline but not by PMSF, indicating the presence of metalloproteinases in the Tityus spp. venoms. The venom peptidase activity on Abz-FLRRV-EDDnp and on dynorphin 1-13 was partially inhibited by therapeutic Brazilian anti-scorpion and anti-arachnidic antivenoms. Dynorphin 1-13 (YGGFLRRIRPKLK) contains two scissile bonds between the residues Leu-Arg and Arg-Arg that are susceptible to cleavage by the Tityus venom metallopeptidase(s). Their cleavage releases leu-enkephalin, an important bioactive peptide. The detection of metalloproteinase(s) with specificity for both dynorphin 1-13 degradation and leu-enkephalin releasing can be important for the mechanistic understanding of hypotension and bradycardia induction in cases of scorpion stings, whereas hyaluronidases might contribute to the diffusion of the toxins present in these venoms. Furthermore, the limited inhibition of the toxic enzymatic activities by commercial antivenoms illustrates the necessity of improvements in current antivenom preparation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Characterizing the biological and biochemical profile of six different scorpion venoms from the Buthidae and Scorpionidae family.

    PubMed

    Estrada-Gómez, Sebastian; Gomez-Rave, Lyz; Vargas-Muñoz, Leidy Johana; van der Meijden, Arie

    2017-05-01

    The objective of this study was to characterize six different scorpion venoms using biological and biochemical methods, including a preliminary MS/MS and a post-translational modifications analysis. Despite the diversity of scorpion species of medical importance in Africa and Colombia, the venoms of these arachnids have been poorly studied in these two regions. We report the biochemical, electrophoretic, chromatographic profile, internal peptide sequences with a post-translational modification report, and a preliminary antitumor activity of five different scorpions of the Buthidae family, Androctonus amoreuxi, Babycurus jacksoni, Grosphus grandidieri, Hottentotta gentili and Tityus fuhrmanni, and one of the Scorpionidae family Pandinus imperator. No L-amino oxidase activity was detected in the evaluated venoms. Proteolytic activity using azocasein was detected only in G. grandidieri and P. imperator, indicating the possible presence of metalloproteinases in these two venoms. Proteolytic activity using NOBA was detected in all venoms indicating the possible presence of serine-proteinases. Phospholipase A2 activity was detected in the venoms of P. imperator, G. grandidieri, H. gentili and A. amoreuxi, with P. imperator venom being the most active. All venoms analyzed contained defensin-like proteins, alpha toxins, metalloproteinases, neuropeptides, DBP affecting ion channels, DBP with antimicrobial activity, among others. Venoms from P. imperator, G. grandidieri and T. fuhrmanni showed a dose-dependent cytotoxic activity over MCF-7 cells. Only two isolated RP-HPLC fractions from P. imperator and T. fuhrmanni showed cytotoxic activity over MCF-7. No cytotoxic activity was found in the venoms from A. amoreuxi, B. jacksoni, and H. gentili.

  11. 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. Copyright © 2015. Published by Elsevier Ltd.

  12. Venomous spiders, snakes, and scorpions in the United States.

    PubMed

    Holve, Steve

    2009-04-01

    Venomous bites and stings are complex poisonings that have local and systemic effects. Mild envenomations can be treated with supportive care. Severe envenomations can be treated definitively with species-specific antivenom, although the use of these products has potential risk of immediate and a more delayed onset form of hypersensitivity reactions. Consultation with a toxicologist is recommended to help guide therapy. Field treatments such as tourniquets and incision likely cause more harm than benefit and should be avoided.

  13. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. 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

    2010-02-03

    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. (c) 2009. Published by Elsevier Ltd.

  15. Biochemical, genetic and physiological characterization of venom components from two species of scorpions: Centruroides exilicauda Wood and Centruroides sculpturatus Ewing.

    PubMed

    Valdez-Cruz, Norma A; Dávila, Sonia; Licea, Alexei; Corona, Miguel; Zamudio, Fernando Z; García-Valdes, Jesús; Boyer, Leslie; Possani, Lourival D

    2004-06-01

    Current literature concerning the taxonomic names of two possibly distinct species of scorpions from the genus Centruroides (sculpturatus and/or exilicauda) is controversial. This communication reports the results of biochemical, genetic and electrophysiological experiments conducted with C. exilicauda Wood of Baja California (Mexico) and C. sculpturatus Ewing of Arizona (USA). The chromatographic profile fractionation of the soluble venom from both species of scorpions is different. The N-terminal amino acid sequence for nine toxins of C. exilicauda was determined and compared with those from C. sculpturatus. Lethality tests conducted in mice support the idea that C. exilicauda venom should be expected to be medically less important than C. sculpturatus. Thirteen genes from the venomous glands of the scorpion C. exilicauda were obtained and compared with previously published sequences from genes of the species C. sculpturatus. Genes coding for cytochrome oxidase I and II of both species were also sequenced. A phylogenetic tree was generated with this information showing important differences between them. Additionally, the results of electrophysiological assays conducted with the venom from both species on the Ca(2+)-dependent K(+)-channels, showed significant differences. These results strongly support the conclusion that C. exilicauda and C. sculpturatus are in fact two distinct species of scorpions.

  16. Anti-proliferative Effects of Androctonus amoreuxi Scorpion and Cerastes cerastes Snake Venoms on Human Prostate Cancer Cells

    PubMed Central

    Akef, Hassan; Kotb, Nahla; Abo-Elmatty, Dina; Salem, Sayed

    2017-01-01

    The present study evaluated the effects of Androctonus amoreuxi scorpion venom, Cerastes cerastes snake venom and their mixture on prostate cancer cells (PC3). An MTT assay was used to determine the anti-proliferative effect of the venoms, while quantitative real time PCR was used to evaluate the expression of apoptosis-related genes (Bax and Bcl-2). Furthermore, colorimetric assays were used to measure the levels of malondialdehyde (MDA) and antioxidant enzymes. Our results show that the venoms significantly reduced PC3 cell viability in a dose-dependent manner. On the other hand, these venoms significantly decreased Bcl-2 gene expression. Additionally, C. cerastes venom significantly reduced Bax gene expression, while A. amoreuxi venom and a mixture of A. amoreuxi & C. cerastes venoms did not alter Bax expression. Consequently, these venoms significantly increased the Bax/Bcl-2 ratio and the oxidative stress biomarker MDA. Furthermore, these venoms also increased the activity levels of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Overall, the venoms have cytotoxic and anti-proliferative effects on PC3 cells. PMID:28382285

  17. Scorpion (Androctonus bicolor) venom exhibits cytotoxicity and induces cell cycle arrest and apoptosis in breast and colorectal cancer cell lines

    PubMed Central

    Al-Asmari, Abdulrahman K.; Riyasdeen, Anvarbatcha; Abbasmanthiri, Rajamohamed; Arshaduddin, Mohammed; Al-Harthi, Fahad Ali

    2016-01-01

    Objectives: The defective apoptosis is believed to play a major role in the survival and proliferation of neoplastic cells. Hence, the induction of apoptosis in cancer cells is one of the targets for cancer treatment. Researchers are considering scorpion venom as a potent natural source for cancer treatment because it contains many bioactive compounds. The main objective of the current study is to evaluate the anticancer property of Androctonus bicolor scorpion venom on cancer cells. Materials and Methods: Scorpions were milked by electrical stimulation of telsons and lyophilized. The breast (MDA-MB-231) and colorectal (HCT-8) cancer cells were maintained in appropriate condition. The venom cytotoxicity was assessed by 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the cellular and nuclear changes were studied with propidium iodide and 4’,6-diamidino-2-phenylindole stain, respectively. The cell cycle arrest was examined using muse cell analyzer. Results: The A. bicolor venom exerted cytotoxic effects on MDA-MB-231 and HCT-8 cells in a dose- and duration-dependent manner and induced apoptotic cell death. The treatment with this venom arrests the cancer cells in G0/G1 phase of cell cycle. Conclusions: The venom selectively induces the rate of apoptosis in MDA-MB-231 and HCT-8 cells as reflected by morphological and cell cycle studies. To the best of our knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by A. bicolor scorpion venom. PMID:27721540

  18. 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.

  19. 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

  20. 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

  1. BmK-YA, an enkephalin-like peptide in scorpion venom.

    PubMed

    Zhang, Yan; Xu, Junyan; 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 His(4)-BmK-YA, all flanked by single amino acid residues. BmK-YA and His(4)-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 His(4)-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.

  2. 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.

  3. [Comparative action of toxins isolated from the venom of the scorpion (Androctonus australis) and the tentacles of the sea anemone (Anemonia Sulcata) on an isolated frog neuromuscular preparation].

    PubMed

    Tazieff-Depierre, F; Métézeau, P

    1978-06-01

    We have shown that, if Scorpion venom is acting a skeletal muscle indirectly by releasing Acetycholine and directly by inducing an increase in intracellular free calcium, the main action of toxin II isolated from Anemonia Sulcata tentacles is presynaptic.

  4. A novel amphipathic linear peptide with both insect toxicity and antimicrobial activity from the venom of the scorpion Isometrus maculatus.

    PubMed

    Miyashita, Masahiro; Sakai, Atsushi; Matsushita, Nobuto; Hanai, Yosuke; Nakagawa, Yoshiaki; Miyagawa, Hisashi

    2010-01-01

    Scorpion venoms are composed of a number of peptides, many of which show neurotoxicity. In addition to these neurotoxins, several antimicrobial peptides have also been isolated from the venoms. The scorpion Isometrus maculatus, belonging to the Buthidae family, is found in many tropical regions including Japan, but little attention has been paid to its biological activity and chemical composition. In this study, we isolated a novel insect toxin, Im-1, by bioassay-guided fractionation of the venom of I. maculatus. Rapid and reversible paralysis was observed after injection of Im-1 into crickets. Im-1 consists of 56 amino acids, and is predicted to form an amphipathic alpha-helix. Since Im-1 shares sequence similarity to an antimicrobial peptide, parabutoporin, we evaluated its effects on several bacterial strains and found that it showed an antimicrobial activity profile similar to parabutoporin. This suggests that Im-1 and parabutoporin exert their antimicrobial effects through similar mechanisms.

  5. 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

  6. Full characterization of three toxins from the Androctonus amoreuxi scorpion venom.

    PubMed

    Abbas, Najwa; Legros, Christian; Ceard, Brigitte; Belghazi, Maya; Hamon, Alain; Bougis, Pierre E; Martin-Eauclaire, Marie-France

    2009-09-15

    In this study, we have characterized the immunological and pharmacological properties of the three major alpha-type toxins from the scorpion Androctonus amoreuxi, AamH1, AamH2 and AamH3, which were previously described as putative toxins from cDNAs [Chen, T. et al., 2003. Regul. Pept. 115, 115-121]. The immunological tests (ELISA, RIA) have demonstrated that AamH1, AamH2 and AamH3 belong to the immunological groups 3 and 4 of alpha-type toxins. Analysis of the three toxin effects on currents through rat brain (rNav1.2), rat muscle (rNav1.4) and Drosophila (DmNav1) sodium channels expressed in Xenopus oocytes revealed that AamH1 and AamH2, but not AamH3, have anti-insect and anti-mammal activities and can be classified as alpha-like toxins. While AamH1 removes fast inactivation only in neuronal rNav1.2 channel and has no effect on muscular rNav1.4 channel, AamH2 affects both neuronal rNav1.2 and muscular rNav1.4 channels. AamH3 was lethal to mice by intracerebroventricular injection despite its lack of activity on the neuronal rNav1.2 channel. Finally, we have shown that the A. amoreuxi venom was better neutralized by the antiserum raised against the venom of Buthus occitanus tunetanus than by the antisera raised against scorpion venoms from the same genus Androctonus.

  7. 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.

  8. [The alterations of apoptosis factor Bcl-2/Bax in the early Parkinson's disease rats and the protective effect of scorpion venom derived activity peptide].

    PubMed

    Xu, Hong; An, Dong; Yin, Sheng-ming; Chen, Wei; Zhao, Dan; Meng, Xu; Yu, De-qin; Sun, Yi-ping; Zhao, Jie; Zhang, Wan-qin

    2015-05-01

    To explore the alterations of apoptosis factor Bcl-2/Bax in the early Parkinson's disease (PD) rats and the protective effect of scorpion venom derived bioactive peptide. Healthy male SD rats (180-220 g) were randomly divided into 4 groups (n = 10): early PD model group, sham operation group, scorpion venom derived bioactive peptide control group, scorpion venom derived bioactive peptide therapy group. 6-hydroxydopamine (6-OHDA) was used to prepare the early PD rat model. The immunohistochemistry was used to detect the expression of Bax and Bcl-2 and further explore the mechanism of anti-apoptosis regarding the neuroprotective effect of scorpion venom derived bioactive peptide. The results indicated that compared with the control rats, the immunostaining of Bax in the brain increased significantly while that of Bcl-2 decreased significantly in the lesion side of 6-OHDA treated rats. Interestingly, scorpion venom derived bioactive peptide could attenuate the above abnormal changes. Up-regulation of Bax and down-regulation of Bcl-2 could participate in the early stage of PD and the anti-apoptotic mechanism could be involved in the neuroprotective effect exerted by scorpion venom derived activity peptide regarding the dopaminergic neuron in the early stage.

  9. Serological, biochemical and enzymatic alterations in rodents after experimental envenomation with Hadruroides lunatus scorpion venom.

    PubMed

    Costal-Oliveira, F; Guerra-Duarte, C; Castro, K L P; Tintaya, B; Bonilla, C; Silva, W; Yarlequé, A; Fujiwara, R; Melo, M M; Chávez-Olórtegui, C

    2015-09-01

    Toxic effects of Peruvian Hadruroides lunatus scorpion venom on different biochemical and enzymatic parameters in blood serum of Wistar rats and Swiss mice were determined after experimental envenomation. An increase in enzymatic activities of Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH) and levels of serum protein and albumin were observed while a decrease in creatinine level in serum was perceived after 30 min of envenomation. No alterations in urea levels and in kidney histology were detected in the envenomed rats. The global leukocytes count was diminished, with decrease in lymphocytes, eosinophils and neutrophils levels in the bloodstream, while no alterations were found in hematological parameters of red series in rats injected with H. lunatus venom. IL-2, IL-4, IL-6, INF-γ, TNF, IL-17A and IL-10 levels were evaluated 0.5, 3 and 6 h after experimental envenomation of mice with H. lunatus venom. From all the analyzed cytokines, only IL-6 showed an increase in serum levels. Taken together, these results point out that envenomation by H. lunatus can impair hematological and immunological parameters and therefore might be monitored in accidents involving this species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 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

  11. 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

    2013-07-29

    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.

  12. Cloning and characterization of cDNA sequences encoding for new venom peptides of the Brazilian scorpion Opisthacanthus cayaporum.

    PubMed

    Silva, Edelyn C N; Camargos, Thalita S; Maranhão, Andrea Q; Silva-Pereira, Ildinete; Silva, Luciano P; Possani, Lourival D; Schwartz, Elisabeth F

    2009-09-01

    Scorpion venom glands produce a large variety of bioactive peptides. This communication reports the identification of venom components obtained by sequencing clones isolated from a cDNA library prepared with venomous glands of the Brazilian scorpion Opisthacanthus cayaporum (Ischnuridae). Two main types of components were identified: peptides with toxin-like sequences and proteins involved in cellular processes. Using the expressed sequence tag (EST) strategy 118 clones were identified, from which 61 code for unique sequences (17 contigs and 44 singlets) with an average length of 531 base-pairs (bp). These results were compared with those previously obtained by the proteomic analysis of the same venom, showing a considerable degree of similarity in terms of the molecular masses expected and DNA sequences found. About 36% of the ESTs correspond to toxin-like peptides and proteins with identifiable open reading frames (ORFs). The cDNA sequencing results also show the presence of sequences whose putative products correspond to a scorpine-like component; three short antimicrobial peptides; three K(+)-channel blockers; and an additional peptide containing 78 amino acid residues, whose sequence resembles peptide La1 from another Ischnuridae scorpion Liocheles australiasiae, thus far with unknown function.

  13. Edematogenic activity of scorpion venoms from the Buthidae family and the role of platelet-activating factor and nitric oxide in paw edema induced by Tityus venoms.

    PubMed

    Severino, D N; Pereira, R L; Knysak, I; Cândido, D M; Kwasniewski, F H

    2009-02-01

    We compared the edematogenic activity of venoms of scorpions from the Buthidae family, Tityus bahiensis (Tbv), Tityus serrulatus (Tsv) and Rhopalurus rochai (Rrv). Three doses (20, 40 and 80 microg/kg sc) of each venom were administrated in hind paw of mice and edema was measured from 5 min to 24 h. Tbv and Tsv both induced edema of rapid onset (135% of increase at 15 min); Rrv induced only a mild edema (40% of increase). We then investigated the involvement of platelet-activating factor (PAF) and endogenous nitric oxide (NO) in Tbv and Tsv-induced paw edema. Pretreatment of mice with a PAF antagonist (WEB-2170) inhibited Tsv but not Tbv-induced edema. Pretreatment with a non selective inhibitor of NO-synthases (L: -NAME) inhibited or increased the edema depending on the dose and the time the edema was measured. In conclusion, the venoms from Tityus are stronger inducers of edema than the venom from the Rhopalurus scorpion. The venoms of Tityus species are similar in potency and time-course edema development. PAF is involved in the edema induced only by Tsv.

  14. A toxin to nervous, cardiac, and endocrine ERG K+ channels isolated from Centruroides noxius scorpion venom.

    PubMed

    Gurrola, G B; Rosati, B; Rocchetti, M; Pimienta, G; Zaza, A; Arcangeli, A; Olivotto, M; Possani, L D; Wanke, E

    1999-05-01

    Toxins isolated from a variety of venoms are tools for probing the physiological function and structure of ion channels. The ether-a-go-go-related genes (erg) codify for the K+ channels (ERG), which are crucial in neurons and are impaired in human long-QT syndrome and Drosophila 'seizure' mutants. We have isolated a peptide from the scorpion Centruroides noxius Hoffmann that has no sequence homologies with other toxins, and demonstrate that it specifically inhibits (IC50=16+/-1 nM) only ERG channels of different species and distinct histogenesis. These results open up the possibility of investigating ERG channel structure-function relationships and novel pharmacological tools with potential therapeutic efficacy.

  15. 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. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Effect of age on body distribution of Tityustoxin from Tityus serrulatus scorpion venom in rats.

    PubMed

    Nunan, Elzíria A; Moraes, Márcio F D; Cardoso, Valbert N; Moraes-Santos, Tasso

    2003-06-06

    Previous research from our Laboratory has shown a greater susceptibility of young animals, when compared to adults, to envenomation by tityustoxin (TsTX), one of the main toxins from Tityus serrulatus scorpion venom. Our hypothesis is that a differential body distribution of TsTX among adult and young animals could account for the worse prognosis of scorpion envenomation in infants. Thus, TsTX labeled with technetium-99m was injected (6 microg, subcutaneous) in adult (150-160 day-old) and young (21-22 day-old) male rats. Groups of animals were sacrificed at different times after TsTX injection (0.08, 1.0, 3.0, 6.0, 12.0 and 24.0 hours) under Urethane anesthesia (140 mg/100 g, i.p.). The brain, heart, lungs, liver, kidneys, spleen and thyroid were excised and blood collected. Young rats presented a shorter latency toxin concentration peak in all studied organs except for the liver and the kidney, when compared to adults. The ratio between the area under the curve of the toxin concentration in each organ and that in blood (Kp) indicates higher accumulation in the organs of young animals mainly for brain, liver and heart. These observations suggest a faster toxin distribution in the organs of young rats. The higher uptake of TsTX in the brain is suggestive of a greater permeability for the toxin along the blood-brain barrier of young rats. In conclusion, the higher uptake in heart, together with data from the brain, may help to elucidate the clinical manifestations frequently observed in children under scorpion envenomation.

  17. Bothriurus bonariensis scorpion venom activates voltage-dependent sodium channels in insect and mammalian nervous systems.

    PubMed

    Dos Santos, Douglas Silva; Carvalho, Evelise Leis; de Lima, Jeferson Camargo; Breda, Ricardo Vaz; Oliveira, Raquel Soares; de Freitas, Thiago Carrazoni; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; Boldo, Juliano Tomazzoni; de Assis, Dênis Reis; da Costa, Jaderson Costa; Dal Belo, Cháriston André; Pinto, Paulo Marcos

    2016-10-25

    Animal venoms have been widely recognized as a major source of biologically active molecules. Bothriurus bonariensis, popularly known as black scorpion, is the arthropod responsible for the highest number of accidents involving scorpion sting in Southern Brazil. Here we reported the first attempt to investigate the neurobiology of B. bonariensis venom (BBV) in the insect and mammalian nervous system. BBV (32 μg/g) induced a slow neuromuscular blockade in the in vivo cockroach nerve-muscle preparations (70 ± 4%, n = 6, p < 0.001), provoking repetitive twitches and significantly decreasing the frequency of spontaneous leg action potentials (SNCAPs) from 82 ± 3 min(-1) to 36 ± 1.3 min(-1) (n = 6, p < 0.05), without affecting the amplitude. When tested in primary cultures of rat hippocampal cells, BBV induced a massive increase of Ca(2+) influx (250 ± 1% peak increase, n = 3, p < 0.0001). The disturbance of calcium homeostasis induced by BBV on the mammalian central nervous system was not accompanied by cellular death and was prevented by the co-treatment of the hippocampal cells with tetrodotoxin, a selective sodium channel blocker. The results suggest that the biological activity of BBV is mostly related to a modulation of sodium channels function. Our biological activity survey suggests that BBV may have a promising insecticidal and therapeutic potential.

  18. 2-Deoxy-D-glucose reverses the Indian red scorpion venom-induced cardiopulmonary abnormalities in anesthetized rats.

    PubMed

    Choudhry, P K; Pandey, R; Deshpande, S B

    2011-01-01

    Role of 2-Deoxy-D-glucose (2-DG) in reversing the Indian red scorpion (Mesobuthus tamulus concanesis Pocock, MBT) venom-induced toxicity was examined. Femoral arterial pressure, ECG and respiratory movements were recorded in urethane anesthetized rats. Plasma glucose and serum insulin levels were also estimated. Intravenous injection of 5 mg/kg MBT venom produced immediate decrease in mean arterial pressure, heart rate and respiratory frequency followed by an increase and subsequent progressive decrease. ECG pattern exhibited ischaemic changes. There was hyperinsulinemia after venom without corresponding decrease in plasma glucose. The animals died within 37 +/- 9 min and demonstrated significant increase in pulmonary water content. 2-DG pretreatment (0.5 g/kg, iv) improved the cardiopulmonary abnormalities induced by venom and the animals survived for nearly 120 min. There was no hyperinsulinemia and increased pulmonary water content in these animals. In insulin (2 IU/kg) treated rats, the MBT venom-induced cardiopulmonary abnormalities were attenuated and ECG abnormalities were reversed. The pulmonary water content in these animals exhibited a decreasing trend and the animals survived for 120 min. Repaglinide (10 microg/kg, iv) pretreatment failed to reverse the venom-induced cardiopulmonary changes including the increased pulmonary water content. The survival time was similar to venom only group. The present results reveal that 2-DG reverses the venom-induced cardiopulmonary toxicity probably by restoring insulin sensitivity.

  19. Characterization of a novel cDNA encoding a short venom peptide derived from venom gland of scorpion Buthus martensii Karsch: trans-splicing may play an important role in the diversification of scorpion venom peptides.

    PubMed

    Zeng, Xian-Chun; Luo, Feng; Li, Wen-Xin

    2006-04-01

    A novel cDNA clone (named BmKT-u) which is a hybrid molecule of the 5'-terminal region of BmKT' cDNA and the 3'-terminal region of an undocumented cDNA (named BmKu), was isolated from a cDNA library made from the venom gland of scorpion Buthus martensii Karsch. BmKT-u codes for a 30 amino acid residue precursor peptide composed of a 20-residue signal sequence, and a putative 10-residue novel mature peptide. Northern blot hybridization showed BmKT-u cDNA is generated from a transcript. RT-PCR experiments excluded the possibility that BmKT-u cDNA is an artifact generated during reverse transcription. Genomic amplifications performed with three pairs of BmKT-u gene-specific primers showed the BmKT-u gene does not exist in the genome of the scorpion as a single transcriptional unit. Genomic cloning for BmKT' showed that the BmKT' gene contains an intron of 509 bp inserted into the region encoding the C-terminal region of the signal peptide. A sequence alignment comparison of the cDNA of BmKT-u with genomic BmKT' revealed that the junction site of the hybrid molecule is located at the 5'-splicing site of the intron. The data suggest that the BmKT-u transcript is a naturally occurring mature mRNA that is generated by trans-splicing. Trans-splicing may contribute to the diversity of venom peptides from venomous animals.

  20. Functional and immuno-reactive characterization of a previously undescribed peptide from the venom of the scorpion Centruroides limpidus.

    PubMed

    Olamendi-Portugal, Timoteo; Restano-Cassulini, Rita; Riaño-Umbarila, Lidia; Becerril, Baltazar; Possani, Lourival D

    2017-01-01

    A previously undescribed toxic peptide named Cl13 was purified from the venom of the Mexican scorpion Centruroides limpidus. It contains 66 amino acid residues, including four disulfide bonds. The physiological effects assayed in 7 different subtypes of voltage gated Na(+)-channels, showed that it belongs to the β-scorpion toxin type. The most notorious effects were observed in subtypes Nav1.4, Nav1.5 and Nav1.6. Although having important sequence similarities with two other lethal toxins from this scorpion species (Cll1m and Cll2), the recently developed single chain antibody fragments (scFv) of human origin were not capable of protecting against Cl13. At the amino acid sequence level, in 3 stretches of peptide Cl13 (positions 7-9, 30-38 and 62-66) some differences with respect to other similar toxins are observed. Some of these differences coincide with contact points with the human antibody fragments.

  1. Cloning and molecular characterization of BumaMPs1, a novel metalloproteinases from the venom of scorpion Buthus martensi Karsch.

    PubMed

    Xia, Xichao; Ma, Yuhong; Xue, Shipeng; Wang, Aimei; Tao, Junliang; Zhao, Yan; Zhang, Qingyuan; Liu, Rongzhi; Lu, Shaoe

    2013-12-15

    Scorpion venoms metalloproteinase is involved in a number of important biological, physiological and pathophysiological processes. In this work, a complete sequence of metalloproteinase was first obtained from venom of scorpion Buthus martensi and named as BumaMPs1. BumaMPs1 has 393 amino acid residues containing with a molecular mass of 44.53 kDa, showing an isoelectric point of 5.66. The primary sequence analysis indicated that the BumaMPs1 contains a zinc-binding motif (HELGHNLGISH), methionine-turn motif (YIM), disintegrin-like domain (ETCD) and N-glycosylation site. The multiple alignment of its deduced amino acid sequence and those of other metalloproteinase showed a high structural similarly, mainly among class reprolysin proteases. The phylogenetic analysis showed early divergence and independent evolution of BumaMPs1 from other metalloproteinase. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Phaiodotoxin, a novel structural class of insect-toxin isolated from the venom of the Mexican scorpion Anuroctonus phaiodactylus.

    PubMed

    Valdez-Cruz, Norma A; Batista, Cesar V F; Zamudio, Fernando Z; Bosmans, Frank; Tytgat, Jan; Possani, Lourival D

    2004-12-01

    A peptide called phaiodotoxin was isolated from the venom of the scorpion Anuroctonus phaiodactylus. It is lethal to crickets, but non toxic to mice at the doses assayed. It has 72 amino acid residues, with a molecular mass of 7971 atomic mass units. Its covalent structure was determined by Edman degradation and mass spectrometry; it contains four disulfide-bridges, of which one of the pairs is formed between cysteine-7 and cysteine-8 (positions Cys63-Cys71). The other three pairs are formed between Cys13-Cys38, Cys23-Cys50 and Cys27-Cys52. Comparative sequence analysis shows that phaiodotoxin belongs to the long-chain subfamily of scorpion peptides. Several genes coding for this peptide and similar ones were cloned by PCR, using cDNA prepared from the RNA of venomous glands of this scorpion. Electrophysiological assays conducted with this toxin in several mammalian cell lines (TE671, COS7, rat GH3 and cerebellum granular cells), showed no effect on Na+ currents. However, it shifts the voltage dependence of activation and inactivation of insect Na+ channels (para/tipE) to more negative and positive potentials, respectively. Therefore, the 'window' current is increased by 225%, which is thought to be the cause of its toxicity toward insects. Phaiodotoxin is the first toxic peptide ever purified from a scorpion of the family Iuridae.

  3. Characterization of six toxins from the venom of the Moroccan scorpion Buthus occitanus mardochei.

    PubMed

    Vargas, O; Martin, M F; Rochat, H

    1987-02-02

    When the venom of the Moroccan scorpion Buthus occitanus mardochei was submitted to a combination of several chromatographic steps (including gel-filtration and ion-exchange chromatographies), seven proteins were obtained, six being lethal to mice. These proteins have been characterized by their chemical, immunological and toxic properties. The amino acid sequence (66 residues) of Bom III, the most noteworthy toxin of the venom as for its amino acid composition, is proposed following automatic sequencing of the reduced and S-methylated protein and of chymotryptic peptides. It was obvious that this sequence is somewhat different from those of toxins belonging to the same structural and immunological group (Bom III was found to be immunologically related to Buthus occitanus tunetanus toxins I and II which both share with it 56% of homology. Furthermore, Bom III was found to be unable to compete (as does Bot I) with toxin II of Androctonus australis Hector (an alpha-type toxin) for neurotoxin binding site 3 on the sodium channel of rat brain synaptosomes. Bom III was also unable to compete with toxin II of Centruroides suffusus suffusus (a beta-type toxin) to neurotoxin binding site 4 of the same channel.

  4. Arachnids of medical importance in Brazil: main active compounds present in scorpion and spider venoms and tick saliva.

    PubMed

    Cordeiro, Francielle A; Amorim, Fernanda G; Anjolette, Fernando A P; Arantes, Eliane C

    2015-01-01

    Arachnida is the largest class among the arthropods, constituting over 60,000 described species (spiders, mites, ticks, scorpions, palpigrades, pseudoscorpions, solpugids and harvestmen). Many accidents are caused by arachnids, especially spiders and scorpions, while some diseases can be transmitted by mites and ticks. These animals are widely dispersed in urban centers due to the large availability of shelter and food, increasing the incidence of accidents. Several protein and non-protein compounds present in the venom and saliva of these animals are responsible for symptoms observed in envenoming, exhibiting neurotoxic, dermonecrotic and hemorrhagic activities. The phylogenomic analysis from the complementary DNA of single-copy nuclear protein-coding genes shows that these animals share some common protein families known as neurotoxins, defensins, hyaluronidase, antimicrobial peptides, phospholipases and proteinases. This indicates that the venoms from these animals may present components with functional and structural similarities. Therefore, we described in this review the main components present in spider and scorpion venom as well as in tick saliva, since they have similar components. These three arachnids are responsible for many accidents of medical relevance in Brazil. Additionally, this study shows potential biotechnological applications of some components with important biological activities, which may motivate the conducting of further research studies on their action mechanisms.

  5. Exploiting cross-reactivity to neutralize two different scorpion venoms with one single chain antibody fragment.

    PubMed

    Riaño-Umbarila, Lidia; Contreras-Ferrat, Gabriel; Olamendi-Portugal, Timoteo; Morelos-Juárez, Citlalli; Corzo, Gerardo; Possani, Lourival D; Becerril, Baltazar

    2011-02-25

    We report the optimization of a family of human single chain antibody fragments (scFv) for neutralizing two scorpion venoms. The parental scFv 3F recognizes the main toxins of Centruroides noxius Hoffmann (Cn2) and Centruroides suffusus suffusus (Css2), albeit with low affinity. This scFv was subjected to independent processes of directed evolution to improve its recognition toward Cn2 (Riaño-Umbarila, L., Juárez-González, V. R., Olamendi-Portugal, T., Ortíz-León, M., Possani, L. D., and Becerril, B. (2005) FEBS J. 272, 2591-2601) and Css2 (this work). Each evolved variant showed strong cross-reactivity against several toxins, and was capable of neutralizing Cn2 and Css2. Furthermore, each variant neutralized the whole venoms of the above species. As far as we know, this is the first report of antibodies with such characteristics. Maturation processes revealed key residue changes to attain expression, stability, and affinity improvements as compared with the parental scFv. Combination of these changes resulted in the scFv LR, which is capable of rescuing mice from severe envenomation by 3 LD(50) of freshly prepared whole venom of C. noxius (7.5 μg/20 g of mouse) and C. suffusus (26.25 μg/20 g of mouse), with surviving rates between 90 and 100%. Our research is leading to the formulation of an antivenom consisting of a discrete number of human scFvs endowed with strong cross-reactivity and low immunogenicity.

  6. Exploiting Cross-reactivity to Neutralize Two Different Scorpion Venoms with One Single Chain Antibody Fragment*

    PubMed Central

    Riaño-Umbarila, Lidia; Contreras-Ferrat, Gabriel; Olamendi-Portugal, Timoteo; Morelos-Juárez, Citlalli; Corzo, Gerardo; Possani, Lourival D.; Becerril, Baltazar

    2011-01-01

    We report the optimization of a family of human single chain antibody fragments (scFv) for neutralizing two scorpion venoms. The parental scFv 3F recognizes the main toxins of Centruroides noxius Hoffmann (Cn2) and Centruroides suffusus suffusus (Css2), albeit with low affinity. This scFv was subjected to independent processes of directed evolution to improve its recognition toward Cn2 (Riaño-Umbarila, L., Juárez-González, V. R., Olamendi-Portugal, T., Ortíz-León, M., Possani, L. D., and Becerril, B. (2005) FEBS J. 272, 2591–2601) and Css2 (this work). Each evolved variant showed strong cross-reactivity against several toxins, and was capable of neutralizing Cn2 and Css2. Furthermore, each variant neutralized the whole venoms of the above species. As far as we know, this is the first report of antibodies with such characteristics. Maturation processes revealed key residue changes to attain expression, stability, and affinity improvements as compared with the parental scFv. Combination of these changes resulted in the scFv LR, which is capable of rescuing mice from severe envenomation by 3 LD50 of freshly prepared whole venom of C. noxius (7.5 μg/20 g of mouse) and C. suffusus (26.25 μg/20 g of mouse), with surviving rates between 90 and 100%. Our research is leading to the formulation of an antivenom consisting of a discrete number of human scFvs endowed with strong cross-reactivity and low immunogenicity. PMID:21156801

  7. 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

    2016-04-04

    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

  8. 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

  9. Venom Components of Iranian Scorpion Hemiscorpius lepturus Inhibit the Growth and Replication of Human Immunodeficiency Virus 1 (HIV-1)

    PubMed Central

    Zabihollahi, Rezvan; Bagheri, Kamran Pooshang; Keshavarz, Zohreh; Motevalli, Fatemeh; Bahramali, Golnaz; Siadat, Seyed Davar; Momen, Seyed Bahman; Shahbazzadeh, Delavar; Aghasadeghi, Mohammad Reza

    2016-01-01

    Background: During the recent years, significant progress has been achieved on development of novel anti-viral drugs. Natural products are assumed as the potential sources of novel anti-viral drugs; therefore, there are some previous studies reporting the anti-viral compounds from venomous animals. Based on the significant value for tracing of non-toxic anti-viral agents from natural resources, this study was aimed to investigate the anti-viral activity of some HPLC purified fractions derived from the venom of Iranian scorpion, Hemiscorpius lepturus, against human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1). Methods: H. Lepturus crude venom was subjected to reverse phase HPLC analysis to determine its active components precisely where four dominant fractions obtained at retention time of 156-160 minutes. The phospholipase A2 and hemolytic activities of the purified fractions were first evaluated. Then the anti-viral activity was measured using single cycle HIV (NL4-3) replication and HSV (KOS) plaque reduction assays. Results: The H. lepturus crude venom inhibited HIV replication by 73% at the concentration of 200 µg/ml, while it did not show significant anti-HSV activity. It also inhibited the cell-free viral particles in a virucidal assay, while it showed no toxicity for the target cells in a proliferation assay. The four HPLC fractions purified from H. lepturus inhibited HIV with IC50 of 20 µg/ml. Conclusion: H. lepturus venom contains components with considerable anti-HIV activity insofar as it has virucidal activity that offers a novel therapeutic approach against HIV infection. Our results suggest a promising pilot for anti-HIV drug discovery with H. lepturus scorpion venom. PMID:27594443

  10. Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins

    PubMed Central

    Cremonez, Caroline M.; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A. A.; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M. C.; Arantes, Eliane C.; Tytgat, Jan

    2016-01-01

    To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx. PMID:27706049

  11. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins.

    PubMed

    Cremonez, Caroline M; Maiti, Mohitosh; Peigneur, Steve; Cassoli, Juliana Silva; Dutra, Alexandre A A; Waelkens, Etienne; Lescrinier, Eveline; Herdewijn, Piet; de Lima, Maria Elena; Pimenta, Adriano M C; Arantes, Eliane C; Tytgat, Jan

    2016-09-30

    To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx.

  13. Bioactivity of Natural and Engineered Antimicrobial Peptides from Venom of the Scorpions Urodacus yaschenkoi and U. manicatus

    PubMed Central

    Luna-Ramirez, Karen; Tonk, Miray; Rahnamaeian, Mohammad; Vilcinskas, Andreas

    2017-01-01

    The spread of multidrug-resistant human pathogens has drawn attention towards antimicrobial peptides (AMPs), which are major players in the innate immune systems of many organisms, including vertebrates, invertebrates, plants and microbes. Scorpion venom is an abundant source of novel and potent AMPs. Here, we investigated natural and engineered AMPs from the scorpions Urodacus yaschenkoi and U. manicatus to determine their antimicrobial spectra as well as their hemolytic/cytotoxic activity. None of the AMPs were active against fungi, but many of them were active at low concentrations (0.25–30 µM) against seven different bacteria. Hemolytic and cytotoxic activities were determined using pig erythrocytes and baby hamster kidney cells, respectively. The amino acid substitutions in the engineered AMPs did not inhibit cytotoxicity, but reduced hemolysis and therefore increased the therapeutic indices. The phylogenetic analysis of scorpion AMPs revealed they are closely related and the GXK motif is highly conserved. The engineered scorpion AMPs offer a promising alternative for the treatment of multidrug-resistant bacterial infections and could be modified further to reduce their hemolytic/cytotoxic activity. PMID:28067810

  14. Bioactivity of Natural and Engineered Antimicrobial Peptides from Venom of the Scorpions Urodacus yaschenkoi and U. manicatus.

    PubMed

    Luna-Ramirez, Karen; Tonk, Miray; Rahnamaeian, Mohammad; Vilcinskas, Andreas

    2017-01-06

    The spread of multidrug-resistant human pathogens has drawn attention towards antimicrobial peptides (AMPs), which are major players in the innate immune systems of many organisms, including vertebrates, invertebrates, plants and microbes. Scorpion venom is an abundant source of novel and potent AMPs. Here, we investigated natural and engineered AMPs from the scorpions Urodacus yaschenkoi and U. manicatus to determine their antimicrobial spectra as well as their hemolytic/cytotoxic activity. None of the AMPs were active against fungi, but many of them were active at low concentrations (0.25-30 µM) against seven different bacteria. Hemolytic and cytotoxic activities were determined using pig erythrocytes and baby hamster kidney cells, respectively. The amino acid substitutions in the engineered AMPs did not inhibit cytotoxicity, but reduced hemolysis and therefore increased the therapeutic indices. The phylogenetic analysis of scorpion AMPs revealed they are closely related and the GXK motif is highly conserved. The engineered scorpion AMPs offer a promising alternative for the treatment of multidrug-resistant bacterial infections and could be modified further to reduce their hemolytic/cytotoxic activity.

  15. Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinoma

    PubMed Central

    Giovannini, Catia; Baglioni, Michele; Baron Toaldo, Marco; Cescon, Matteo; Bolondi, Luigi; Gramantieri, Laura

    2017-01-01

    Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC. PMID:28322221

  16. Novel K(+)-channel-blocking toxins from the venom of the scorpion Centruroides limpidus limpidus Karsch.

    PubMed Central

    Martin, B M; Ramirez, A N; Gurrola, G B; Nobile, M; Prestipino, G; Possani, L D

    1994-01-01

    Two novel toxins were purified from the venom of the Mexican scorpion Centruroides limpidus limpidus, using an immunoassay based on antibodies raised against noxiustoxin (NTX), a known K(+)-channel-blocker-peptide. The primary structure of C. l. limpidus toxin 1 was obtained by Edman degradation and was shown to be composed of 38 amino acid residues, containing six half-cystines. The first 36 residues of C. l. limpidus toxin 2 were also determined. Both toxins are capable of displacing the binding of radio-labelled NTX to rat brain synaptosomes with high affinity (about 100 pM). These toxins are capable of inhibiting transient K(+)-currents (resembling IA-type currents), in cultured rat cerebellar granule cells. About 50% of the peak currents are reduced by application of a 1.5 microM solution of toxins 1 and 2 The K+ current reduction is partially reversible, under washing but not voltage-dependent. Comparison of the primary structure of C. l. limpidus toxin 1 with other known toxins shows 74% identity with margatoxin, 64% with NTX, 51% with kaliotoxin, 39% with iberiotoxin, 37% with charybdotoxin and Lq2, and 29% with leirutoxin 1. The only invariant amino acids in all these toxins are the six cysteines, a glycine in position 26 and two lysines at positions 28 and 33, respectively. The relevance of these differences in terms of possible structure-function relationships is discussed. PMID:7998956

  17. Phospholipid dependent mechanism of smp24, an α-helical antimicrobial peptide from scorpion venom.

    PubMed

    Harrison, Patrick L; Heath, George R; Johnson, Benjamin R G; Abdel-Rahman, Mohamed A; Strong, Peter N; Evans, Stephen D; Miller, Keith

    2016-11-01

    Determining the mechanism of action of antimicrobial peptides (AMPs) is critical if they are to be developed into the clinical setting. In recent years high resolution techniques such as atomic force microscopy (AFM) have increasingly been utilised to determine AMP mechanism of action on planar lipid bilayers and live bacteria. Here we present the biophysical characterisation of a prototypical AMP from the venom of the North African scorpion Scorpio maurus palmatus termed Smp24. Smp24 is an amphipathic helical peptide containing 24 residues with a charge of +3 and exhibits both antimicrobial and cytotoxic activity and we aim to elucidate the mechanism of action of this peptide on both membrane systems. Using AFM, quartz crystal microbalance-dissipation (QCM-D) and liposomal leakage assays the effect of Smp24 on prototypical synthetic prokaryotic (DOPG:DOPC) and eukaryotic (DOPE:DOPC) membranes has been determined. Our data points to a toroidal pore mechanism against the prokaryotic like membrane whilst the formation of hexagonal phase non-lamellar phase structures is seen in eukaryotic like membrane. Also, phase segregation is observed against the eukaryotic membrane and this study provides direct evidence of the same peptide having multiple mechanisms of action depending on the membrane lipid composition.

  18. Inhibitory activity and mechanism of two scorpion venom peptides against herpes simplex virus type 1.

    PubMed

    Hong, Wei; Li, Tian; Song, Yu; Zhang, Runhong; Zeng, Zhengyang; Han, Shisong; Zhang, Xianzheng; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

    2014-02-01

    Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen that causes severe diseases, but there are not effective and safe drugs in clinical therapy besides acyclovir (ACV) and related nucleoside analogs. In this study, two new venom peptides from the scorpion Heterometrus petersii were identified with effective inhibitory effect on HSV-1 infection in vitro. Both Hp1036 and Hp1239 peptides exhibited potent virucidal activities against HSV-1 (EC50=0.43±0.09 and 0.41±0.06μM, respectively) and effective inhibitory effects when added at the viral attachment (EC50=2.87±0.16 and 5.73±0.61μM, respectively), entry (EC50=4.29±0.35 and 4.32±0.47μM, respectively) and postentry (EC50=7.86±0.80 and 8.41±0.73μM, respectively) steps. Both Hp1036 and Hp1239 peptides adopted α-helix structure in approximate membrane environment and resulted in the destruction of the viral morphology. Moreover, Hp1036 and Hp1239 peptides entered Vero cells and reduced the intracellular viral infectivity. Taken together, Hp1036 and Hp1239 peptides are two anti-viral peptides with effective inhibitory effect on multiple steps of HSV-1 life cycle and therefore are good candidate for development as virucides.

  19. 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.

  20. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Scorpions: a presentation.

    PubMed

    Goyffon, Max; Tournier, Jean-Nicolas

    2014-07-21

    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.

  2. 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

  3. Antifungal Activity against Filamentous Fungi of Ts1, a Multifunctional Toxin from Tityus serrulatus Scorpion Venom

    PubMed Central

    Santussi, Welligton M.; Bordon, Karla C. F.; Rodrigues Alves, Ana P. N.; Cologna, Camila T.; Said, Suraia; Arantes, Eliane C.

    2017-01-01

    Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A. nidulans, A. niger, A. terreus, Neurospora crassa, Penicillium corylophilum, P. ochrochloron, P. verrucosum, P. viridicatum, P. waksmanii, and Talaromyces flavus) was evaluated by quantitative microplate reader assay. Tsv (100 and 500 μg/well, which correspond to 1 and 5 mg/mL, respectively, of total soluble protein) was active in inhibiting growth of A. nidulans, A. terreus, P. corylophilum, and P. verrucosum, especially in the higher concentration used and at the first 30 h. After this period, fungi might have used Tsv components as alternative sources of nutrients, and therefore, increased their growth tax. Only fractions IX, X, XI, XIIA, XIIB (3 and 7.5 μg/well, which correspond to 30 and 75 μg/mL, respectively, of total soluble protein) and Ts1 (1.5, 3, and 6 μg/well, which correspond to 2.18, 4.36, and 8.72 μM, respectively) showed antifungal activity. Ts1 showed to be a non-morphogenic toxin with dose-dependent activity against A. nidulans, inhibiting 100% of fungal growth from 3 μg/well (4.36 μM). The inhibitory effect of Ts1 against A. nidulans growth was accompanied by fungistatic effects and was not amended by 1 mM CaCl2 or tetrodotoxin (46.98 and 93.96 μM). The structural differences between Ts1 and drosomycin, a potent cysteine-rich antifungal peptide, are discussed here. Our results highlight the antifungal potential of the first cysteine

  4. 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.

  5. 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

  6. A Novel Defensin-Like Peptide Associated with Two Other New Cationic Antimicrobial Peptides in Transcriptome of the Iranian Scorpion Venom

    PubMed Central

    Baradaran, Masoumeh; Jalali, Amir; soorki, Maryam Naderi; Galehdari, Hamid

    2017-01-01

    Introduction: Scorpion venom is a source of bioactive peptides, and some antimicrobial peptides (AMPs) have been found in the venom gland of scorpions. Therefore, the discovery of new anti-infective agents is an essential need to overcome the problem of antibiotic resistance of clinical isolates. Here, we describe three new cationic AMPs, including meuVAP-6, meuAP-18-1, and meuPep34 from the venom gland of the Iranian scorpion, Mesobuthus eupeus. Methods: The cDNA sequences encoding all the three peptides were obtained from the cDNA library of scorpion venom gland and were deposited in the GenBank database. Results: MeuVAP-6 and meuAP-18-1 are non-disulphide-bridged antimicrobial peptides, while meuPep34 is a cysteine-rich defensin-like peptide. Discussion: All three identified AMPs are rich in arginine and tryptophan. The overall results from the length, net charge, and hydrophobicity index suggested that meuPep34 could be the most active AMPs with the potential ability of biofilm inhibition. The data from molecular characterization of identified AMPs can provide a platform with application in drug discovery programs. PMID:27794585

  7. Cloning and functional characterization of a new antimicrobial peptide gene StCT1 from the venom of the scorpion Scorpiops tibetanus.

    PubMed

    Yuan, Wenying; Cao, Luyang; Ma, Yibao; Mao, Panyong; Wang, Weipeng; Zhao, Ruiming; Wu, Yingliang; Cao, Zhijian; Li, Wenxin

    2010-01-01

    Scorpion has an innovative venom gland, which is an important determinant in contributing to its successful survival for more than 400 million years. Scorpion venom contains a diversity of bioactive peptides, which represent a tremendous hitherto unexplored resource for use in drug design and development. Here, StCT1, a new antimicrobial peptide gene, was screened and isolated from the venomous gland cDNA library of the scorpion Scorpiops tibetanus. The full-length cDNA of StCT1 is 369 nucleotides encoding the precursor that contains a putative 24-residue signal peptide, a presumed 14-residue mature peptide, and an uncommon 37-residue acidic propeptide at the C-terminus. The minimal inhibitory concentrations (MICs) of the synthetic StCT1 peptide against Staphylococcus aureus and Micrococcus luteus were 12.5microg/ml and 100microg/ml, respectively. The MICs of StCT1 against clinical antibiotics-resistant bacterial strains, were 50-250microg/ml, 2-40 folds lower than those of penicillin. These results show that the antimicrobial peptide encoded by StCT1 gene from the venom of the scorpion S. tibetanus is a potential anti-infective polypeptide or lead compound, especially for treating antibiotics-resistant pathogens.

  8. A Novel Defensin-Like Peptide Associated with Two Other New Cationic Antimicrobial Peptides in Transcriptome of the Iranian Scorpion Venom.

    PubMed

    Baradaran, Masoumeh; Jalali, Amir; Naderi Soorki, Maryam; Galehdari, Hamid

    2017-05-01

    Scorpion venom is a source of bioactive peptides, and some antimicrobial peptides (AMPs) have been found in the venom gland of scorpions. Therefore, the discovery of new anti-infective agents is an essential need to overcome the problem of antibiotic resistance of clinical isolates. Here, we describe three new cationic AMPs, including meuVAP-6, meuAP-18-1, and meuPep34 from the venom gland of the Iranian scorpion, Mesobuthus eupeus. The cDNA sequences encoding all the three peptides were obtained from the cDNA library of scorpion venom gland and were deposited in the GenBank database. MeuVAP-6 and meuAP-18-1 are non-disulphide-bridged antimicrobial peptides, while meuPep34 is a cysteine-rich defensin-like peptide. All three identified AMPs are rich in arginine and tryptophan. The overall results from the length, net charge, and hydrophobicity index suggested that meuPep34 could be the most active AMPs with the potential ability of biofilm inhibition. The data from molecular characterization of identified AMPs can provide a platform for further investigations in the drug design.

  9. 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.

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

    PubMed

    Cecchini, Alessandra L; Vasconcelos, Flávio; Amara, Susan G; Giglio, José Roberto; Arantes, Eliane Candiani

    2006-12-01

    Scorpion neurotoxins targeting the Na(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 (3)H-Glu uptake. On the other hand, Ts venom (0.13 microg/mg) significantly inhibited both (3)H-GABA and (3)H-DA uptake ( approximately 50%). TsTX-V showed IC(50) values of 9.37 microM and 22.2 microM for the inhibition of (3)H-GABA and (3)H-DA uptake, respectively. These effects were abolished by pre-treatment with tetrodotoxin (TTX, 1 microM), indicating the involvement of voltage-gated Na(+) channels in this process. In the absence of Ca(2+), and at low Ts venom concentrations, the reduction of (3)H-GABA uptake was not as marked as in the presence of Ca(2+). TsTX-V did not reduce (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 (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 (3)H-GABA and (3)H-DA uptake in a Ca(2+)-dependent manner, not directly affecting GABA transporters, but, in consequence of depolarization, involving voltage-gated Na(+) channels.

  11. OcyKTx2, a new K⁺-channel toxin characterized from the venom of the scorpion Opisthacanthus cayaporum.

    PubMed

    Schwartz, Elisabeth F; Bartok, Adam; Schwartz, Carlos Alberto; Papp, Ferenc; Gómez-Lagunas, Froylan; Panyi, Gyorgy; Possani, Lourival D

    2013-08-01

    Opisthacanthus cayaporum belongs to the Liochelidae family, and the scorpions from this genus occur in southern Africa, Central America and South America and, therefore, can be considered a true Gondwana heritage. In this communication, the isolation, primary structure characterization, and K⁺-channel blocking activity of new peptide from this scorpion venom are reported. OcyKTx2 is a 34 amino acid long peptide with four disulfide bridges and molecular mass of 3807 Da. Electrophysiological assays conducted with pure OcyKTx2 showed that this toxin reversibly blocks Shaker B K⁺-channels with a Kd of 82 nM, and presents an even better affinity toward hKv1.3, blocking it with a Kd of ∼18 nM. OcyKTx2 shares high sequence identity with peptides belonging to subfamily 6 of α-KTxs that clustered very closely in the phylogenetic tree included here. Sequence comparison, chain length and number of disulfide bridges analysis classify OcyKTx2 into subfamily 6 of the α-KTx scorpion toxins (systematic name, α-KTx6.17).

  12. Amino acid sequence and physiological characterization of toxins from the venom of the scorpion Centruroides limpidus tecomanus Hoffmann.

    PubMed

    Martin, B M; Carbone, E; Yatani, A; Brown, A M; Ramírez, A N; Gurrola, G B; Possani, L D

    1988-01-01

    The complete amino acid sequence of the major toxic component (II.20.3.4), named toxin 1, from the venom of the Mexican scorpion C. l. tecomanus is reported. The sequence (66 amino acids) was obtained by direct Edman degradation of reduced and alkylated toxin, followed by sequence determination of selected peptides separated after enzymatic cleavage with S. aureus V8 protease. In cultured chick dorsal root ganglion cells, 0.5 microM toxin 1 slowed down specifically the time course of Na+ current inactivation, while Ca2+ currents from the same preparation were little affected. In neonatal rat ventricular heart cells, toxin 1, at concentrations between 0.1 and 0.5 microM, reduced Na+ currents without changing the kinetics and Ca2+ currents were unaffected. Comparative analysis of the primary structure of this toxin with other scorpion toxins shows a high degree of similarity with the north American scorpion toxins. This analysis suggests that the 'fine tuning' of the molecular mechanism of action of these toxins is related to variations in the primary structure as well as to the type of membrane under study (tissue specificity).

  13. Isolation and primary structure of a potent toxin from the venom of the scorpion Centruroides sculpturatus Ewing.

    PubMed

    Pete, M J; Conlon, J M; Murphy, R F

    1992-12-01

    A potent toxin has been purified from the venom of the scorpion Centruroides sculpturatus Ewing using the ion-exchange resin CM-Sepharose CL-6B at basic pH. The toxin, designated CsE M1, comprised 65 amino acid residues and its primary structure was established as: Lys-Glu-Gly-Tyr-Leu-Val-Asn-Ser-Tyr-Thr10-Gly-Cys-Lys-Tyr-Glu-Cys- Leu-Lys-Leu- Gly20-Asp-Asn-Asp-Tyr-Cys-Leu-Arg-Glu-Cys-Arg30-Gln-Gln-Tyr- Gly-Lys-Ser-Gly-Gly - Tyr-Cys40-Tyr-Ala-Phe-Ala-Cys-Trp-Cys-Thr-His-Leu50-Tyr-Glu- Gln-Ala-Val-Val-Trp - Pro-Leu-Pro60-Asn-Lys-Thr-Cys-Asn. CsE M1 is the most lethal protein to be identified in C. sculpturatus venom and the LD50 of the toxin, determined by subcutaneous injection into Swiss mice, is 87 micrograms/kg. CsE M1 shows strong structural similarity (92% positional identity) to the most potent beta-toxin, Css II, from the Mexican scorpion, Centruroides suffusus suffusus but is quite dissimilar to the previously characterized toxins with low potency isolated from C. sculpturatus Ewing.

  14. Isolation and molecular cloning of beta-neurotoxins from the venom of the scorpion Centruroides suffusus suffusus.

    PubMed

    Espino-Solis, Gerardo Pavel; Estrada, Georgina; Olamendi-Portugal, Timoteo; Villegas, Elba; Zamudio, Fernando; Cestele, Sandrine; Possani, Lourival D; Corzo, Gerardo

    2011-04-01

    This communication reports the identification and characterization of two new toxins from the venom of the scorpion Centruroides suffusus suffusus, named: CssVIII and CssIX, according to the original nomenclature of toxins previously described for this scorpion. The isolation was obtained by means of two chromatographic steps, and a cDNA library was used to fully identify their precursors. CssVIII and CssIX contain signal peptides of 19 and 17 amino acid residues, and mature peptides of 66 and 65 residues, respectively. Intracranial injections into mice of both purified toxins showed toxicity results similar to those found for toxins CssII and CssIV. Additionally, they compete with the parent toxin CssIV, in binding and displacement experiments, conducted with brain synaptosomes showing nanomolar affinities. These results strongly support the conclusion that they are new β-neurotoxins and certainly would be of the interest of researchers in the field of venomics for studying sodium channels.

  15. Isolation and characterization of a novel type of neurotoxic peptide from the venom of the South African scorpion Parabuthus transvaalicus (Buthidae).

    PubMed

    Inceoglu, B; Lango, J; Wu, J; Hawkins, P; Southern, J; Hammock, B D

    2001-10-01

    The venom of the South African scorpion Parabuthus transvaalicus was characterized using a combination of mass spectrometry and RP-HPLC separation and bioassays. The crude venom was initially separated into 10 fractions. A novel, moderately toxic but very high abundance peptide (birtoxin) of 58 amino-acid residues was isolated, identified and characterized. Each purification step was followed by bioassays and mass spectroscopy. First a C4 RP-HPLC column was used, then a C18 RP Microbore column purification resulted in > 95% purity in the case of birtoxin from a starting material of 230 microg of crude venom. About 12-14% of the D214 absorbance of the total venom as observed after the first chromatography step was composed of birtoxin. This peptide was lethal to mice at low microgram quantities and it induced serious symptoms including tremors, which lasted up to 24 h post injection, at submicrogram amounts. At least seven other fractions that showed different activities including one fraction with specificity against blowfly larvae were identified. Identification of potent components is an important step in designing and obtaining effective anti-venom. Antibodies raised against the critical toxic components have the potential to block the toxic effects and reduce the pain associated with the scorpion envenomation. The discovery of birtoxin, a bioactive long chain neurotoxin peptide with only three disulfide bridges, offers new insight into understanding the role of conserved disulfide bridges with respect to scorpion toxin structure and function.

  16. 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.

  17. Nephrotic syndrome after scorpion sting.

    PubMed

    Boju, Sangeetha Lakshmi; Mogili, Hari Krishna Reddy; Ram, R; Vishnubotla, Siva Kumar

    2016-05-01

    Scorpion venom is a water soluble, antigenic and heterogeneous mixture. The venom is composed of varying concentration of neurotoxin, cardiotoxin, nephrotoxin, haemolytic toxin, phosphodiesterase, phospholipases, hyaluronidases, glycosaminoglycans, histamine, serotonins, and tryptophan and cytokine releasers. The reported incidence of scorpion sting in India is 0.6 %. Scorpion sting resulting in acute renal failure has been reported in the past, but not the nephrotic syndrome. We report a patient of nephrotic syndrome after scorpion sting. The lacunae in the present knowledge linking scorpion sting venom with nephrotic syndrome would only be replete with publications of similar reports.

  18. Scorpions and scorpionism in Iran's central desert.

    PubMed

    Nejati, Jalil; Saghafipour, Abedin; Mozaffari, Ehsan; Keyhani, Amir; Jesri, Nahid

    2017-02-01

    Venomous scorpions have extreme importance in field of medicine and public health. This descriptive - analytic study was done to identify scorpion fauna, their ecological aspects as well as scorpionism for risk management and prevention of this health problem in Iran's central desert. Four urban and fifteen rural areas with various climates and topography locations were selected for monthly scorpion collection through a randomly cluster sampling in 2013. The clinical data was obtained from questionnaires provided in 2009-2014. Totally, 1481 scorpion sting cases were recorded. The majority were treated less than 6h after the sting. Statistical tests showed significant difference between season, scorpion's color, living place of patients and scorpionism cases. Plain areas had the most occurrence of scorpionism followed by foothills. Moreover, 311 scorpion samples belonged to 7 species of Buthidae were collected. Mesobuthus eupeus was the dominant species in both rural and urban areas. Most of the collected samples were from indoors, yards and around the houses. The most scorpion activity was recorded in the summer. The studied areas had rich scorpion fauna due to various climates and topography locations. Scorpion stings can be important and fatal in this area, particularly in the plain regions with semi-desert climate. An investigation for assessment of peoples' awareness on prevention methods of scorpionism and also the determination and the assessment of effective factors on reducing the elapsed time between scorpion stings and receiving medical care are here recommended. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Characterization of the first K⁺ channel blockers from the venom of the Moroccan scorpion Buthus occitanus Paris.

    PubMed

    Martin-Eauclaire, Marie-France; Céard, Brigitte; Belghazi, Maya; Lebrun, Régine; Bougis, Pierre E

    2013-12-01

    The availability of a large variety of specific blockers, which inhibit different K(+) currents, would help to elucidate their differences in physiological function. Short peptide toxins isolated from scorpion venoms are able to block voltage-dependent or Ca(2+)-activated K(+) channels. Here, we have studied the venom of the Moroccan scorpion Buthus occitanus Paris (BoP) in order to find new peptides, which could enlarge our structure-function relationship knowledge on the Kv1.3 blocker Kaliotoxin (KTX) that belongs to the α-KTx3.1 family. Indeed and since more a decade, KTX is widely used by international investigators because it exhibits a quite sharp specificity and a high-affinity for the Kv1.3 channel, which is not only a neuronal channel but also a therapeutic target for diverse autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. The BoP venom was first investigated using HPLC and MALDI-TOF/MS. Further, the HPLC fractions were screened by ELISA with antibodies raised against KTX. These antibodies recognized at least three components toxic in mice by intracerebroventricular injection. They were further pharmacologically characterized by competition using (125)I-KTX bound to its specific binding sites on rat brain synaptosomes. A single component (4161 Da) inhibited totally the (125)I-KTX binding and with high-affinity (IC50 = 0.1 nM), while the two other components poorly competed with (IC50 > 100 nM). These toxins were sequenced in full by Edman's degradation. The high-affinity ligand (BoPKTX) shares 86% sequence identity with KTX and was classified as toxin α-KTx3.17. The two others peptides (BoP1 and BoP2, 4093 Da and 4121 Da, respectively) only differ by a Lys/Arg mutation. Their amino acid sequences were related to Martentoxin, which has been characterized from the Chinese scorpion Buthus martenzi Karch and described as both a BKCa and Kv1.3 blocker. Accordingly, they belong to the α-KTx16 family.

  20. 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

  1. 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.

  2. 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.

  3. Functional depletion of capsaicin-sensitive primary afferent fibers attenuates rat pain-related behaviors and paw edema induced by the venom of scorpion Buthus martensi Karch.

    PubMed

    Bai, Zhan-Tao; Liu, Tong; Pang, Xue-Yan; Jiang, Feng; Cheng, Ming; Ji, Yong-Hua

    2008-10-01

    The role of capsaicin-sensitive primary afferent fibers in rat pain-related behaviors and paw edema induced by scorpion Buthus martensi Karch (BmK) venom was investigated in this study. It was found that functional depletion of capsaicin-sensitive primary afferent fibers with a single systemic injection of resiniferatoxin (RTX) dramatically decreased spontaneous nociceptive behaviors, prevented the development of primary mechanical and thermal hyperalgesia as well as mirror-image mechanical hyperalgesia. RTX treatment significantly attenuated BmK venom-induced c-Fos expression in all laminaes of bilateral L4-L5 lumbar spinal cord, especially in superficial laminaes. Moreover, RTX treatment markedly reduced the early paw edema induced by BmK venom. Thus, the results indicate that capsaicin-sensitive primary afferent fibers play a critical role in various pain-related behaviors and paw edema induced by BmK venom in rats.

  4. 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.

  5. Cloning and molecular characterization of BmHYA1, a novel hyaluronidase from the venom of Chinese red scorpion Buthus martensi Karsch.

    PubMed

    Feng, Luo; Gao, Rong; Meng, Jun; Gopalakrishnakone, Ponnampalam

    2010-09-01

    In this communication, the full protein sequence of a novel venom hyaluronidase BmHYA1 was reported. It is the first full hyaluronidase amino acid sequence from scorpion venom. It was deduced from nucleotide sequence by 3' Rapid Amplification of cDNA Ends (RACE) PCR cloning, followed by alignment with the N-terminal amino acid sequence, which was obtained by Edman degradation. BmHYA1 has 385 amino acid residues containing five potential N-glycosylation sites. The phylogenetic analysis indicates early divergence and independent evolution of BmHYA1 from other hyaluronidases.

  6. Effect of Tityus serrulatus scorpion venom on the rabbit isolated corpus cavernosum and the involvement of NANC nitrergic nerve fibres

    PubMed Central

    Teixeira, Cleber E; Bento, Antonio C; Lopes-Martins, Rodrigo A B; Teixeira, Simone A; von Eickestedt, Vera; Muscará, Marcelo N; Arantes, Eliane C; Giglio, Jose R; Antunes, Edson; de Nucci, Gilberto

    1998-01-01

    The effect of Tityus serrulatus scorpion venom and its toxin components on the rabbit isolated corpus cavernosum was investigated by use of a bioassay cascade. Tityus serrulatus venom (3–100 μg), acetylcholine (ACh; 0.3–30 nmol) and glyceryl trinitrate (GTN; 0.5–10 nmol) dose-dependently relaxed rabbit isolated corpus cavernosum preparations precontracted with noradrenaline (3 μM). The selective soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-alquinoxalin-1-one] (ODQ; 30 μM) increased the basal tone of the rabbit isolated corpus cavernosum and abolished the relaxations induced by the agents mentioned above. Methylene blue (30 μM) also inhibited the relaxations induced by Tityus serrulatus venom but, in contrast to ODQ, the inhibition was irreversible. The non-selective NO synthase (NOS) inhibitors NΩ-nitro-L-arginine methyl ester (L-NAME; 10 μM) and NG-iminoethyl-L-ornithine (L-NIO; 30 μM) also increased the tone of the rabbit isolated corpus cavernosum and markedly reduced both ACh- and Tityus serrulatus venom-induced relaxations without affecting those evoked by GTN. The inhibitory effect was reversed by infusion of L-arginine (300 μM), but not D-arginine (300 μM). The neuronal NOS inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM, 100 μM) did not affect either the tone of the rabbit isolated corpus cavernosum or the relaxations induced by ACh, bradykinin (Bk), Tityus serrulatus venom and GTN. TRIM was approximately 1,000 times less potent than L-NAME in inhibiting rabbit cerebellar NOS in vitro, as measured by the conversion of [3H]-L-arginine to [3H]-L-citrulline. The protease inhibitor aprotinin (Trasylol; 10 μg ml−1) and the bradykinin B2 receptor antagonist Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7, Oic8]-BK; 50 nM) did not affect the rabbit isolated corpus cavernosum relaxations induced by Tityus serrulatus venom. The ATP-dependent K+ channel antagonist glibenclamide (10 μM) and the Ca2+-activated

  7. 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.

  8. Scorpion venom peptide SPVII promotes irradiated cells proliferation and increases the expression of the IL-3 receptor

    PubMed Central

    2013-01-01

    Background The previous investigation demonstrated the radioprotective efficacy of peptides isolated from the venom of Buthus Martti Karsch. In this study, the effect of isolated scorpion venom peptide II (SVPII) on irradiated M-NFS-60 cells and mouse bone marrow mononuclear cells (BM-MNCs) was observed. The AlamarBlue cell viability assay, a colony-forming unit (CFU) assay, flow cytometry (FCM), immunofluorescence, and Western blotting were used to evaluate cell proliferation, cell cycle progression, and the expression of the IL-3 receptor (IL-3R) protein in non-irradiated and irradiated cells. Results Proliferation of irradiated M-NFS-60 cells was significantly accelerated by SPVII, and this effect was further enhanced by co-application of IL-3. Similarly, SPVII increased the number of BM-MNC CFUs and this proliferative effect was greater in the presence of SVPII plus IL-3. In addition, SPVII significantly altered cell cycle progression; SVPII enhanced the fraction of unirradiated M-NFS-60 cells in S phase and the fraction of irradiated M-NFS-60 cells arrested in G2/M. The expression of IL-3R protein by unirradiated M-NFS-60 cells was enhanced significantly by SVPII, and SVPII-induced IL-3R overexpression was 10-fold greater in irradiated M-NFS-60 cells. Conclusions These results indicated the hematopoietic growth factor (HGF)-like effects of SVPII on irradiated cells, possibly mediated by upregulation of IL-3R. PMID:23835458

  9. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Proteomic analysis of the venom and characterization of toxins specific for Na+ - and K+ -channels from the Colombian scorpion Tityus pachyurus.

    PubMed

    Barona, Jacqueline; Batista, Cesar V F; Zamudio, Fernando Z; Gomez-Lagunas, Froylan; Wanke, Enzo; Otero, Rafael; Possani, Lourival D

    2006-01-01

    The Colombian scorpion Tityus pachyurus is toxic to humans and is capable of producing fatal accidents, but nothing is known about its venom components. This communication reports the separation of at least 57 fractions from the venom by high performance liquid chromatography. From these, at least 104 distinct molecular weight compounds were identified by mass spectrometry analysis. The complete amino acid sequences of three peptides were determined and the partial sequences of three others were also identified. Electrophysiological experiments conducted with ion-channels expressed heterologously on Sf9 cells showed the presence of a potent Shaker B K(+)-channel blocker. This peptide (trivial name Tpa1) contains 23 amino acid residues closely packed by three disulfide bridges with a molecular mass of 2,457 atomic mass units. It is the third member of the sub-family 13, for which the systematic name is proposed to be alpha-KTx13.3. The mice assay showed clearly the presence of toxic peptides to mammals. One of them named Tpa2, containing 65 amino acid residues with molecular mass of 7,522.5 atomic mass units, is stabilized by four disulfide bridges. It was shown to modify the Na(+)-currents of F-11 and TE671 cells in culture, similar to the beta scorpion toxins. These results demonstrate the presence of toxic peptides in the venom of T. pachyurus and confirm that accidents with this species of scorpion should be considered an important human hazard in Colombia.

  11. Involvement of spinal nitric oxide (NO) in rat pain-related behaviors induced by the venom of scorpion Buthus martensi Karsch.

    PubMed

    Liu, Tong; Pang, Xue-Yan; Jiang, Feng; Ji, Yong-Hua

    2008-07-01

    In the present study, we investigated the role of spinal nitric oxide (NO) in rat pain-related behaviors induced by the venom of scorpion Buthus martensi Karsch (BmK). The results showed that the number of neuronal NO synthase (nNOS) positive neurons significantly increased in superficial (I-II), deep (V-VI) dorsal horn laminae and the ventral gray laminae (VII-X), but not in the nucleus proprius (III and IV) of bilateral L4-L5 lumbar spinal cord after unilateral intraplantar injection of BmK venom from 2h to 7d. This increase on the ipsilateral side to BmK venom injection was always greater than that on the contralateral side. Western blotting analysis confirmed that spinal nNOS expression was significantly up-regulated following BmK venom administration. In addition, intrathecal delivery of N(omega)-nitro-l-arginine methyl ester hydrochloride (l-NAME; a NOS inhibitor) before intraplantar injection of BmK venom by 10 min significantly attenuated spontaneous nociceptive responses and prevented the development of primary thermal hyperalgesia as well as bilateral mechanical hyperalgesia. Intrathecal injection of l-NAME could also partially inhibit BmK venom-induced c-Fos expression in lumbar spinal cord at 2 h. Thus, the results suggest that spinal NO as a critical mediator is involved in various pain-related behaviors and c-Fos expression induced by BmK venom in rats.

  12. Stigmurin and TsAP-2 from Tityus stigmurus scorpion venom: Assessment of structure and therapeutic potential in experimental sepsis.

    PubMed

    Daniele-Silva, Alessandra; Machado, Richele J A; Monteiro, Norberto K V; Estrela, Andréia B; Santos, Elizabeth C G; Carvalho, Eneas; Araújo Júnior, Raimundo F; Melo-Silveira, Raniere F; Rocha, Hugo Alexandre O; Silva-Júnior, Arnóbio A; Fernandes-Pedrosa, Matheus F

    2016-10-01

    Microbial resistance to conventional antibiotics is a public health problem worldwide, motivating the search for new therapeutic alternatives in varied natural sources. Cationic peptides without disulfide bridges from scorpions have been targeted in this context, mainly due to their multifunctional action and the limited ability of microorganisms to develop resistance against them. The present study was focused on Stigmurin and TsAP-2, cationic peptides found in the transcriptome of the venom gland from the scorpion Tityus stigmurus. The aims were: to assess the secondary structure of TsAP-2 and the structural stability of both peptides by circular dichroism; to evaluate their antiproliferative effect, and antimicrobial activities in vitro, ex vivo and in vivo; and to investigate their therapeutic potential in a murine model of polymicrobial sepsis. Stigmurin and TsAP-2 secondary structures responded similarly to environment polarity changes, and were stable to temperature and pH variation. Both peptides showed antiproliferative effect on tumor cells. TsAP-2 showed lower cytotoxicity to normal cells, and had a mitogenic activity on murine macrophages. Stigmurin demonstrated bactericidal and bacteriostatic activity, depending on the microorganism, whereas TsAP-2 had bactericidal action upon different bacterial strains analyzed. Both peptides were able to reduce leukocyte migration, TNF-α levels and microorganism load in the peritoneal cavity after induction of experimental sepsis, decreasing inflammation in the lung and cecum of septic animals. TsAP-2 also reduced the release of nitric oxide in the peritoneal cavity. Taken together, these data suggest that Stigmurin and TsAP-2 are structurally stable molecules and are efficient in the control of the infectious focus in polymicrobial sepsis, with potential use as a prototype for the rational design of novel therapeutic agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. 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

  14. 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

    2015-03-27

    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.

  15. 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.

  16. 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

    2016-02-23

    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.

  17. Separation and partial characterization of smooth muscle contractile material in the venom of the scorpion Heterometrus bengalensis.

    PubMed

    Kar, P K; Sarangi, B; Datta, A; Gomes, A; Lahiri, S C

    1983-01-01

    A smooth muscle contractile material was separated from crude venom of the scorpion Heterometrus bengalensis (found in Eastern India) by solvent extraction, gel filtration and thin layer chromatography. Smooth muscle contractile material could be extracted, in descending order of efficiency, with methanol, butanol, ethanol and acetone. The contractile material separated by gel filtration (Sephadex G-25) when further extracted, using the Folch procedure, showed a single spot in thin layer chromatography with one solvent system. Rechromatography of an eluate from this spot with another solvent system resolved it into three spots (SL1, SL2 and SL3, the mixture being designated as Substance L) which could be visualized either with iodine vapour, ninhydrin or molybdenum reagent. Eluates from the three spots contracted guinea-pig ileum which had been pretreated with antagonists of ACh, histamine, 5-HT and prostaglandins. Substance L and its fractions (SL1, SL2 and SL3) contain inorganic phosphorus, amino nitrogen and amino sugar, which point to the likelihood of their being glycophosphatides.

  18. Fast K(+) currents from cerebellum granular cells are completely blocked by a peptide purified from Androctonus australis Garzoni scorpion venom.

    PubMed

    Pisciotta, M; Coronas, F I; Bloch, C; Prestipino, G; Possani, L D

    2000-09-29

    A novel peptide was purified from the venom of the scorpion Androctonus australis Garzoni (abbreviated Aa1, corresponding to the systematic number alpha KTX4.4). It contains 37 amino acid residues, has a molecular mass of 3850 Da, is closely packed by three disulfide bridges and a blocked N-terminal amino acid. This peptide selectively affects the K(+) currents recorded from cerebellum granular cells. Only the fast activating and inactivating current, with a kinetics similar to I(A)-type current, is completely blocked by the addition of low micromolar concentrations (K(i) value of 150 nM) of peptide Aa1 to the external side of the cell preparation. The blockade is partially reversible in our experimental conditions. Aa1 blocks the channels in both the open and the closed states. The blockage is test potential independent and is not affected by changes in the holding potential. The kinetics of the current are not affected by the addition of Aa1 to the preparation; it means that the block is a simple 'plugging mechanism', in which a single toxin molecule finds a specific receptor site in the external vestibule of the K(+) channel and thereby occludes the outer entry to the K(+) conducting pore.

  19. Differential effects of Tityus bahiensis scorpion venom on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium currents.

    PubMed

    Moraes, Eder R; Kalapothakis, Evanguedes; Naves, Lígia A; Kushmerick, Christopher

    2011-01-01

    We examined modification of sodium channel gating by Tityus bahiensis scorpion venom (TbScV), and compared effects on native tetrodotoxin-sensitive and tetrodotoxin-resistant sodium currents from rat dorsal root ganglion neurons and cardiac myocytes. In neurons, TbScV dramatically reduced the rate of sodium current inactivation, increased current amplitude, and caused a negative shift in the voltage-dependence of activation and inactivation of tetrodotoxin-sensitive channels. Enhanced activation of modified sodium channels was independent of a depolarizing prepulse. We identified two components of neuronal tetrodotoxin-resistant current with biophysical properties similar to those described for NaV1.8 and NaV1.9. In contrast to its effects on neuronal tetrodotoxin-sensitive current, TbScV caused a small decrease in neuronal tetrodotoxin-resistant sodium current amplitude and the gating modifications described above were absent. A third tetrodotoxin-resistant current, NaV1.5 recorded in rat cardiac ventricular myocytes, was inhibited approximately 50% by TbScV, and the remaining current exhibited markedly slowed activation and inactivation. In conclusion, TbScV has very different effects on different sodium channel isoforms. Among the neuronal types, currents resistant to tetrodotoxin are also resistant to gating modification by TbScV. The cardiac tetrodotoxin-resistant current has complex sensitivity that includes both inhibition of current amplitude and slowing of activation and inactivation.

  20. Ctriporin, a New Anti-Methicillin-Resistant Staphylococcus aureus Peptide from the Venom of the Scorpion Chaerilus tricostatus ▿

    PubMed Central

    Fan, Zheng; Cao, Luyang; He, Yawen; Hu, Jun; Di, Zhiyong; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

    2011-01-01

    Antibiotic-resistant microbes, such as methicillin-resistant Staphylococcus aureus, seriously threaten human health. The outbreak of “superbugs” in recent years emphasizes once again the need for the development of new antimicrobial agents or resources. Antimicrobial peptides have an evident bactericidal effect against multidrug-resistant pathogens. In the present study, a new antimicrobial peptide, ctriporin, was cloned and characterized from the venom of the scorpion Chaerilus tricostatus, an animal which has not yet been explored for toxic peptide resources. The MICs of ctriporin against Staphylococcus aureus, Bacillus thuringiensis, Bacillus subtilis, Micrococcus luteus, and Candida albicans are 5 to 20 μg/ml. Meanwhile, it MIC against clinical antibiotic-resistant bacterial strains is 10 μg/ml. Furthermore, the potential for ctriporin to be used as a topical antibiotic for treating staphylococcal skin infections was investigated. External use of the peptide ctriporin dramatically decreased the bacterial counts and cured skin infections in mice. In addition, ctriporin demonstrates antimicrobial efficacy via the bactericidal mechanism of rapid cell lysis. Together, these results suggest the potential of developing ctriporin as a new topical antibiotic. PMID:21876042

  1. 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

  2. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Ctriporin, a new anti-methicillin-resistant Staphylococcus aureus peptide from the venom of the scorpion Chaerilus tricostatus.

    PubMed

    Fan, Zheng; Cao, Luyang; He, Yawen; Hu, Jun; Di, Zhiyong; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

    2011-11-01

    Antibiotic-resistant microbes, such as methicillin-resistant Staphylococcus aureus, seriously threaten human health. The outbreak of "superbugs" in recent years emphasizes once again the need for the development of new antimicrobial agents or resources. Antimicrobial peptides have an evident bactericidal effect against multidrug-resistant pathogens. In the present study, a new antimicrobial peptide, ctriporin, was cloned and characterized from the venom of the scorpion Chaerilus tricostatus, an animal which has not yet been explored for toxic peptide resources. The MICs of ctriporin against Staphylococcus aureus, Bacillus thuringiensis, Bacillus subtilis, Micrococcus luteus, and Candida albicans are 5 to 20 μg/ml. Meanwhile, it MIC against clinical antibiotic-resistant bacterial strains is 10 μg/ml. Furthermore, the potential for ctriporin to be used as a topical antibiotic for treating staphylococcal skin infections was investigated. External use of the peptide ctriporin dramatically decreased the bacterial counts and cured skin infections in mice. In addition, ctriporin demonstrates antimicrobial efficacy via the bactericidal mechanism of rapid cell lysis. Together, these results suggest the potential of developing ctriporin as a new topical antibiotic.

  4. Taxonomical and geographical occurrence of Libyans scorpions.

    PubMed

    Zourgui, L; Maammar, M; Emetris, R

    2008-01-01

    Nine different species of scorpions can be recognized from more than 5000 samples collected from different areas in Libya: Leiurus quinquestriatus, Androctonus bicolor, Androctonus australis, Androctonus amoreuxi, Buthacus leptochelys, Buthus occitanus, Buthacus arenicola, Orthochirus innesi and Scorpio maurus. The geographical occurrence showed that Leiurus quinquestriatus seems to be restricted to the Southern areas. On the contrary, Buthus occitanus was found in the costal regions. Other species such as Androctonus were widely spread in all regions. Buthacus Leptochelys, Orthochirus innesi and Scorpio maurus were found, in the East (Aujlah, Jalu), the South (Wadi-Atbah) and the Western cost of Libya respectively.

  5. Short-chain peptides identification of scorpion Buthus martensi Karsch venom by employing high orthogonal 2D-HPLC system and tandem mass spectrometry.

    PubMed

    Xu, Junyan; Zhang, Xiuli; Guo, Zhimou; Yan, Jingyu; Yu, Long; Li, Xiuling; Xue, Xingya; Liang, Xinmiao

    2012-10-01

    Scorpion venom contains a considerable variety of neurotoxic peptides that can act on ionic channels. Here, we describe an orthogonal 2D-reversed phase/hydrophilic interaction chromatography system (RPLC/HILIC) and use it to separate short-chain peptides from Asian scorpion Buthus martensi Karsch (BmK) venom in a high throughput format. Due to its high orthogonality and efficiency, 18 homogenous peptides were purified and sequence identified by MS/MS with collision-induced dissociation. Among them, four peptides were discovered, which only have evidence at transcript-level, were first purified from crude venom in this study. Two peptides named BmKK2-b and Martentoxin-b were found the new cleaved chains of known BmKK2 and Martentoxin. In addition, two novel peptides named BmKK12 and BmKK16 in this paper were sequenced by de novo MS/MS, which we predict, are members of potassium channel toxin α-KTx 17 subfamily by homology to other known peptides found in the Swiss-Prot protein database.

  6. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Vasosensory responses elicited by Indian red scorpion venom last longer than capsaicin-induced responses.

    PubMed

    Singh, Sanjeev K; Deshpande, Shripad B

    2008-11-01

    The present study was conducted to compare the time-related cardiorespiratory changes occurring after the injection of Mesobuthus tamulus (BT; 1 mg/kg) venom and capsaicin (1.2 ng/kg) in the peripheral end of femoral artery in urethane anaesthetised rats. Blood pressure (BP), electrocardiogram (for heart rate; HR) and respiratory movements were recorded for 60 min after venom/capsaicin intra-arterially. Minute ventilation (MV) was computed by using appropriate calibrations. After intraarterial injection of BT venom, there was immediate (within 2 sec) increase in respiratory rate (RR) and MV which reached to 40% within 30 sec, followed by a 40% decrease in RR without any change in MV. Further, there was sustained increase in RR (50%) and MV (65%) up to 60 min. The BP began to increase at 40 sec, peaking at 5 min (50%) and remained above the initial level up to 60 min. The bradycardiac response began after 5 min which peaked (50% of the initial) at 25 min and remained at that level up to 60 min. In capsaicin treated group, there was immediate hyperventilatory (increase in RR and MV) changes within 2 sec which returned to the initial level within 2 min and remained at that level up to 60 min. The capsaicin-induced hypotensive response began within 5 sec which returned to the initial level by 5 min and remained at that level throughout. Capsaicin did not produce any change in HR. These observations suggest that intraarterial injection of BT venom produces prolonged cardiorespiratory alterations as compared to the capsaicin-induced responses.

  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. Hepato- and nephroprotective effects of bradykinin potentiating factor from scorpion (Buthus occitanus) venom on mercuric chloride-treated rats.

    PubMed

    Salman, Muhammad M A; Kotb, Ahmed M; Haridy, Mohie A M; Hammad, Seddik

    2016-01-01

    Bioactive peptides such as bradykinin potentiating factor (BPF), have, anti-oxidative, anti-inflammatory, immunomodulatory and ameliorative effects in chronic diseases and play a potential role in cancer prevention. It is known that the liver and kidney accumulate inorganic mercury upon exposure, which often leads to mercury intoxication in these organs. In this study, we investigated the effect of bradykinin potentiating factor (BPF), a scorpion venom peptide, on mercuric chloride-induced hepatic and renal toxicity in rats. We used 20 adult male Albino rats divided into four equal groups: the first group was injected with saline (control); the second group was administered daily with mercuric chloride (HgCl2) for 2 weeks; the third group was administered with BPF twice weekly for 2 successive weeks, while the fourth group was exposed to BPF followed by HgCl2. We observed that HgCl2 treated rats had a significant increase in serum ALT, AST, ALP, creatinine and urea levels compared to control. Furthermore, HgCl2 treated rats showed a marked decrease in total proteins, albumin and uric acids compared to control. The previously studied parameters were not significantly changed in BPF pretreated rats compared to control. Moreover, a significant decrease in the activities of glutathione perioxidase (GSH), superoxide dismutase (SOD), and catalase (CAT), in addition to a significant increase in the level of malondialdehyde (MDA) were observed in hepatic and renal tissues of rats after HgCl2 treatment. In contrast, the HgCl2/BPF treated rats showed a significant elevation in the activity of GSH, SOD, and CAT accompanied with a significant regression in the level of MDA compared to the HgCl2 exposed rats. We conclude that treatment with BPF is a promising prophylactic approach for the management of mercuric chloride-induced hepato- and nephro-toxicities.

  10. Hepato- and nephroprotective effects of bradykinin potentiating factor from scorpion (Buthus occitanus) venom on mercuric chloride-treated rats

    PubMed Central

    Salman, Muhammad M. A.; Kotb, Ahmed M.; Haridy, Mohie A. M.; Hammad, Seddik

    2016-01-01

    Bioactive peptides such as bradykinin potentiating factor (BPF), have, anti-oxidative, anti-inflammatory, immunomodulatory and ameliorative effects in chronic diseases and play a potential role in cancer prevention. It is known that the liver and kidney accumulate inorganic mercury upon exposure, which often leads to mercury intoxication in these organs. In this study, we investigated the effect of bradykinin potentiating factor (BPF), a scorpion venom peptide, on mercuric chloride-induced hepatic and renal toxicity in rats. We used 20 adult male Albino rats divided into four equal groups: the first group was injected with saline (control); the second group was administered daily with mercuric chloride (HgCl2) for 2 weeks; the third group was administered with BPF twice weekly for 2 successive weeks, while the fourth group was exposed to BPF followed by HgCl2. We observed that HgCl2 treated rats had a significant increase in serum ALT, AST, ALP, creatinine and urea levels compared to control. Furthermore, HgCl2 treated rats showed a marked decrease in total proteins, albumin and uric acids compared to control. The previously studied parameters were not significantly changed in BPF pretreated rats compared to control. Moreover, a significant decrease in the activities of glutathione perioxidase (GSH), superoxide dismutase (SOD), and catalase (CAT), in addition to a significant increase in the level of malondialdehyde (MDA) were observed in hepatic and renal tissues of rats after HgCl2 treatment. In contrast, the HgCl2/BPF treated rats showed a significant elevation in the activity of GSH, SOD, and CAT accompanied with a significant regression in the level of MDA compared to the HgCl2 exposed rats. We conclude that treatment with BPF is a promising prophylactic approach for the management of mercuric chloride-induced hepato- and nephro-toxicities. PMID:28337111

  11. Structural Insights into Antibody Sequestering and Neutralizing of Na+ Channel α-Type Modulator from Old World Scorpion Venom

    PubMed Central

    Fabrichny, Igor P.; Mondielli, Grégoire; Conrod, Sandrine; Martin-Eauclaire, Marie-France; Bourne, Yves; Marchot, Pascale

    2012-01-01

    The Old World scorpion Androctonus australis hector (Aah) produces one of the most lethal venoms for humans. Peptidic α-toxins AahI to AahIV are responsible for its potency, with AahII accounting for half of it. All four toxins are high affinity blockers of the fast inactivation phase of mammalian voltage-activated Na+ channels. However, the high antigenic polymorphism of α-toxins prevents production of a polyvalent neutralizing antiserum, whereas the determinants dictating their trapping by neutralizing antibodies remain elusive. From an anti-AahII mAb, we generated an antigen binding fragment (Fab) with high affinity and selectivity for AahII and solved a 2.3 Å-resolution crystal structure of the complex. Sequestering of the C-terminal region of the bound toxin within a groove formed by the Fab combining loops is associated with a toxin orientation and main and side chain conformations that dictate the AahII antigenic specificity and efficient neutralization. From an anti-AahI mAb, we also preformed and crystallized a high affinity AahI-Fab complex. The 1.6 Å-resolution structure solved revealed a Fab molecule devoid of a bound AahI and with combining loops involved in packing interactions, denoting expulsion of the bound antigen upon crystal formation. Comparative analysis of the groove-like combining site of the toxin-bound anti-AahII Fab and planar combining surface of the unbound anti-AahI Fab along with complementary data from a flexible docking approach suggests occurrence of distinctive trapping orientations for the two toxins relative to their respective Fab. This study provides complementary templates for designing new molecules aimed at capturing Aah α-toxins and suitable for immunotherapy. PMID:22371498

  12. Analysis of the immune response induced by a scorpion venom sub-fraction, a pure peptide and a recombinant peptide, against toxin Cn2 of Centruroides noxius Hoffmann.

    PubMed

    Garcia, Consuelo; Calderón-Aranda, Emma S; Anguiano, Gerardo A V; Becerril, Baltazar; Possani, Lourival D

    2003-03-01

    Three different immunogens from the venom of the Mexican scorpion Centruroides noxius Hoffmann were used to study protective antibody response in mice and rabbits, challenged with toxin Cn2, one of the most abundant toxic peptide of this venom. The immunogens were: Cn5, a crustacean specific toxin; a recombinant protein containing the peptide Cn5 linked to the maltose transporter and a sub-fraction (F.II.5) containing 25 distinct peptides, among which is Cn5. Mice immunized with these three preparations, when directly challenged with Cn2 presented no apparent protection, whereas anti-sera produced in rabbits with these three immunogens were capable of partially neutralizing the effect of Cn2, when injected into naive mice. Cn5 rabbit anti-serum showed a better protective effect on mice, than the rabbit sera obtained against the two other antigens. The subcutaneous route of challenging mice was shown to be better than intraperitoneal injections. Comparative structural analysis of Cn5 with other toxins of this venom showed that our results are important to be taken into consideration, when choosing appropriate immunogens aimed at the production of better anti-venoms or for the rational design of possible vaccines.

  13. 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.

  14. The Snake with the Scorpion's Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus).

    PubMed

    Yang, Daryl C; Deuis, Jennifer R; Dashevsky, Daniel; Dobson, James; Jackson, Timothy N W; Brust, Andreas; Xie, Bing; Koludarov, Ivan; Debono, Jordan; Hendrikx, Iwan; Hodgson, Wayne C; Josh, Peter; Nouwens, Amanda; Baillie, Gregory J; Bruxner, Timothy J C; Alewood, Paul F; Lim, Kelvin Kok Peng; Frank, Nathaniel; Vetter, Irina; Fry, Bryan G

    2016-10-18

    species including cone snails, scorpions, spiders, and anemones. Enhanced activation or delayed inactivation of sodium channels by toxins is associated with the extremely rapid onset of tetanic/excitatory paralysis in envenomed prey animals. A strong selection pressure exists for the evolution of such toxins where there is a high chance of prey escape. However, despite their prevalence in other venomous species, toxins causing delay of sodium channel inhibition have never previously been described in vertebrate venoms. Here we show that NaV modulators, convergent with those of invertebrates, have evolved in the venom of the long-glanded coral snake. Calliotoxin represents a functionally novel class of 3FTx and a structurally novel class of NaV toxins that will provide significant insights into the pharmacology and physiology of NaV. The toxin represents a remarkable case of functional convergence between invertebrate and vertebrate venom systems in response to similar selection pressures. These results underscore the dynamic evolution of the Toxicofera reptile system and reinforces the value of using evolution as a roadmap for biodiscovery.

  15. Activity of Scorpion Venom-Derived Antifungal Peptides against Planktonic Cells of Candida spp. and Cryptococcus neoformans and Candida albicans Biofilms

    PubMed Central

    Guilhelmelli, Fernanda; Vilela, Nathália; Smidt, Karina S.; de Oliveira, Marco A.; da Cunha Morales Álvares, Alice; Rigonatto, Maria C. L.; da Silva Costa, Pedro H.; Tavares, Aldo H.; de Freitas, Sônia M.; Nicola, André M.; Franco, Octávio L.; Derengowski, Lorena da Silveira; Schwartz, Elisabeth F.; Mortari, Márcia R.; Bocca, Anamélia L.; Albuquerque, Patrícia; Silva-Pereira, Ildinete

    2016-01-01

    The incidence of fungal infections has been increasing in the last decades, while the number of available antifungal classes remains the same. The natural and acquired resistance of some fungal species to available therapies, associated with the high toxicity of these drugs on the present scenario and makes an imperative of the search for new, more efficient and less toxic therapeutic choices. Antimicrobial peptides (AMPs) are a potential class of antimicrobial drugs consisting of evolutionarily conserved multifunctional molecules with both microbicidal and immunomodulatory properties being part of the innate immune response of diverse organisms. In this study, we evaluated 11 scorpion-venom derived non-disulfide-bridged peptides against Cryptococcus neoformans and Candida spp., which are important human pathogens. Seven of them, including two novel molecules, showed activity against both genera with minimum inhibitory concentration values ranging from 3.12 to 200 μM and an analogous activity against Candida albicans biofilms. Most of the peptides presented low hemolytic and cytotoxic activity against mammalian cells. Modifications in the primary peptide sequence, as revealed by in silico and circular dichroism analyses of the most promising peptides, underscored the importance of cationicity for their antimicrobial activity as well as the amphipathicity of these molecules and their tendency to form alpha helices. This is the first report of scorpion-derived AMPs against C. neoformans and our results underline the potential of scorpion venom as a source of antimicrobials. Further characterization of their mechanism of action, followed by molecular optimization to decrease their cytotoxicity and increase antimicrobial activity, is needed to fully clarify their real potential as antifungals. PMID:27917162

  16. Efficacy and safety of scorpion antivenom plus prazosin compared with prazosin alone for venomous scorpion (Mesobuthus tamulus) sting: randomised open label clinical trial

    PubMed Central

    2011-01-01

    Objective Envenomation by Mesobuthus tamulus scorpion sting can result in serious cardiovascular effects. Scorpion antivenom is a specific treatment for scorpion sting. Evidence for the benefit of scorpion antivenom and its efficacy compared with that of commonly used vasodilators, such as prazosin, is scarce. We assessed the efficacy of prazosin combined with scorpion antivenom, compared with prazosin alone, in individuals with autonomic storm caused by scorpion sting. Design Prospective, open label randomised controlled trial. Setting General hospital inpatients (Bawaskar Hospital and Research Centre Mahad Dist-Raigad Maharashtra, India). Participants Seventy patients with grade 2 scorpion envenomation, older than six months, with no cardiorespiratory or central nervous system abnormalities. Intervention Scorpion antivenom plus prazosin (n=35) or prazosin alone (n=35) assigned by block randomisation. Treatment was not masked. Analysis was by intention to treat. Main outcome measures The primary end point was the proportion of patients achieving resolution of the clinical syndrome (sweating, salivation, cool extremities, priapism, hypertension or hypotension, tachycardia) 10 hours after administration of study drugs. Secondary end points were time required for complete resolution of clinical syndrome, prevention of deterioration to higher grade, doses of prazosin required overall and within 10 hours, and adverse events. The study protocol was approved by the independent ethics committee of Mumbai. Results Mean (SD) recovery times in hours for the prazosin plus scorpion antivenom group compared with the prazosin alone groups were: sweating 3 (1.1) v 6.6 (2.6); salivation 1.9 (0.9) v 3 (1.9); priapism 4.7 (1.5) v 9.4 (1.5). Mean (SD) doses of prazosin in the groups were 2 (2.3) and 4 (3.5), respectively. 32 patients (91.4%, 95% confidence interval 76.9% to 97.8%) in the prazosin plus antivenom group showed complete resolution of the clinical syndrome within 10 hours

  17. Efficacy and safety of scorpion antivenom plus prazosin compared with prazosin alone for venomous scorpion (Mesobuthus tamulus) sting: randomised open label clinical trial.

    PubMed

    Bawaskar, Himmatrao Saluba; Bawaskar, Pramodini Himmatrao

    2011-01-05

    Envenomation by Mesobuthus tamulus scorpion sting can result in serious cardiovascular effects. Scorpion antivenom is a specific treatment for scorpion sting. Evidence for the benefit of scorpion antivenom and its efficacy compared with that of commonly used vasodilators, such as prazosin, is scarce. We assessed the efficacy of prazosin combined with scorpion antivenom, compared with prazosin alone, in individuals with autonomic storm caused by scorpion sting. Prospective, open label randomised controlled trial. General hospital inpatients (Bawaskar Hospital and Research Centre Mahad Dist-Raigad Maharashtra, India). Seventy patients with grade 2 scorpion envenomation, older than six months, with no cardiorespiratory or central nervous system abnormalities. Scorpion antivenom plus prazosin (n=35) or prazosin alone (n=35) assigned by block randomisation. Treatment was not masked. Analysis was by intention to treat. The primary end point was the proportion of patients achieving resolution of the clinical syndrome (sweating, salivation, cool extremities, priapism, hypertension or hypotension, tachycardia) 10 hours after administration of study drugs. Secondary end points were time required for complete resolution of clinical syndrome, prevention of deterioration to higher grade, doses of prazosin required overall and within 10 hours, and adverse events. The study protocol was approved by the independent ethics committee of Mumbai. Mean (SD) recovery times in hours for the prazosin plus scorpion antivenom group compared with the prazosin alone groups were: sweating 3 (1.1) v 6.6 (2.6); salivation 1.9 (0.9) v 3 (1.9); priapism 4.7 (1.5) v 9.4 (1.5). Mean (SD) doses of prazosin in the groups were 2 (2.3) and 4 (3.5), respectively. 32 patients (91.4%, 95% confidence interval 76.9% to 97.8%) in the prazosin plus antivenom group showed complete resolution of the clinical syndrome within 10 hours of administration of treatment compared with eight patients in the prazosin

  18. 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.

  19. Intrathecal injection of glutamate receptor antagonists/agonist selectively attenuated rat pain-related behaviors induced by the venom of scorpion Buthus martensi Karsch.

    PubMed

    Liu, Tong; Pang, Xue-Yan; Bai, Zhan-Tao; Chai, Zhi-Fang; Jiang, Feng; Ji, Yong-Hua

    2007-12-15

    The present study investigated the involvement of spinal glutamate receptors in the induction and maintenance of the pain-related behaviors induced by the venom of scorpion Buthus martensi Karsch (BmK). (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-10-imine hydrogen maleate (MK-801; 40nmol; a non-competitive NMDA receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 40nmol; a non-NMDA receptor antagonist), dl-amino-3-phosphonopropionic acid (dl-AP3; 100nmol; a group I metabotropic glutamate receptor antagonist) and 4-aminopyrrolidine-2,4-dicarboxylate (APDC; 100nmol; a group II metabotropic glutamate receptor agonist) were employed. On intrathecal injection of glutamate receptor antagonists/agonist before BmK venom administration by 10min, BmK venom-induced spontaneous nociceptive responses could be suppressed by all tested agents. Primary thermal hyperalgesia could be inhibited by MK-801 and dl-AP3, while bilateral mechanical hyperalgesia could be inhibited by CNQX and dl-AP3 and contralateral mechanical hyperalgesia could be inhibited by APDC. On intrathecal injection of glutamate receptor antagonists/agonist after BmK venom injection by 4.5h, primary thermal hyperalgesia could be partially reversed by all tested agents, while bilateral mechanical hyperalgesia could only be inhibited by APDC. The results suggest that the role of spinal glutamate receptors may be different on the various manifestations of BmK venom-induced pain-related behaviors.

  20. Chemical synthesis of La1 isolated from the venom of the scorpion Liocheles australasiae and determination of its disulfide bonding pattern.

    PubMed

    Nagao, Junya; Miyashita, Masahiro; Nakagawa, Yoshiaki; Miyagawa, Hisashi

    2015-08-01

    La1 is a 73-residue cysteine-rich peptide isolated from the scorpion Liocheles australasiae venom. Although La1 is the most abundant peptide in the venom, its biological function remains unknown. Here, we describe a method for efficient chemical synthesis of La1 using the native chemical ligation (NCL) strategy, in which three peptide components of less than 40 residues were sequentially ligated. The peptide thioester necessary for NCL was synthesized using an aromatic N-acylurea approach with Fmoc-SPPS. After completion of sequential NCL, disulfide bond formation was carried out using a dialysis method, in which the linear peptide dissolved in an acidic solution was dialyzed against a slightly alkaline buffer to obtain correctly folded La1. Next, we determined the disulfide bonding pattern of La1. Enzymatic and chemical digests of La1 without reduction of disulfide bonds were analyzed by liquid chromatography/mass spectrometry (LC/MS), which revealed two of four disulfide bond linkages. The remaining two linkages were assigned based on MS/MS analysis of a peptide fragment containing two disulfide bonds. Consequently, the disulfide bonding pattern of La1 was found to be similar to that of a von Willebrand factor type C (VWC) domain. To our knowledge, this is the first report of the experimental determination of the disulfide bonding pattern of peptides having a single VWC domain as well as their chemical synthesis. La1 synthesized in this study will be useful for investigation of its biological role in the venom.

  1. The scorpion venom peptide BmKn2 induces apoptosis in cancerous but not in normal human oral cells.

    PubMed

    Satitmanwiwat, Saranya; Changsangfa, Chinarat; Khanuengthong, Anuson; Promthep, Kornkanok; Roytrakul, Sittiruk; Arpornsuwan, Teerakul; Saikhun, Kulnasan; Sritanaudomchai, Hathaitip

    2016-12-01

    This study aimed to investigate the mechanism of the induction of apoptosis of human oral cancer cells by the scorpion venom peptide BmKn2. Human oral squamous carcinoma cells (HSC4), mouth epidermoid carcinoma cells (KB), human normal gingival cells (HGC) and dental pulp cells (DPC) were treated with BmKn-2 peptide for 24h. Cell viability was determined by the MTT assay. Apoptosis was assessed using phase contrast microscopy, by propidium iodide (PI) staining to assess nuclear morphology and by Annexin V staining. Apoptotic signaling pathways were investigated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western blotting. BmKn-2 showed potent cytotoxic effects towards both HSC4 and KB cells with the associated induction of apoptosis. The cells showed distinct morphological changes, nuclear disintegration and an increase in the number of Annexin V-positive cells. Interestingly, at concentrations which kill cancerous cells, BmKn-2 did not affect cell viability or mediate the induction of apoptosis in normal HGC or DPC. Induction of apoptosis by BmKn-2 in HSC4 and KB cells was associated with the activation of tumor suppress p53. Pro-apoptotic BAX expression was increased, whereas antiapoptotic BCL-2 expression was decreased in BmKn-2 exposed HSC4 and KB cells. BmKn-2 treated-oral cancer cells showed distinct upregulation of initiator caspase-9, with no effect on caspase-8 expression. Increased expression levels of executor caspases-3 and -7 were also found in treated cells for both oral cancers. This study has suggested for the first time that BmKn-2 exerts selective cytotoxic effects on human oral cancer cells by inducting apoptosis via a p53-dependent intrinsic apoptotic pathway. BmKn-2 peptide originally derived from a natural source shows great promise as a candidate treatment for oral cancer, with minimal effects on healthy tissue. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Mediators involved in the febrile response induced by Tityus serrulatus scorpion venom in rats.

    PubMed

    Pessini, Andréa C; Santos, Danielle R; Arantes, Eliane C; Souza, Glória E P

    2006-10-01

    Tityus serrulatus venom (Tsv) was intraperitoneally (ip) injected at doses of 75, 150 and 300mug/kg and IL-1beta (2.0 microg/kg) was given intravenously (iv) to male Wistar rats. Rectal temperature was measured by radiotelemetry. Vagotomy was performed according to Bluthe et al. [1994. Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad. Sci. 317(6), 499-503]. Cerebrospinal fluid (CSF) and peritoneal fluid (PF) levels of bradykinin (BK) were measured by ELISA. B(1) (des-Arg(9)-[Leu(8)]-BK; DALBK) and B(2) kinin receptor (icatibant) antagonists (1.0 mg/kg each), the induced nitric oxide synthase inhibitor aminoguanidine (50.0 mg/kg), the neuronal nitric oxide synthase inhibitor 7-nitroindazole (30.0 mg/kg), the dual cyclooxygenase inhibitor ibuprofen (10.0 mg/kg), the selective interleukin-1 receptor antagonist IL-ra (2.0 mg/kg) and dipyrone (120 mg/kg) were given ip. Celecoxib (5 mg/kg) was given per os (po). Tsv at doses of 75 microg/kg evoked no change in rectal temperature while at doses of 150 and 300 microg/kg it promoted long-lasting fever (2 degrees C+/-0.1). Tsv (150 microg/kg) increased by nearly 3 and 5 times, respectively BK concentration in the CSF and in the PF. Subdiaphragmatic vagotomy or 7-nitroindazole reduced, icatibant, DALBK, IL-1ra, aminoguanidine and dipyrone abolished, while ibuprofen and celecoxib failed to affect Tsv-induced fever. These results suggest that PGs do not play a relevant role, whereas, kinins via their B(1) and B(2) receptors, IL-1, nitric oxide and vagal neurotransmission are involved in Tsv-induced fever.

  3. Characterization of hadrucalcin, a peptide from Hadrurus gertschi scorpion venom with pharmacological activity on ryanodine receptors

    PubMed Central

    Schwartz, Elisabeth F; Capes, E Michelle; Diego-García, Elia; Zamudio, Fernando Z; Fuentes, Oscar; Possani, Lourival D; Valdivia, Héctor H

    2009-01-01

    Background and purpose: Members of the calcin family, presently including imperatoxin A, maurocalcin, opicalcins and hemicalcin, are basic, 33-mer peptide activators of ryanodine receptors (RyRs), the calcium channels of the sarcoplasmic reticulum (SR) that provide the majority of calcium for muscle contraction. Here we describe hadrucalcin, a novel member of this family. Experimental approach: Hadrucalcin was isolated from the venom of Hadrurus gertschi. Amino acid sequence and mass were determined by Edman degradation and mass spectrometry respectively. A cDNA library was constructed to generate clones for DNA sequence determination. Biological activity of native toxin was confirmed with [3H]ryanodine binding, by using SR vesicles from cardiac and skeletal muscle, and with single skeletal (RyR1) and cardiac (RyR2) channels reconstituted in lipid bilayers. Hadrucalcin was applied to intact ventricular myocytes to investigate effects on calcium transients. The secondary structure of hadrucalcin was computer-modelled by using atomic coordinates from maurocalcin, a structurally similar peptide. Key results: Hadrucalcin is distinguished from previously described congeners by two additional amino acids in its primary sequence and the lack of prominent amphipathicity. Hadrucalcin activated RyRs with high affinity (EC50= 37 nmol·L−1), induced a long-lasting subconductance state on RyR1 and RyR2, and rapidly (lag time ∼2 s) penetrated ventricular cardiomyocytes, eliciting discharge of internal calcium stores and spontaneous contractions. Conclusions and implications: Hadrucalcin is a cell-permeant, powerful activator of RyRs, which has translational potential for targeted delivery of drugs to RyR as novel therapeutic intervention in arrhythmogenic disease. PMID:19389159

  4. OD1, the first toxin isolated from the venom of the scorpion Odonthobuthus doriae active on voltage-gated Na+ channels.

    PubMed

    Jalali, Amir; Bosmans, Frank; Amininasab, Mehriar; Clynen, Elke; Cuypers, Eva; Zaremirakabadi, Abbas; Sarbolouki, Mohammad-Nabi; Schoofs, Liliane; Vatanpour, Hossein; Tytgat, Jan

    2005-08-01

    In this study, we isolated and pharmacologically characterized the first alpha-like toxin from the venom of the scarcely studied Iranian scorpion Odonthobuthus doriae. The toxin was termed OD1 and its primary sequence was determined: GVRDAYIADDKNCVYTCASNGYCNTECTKNGAESGYCQWIGRYGNACWCIKLPDEVPIRIPGKCR. Using the two-electrode voltage clamp technique, the pharmacological effects of OD1 were studied on three cloned voltage-gated Na+ channels expressed in Xenopus laevis oocytes (Na(v)1.2/beta1, Na(v)1.5/beta1, para/tipE). The inactivation process of the insect channel, para/tipE, was severely hampered by 200 nM of OD1 (EC50 = 80+/-14 nM) while Na(v)1.2/beta1 still was not affected at concentrations up to 5 microM. Na(v)1.5/beta1 was influenced at micromolar concentrations.

  5. 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.

  6. Amino acid sequence and immunological characterization with monoclonal antibodies of two toxins from the venom of the scorpion Centruroides noxius Hoffmann.

    PubMed

    Zamudio, F; Saavedra, R; Martin, B M; Gurrola-Briones, G; Hérion, P; Possani, L D

    1992-02-15

    Two toxins, which we propose to call toxins 2 and 3, were purified to homogeneity from the venom of the scorpion Centruroides noxius Hoffmann. The full primary structures of both peptides (66 amino acid residues each) was determined. Sequence comparison indicates that the two new toxins display 79% identity and present a high similarity to previously characterized Centruroides toxins, the most similar toxins being Centruroides suffusus toxin 2 and Centruroides limpidus tecomanus toxin 1. Six monoclonal antibodies (mAb) directed against purified fraction II-9.2 (which contains toxins 2 and 3) were isolated in order to carry out the immunochemical characterization of these toxins. mAb BCF2, BCF3, BCF7 and BCF9 reacted only with toxin 2, whereas BCF1 and BCF8 reacted with both toxins 2 and 3 with the same affinity. Simultaneous binding of mAb pairs to the toxin and cross-reactivity of the venoms of different scorpions with the mAb were examined. The results of these experiments showed that the mAb define four different epitopes (A-D). Epitope A (BCF8) is topographically unrelated to epitopes B (BCF2 and BCF7), C (BCF3) and D (BCF9) but the latter three appear to be more closely related or in close proximity to each other. Epitope A was found in all Centruroides venoms tested as well as on four different purified toxins of C. noxius, and thus seems to correspond to a highly conserved structure. Based on the cross-reactivity of their venoms with the mAb, Centruroides species could be classified in the following order: Centruroides elegans, Centruroides suffusus suffusus = Centruroides infamatus infamatus, Centruroides limpidus tecomanus, Centruroides limpidus limpidus, and Centruroides limpidus acatlanensis, according to increasing immunochemical relatedness of their toxins to those of Centruroides noxius. All six mAb inhibited the binding of toxin 2 to rat brain synaptosomal membranes, but only mAb BCF2, which belongs to the IgG2a subclass, displayed a clear

  7. MeuTXKbeta1, a scorpion venom-derived two-domain potassium channel toxin-like peptide with cytolytic activity.

    PubMed

    Zhu, Shunyi; Gao, Bin; Aumelas, André; del Carmen Rodríguez, Maria; Lanz-Mendoza, Humberto; Peigneur, Steve; Diego-Garcia, Elia; Martin-Eauclaire, Marie-France; Tytgat, Jan; Possani, Lourival D

    2010-04-01

    Recent studies have demonstrated that scorpion venom contains unique two-domain peptides with the peculiarity of possessing different functions, i.e. neurotoxic and cytolytic activities. Here we report systematic characterization of a new two-domain peptide (named MeuTXKbeta1) belonging to the TsTXKbeta molecular subfamily from the scorpion Mesobuthus eupeus by molecular cloning, biochemical purification, recombinant expression, functional assays, CD and NMR studies. Its full-length bioactive form as well as 1-21 and 22-72 fragments (named N(1-21) and C(22-72), respectively) was produced in Escherichia coli by an on-column refolding approach. Recombinant peptide (rMeuTXKbeta1) exhibited a low affinity for K(+) channels and cytolytic effects against bacteria and several eukaryotic cells. N(1-21) was found to preserve anti-Plasmodium activity in contrast to haemolytic activity, whereas C(22-72) retains these two activities. Circular dichroism analysis demonstrates that rMeuTXKbeta1 presents a typical scorpion toxin scaffold in water and its alpha-helical content largely increases in a membrane-mimicking environment, consistent with the NMR structure of N(1-21) and an ab initio structure model of MeuTXKbeta1 predicted using I-TASSER algorithm. Our structural and functional data clearly indicate an evolutionary link between TsTXKbeta-related peptides and antiparasitic scorpines which both comprise the betaSPN (beta-KTxs and scorpines) family. Copyright 2009 Elsevier B.V. All rights reserved.

  8. Involvement of Cholinergic and Adrenergic Receptors in Pathogenesis and Inflammatory Response Induced by Alpha-Neurotoxin Bot III of Scorpion Venom.

    PubMed

    Nakib, Imene; Martin-Eauclaire, Marie-France; Laraba-Djebari, Fatima

    2016-10-01

    Bot III neurotoxin is the most lethal α neurotoxin purified from Buthus occitanus tunetanus scorpion venom. This toxin binds to the voltage-gated sodium channel of excitable cells and blocks its inactivation, inducing an increased release of neurotransmitters (acetylcholine and catecholamines). This study aims to elucidate the involvement of cholinergic and adrenergic receptors in pathogenesis and inflammatory response triggered by this toxin. Injection of Bot III to animals induces an increase of peroxidase activities, an imbalance of oxidative status, tissue damages in lung parenchyma, and myocardium correlated with metabolic disorders. The pretreatment with nicotine (nicotinic receptor agonist) or atropine (muscarinic receptor antagonist) protected the animals from almost all disorders caused by Bot III toxin, especially the immunological alterations. Bisoprolol administration (selective β1 adrenergic receptor antagonist) was also efficient in the protection of animals, mainly on tissue damage. Propranolol (non-selective adrenergic receptor antagonist) showed less effect. These results suggest that both cholinergic and adrenergic receptors are activated in the cardiopulmonary manifestations induced by Bot III. Indeed, the muscarinic receptor appears to be more involved than the nicotinic one, and the β1 adrenergic receptor seems to dominate the β2 receptor. These results showed also that the activation of nicotinic receptor leads to a significant protection of animals against Bot III toxin effect. These findings supply a supplementary data leading to better understanding of the mechanism triggered by scorpionic neurotoxins and suggest the use of drugs targeting these receptors, especially the nicotinic one in order to counteract the inflammatory response observed in scorpion envenomation.

  9. Effects of scorpion venom bioactive polypolypeptides on platelet aggregation and thrombosis and plasma 6-keto-PG F1alpha and TXB2 in rabbits and rats.

    PubMed

    Song, Yi-Min; Tang, Xue-Xi; Chen, Xi-Guang; Gao, Ben-Bo; Gao, Er; Bai, Lin; Lv, Xin-Ran

    2005-08-01

    Effects of scorpion venom active polypeptide (SVAP) from scorpion venom of Buthus Martensii Karsch of Chinese on platelet aggregation in ex vivo and vitro in rabbits, thrombosis in carotid artery of rats and plasma 6-keto-PG F1alpha and TXB2 in rats were studied by the turbidimetry, the duplicated thrombosis model by electrostimulation and RIA, respectively. The results showed that SVAP 0.125, 0.25, 0.5 mg/ml inhibited significantly the rabbit platelet aggregation triggered by 0.3 U/ml thrombin, 10 microM ADP in vitro (P<0.05 or 0.01) and SVAP at the dose of 0.32, 0.64 mg/kg iv prolonged distinctively the occlusion time of thrombosis that were induced by electrical stimulation. Increased% of 0.16, 0.32 and 0.64 mg/kg were 30.16, 71.74, 98.27%, respectively, which showed a good dose-effect relationship. SVAP 0.22 mg/ml (in vitro) or 0.2, 0.4 mg/kg (in ex vivo) could obviously increase the plasma concentration of 6-keto-PG F1alpha, but slightly effect rats plasma concentration of TXB2 in vitro and in ex vivo and significantly increase of value of PG I2/TXA2, which suggested that the mechanism of the antithrombotic action of SVAP is related to the resistance against platelet aggregation, increase of the concentration of PG I2 in plasma.

  10. Imperatoxin A, a Cell-Penetrating Peptide from Scorpion Venom, as a Probe of Ca2+-Release Channels/Ryanodine Receptors

    PubMed Central

    Gurrola, Georgina B.; Capes, E. Michelle; Zamudio, Fernando Z.; Possani, Lourival D.; Valdivia, Héctor H.

    2010-01-01

    Scorpion venoms are rich in ion channel-modifying peptides, which have proven to be invaluable probes of ion channel structure-function relationship. We previously isolated imperatoxin A (IpTxa), a 3.7 kDa peptide activator of Ca2+-release channels/ryanodine receptors (RyRs) [1,2,3] and founding member of the calcin family of scorpion peptides. IpTxa folds into a compact, mostly hydrophobic molecule with a cluster of positively-charged, basic residues polarized on one side of the molecule that possibly interacts with the phospholipids of cell membranes. To investigate whether IpTxa permeates external cellular membranes and targets RyRs in vivo, we perfused IpTxa on intact cardiomyocytes while recording field-stimulated intracellular Ca2+ transients. To further investigate the cell-penetrating capabilities of the toxin, we prepared thiolated, fluorescent derivatives of IpTxa. Biological activity and spectroscopic properties indicate that these derivatives retain high affinity for RyRs and are only 5- to 10-fold less active than native IpTxa. Our results demonstrate that IpTxa is capable of crossing cell membranes to alter the release of Ca2+ in vivo, and has the capacity to carry a large, membrane-impermeable cargo across the plasma membrane, a finding with exciting implications for novel drug delivery. PMID:20668646

  11. 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

    2015-07-07

    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.

  12. Identification of the immunogenic epitopes of the whole venom component of the Hemiscorpius lepturus scorpion using the phage display peptide library.

    PubMed

    Jahdasani, Roghaye; Jamnani, Fatemeh Rahimi; Behdani, Mahdi; Habibi-Anbouhi, Mahdi; Yardehnavi, Najmeh; Shahbazzadeh, Delavar; Kazemi-Lomedasht, Fatemeh

    2016-12-15

    The venom of the Hemiscorpius lepturus scorpion contains mixtures of bioactive compounds that disturb biochemical and physiological functions of the victims. Hemiscorpius lepturus envenomation is recognized as a serious health concern in tropical regions. So far, there is no preventive procedure, and the main focus is on treatment of victims with an antiserum purified from hyper-immunized horses. Although antisera can neutralize the venom, they, in some cases, lead to anaphylactic shock and even death. Selection of peptides mimicking antigenic and immunogenic epitopes of toxins from random peptide libraries is a novel approach for the development of recombinant toxins and poly-epitopic vaccine. To achieve this aim, a phage display peptide library and three rounds of biopanning were performed on immobilized antibodies (IgGs) purified from the sera of hyper-immunized horses. The results show that the highest binding of the phage to immobilized horse antibodies occurred in the third round of biopanning. Over 125 individual clones carrying mimotopes of Hemiscorpius lepturus toxins were selected and subjected for sequencing. The sequencing results identified unique peptides mimicking the antigenic and immunogenic epitopes of Hemiscorpius lepturus toxins. The results of this study provide a basis for further studies and the development of a putative epitopic vaccine and a recombinant toxin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Orthogonal separation and identification of long-chain peptides from scorpion Buthus martensi Karsch venom by using two-dimensional mixed-mode reversed phase-reversed phase chromatography coupled to tandem mass spectrometry.

    PubMed

    Xu, Junyan; Zhang, Xiuli; Guo, Zhimou; Yan, Jingyu; Yu, Long; Li, Xiuling; Xue, Xingya; Liang, Xinmiao

    2013-03-21

    Peptide components of scorpion venom have been employed as useful pharmacological tools in the study of ion channel function. The isolation of individual components is necessary for determination of their biological significance. Here, we have described a novel reversed phase (RP)/ion exchange stationary phase, Click oligo ethylene glycol (Click OEG), and the chromatographic efficiency of its mixed-mode sorbent in peptide separation experiments. The Click OEG presents a mixed-mode RP/weak anion-exchange type stationary phase at pH 3.5 and mixed-mode RP/weak cation-exchange type stationary phase at pH 6.0, and it was suitable for separation of long-chain peptides in scorpion venom. Subsequently, a two dimensional mixed-mode RP-RP system based Click OEG and C18 with different pH values in two dimensions was developed for orthogonal separation of scorpion venom. Furthermore, two fractions were analyzed in depth, and 11 long-chain peptides were purified and sequences were identified by using tandem mass spectrometry incorporating the tryptic approach. Among these, we isolated six novel peptides including one peptide with a new sequence and five transcript-level peptides, and speculated on their possible bioactivities.

  14. Characterization of BmKbpp, a multifunctional peptide from the Chinese scorpion Mesobuthus martensii Karsch: gaining insight into a new mechanism for the functional diversification of scorpion venom peptides.

    PubMed

    Zeng, Xian-Chun; Wang, Sanxia; Nie, Yao; Zhang, Lei; Luo, Xuesong

    2012-01-01

    BmKbpp is a novel cationic and α-helical peptide from the Chinese scorpion Mesobuthus martensii Karsch, of which function or biological activity has not been characterized so far. Here we showed that BmKbpp possesses strong antimicrobial activity against both Gram-positive and Gram-negative bacteria with a MIC range from 2.3 μM to 68.2 μM for the majority of tested bacteria. BmKbpp also inhibits the growth of tested fungi with an IC50 range from 0.2 μM to 3.1 μM. Because BmKbpp potently inhibits the growth of some antibiotics-resistant pathogens, and shows very weak hemolytic activity, it has considerable potentials for therapeutic applications. Moreover, we found that BmKbpp markedly inhibits the superoxide production in granulocytes or HL-60 cells at the concentrations of submicromolar level; this suggests that BmKbpp can act as a signaling molecule involving innate immune regulation at low concentrations. The C-terminal region of BmKbpp (BmKbpp-C) shows 72% similarity to the peptide K-12, a bradykinin-potentiating peptide. We found that both BmKbpp and BmKbpp-C possess bradykinin-potentiating activity, and the activity of BmKbpp-C is stronger than that of BmKbpp. PCR amplification for the genomic gene of BmBpp showed that it is not a continuous sequence in the genome; it suggests that BmKbpp could come from a recombination event in transcript level. Taken together, our data suggest that multi-functionalization of a single peptide, which is probably mediated by trans-splicing, could be a new mechanism for the functional diversification of scorpion venom peptides.

  15. 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.

  16. Overview of scorpion species from China and their toxins.

    PubMed

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

    2014-02-26

    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.

  17. 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

  18. Structure, molecular modeling, and function of the novel potassium channel blocker urotoxin isolated from the venom of the Australian scorpion Urodacus yaschenkoi.

    PubMed

    Luna-Ramírez, Karen; Bartok, Adam; Restano-Cassulini, Rita; Quintero-Hernández, Veronica; Coronas, Fredy I V; Christensen, Janni; Wright, Christine E; Panyi, Gyorgy; Possani, Lourival D

    2014-07-01

    This communication reports the structural and functional characterization of urotoxin, the first K(+) channel toxin isolated from the venom of the Australian scorpion Urodacus yaschenkoi. It is a basic peptide consisting of 37 amino acids with an amidated C-terminal residue. Urotoxin contains eight cysteines forming four disulfide bridges with sequence similarities resembling the α-potassium channel toxin 6 (α-KTx-6) subfamily of peptides; it was assigned the systematic number of α-KTx-6.21. Urotoxin is a potent blocker of human voltage-gated potassium channel (Kv)1.2 channels, with an IC50 of 160 pM, whereas its affinity for other channels tested was in the nanomolar range (hKv1.1, IC50 = 253 nM; hKv1.3, IC50 = 91 nM; and hKCa3.1, IC50 = 70 nM). The toxin had no effect on hKv1.4, hKv1.5, human ether-à-go-go-related gene type 1 (hERG1), or human ether-à-go-go-like (hELK2) channels. Multiple sequence alignments from the venom gland transcriptome showed the existence of four other new peptides similar to urotoxin. Computer modeling of urotoxin's three-dimensional structure suggests the presence of the α/β-scaffold characteristic of other scorpion toxins, although very likely forming an uncommon disulfide pairing pattern. Using molecular dynamics, a model for the binding of this peptide to human Kv1.2 and hKv1.1 channels is presented, along with the binding of an in silico mutant urotoxin (Lys25Ala) to both channels. Urotoxin enriches our knowledge of K(+) channel toxins and, due to its high affinity for hKv1.2 channels, it may be a good candidate for the development of pharmacologic tools to study the physiologic functions of K(+) channels or related channelopathies and for restoring axonal conduction in demyelinated axons.

  19. Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses.

    PubMed

    Li, Qiaoli; Zhao, Zhenhuan; Zhou, Dihan; Chen, Yaoqing; Hong, Wei; Cao, Luyang; Yang, Jingyi; Zhang, Yan; Shi, Wei; Cao, Zhijian; Wu, Yingliang; Yan, Huimin; Li, Wenxin

    2011-07-01

    Outbreaks of SARS-CoV, influenza A (H5N1, H1N1) and measles viruses in recent years have raised serious concerns about the measures available to control emerging and re-emerging infectious viral diseases. Effective antiviral agents are lacking that specifically target RNA viruses such as measles, SARS-CoV and influenza H5N1 viruses, and available vaccinations have demonstrated variable efficacy. Therefore, the development of novel antiviral agents is needed to close the vaccination gap and silence outbreaks. We previously identified mucroporin, a cationic host defense peptide from scorpion venom, which can effectively inhibit standard bacteria. The optimized mucroporin-M1 can inhibit gram-positive bacteria at low concentrations and antibiotic-resistant pathogens. In this investigation, we further tested mucroporin and the optimized mucroporin-M1 for their antiviral activity. Surprisingly, we found that the antiviral activities of mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses were notably increased with an EC₅₀ of 7.15 μg/ml (3.52 μM) and a CC₅₀ of 70.46 μg/ml (34.70 μM) against measles virus, an EC₅₀ of 14.46 μg/ml (7.12 μM) against SARS-CoV and an EC₅₀ of 2.10 μg/ml (1.03 μM) against H5N1, while the original peptide mucroporin showed no antiviral activity against any of these three viruses. The inhibition model could be via a direct interaction with the virus envelope, thereby decreasing the infectivity of virus. This report provides evidence that host defense peptides from scorpion venom can be modified for antiviral activity by rational design and represents a practical approach for developing broad-spectrum antiviral agents, especially against RNA viruses. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. 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.

  1. Solution structure of BmKalphaTx11, a toxin from the venom of the Chinese scorpion Buthus martensii Karsch.

    PubMed

    Zhu, Jing; Tong, Xiaotian; Cao, Chunyang; Wu, Gong; Zhang, Naixia; Wu, Houming

    2010-01-01

    The solution structure of BmKalphaTx11 presented by this paper is distinctive from any other structures of wide-type scorpion alpha-toxins reported so far, for its trans-9,10 peptide bond conformation is accompanied by 'protruding' topology of the 'NC-domain'. The orientation of the C-tail of BmKalphaTx11 is obviously different from that of classical alpha-toxins (e.g., AaH2, BmK-M8), despite the fact that they share common trans conformation of peptide bond between residues 9 and 10. Accordingly, there must be other structural factors dominating the orientation of the C-tail except the conformation of peptide bond 9-10. Our study reveals that residues at position 58 play an important role in it, and different type of residues at this position (e.g., Lys, Arg, Met, Ile) result in different spatial relationship between the C-terminus and the 'five-residue-turn' and then different topology of the 'NC-domain', therefore residues at position 58 are believed to function as structure and bioactivity switch for specificity of scorpion alpha-toxins. The mechanism for stabilizing the geometry of the 'NC-domain' in wide-type scorpion alpha-toxins is also discussed.

  2. Scorpion Stings

    MedlinePlus

    Scorpion sting Overview By Mayo Clinic Staff Scorpion stings are painful but rarely life-threatening. Young children, and sometimes ... to be fatal. But with millions of scorpion stings occurring each year, often in areas with a ...

  3. A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus.

    PubMed

    Corzo, Gerardo; Papp, Ferenc; Varga, Zoltan; Barraza, Omar; Espino-Solis, Pavel G; Rodríguez de la Vega, Ricardo C; Gaspar, Rezso; Panyi, Gyorgy; Possani, Lourival D

    2008-10-30

    A novel potassium channel blocker peptide was purified from the venom of the scorpion Centruroides suffusus suffusus by high-performance liquid chromatography and its amino acid sequence was completed by Edman degradation and mass spectrometry analysis. It contains 38 amino acid residues with a molecular weight of 4000.3Da, tightly folded by three disulfide bridges. This peptide, named Css20, was shown to block preferentially the currents of the voltage-dependent K+-channels Kv1.2 and Kv1.3. It did not affect several other ion channels tested at 10 nM concentration. Concentration-response curves of Css20 yielded an IC50 of 1.3 and 7.2 nM for Kv1.2- and Kv1.3-channels, respectively. Interestingly, despite the similar affinities for the two channels the association and dissociation rates of the toxin were much slower for Kv1.2, implying that different interactions may be involved in binding to the two channel types; an implication further supported by in silico docking analyses. Based on the primary structure of Css20, the systematic nomenclature proposed for this toxin is alpha-KTx 2.13.

  4. Solution structure of Cn5, a crustacean toxin found in the venom of the scorpions Centruroides noxius and Centruroides suffusus suffusus.

    PubMed

    Corzo, Gerardo; Prochnicka-Chalufour, Ada; García, Blanca I; Possani, Lourival D; Delepierre, Muriel

    2009-11-01

    The crustacean toxin Cn5 from Centruroides noxius Hoffmann and peptide Css39.8 from Centruroides suffusus suffusus scorpion venoms are identical peptides, as confirmed by amino acid sequence of purified toxins and by DNA sequencing of the two respective cloned genes. Therefore in this communication they will be simply named Cn5. Cn5 is a 66 amino acid long peptide with four disulfide bridges, formed between pairs of cysteines: C1-C8, C2-C5, C3-C6, and C4-C7 (the numbers indicate the relative positions of the cysteine residues in the primary structure). This peptide is non-toxic to mammals but deadly to arthropods (LD(50) 28.5 mg/g body weight of crayfish). Its three-dimensional structure was determined by NMR using a total of 965 meaningful distance constraints derived from the volume integration of the 2D NOESY spectra. The Cn5 structure displays a mixed alpha/beta fold stabilized by four disulfide bridges, with a kink induced by a cis-proline in its C-terminal part. Cn5 electrostatic surface is compared to that of Cn2 toxin toxic to mammals. The local differences produced by additional or substituted residues that would influence toxin selectivity towards mammalian or crustacean Na(+) channels are discussed.

  5. Structure and in vitro activities of a Copper II-chelating anionic peptide from the venom of the scorpion Tityus stigmurus.

    PubMed

    Melo, Menilla M A; Daniele-Silva, Alessandra; Teixeira, Diego G; Estrela, Andréia B; Melo, Karolline R T; Oliveira, Verônica S; Rocha, Hugo A O; Ferreira, Leandro de Santis; Pontes, Daniel L; Lima, João P M S; Silva-Júnior, Arnóbio A; Barbosa, Euzebio G; Carvalho, Eneas; Fernandes-Pedrosa, Matheus F

    2017-08-01

    Anionic Peptides are molecules rich in aspartic acid (Asp) and/or glutamic acid (Glu) residues in the primary structure. This work presents, for the first time, structural characterization and biological activity assays of an anionic peptide from the venom of the scorpion Tityus stigmurus, named TanP. The three-dimensional structure of TanP was obtained by computational modeling and refined by molecular dynamic (MD) simulations. Furthermore, we have performed circular dichroism (CD) analysis to predict TanP secondary structure, and UV-vis spectroscopy to evaluate its chelating activity. CD indicated predominance of random coil conformation in aqueous medium, as well as changes in structure depending on pH and temperature. TanP has chelating activity on copper ions, which modified the peptide's secondary structure. These results were corroborated by MD data. The molar ratio of binding (TanP:copper) depends on the concentration of peptide: at lower TanP concentration, the molar ratio was 1:5 (TanP:Cu(2+)), whereas in concentrated TanP solution, the molar ratio was 1:3 (TanP:Cu(2+)). TanP was not cytotoxic to non-neoplastic or cancer cell lines, and showed an ability to inhibit the in vitro release of nitric oxide by LPS-stimulated macrophages. Altogether, the results suggest TanP is a promising peptide for therapeutic application as a chelating agent. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Enhanced Antimicrobial Activity of AamAP1-Lysine, a Novel Synthetic Peptide Analog Derived from the Scorpion Venom Peptide AamAP1

    PubMed Central

    Almaaytah, Ammar; Tarazi, Shadi; Abu-Alhaijaa, Ahmad; Altall, Yara; Alshar’i, Nizar; Bodoor, Khaldon; Al-Balas, Qosay

    2014-01-01

    There is great interest in the development of antimicrobial peptides as a potentially novel class of antimicrobial agents. Several structural determinants are responsible for the antimicrobial and cytolytic activity of antimicrobial peptides. In our study, a new synthetic peptide analog, AamAP1-Lysine from the naturally occurring scorpion venom antimicrobial peptide AamAP1, was designed by modifying the parent peptide in order to increase the positive charge and optimize other physico-chemical parameters involved in antimicrobial activity. AamAP1-Lysine displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration was in the range of 5 to 15 µM with a 10 fold increase in potency over the parent peptide. The hemolytic and antiproliferative activity of AamAP1-Lysine against eukaryotic mammalian cells was minimal at the concentration range needed to inhibit bacterial growth. The antibacterial mechanism analysis indicated that AamAP1-Lysine is probably inducing bacterial cell death through membrane damage and permeabilization determined by the release of β-galactosidase enzyme from peptide treated E. coli cells. DNA binding studies revealed that AamAP1-Lysine caused complete retardation of DNA migration and could display intracellular activities in addition to the membrane permeabilization mode of action reported earlier. In conclusion, AamAP1-Lysine could prove to be a potential candidate for antimicrobial drug development in future studies. PMID:24776889

  7. Fatal intracerebral haemorrhage following scorpion sting.

    PubMed

    Dube, Simmi; Sharma, V K; Dubey, T N; Gouda, Narendra B; Shrivastava, Vikrant

    2011-03-01

    Though uncommon, scorpion stings can cause cerebrovascular accidents by various mechanisms such as venom induced autonomic storm leading to hypertension, hypotension, myocarditis, DIC or vasculitis by direct actions. We present a case of intracerebral bleed following scorpion sting, which is a rare presentation and seldom reported.

  8. Structural mapping of the voltage-dependent sodium channel. Distance between the tetrodotoxin and Centruroides suffusus suffusus II beta-scorpion toxin receptors.

    PubMed

    Darbon, H; Angelides, K J

    1984-05-25

    A 7- dimethylaminocoumarin -4-acetate fluorescent derivative of toxin II from the venom of the scorpion Centruroides suffusus suffusus (Css II) has been prepared to study the structural, conformational, and cellular properties of the beta-neurotoxin receptor site on the voltage-dependent sodium channel. The derivative retains high affinity for its receptor site on the synaptosomal sodium channel with a KD of 7 nM and site capacity of 1.5 pmol/mg of synaptosomal protein. The fluorescent toxin is very environmentally sensitive and the fluorescence emission upon binding indicates that the Css II receptor is largely hydrophobic. Binding of tetrodotoxin or batrachotoxin does not alter the spectroscopic properties of bound Css II, whereas toxin V from Leiurus quinquestriatus effects a 10-nm blue shift to a more hydrophobic environment. This is the first direct indication of conformational coupling between these separate neurotoxin receptor sites. The distance between the tetrodotoxin and Css II scorpion toxin receptors on the sodium channel was measured by fluorescence resonance energy transfer. Efficiencies were measured by both donor quenching and acceptor-sensitized emission. The distance between these two neurotoxin sites is about 34 A. The implications of these receptor locations together with other known molecular distances are discussed in terms of a molecular structure of the voltage-dependent sodium channel.

  9. Differential involvement of disulfide bridges on the folding of a scorpion toxin.

    PubMed

    Calabro, V; Sabatier, J M; Blanc, E; Lecomte, C; Van Rietschoten, V; Darbon, H

    1997-07-01

    Leiurotoxin I is a neurotoxin, blocker of Ca(2+)-activated apamin-sensitive K+ channel, purified from the venom of the scorpion Leiurus quinquestriatus hebraeus. It is a 31-residue polypeptide reticulated by three disulfide bridges, i.e. Cys3-Cys21, Cys8-Cys26 and Cys12-Cys28. To investigate the role of these disulfide bridges in the folding of this toxin, analogs lacking one disulfide bridge were synthesized. The structures of two analogs in which two half-cystines were placed by alpha-aminobutyrate residues to suppress one disulfide bridge, were analyzed by 1H NMR. The NMR studies reveal a three-dimensional structure identical with the native toxin for the analog lacking disulfide bridge Cys3-Cys21 and a loss of organized structure for another analog lacking disulfide bridge Cys12-Cys28. These analogs are, respectively, fully active and weakly active (2% of the residual activity) when tested in vitro for their ability to interact with their receptor channel and in vivo for their neurotoxic activity in mice. This suggest that disulfide bridge Cys12-Cys28 is essential for the folding process. In contrast, the lack of disulfide bridge Cys3-Cys21 does not affect the folding and the maintenance of bioactive conformation of Leiurotoxin I.

  10. 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

  11. Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-K(alpha) and pandinustoxin-K(alpha).

    PubMed

    Juhng, K N; Kokate, T G; Yamaguchi, S; Kim, B Y; Rogowski, R S; Blaustein, M P; Rogawski, M A

    1999-04-01

    The scorpion venom peptide toxins tityustoxin-K(alpha) (TsTx-K(alpha)) and pandinustoxin-K(alpha) (PiTx-K(alpha)) are novel, highly potent and selective blockers of voltage-activated K+ channels. PiTx-K(alpha) preferentially blocks rapidly inactivating (A-type) K+ channels whereas TsTx-K(alpha) is selective for slowly inactivating (delayed rectifier-type) channels. K+ channel blockers are known to induce seizures, but the specific K channel types that can serve as convulsant targets are not well defined. To address this issue, we examined for convulsant activity the K+ channel type-specific scorpion toxins and the selective K+ channel antagonists 4-aminopyridine (4-AP), an inhibitor of A-type voltage-activated K+ channels, and paxilline, a selective blocker of large conductance (maxi K) Ca(2+)-activated K+ channels. Intracerebroventricular injection of recombinant TsTx-K(alpha) and PiTx-K(alpha) in mice produced limbic and clonic-tonic seizures. The severity of the seizures increased during the 60-min period following injection, culminating in continuous clonic seizure activity (status epilepticus), tonic hindlimb extension, and eventually in death. The estimated doses producing limbic and clonic seizures in 50% of animals (CD50) for TsTx-K(alpha) and PiTx-K(alpha) were 9 and 33 ng, respectively. 4-AP produced seizure activity similar to the toxins (CD50, 76 ng) whereas paxilline failed to induce seizures at doses up to 13.5 microg. Carbamazepine protected fully against the toxin- and 4-AP-induced seizures whereas phenytoin had variable activity against the clonic component although it was protective against tonic hindlimb extension. The AMPA receptor antagonist GYKI 52466 also conferred full protection against toxin-induced seizures, but the NMDA receptor antagonists (R)-CPP and dizocilpine failed to affect limbic and clonic seizures, although they protected against hindlimb extension. We conclude that selective blockade of delayed rectifier- or A-type voltage

  12. Evidence for the existence of a common ancestor of scorpion toxins affecting ion channels.

    PubMed

    Zhijian, Cao; Yingliang, Wu; Jiqun, Sheng; Wanhong, Liu; Fan, Xiao; Xin, Mao; Hui, Liu; Dahe, Jiang; Wenxin, Li

    2003-01-01

    All scorpion toxins from different 30 species are simply reviewed. A new classification system of scorpion toxins is first proposed: scorpion toxins are classified into three families (long-chain scorpion toxins with 4 disulfide bridges, short-chain scorpion toxins with 3 disulfide bridges, and intermediate-type scorpion toxins with 3 or 4 disulfide bridges). Intermediate-type scorpion toxins provide a strong proof for the conclusion that channel toxins from scorpion venoms evolve from a common ancestor. Common organization of precursor nucleotides and genomic sequence, similar 3-dimensional structure, and the existence of intermediate type scorpion toxins and functionally intercrossing scorpion toxins show that all scorpion toxins affecting ion channels evolve from the common ancestor, which produce millions of scorpion toxins with function-diversity. Copyright 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:235-238, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10083

  13. Role of individual disulfide bridges in the conformation and activity of spinoxin (α-KTx6.13), a potassium channel toxin from Heterometrus spinifer scorpion venom.

    PubMed

    Yamaguchi, Yoko; Peigneur, Steve; Liu, Junyi; Uemura, Shiho; Nose, Takeru; Nirthanan, Selvanayagam; Gopalakrishnakone, Ponnampalam; Tytgat, Jan; Sato, Kazuki

    2016-11-01

    Spinoxin (SPX; α-KTx6.13), isolated from venom of the scorpion Heterometrus spinifer, is a K(+) channel-specific peptide toxin (KTx), which adopts a cysteine-stabilized α/β scaffold that is cross-linked by four disulfide bridges (Cys1-Cys5, Cys2-Cys6, Cys3-Cys7, and Cys4-Cys8). To investigate the role of the individual disulfide bonds in the structure-activity relationship of SPX, we synthesized four SPX analogs in which each pair of cysteine residues was replaced by alanine residues. The analysis of circular dichroism spectra and inhibitory activity against Kv1.3 channels showed that the SPX analogs lacking any of three specific disulfide bonds (Cys1-Cys5, Cys2-Cys6, and Cys3-Cys7) were unable to form the native secondary structure and completely lost inhibitory activities. Thus, we conclude that Cys1-Cys5, Cys2-Cys6, and Cys3-Cys7 are required for the inhibition of the Kv1.3 channel by SPX. In contrast, the analog lacking Cys4-Cys8 retained both native secondary structure and inhibitory activity. Interestingly, one of the isomers of the analog lacking Cys1-Cys5 also showed inhibitory activities, although its inhibition was ∼18-fold weaker than native SPX. This isomer had an atypical disulfide bond pairing (Cys3-Cys4 and Cys7-Cys8) that corresponds to that of maurotoxin (MTX), another α-KTx6 family member. These results indicate that the Cys1-Cys5 and Cys2-Cys6 bonds are important for restricting the toxin from forming an atypical (MTX-type) disulfide bond pairing among the remaining four cysteine residues (Cys3, Cys4, Cys7, and Cys8) in native SPX.

  14. Pi5 and Pi6, two undescribed peptides from the venom of the scorpion Pandinus imperator and their effects on K(+)-channels.

    PubMed

    Olamendi-Portugal, T; Csoti, A; Jimenez-Vargas, J M; Gomez-Lagunas, F; Panyi, G; Possani, L D

    2017-07-01

    This work reports the isolation, chemical and functional characterization of two previously unknown peptides purified from the venom of the scorpion Pandinus imperator, denominated Pi5 and Pi6. Pi5 is a classical K(+)-channel blocking peptide containing 33 amino acid residues with 4 disulfide bonds. It is the first member of a new subfamily, here defined by the systematic number α-KTx 24.1. Pi6 is a peptide of unknown real function, containing only two disulfide bonds and 28 amino acid residues, but showing sequence similarities to the κ-family of K-channel toxins. The systematic number assigned is κ-KTx2.9. The function of both peptides was assayed on Drosophila Shab and Shaker K(+)-channels, as well as four different subtypes of voltage-dependent K(+)-channels: hKv1.1, hKv1.2, hKv1.3 and hKv1.4. The electrophysiological assays showed that Pi5 inhibited Shaker B, hKv1.1, hKv1.2 and hKv1.3 channels with Kd = 540 nM, Kd = 92 nM and Kd = 77 nM, respectively, other studied channels were not affected. Of the channels tested only hKv1.2 and hKv1.3 were inhibited at 100 nM concentration of Pi6, the remaining current fractions were 68% and 77%, respectively. Thus, Pi5 and Pi6 are high nanomolar affinity non-selective blockers of hKv1.2 and hKv1.3 channels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Antibacterial activity of six novel peptides from Tityus discrepans scorpion venom. A fluorescent probe study of microbial membrane Na+ permeability changes.

    PubMed

    Díaz, Patricia; D'Suze, Gina; Salazar, Víctor; Sevcik, Carlos; Shannon, John D; Sherman, Nicholas E; Fox, Jay W

    2009-11-01

    Six novel peptides (named bactridines) were isolated from Tityus discrepans scorpion venom. From mass spectrometry molecular masses were 6916, 7362, 7226, 7011, 7101 and 7173 Da (bactridines 1-6). Bactridines 1 and 2 were sequenced by Edman degradation. The sequences and in silico analysis, indicated that they are positively charged polypeptides comprised of 61 and 64 amino acids (AA), respectively, bactridine 1 and bactridine 2 containing 4 disulfide bridges. Bactridine 1 was only toxic to cockroaches and crabs, and bactridine 2-6 were only toxic to mice. Bactridine 1 has a 78% sequence identity with ardiscretin. Ardisctretin is an insect specific sodium toxin which also produces a small depolarization and induces repetitive firing in squid axons resembling those of DDT [1,10(pchlorobenzyl) 2-trichloretane] in its ability to slow down action potential, to induce repetitive firing. Measured as the minimal inhibitory concentration, bactridines had high antibacterial activity against a wide range of gram positive and gram negative bacteria. Complete bacterial growth inhibition occurred at concentrations from 20 to 80 microM depending on the bacteria and peptide tested. Effects on membrane Na(+) permeability induced by bactridines were observed on Yersinia enterocolitica loaded with 1 microM CoroNa Red. CoroNa Red fluorescence leakage from bacteria was observed after exposure to 0.3 microM of any bactridine tested, indicating that they modified Na(+) membrane permeability. This effect was blocked by 10 microM amiloride and by 25 microM mibefradil drugs that affect Na(+) and Ca(2+) channels respectively. We found no evidence of changes of K(+) or Ca(2+) concentrations neither inside nor outside the bacteria in experiments using the fluorescent dyes Fluo 4AM (10 microM) and PBFI (20 microM).

  16. A high molecular weight protein Bengalin from the Indian black scorpion (Heterometrus bengalensis C.L. Koch) venom having antiosteoporosis activity in female albino rats.

    PubMed

    Haldar, Subhash; Das Gupta, Shubho; Gomes, Aparna; Giri, Biplab; Dasgupta, Subir Chandra; Biswas, Ajay; Mishra, Roshnara; Gomes, Antony

    2010-01-01

    This study reports the presence of a high molecular weight protein (Bengalin) from the Indian black scorpion (Heterometrus bengalensis) venom having antiosteoporosis activity in experimental osteoporosis developed in female albino Wister rats. Bengalin was purified through DEAE-cellulose ion exchange chromatography and high performance liquid chromatography. The molecular weight of the Bengalin was found to be 72kDa and the first 20 amino acid sequence was found to be G-P-L-T-I-L-H-I-N-D-V-H-A-A/R-F-E-Q/G-F/G-N-T. Bengalin exhibited significant antiosteoporosis activity in experimental female rats, which was confirmed through analysis of urine Ca(2+), PO(4)(3-), CRE & OH-P. Bengalin (3 microg and 5 microg/100g rat/i.p.) antagonized osteoporosis by restoring urinary Ca(2+), PO(4)(3-), CRE and OH-P, serum/plasma Ca(2+), PO(4)(3-), ALP, TRAP, PTH, T(3), TSH, Osteocalcin, IL1, IL6 and TNF alpha and bone minerals Ca(2+), P, Mg(2+), Zn(2+), Na(+), as compared with the sham operated control rats. Bone minerals density of osteoporosis female rats was improved due to Bengalin, observed through DEXA scan. Subacute toxicity studies in male albino mice, Bengalin showed cardiotoxicity. In vivo experiments, Bengalin showed cardiotoxicity on isolated guinea pig heart, guinea pig auricle, and neurotoxicity on isolated rat phrenic nerve diaphragm preparation. Further detail studies on the toxicity, antiosteoporosis and structural identity of Bengalin are warranted. Copyright 2009 Elsevier Ltd. All rights reserved.

  17. Solution structure of native and recombinant expressed toxin CssII from the venom of the scorpion Centruroides suffusus suffusus, and their effects on Nav1.5 sodium channels.

    PubMed

    Saucedo, Alma L; del Rio-Portilla, Federico; Picco, Cristiana; Estrada, Georgina; Prestipino, Gianfranco; Possani, Lourival D; Delepierre, Muriel; Corzo, Gerardo

    2012-03-01

    The three-dimensional structures of the long-chain mammalian scorpion β-toxin CssII from Centruroides suffusus suffusus and of its recombinant form, HisrCssII, were determined by NMR. The neurotoxin CssII (nCssII) is a 66 amino acid long peptide with four disulfide bridges; it is the most abundant and deadly toxin from the venom of this scorpion. Both native and recombinant CssII structures were determined by nuclear magnetic resonance using a total of 828 sequential distance constraints derived from the volume integration of the cross peaks observed in 2D NOESY spectra. Both nCssII and HisrCssII structures display a mixed α/β fold stabilized by four disulfide bridges formed between pairs of cysteines: C1-C8, C2-C5, C3-C6, and C4-C7 (the numbers indicate the relative positions of the cysteine residues in the primary structure), with a distortion induced by two cis-prolines in its C-terminal part. The native CssII electrostatic surface was compared to both the recombinant one and to the Cn2 toxin, from the scorpion Centruroides noxius, which is also toxic to mammals. Structural features such N- and C-terminal differences could influence toxin specificity and affinity towards isoforms of different sub-types of Na(v) channels.

  18. Amino acid sequence of TsTX-V, an alpha-toxin from Tityus serrulatus scorpion venom, and its effect on K+ permeability of beta-cells from isolated rat islets of Langerhans.

    PubMed

    Marangoni, S; Toyama, M H; Arantes, E C; Giglio, J R; da Silva, C A; Carneiro, E M; Gonçalves, A A; Oliveira, B

    1995-04-13

    Highly purified Tityustoxin V (TsTX-V), an alpha-toxin isolated from the venom of the Brazilian scorpion Tityus serrulatus, was obtained by ion exchange chromatography on carboxymethylcellulose-52. It was shown to be homogeneous by reverse phase high performance liquid chromatography, N-terminal sequencing (first 39 residues) of the reduced and alkylated protein and by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate and tricine. Following enzymatic digestion, the complete amino acid sequence (64 residues) was determined. The sequence showed higher homology with the toxins from the venoms of the North African than with those of the North and South American scorpions. Using the rate of 86Rb+ release from depolarized rat pancreatic beta-cells as a measure of K+ permeability changes, TsTX-V (5.6 micrograms/ml) was found to increase by 2.0-2.4-fold the rate of marker outflow in the presence of 8.3 mM glucose. This effect was persistent and slowly reversible, showing similarity to that induced by 100 microM veratridine, an agent that increases the open period of Na+ channels, delaying their inactivation. It is suggested that, by extending the depolarized period, TsTX-V indirectly affects beta-cell voltage-dependent K+ channels, thus increasing K+ permeability.

  19. Heterologous expressed toxic and non-toxic peptide variants of toxin CssII are capable to produce neutralizing antibodies against the venom of the scorpion Centruroides suffusus suffusus.

    PubMed

    Hernández-Salgado, Kenya; Estrada, Georgina; Olvera, Alejandro; Coronas, Fredy I; Possani, Lourival D; Corzo, Gerardo

    2009-08-15

    Two toxic and one non-toxic recombinant peptide variants of the mammalian neurotoxin CssII was cloned into the expression vector pQE30 containing a 6His-tag and a Factor Xa proteolytic cleavage site. The toxic recombinant peptides rCssII, HisrCssII and the non-toxic rCssIIE15R were expressed under induction with isopropyl thiogalactoside (IPTG), isolated using chromatographic techniques and folded correctly in vitro. The three recombinant variants showed similar secondary structures as the native CssII, but only the rCssIIE15R was not toxic to mice at concentrations up to 30microg/20g mouse body weight when injected intraperitoneally. All three recombinant peptides were capable of displacing the native CssII from their receptor sites in rat brain synaptosomes, suggesting that they had similar structural and functional characteristics of the native peptides. The three recombinant variants of CssII and the native one were used as antigens for immunization of New Zealand rabbits. The antibodies present in the rabbit antisera were able to recognize the native CssII. Additionally and more importantly, the sera of the immunized rabbits were able to neutralize both the native toxin CssII and the whole soluble venom of the scorpion Centruroides suffusus suffusus. These results indicate that the recombinant peptides can be used to produce antidotes against the venom of this species of scorpion.

  20. Purification and pharmacological characterization of BmKK2 (alpha-KTx 14.2), a novel potassium channel-blocking peptide, from the venom of Asian scorpion Buthus martensi Karsch.

    PubMed

    Li, Ming-Hua; Zhang, Nai-Xia; Chen, Xue-Qin; Wu, Gong; Wu, Houming; Hu, Guo-Yuan

    2004-06-15

    BmKK2 (alpha-KTx 14.2) is one of the novel short-chain peptides found in molecular cloning of a venom gland cDNA library from Asian scorpion Buthus martensi Karsch. Based upon its amino acid sequence, the peptide was proposed to adopt a classical alpha/beta-scaffold for alpha-KTxs. In the present study, we purified BmKK2 from the venom of B. martensi Karsch, and investigated its action on voltage-dependent K+ currents in dissociated hippocampal neurons from neonatal rats. BmKK2 (10-100 microM) selectively inhibited the delayed rectifier K+ current, but did not affect the fast transient K+ current. The inhibition of BmKK2 on the delayed rectifier K+ current was reversible and voltage-independent. The peptide did not affect the steady-state activation of the current, but caused a depolarizing shift (about 9 mV) of its steady-state inactivation curve. The results demonstrate that BmKK2 is a novel K+ channel-blocking scorpion peptide.

  1. Macrophage alteration induced by inflammatory toxins isolated from Tityus discrepans scorpion venom. The role of Na(+)/Ca(2+) exchangers.

    PubMed

    Ramírez-Bello, Vanesa; Sevcik, Carlos; Peigneur, Steve; Tytgat, Jan; D'Suze, Gina

    2014-05-01

    We study the effect of all Tityus discrepans venom components on macrophage alterations. Only seven toxins called "Inflammatory Toxin" (InfTx1-7) induced cell changes. Incubation with InfTx1 through InfTx5 rose macrophage NO level at 2 h toxin exposure. Cells rose NO release by 4 h exposure with InfTx2 and InfTx5, the NO levels reached concentrations similar or higher than the induced by lipopolysaccharides (LPS) incubation. InfTx2, -6 and -7 increased cell TNF-α release. InfTx2 as LPS roses cell TNF-α secretion gradually in time. Macrophages were loaded with fluorescent dyes, exposed to all toxins and observed with a 3D wide field deconvolution setup. Cells exposed to whole venom or InfTx4 through InfTx7 developed pseudopodia, cytoplasm prolongations, blebs, and loss their rounded form. The molecular masses and N-terminal sequences of InfTx4 through InfTx7 were analyzed by MALDI-TOF mass spectrometry and Edman degradation. InfTx4-7 induced a remarkable increase of intracellular Ca(2+) levels ([Ca(2+)]i), measured as a rise of normalized cell green fluorescence intensity (FI) ×2.7, ×2.6, ×95 and ×2.9 the controls, respectively. InfTx6-7 action mechanisms were studied under different conditions. Results suggested that InfTx6 interact with a membrane sodium channel inducing cell depolarization with a consequent increase on intracellular [Na(+)], this would activate Na(+)/Ca(2+) exchanger 3 (NCX) in the reverse mode and the phospholipase C inositol 1,4,5-trisphosphate (PLC-IP3) signaling pathway inducing [Ca(2+)]i overload. Inftx7 should activate the NCX in reverse mode and/or should activate the Na(+)/H(+) exchanger, increasing intracellular [Na(+)] which indirectly induce the activation of NCX3rv and the PLC-IP3 signaling pathway. All these mechanisms would cooperate with the [Ca(2+)]i overload. A rise of [Ca(2+)]i activates the synthesis and secretion of inflammatory molecules like TNF-α, which in turn, increases the gene transcription for inducible nitric

  2. [Scorpion envenomation in Morocco: scorpions of the genus Androctonus, Buthus and Hottentota].

    PubMed

    Aboumaâd, B; Iba, N; Dersi, N

    2014-02-01

    Around the world and especially in summer, the scorpion envenomation is a real public health problem. In Morocco, its gravity is due to the diversity of genera of the Buthidae family whose their venom is potentially lethal, mainly the genus Androctonus, Buthus and Hottentota. The areas most affected by this problematic are the central and southern of Morocco. The lethality of scorpion's venom primarily affects children. It is rich in neurotoxic polypeptides that have targeted ion channel membrane Na(+), K(+) activated or not by Ca(++). The toxins polymorphism causes pathophysiological disorders. The diversity of symptomatic treatment in the absence of immunotherapy is due to variability in clinical pictures, which depends on the species involved and the patient at risk. The objective of this review is to highlight the magnitude of the scorpion envenomation by describing its epidemiological characteristics, elucidate the pathophysiological effects of the venom of the most dangerous scorpions in Morocco the genus Androctonus, Buthus and Hottentota, and their therapeutic treatment.

  3. Homology modeling, vasorelaxant and bradykinin-potentiating activities of a novel hypotensin found in the scorpion venom from Tityus stigmurus.

    PubMed

    Machado, Richele J A; Junior, Leônidas G M; Monteiro, Norberto K V; Silva-Júnior, Arnóbio A; Portaro, Fernanda C V; Barbosa, Euzébio G; Braga, Valdir A; Fernandes-Pedrosa, Matheus F

    2015-07-01

    In a recent work by our group involving a transcriptomics approach applied to the venom glands from Tityus stigmurus we identified a new family of peptides called Hypotensins (TSTI0006C) (Almeida et al., 2012). The cluster TSTI0006C was analyzed in the main 25 amino acid residues and named T. stigmurus Hypotensin (TistH), showing a molecular mass of 2.7 kDa, an absence of cysteines and the presence of two C-terminal proline residues, which are a bradykinin-potentiating peptide (BPP) signature. Here, we describe the homology modeling of the three-dimensional structure of TistH. In addition, we evaluated the cardiovascular effects elicited by TistH in normotensive rats. Firstly, TistH showed no cytotoxic effect on horse erythrocyte. Furthermore, in normotensive rats TistH was able to potentiate the hypotensive action of bradykinin (BK) and induced a vasorelaxant effect in mesenteric artery rings by endothelium-dependent release of nitric oxide (NO) and demonstrated independent inhibition of angiotensin converting enzyme (ACE). Our data can contribute to a better understanding of the structural and functional characteristics of TistH and suggest its potential use in cardiovascular diseases.

  4. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. 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

  6. 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

  7. Scorpion bite, a sting to the heart!

    PubMed Central

    Agrawal, Avinash; Kumar, Anand; Consul, Shuchi; Yadav, Ambuj

    2015-01-01

    Scorpion bites are common in India. Usually, these bites are harmless but sometimes have serious clinical sequelae, including death. We report herein a case of scorpion bite with electrocardiographic abnormalities simulating early myocardial infarction. Pulmonary edema and congestive heart failure accompanied these electrocardiographic changes as well as serum cardiac markers. The etiology of cardiovascular manifestations in severe scorpion sting is related to venom effect on sympathetic nervous system and the adrenal secretion of catecholamines as well as to the toxic effect of the venom on the myocardium itself. It is a rare case of scorpion sting presented as myocardial infarction and heart failure, successfully treated with Intensive Care Unit care, noninvasive ventilation, vasopressors, and antiischemic treatment. PMID:25878433

  8. A strategy for the generation of specific human antibodies by directed evolution and phage display. An example of a single-chain antibody fragment that neutralizes a major component of scorpion venom.

    PubMed

    Riaño-Umbarila, Lidia; Juárez-González, Victor Rivelino; Olamendi-Portugal, Timoteo; Ortíz-León, Mauricio; Possani, Lourival Domingos; Becerril, Baltazar

    2005-05-01

    This study describes the construction of a library of single-chain antibody fragments (scFvs) from a single human donor by individual amplification of all heavy and light variable domains (1.1 x 10(8) recombinants). The library was panned using the phage display technique, which allowed selection of specific scFvs (3F and C1) capable of recognizing Cn2, the major toxic component of Centruroides noxius scorpion venom. The scFv 3F was matured in vitro by three cycles of directed evolution. The use of stringent conditions in the third cycle allowed the selection of several improved clones. The best scFv obtained (6009F) was improved in terms of its affinity by 446-fold, from 183 nm (3F) to 410 pm. This scFv 6009F was able to neutralize 2 LD(50) of Cn2 toxin when a 1 : 10 molar ratio of toxin-to-antibody fragment was used. It was also able to neutralize 2 LD(50) of the whole venom. These results pave the way for the future generation of recombinant human antivenoms.

  9. A forward to optimization of antivenom therapy: An in vivo study upon the effectiveness of the antivenom against early and delayed nephrotoxicity induced by the venom of the Iranian scorpion Hemiscorpius lepturus in rat.

    PubMed

    Pipelzadeh, Mohammad Hassan; Jalali, Amir; Dezfulian, Abdul Rahman; Khorasgani, Zahra Nazari; Sarvestani, Somie; Ghalambor, Amir Hossein; Azarpanah, Armita

    2015-06-15

    The aim of the present in vivo study was to identify the optimal effective dose, the most favorable time and the route of administration of the available polyvalent scorpion antivenom against the toxic effects induced by Hemiscorpius lepturus (H. lepturus) venom in rat. The end point for assessment included measurement of alanin-amino-peptidase (AAP) and N-acetyl-b-d-glucosaminidase (NAG), biochemical urine analysis and histopathological assessment. The results showed that a single subcutaneous 50 μg of the venom produced significant increase in the AAP and NAG enzyme activity, urinary biochemical parameters and induced histopathological structural abnormalities in the renal system. The optimal effective co-administered dose of the antivenom was 0.5 ml, which when administered 1 and 2 h of envenomation by intravenous (IV) and subcutaneous (SC) routes respectively produced significant protection against these toxic effects. Prudently, the significance of these findings need to be assessed in further clinical studies.

  10. IgY antibodies anti-Tityus caripitensis venom: purification and neutralization efficacy.

    PubMed

    Alvarez, Aurora; Montero, Yuyibeth; Jimenez, Eucarys; Zerpa, Noraida; Parrilla, Pedro; Malavé, Caridad

    2013-11-01

    Tityus caripitensis is responsible for most of scorpion stings related to human incidents in Northeastern Venezuela. The only treatment for scorpion envenomation is immunotherapy based on administration of scorpion anti-venom produced in horses. Avian antibodies (IgY) isolated from chicken egg yolks represent a new alternative to be applied as anti-venom therapy. For this reason, we produced IgY antibodies against T. caripitensis scorpion venom and evaluated its neutralizing capacity. The anti-scorpion venom antibodies were purified by precipitation techniques with polyethylene glycol and evaluated by Multiple Antigen Blot Assay (MABA), an indirect ELISA, and Western blot assays. The lethality neutralization was evaluated by preincubating the venom together with the anti-venom prior to testing. The IgY immunoreactivity was demonstrated by a dose-dependent inhibition in Western blot assays where antibodies pre-absorbed with the venom did not recognize the venom proteins from T. caripitensis. The anti-venom was effective in neutralizing 2LD50 doses of T. caripitensis venom (97.8 mg of IgY neutralized 1 mg of T. caripitensis venom). Our results support the future use of avian anti-scorpion venom as an alternative to conventional equine anti-venom therapy in our country. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Toxicity of crude and detoxified Tityus serrulatus venom in anti-venom-producing sheep

    PubMed Central

    Ferreira, Marina G.; Duarte, Clara G.; Oliveira, Maira S.; Castro, Karen L. P.; Teixeira, Maílson S.; Reis, Lílian P. G.; Zambrano, José A.; Kalapothakis, Evanguedes; Michel, Ana Flávia R. M.; Soto-Blanco, Benito; Chávez-Olórtegui, Carlos

    2016-01-01

    Specific anti-venom used to treat scorpion envenomation is usually obtained from horses after hyperimmunization with crude scorpion venom. However, immunized animals often become ill because of the toxic effects of the immunogens used. This study was conducted to evaluate the toxic and immunogenic activities of crude and detoxified Tityus serrulatus (Ts) venom in sheep during the production of anti-scorpionic anti-venom. Sheep were categorized into three groups: G1, control, immunized with buffer only; G2, immunized with crude Ts venom; and G3, immunized with glutaraldehyde-detoxified Ts venom. All animals were subjected to clinical exams and supplementary tests. G2 sheep showed mild clinical changes, but the other groups tolerated the immunization program well. Specific antibodies generated in animals immunized with either Ts crude venom or glutaraldehyde-detoxified Ts venom recognized the crude Ts venom in both assays. To evaluate the lethality neutralization potential of the produced sera, individual serum samples were pre-incubated with Ts crude venom, then subcutaneously injected into mice. Efficient immune protection of 56.3% and 43.8% against Ts crude venom was observed in G2 and G3, respectively. Overall, the results of this study support the use of sheep and glutaraldehyde-detoxified Ts venom for alternative production of specific anti-venom. PMID:27297422

  12. Toxicity of crude and detoxified Tityus serrulatus venom in anti-venom-producing sheep.

    PubMed

    Ferreira, Marina G; Duarte, Clara G; Oliveira, Maira S; Castro, Karen L P; Teixeira, Maílson S; Reis, Lílian P G; Zambrano, José A; Kalapothakis, Evanguedes; Michel, Ana Flávia R M; Soto-Blanco, Benito; Chávez-Olórtegui, Carlos; Melo, Marília M

    2016-12-30

    Specific anti-venom used to treat scorpion envenomation is usually obtained from horses after hyperimmunization with crude scorpion venom. However, immunized animals often become ill because of the toxic effects of the immunogens used. This study was conducted to evaluate the toxic and immunogenic activities of crude and detoxified Tityus serrulatus (Ts) venom in sheep during the production of anti-scorpionic anti-venom. Sheep were categorized into three groups: G1, control, immunized with buffer only; G2, immunized with crude Ts venom; and G3, immunized with glutaraldehyde-detoxified Ts venom. All animals were subjected to clinical exams and supplementary tests. G2 sheep showed mild clinical changes, but the other groups tolerated the immunization program well. Specific antibodies generated in animals immunized with either Ts crude venom or glutaraldehyde-detoxified Ts venom recognized the crude Ts venom in both assays. To evaluate the lethality neutralization potential of the produced sera, individual serum samples were pre-incubated with Ts crude venom, then subcutaneously injected into mice. Efficient immune protection of 56.3% and 43.8% against Ts crude venom was observed in G2 and G3, respectively. Overall, the results of this study support the use of sheep and glutaraldehyde-detoxified Ts venom for alternative production of specific anti-venom.

  13. 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

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

    PubMed

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

    2014-12-19

    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.

  15. 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.

  16. Epidemiological Review of Scorpion Envenomation in Iran

    PubMed Central

    Jalali, Amir; Rahim, Fakher

    2014-01-01

    This epidemiological review was carried out to display the magnitude and the geographic distribution of scorpion envenomation in Iran with focus on the southwestern region of Iran, particularly. The Iranian recognized scorpions belonging to two families, including Buthidae and Scorpionidae. Buthidae family consists of 14 genuses, 26 species, and 18 sub-species, while Scorpionidae family has three genuses and four species. The lack of basic knowledge, including the geographical distribution, clinical manifestations, and specific treatments related to scorpiofauna justifies such multidisciplinary studies. The venom of two endemic Iranian scorpions, including Hemiscorpius lepturus (H. lepturus) and Odonthubuthus doriae (O.doriae) have considered as an effective source of new neurotoxin peptides for the further development of physio-pharmacological probes and designing the clinical trials. Such epidemiological information may improve the determinants of Iranian scorpion stings in order to plan and implement effective public health intervention. PMID:25276176

  17. 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.

  18. Epidemiological review of scorpion envenomation in iran.

    PubMed

    Jalali, Amir; Rahim, Fakher

    2014-01-01

    This epidemiological review was carried out to display the magnitude and the geographic distribution of scorpion envenomation in Iran with focus on the southwestern region of Iran, particularly. The Iranian recognized scorpions belonging to two families, including Buthidae and Scorpionidae. Buthidae family consists of 14 genuses, 26 species, and 18 sub-species, while Scorpionidae family has three genuses and four species. The lack of basic knowledge, including the geographical distribution, clinical manifestations, and specific treatments related to scorpiofauna justifies such multidisciplinary studies. The venom of two endemic Iranian scorpions, including Hemiscorpius lepturus (H. lepturus) and Odonthubuthus doriae (O.doriae) have considered as an effective source of new neurotoxin peptides for the further development of physio-pharmacological probes and designing the clinical trials. Such epidemiological information may improve the determinants of Iranian scorpion stings in order to plan and implement effective public health intervention.

  19. Experimental envenoming of mice with venom from the scorpion Centruroides limpidus limpidus: differences in mortality and symptoms with and without antibody therapy relating to differences in age, sex and strain of mouse.

    PubMed

    Padilla, Alejandro; Govezensky, Tzipe; Possani, Lourival D; Larralde, Carlos

    2003-06-01

    C57Bl/6J and BALB/cAnN inbred strains of mice differed significantly in mortality and symptoms when intoxicated subcutaneously with one LD(50) of venom from Centruroides limpidus limpidus. Higher mortality was observed in C57Bl/6J than in BALB/cAnN. Also, C57Bl/6J mice more quickly developed muscular and respiratory collapse whilst BALB/cAnN mice were hyperactive before dying. Also, the symptoms in the survivors lasted for 24 h in C57Bl/6J and for 2 h in BALB/cAnN. The age and sex of mice were also related to mortality: younger mice were more resistant than older mice and females were more susceptible than males, especially in the younger groups. Antivenom (horse F(ab')(2)) administration 5-10 min after envenoming of mice with one LD(50) rescued 60% of BALB/cAnN and 52% of C57Bl/6J mice, respectively. Results indicate that genetic background, gender and age differences are of consequence in the pathogenesis of C. limpidus scorpion envenomation in mice, and that timely treatment with active antivenom F(ab')(2) saves a significant fraction of intoxicated mice without statistically significant distinction of strains.

  20. Photoaffinity labeling of alpha- and beta- scorpion toxin receptors associated with rat brain sodium channel.

    PubMed

    Darbon, H; Jover, E; Couraud, F; Rochat, H

    1983-09-15

    Azido nitrophenylaminoacetyl [125I]iodo derivative of toxin II from Centruroides suffusus suffusus, a beta-toxin, and azido nitrophenylaminoacetyl [125I]iodo derivative of toxin V from Leiurus quinquestriatus quinquestriatus, an alpha-toxin, have been covalently linked after binding to their receptor sites that are related to the voltage sensitive sodium channel present in rat brain synaptosomes. Both derivatives labeled two polypeptides of 253000 +/- 20000 and 35000 +/- 2000 mol. wt. Labeling was blocked for each derivative by a large excess of the corresponding native toxin but no cross inhibition was obtained. These results suggest that both alpha - and beta - scorpion toxin receptors are located on or near the same two membrane polypeptides which may be part of the voltage dependent sodium channel.

  1. Updating knowledge on new medically important scorpion species in Mexico.

    PubMed

    Riaño-Umbarila, Lidia; Rodríguez-Rodríguez, Everardo R; Santibañez-López, Carlos E; Güereca, Leopoldo; Uribe-Romero, Selene J; Gómez-Ramírez, Ilse V; Cárcamo-Noriega, Edson N; Possani, Lourival D; Becerril, Baltazar

    2017-11-01

    The increment in the number of scorpion envenoming cases in Mexico is mainly associated to the rapid growth of the urban areas, and consequently, to the invasion of natural habitats of these arachnids. On the other hand, there is a great diversity of scorpion species, so it is indispensable to identify those of medical importance, which we now know are many more than the 7-8 previously reported as dangerous to humans. Because different LD50 values have been reported for the venom of the same species, probably due to variations in the experimental conditions used, in this work we determined the LD50 values for the venoms of 13 different species of scorpions using simple but systematic procedures. This information constitutes a referent on the level of toxicity of medically important scorpion species from Mexico and establishes the bases for a more comprehensive assessment of the neutralizing capacity of current and developing antivenoms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. A novel toxin from the venom of the scorpion Tityus trivittatus, is the first member of a new alpha-KTX subfamily.

    PubMed

    Abdel-Mottaleb, Yousra; Coronas, Fredy V; de Roodt, Adolfo R; Possani, Lourival D; Tytgat, Jan

    2006-01-23

    The first example of a new sub-family of toxins (alpha-KTx20.1) from the scorpion Tityus trivittatus was purified, sequenced and characterized physiologically. It has 29 amino acid residues, three disulfide bridges assumed to adopt the cysteine-stabilized alpha/beta scaffold with a pI value of 8.98. The sequence identities with all the other known alpha-KTx are less than 40%. Its effects were verified using seven different cloned K(+) channels (vertebrate Kv1.1-1.5, Shaker IR and hERG) expressed in Xenopus leavis oocytes. The toxin-induced effects show large differences among the different K(+) channels and a preference towards Kv1.3 (EC50=7.9+/-1.4 nM).

  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. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  4. 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

    2015-01-23

    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.

  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 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

  6. 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.

  7. Bilateral cerebellar infarction: a rare complication of scorpion sting.

    PubMed

    Gadwalkar, S R; Bushan, S; Pramod, K; Gouda, Chandra; Kumar, P M

    2006-07-01

    Complications following scorpion sting are common in India and can be fatal. Stroke following scorpion sting is a rare complication and can occur by various mechanisms such as hypertension, hypotension, DIC, myocarditis and venom-induced vasculitis. We present a rare case of extensive cerebellar infarction following scorpion sting, which has rarely been reported in medical literature. To study the clinical profile of two patients presenting with an acute onset of cerebellar symptoms following a scorpion sting. To evaluate the possible causes of the stroke and to study the relation of their symptoms to the scorpion sting. Two young women presented with a history of acute onset of dysarthria, ataxia and incoordination following scorpion sting. They did not have any known risk factors for stroke. They had cerebellar type of dysarthria and cerebellar signs on both sides along with incoordination. A CT-scan of the brain showed bilateral extensive cerebellar infarctions. They were investigated for other causes of stroke without any positive results. With treatment the patients made a gradual but complete recovery. Since there was no evidence of hypertension, hypotension, myocarditis or disseminated intravascular coagulation, we can conclude that the patients had suffered a thrombotic stroke caused by the vasculotoxic action of the scorpion venom.

  8. 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

    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.

  9. Target-Driven Evolution of Scorpion Toxins.

    PubMed

    Zhang, Shangfei; Gao, Bin; Zhu, Shunyi

    2015-10-07

    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.

  10. 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

  11. Global transcriptome analysis of the scorpion Centruroides noxius: new toxin families and evolutionary insights from an ancestral scorpion species.

    PubMed

    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

  12. Solution structure of BmKalphaIT01, an alpha-insect toxin from the venom of the Chinese scorpion Buthus martensii Karsch.

    PubMed

    Tong, Xiaotian; Zhu, Jing; Ma, Yuguang; Chen, Xiang; Wu, Gong; He, Fahu; Cao, Chunyang; Wu, Houming

    2007-10-09

    The solution structure of an alpha-insect toxin from Buthus martensii Karsch, BmKalphaIT01, has been determined by two-dimensional NMR spectroscopy and molecular modeling techniques. Combining the sequence homology comparison and toxicity bioassays, BmKalphaIT01 has been suggested to be a natural mutant of alpha-insect toxins and so can serve as a tool to study the relationship of structure-function among this group of toxins. The overall structure of BmKalphaIT01 shares a common core structure consisting of an alpha-helix packed against a three-stranded antiparallel beta-sheet, which exhibits distinctive local conformations within the loops connecting these secondary structure elements. The solution structure of BmKalphaIT01 features a non-proline cis peptide bond between Asn9 and Tyr10, which is proposed to mediate the spatial closing of the five-residue turn (Gln8-Cys12) and the C-terminal segment (Arg58-His64) to form the NC domain and confer the toxin insect-specific bioactivity. Conformational heterogeneity is observed in the solution of BmKalphaIT01 and could be attributed to the cis-trans isomerization of the peptide bond between residues 9 and 10. The minor conformation of BmKalphaIT01 with a trans peptide bond between Asn9 and Tyr10 may be responsible for its moderate bioactivity against mammals. The cis-trans isomerization of the peptide bond between residues 9 and 10 may be the structural basis of dual pharmacological activities of alpha-insect and alpha-like scorpion toxins, which is supported by the fact that conformational heterogeneity occurs in the solution structures of LqhalphaIT, LqqIII, and LqhIII and by comparison of the solution structure of BmKalphaIT01 with those of some relevant alpha-type toxins.

  13. Animal venoms as antimicrobial agents.

    PubMed

    Perumal Samy, Ramar; Stiles, Bradley G; Franco, Octavio L; Sethi, Gautam; Lim, Lina H K

    2017-06-15

    Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 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

  15. Efficacy of serotherapy in scorpion sting: a matched-pair study.

    PubMed

    Belghith, M; Boussarsar, M; Haguiga, H; Besbes, L; Elatrous, S; Touzi, N; Boujdaria, R; Bchir, A; Nouira, S; Bouchoucha, S; Abroug, F

    1999-01-01

    Although evidence of scorpion antivenin effectiveness in the clinical setting is lacking, scorpion antivenin is generally considered the only specific treatment for scorpion sting irrespective of its clinical severity. We conducted a matched-pair study to assess the efficacy of systematic administration of scorpion antivenin. Among 600 stung patients who participated in a study on the efficacy of high-dose hydrocortisone after scorpion sting, 135 (cases) had been treated with 10 to 20 mL intravenous scorpion antivenin (neutralizing 10 LD50 venom/mL). Controls were matched on disease severity on arrival to the emergency department. The severity of envenomation was graded I or II according to the absence (grade I) or the presence (grade II) of systemic manifestations of scorpion envenomation. Assessment of scorpion antivenin efficacy was based on the rate of changing severity grade in both groups (clinical improvement or worsening during an observation period of at least 4 hours). Both groups were similar with respect to clinical severity (36 patients were graded II in each group), age, sex, time-lapse between scorpion sting and ED arrival, and the administration of adjunctive therapy such as hydrocortisone. By the 4-hour evaluation, 50% and 64% of patients initially graded II exhibited a substantial clinical improvement in cases and controls, respectively, suggesting similar effects in cases and controls. There was no difference in preventive effects: 13% and 10% of cases and controls developed systemic manifestations of scorpion envenomation during the 4-hour observation period; 23% of cases and 17% controls were hospitalized by this time. There was no difference in the duration of hospitalization. Three cases developed anaphylactic shock as a consequence of scorpion antivenin administration, while 1 scorpion antivenin-untreated patient died from refractory shock. Systematic administration of scorpion antivenin irrespective of clinical severity did not alter the

  16. Study on Distribution of Scorpions to Provide Prevention and Interventions in Combating Scorpionism in Poldokhtar County, Lorestan Province, Iran.

    PubMed

    Nazari, Mansour; Hassan, Rastgar

    2016-12-01

    Scorpions are arthropods of medical importance classified in the class Arachnida, inhabiting hot and dry environments. All scorpions have a venomous sting and several thousand people die each year from scorpion stings, but this mortality is due to the venom of about 25 species located in northern Africa, the Middle East, India, Mexico and parts of South America. Poldokhtar County belongs to one of the southern cities of Lorestan Province, providing suitable habitats for many different species of scorpions due to its specific climatic conditions. To examine the fauna of scorpion and its distribution in the Poldokhtar County and to provide appropriate preventive and medical interventions in combating scorpionism. This present study was a descriptive and analytical cross-sectional study. This study was conducted from April 2014 to November 2014 in regions of Poldokhtar County, Lorestan Province, and west of Iran. Cluster sampling methodology was employed in the sampling and scorpion collection procedure. Sampling was undertaken for an eight-month period, in villages and districts, namely, Myankuhe sharqi, Jayedar, Jelogir and Malavi within the county. The Chi-square test and the Fisher-exact test for homogeneity of proportions were used to compare quantitative variables. Totally, 393 specimens were captured entailing 193 (49.1%) males and 200 (50.9%) females. There were at least seven species of scorpions belonging to three families; BU= Buthidae, HE = Hemiscorpiidae, SCN = Scorpionidae in Poldokhtar. Out of 393 collected scorpions, seven species, Androctonus crassicauda, Hottentotta (Buthotus) saulcyi, Compsobuthus matthiesseni, Compsobuthus rugosulus, Orthochirus scrobiculosus, Scorpio maurus and Hemiscorpius lepturus were identified. The overall sex ratio of females to males was 1:1.03. It is crucial to improve the knowledge of residents in this region regarding preventive methods towards scorpion stinging. All the known dangerous Iranian scorpions having medical

  17. [Spatial distribution of scorpion stings in Ponta Grossa, Paraná State, Brazil].

    PubMed

    Kotviski, Bianca Mayara; Barbola, Ivana de Freitas

    2013-09-01

    Among all bites and stings by venomous animals, scorpion stings have increased significantly in urban areas all over Brazil. Considering that Ponta Grossa is the city in Paraná State with the highest incidence of reported scorpion stings, the current study aimed to assess trends in scorpion stings based on notification records and complaints from January 2008 to December 2010. The geographic coordinates of addresses with reported scorpion stings were collected, digitized, and spatialized, resulting in a cartogram of the georeferenced scorpion stings in the city. The incidence coefficients for this period showed that Ponta Grossa had 113.3 cases per 100,000 inhabitants, and that Colônia Dona Luiza, Neves, and Chapada were the neighborhoods with the highest rates. Investigation of determinants of scorpion stings used visual and statistical analysis, indicating wooded or green areas, water mains, and the sewer system as the main correlated variables.

  18. Epidemiological characteristics of scorpion sting in León, Guanajuato, México.

    PubMed

    Dehesa-Dávila, M

    1989-01-01

    Poisoning with scorpion venom in the city of León, Guanajuato state, México, is a significant public health problem. The hospital of the Mexican Red Cross gave medical attention to 38,068 cases of envenomation by scorpion sting during 1981-1986; 77% of all accidents occurred among persons under 30 years of age. The 100% survival rate can be attributed to prompt serotherapy. Most stings were due to scorpions from the species Centruroides infamatus infamatus. Scorpion stings increase dramatically in the spring and are lowest during winter. The distribution of scorpions throughout the city is uniform and accidents occur at any time of day or night with no preference in regard to the sex of the affected persons. The epidemiological aspects of scorpion poisoning are emphasized.

  19. [Fifteen years' experience in scorpion envenomation control in Algeria].

    PubMed

    Benguedda, A C; Laraba-Djébari, F; Ouahdi, M; Hellal, H; Griene, L; Guerenik, M; Laid, Y

    2002-08-01

    In Algeria, scorpion envenomation is real public health problem. Since the creation of the National Committee of Control of Scorpion envenomations (CNLES), several steps have been taken to deal with this problem. After a brief historical introduction, we present the main elements of the action carried out both in terms of treatment and of prevention of scorpion proliferation. The epidemiological situation is presented by stressing the difficulties involved in collecting reliable data. We also address the question of citizen and stakeholder awareness since public participation is crucial in all prevention programmes. Training for healthcare providers is also one of the principal axes of the Committee's programme which includes national, regional, and even local seminars. We describe the improvement of production and research on venoms carried out by the Institute Pasteur of Algeria. We conclude by discussing the action plan for 2001 and prospects for an enhanced strategy in the fight against the scorpion envenomation.

  20. Evolution stings: the origin and diversification of scorpion toxin peptide scaffolds.

    PubMed

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

    2013-12-13

    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

  1. 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

  2. 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

    2015-09-14

    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.

  3. 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

  4. Emergent management of scorpion sting.

    PubMed

    Kluz-Zawadzka, Jolanta; Hartman-Ksycińska, Anna; Lewandowski, Bogumił

    2014-01-01

    Scorpionism (syndrome of scorpion stings) is an important public health problem in many regions of the world, not only in tropics and subtropics. As scorpions may be unintentionally transported to any place in the world and keeping scorpions as pets is becoming more popular, scorpion stings occur also in Poland. Therefore, health professionals should have the knowledge on the management of scorpion stings. This article discusses a case who was stung by scorpion and proposes an algorithm of management with such patients.

  5. Scorpion fish sting

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002849.htm Scorpion fish sting To use the sharing features on this page, ... are also found in aquariums worldwide. Symptoms A scorpion fish sting causes intense pain and swelling at the site ...

  6. Insects and Scorpions

    MedlinePlus

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

  7. Study on Distribution of Scorpions to Provide Prevention and Interventions in Combating Scorpionism in Poldokhtar County, Lorestan Province, Iran

    PubMed Central

    Hassan, Rastgar

    2016-01-01

    Introduction Scorpions are arthropods of medical importance classified in the class Arachnida, inhabiting hot and dry environments. All scorpions have a venomous sting and several thousand people die each year from scorpion stings, but this mortality is due to the venom of about 25 species located in northern Africa, the Middle East, India, Mexico and parts of South America. Poldokhtar County belongs to one of the southern cities of Lorestan Province, providing suitable habitats for many different species of scorpions due to its specific climatic conditions. Aim To examine the fauna of scorpion and its distribution in the Poldokhtar County and to provide appropriate preventive and medical interventions in combating scorpionism. Materials and Methods This present study was a descriptive and analytical cross-sectional study. This study was conducted from April 2014 to November 2014 in regions of Poldokhtar County, Lorestan Province, and west of Iran. Cluster sampling methodology was employed in the sampling and scorpion collection procedure. Sampling was undertaken for an eight-month period, in villages and districts, namely, Myankuhe sharqi, Jayedar, Jelogir and Malavi within the county. The Chi-square test and the Fisher-exact test for homogeneity of proportions were used to compare quantitative variables. Results Totally, 393 specimens were captured entailing 193 (49.1%) males and 200 (50.9%) females. There were at least seven species of scorpions belonging to three families; BU= Buthidae, HE = Hemiscorpiidae, SCN = Scorpionidae in Poldokhtar. Out of 393 collected scorpions, seven species, Androctonus crassicauda, Hottentotta (Buthotus) saulcyi, Compsobuthus matthiesseni, Compsobuthus rugosulus, Orthochirus scrobiculosus, Scorpio maurus and Hemiscorpius lepturus were identified. The overall sex ratio of females to males was 1:1.03. Conclusion It is crucial to improve the knowledge of residents in this region regarding preventive methods towards scorpion stinging

  8. 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.

  9. 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

  10. 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.

  11. Scorpion bite prevalence and complications: report from a referral centre in southern Iran.

    PubMed

    Sagheb, Mohammad Mahdi; Sharifian, Maryam; Moini, Maryam; Sharifian, Amir Hossein

    2012-04-01

    In this study we describe the clinical features of scorpion bites in southern Iran. The records of scorpion bite victims from January 2000 to January 2009 were obtained from the record library of the Shiraz Nemazi Hospital, Shiraz, Iran. A total of 232 scorpion bite patients were included. Only 14 patients (6%) developed systemic complications. Acute renal failure (ARF) and disseminated intravascular coagulation (DIC) were the most prevalent systemic complications. The renal toxicity of scorpion envenomation is mostly due to Hemiscorpius lepturus stings and this complication is more common in younger children. This may be due to a higher ratio of venom to body mass compared with adults. H. lepturus venom is naturally cytotoxic and may bind directly to kidney tissue causing tubular injury and inducing DIC and haemolysis.

  12. Antivenom for critically ill children with neurotoxicity from scorpion stings.

    PubMed

    Boyer, Leslie V; Theodorou, Andreas A; Berg, Robert A; Mallie, Joanne; Chávez-Méndez, Ariana; García-Ubbelohde, Walter; Hardiman, Stephen; Alagón, Alejandro

    2009-05-14

    Clinically significant scorpion envenomation by Centruroides sculpturatus produces a dramatic neuromotor syndrome and respiratory insufficiency that often necessitate intensive supportive care. We hypothesized that a scorpion-specific F(ab')(2) antivenom would promptly resolve clinical symptoms in children with this syndrome. In a randomized, double-blind study, the efficacy of scorpion-specific F(ab')(2) antivenom, as compared with placebo, was assessed in 15 children 6 months to 18 years of age who were admitted to a pediatric intensive care unit with clinically significant signs of scorpion envenomation. The primary end point was the resolution of the clinical syndrome within 4 hours after administration of the study drug. Secondary end points included the total dose of concomitant midazolam for sedation and quantitative plasma venom levels, before and after treatment. The clinical syndrome resolved more rapidly among recipients of the antivenom than among recipients of placebo, with a resolution of symptoms in all eight antivenom recipients versus one of seven placebo recipients within 4 hours after treatment (P=0.001). More midazolam was administered in the placebo recipients than in the antivenom recipients (mean cumulative dose, 4.61 vs. 0.07 mg per kilogram of body weight; P=0.01). Plasma venom concentrations were undetectable in all eight antivenom recipients but in only one placebo recipient 1 hour after treatment (P=0.001). Among critically ill children with neurotoxic effects of scorpion envenomation, intravenous administration of scorpion-specific F(ab')(2) antivenom resolved the clinical syndrome within 4 hours, reduced the need for concomitant sedation with midazolam, and reduced the levels of circulating unbound venom. (ClinicalTrials.gov number, NCT00685230.) 2009 Massachusetts Medical Society

  13. A novel class of antimicrobial peptides from the scorpion Heterometrus spinifer.

    PubMed

    Nie, Yao; Zeng, Xian-Chun; Yang, Ye; Luo, Feng; Luo, Xuesong; Wu, Shifen; Zhang, Lei; Zhou, Jianping

    2012-12-01

    The venom peptides from the scorpion Heterometrus spinifer have been poorly characterized so far. Here, we identified a novel class of antimicrobial peptides from the venom gland of H. spinifer, which were referred to as HsAp, HsAp2, HsAp3 and HsAp4, respectively. Each of the four peptides consists of 29 amino acid residues, and is cationic and weakly amphipathic. They display no significant homology to any other known peptides, and thus represent a new family of venom peptides from scorpions. Antimicrobial assay showed that HsAp is able to inhibit the growth of both Gram-negative and Gram-positive bacteria with the MIC values of 11.8-51.2 μM. HsAp is also able to inhibit the growth of the tested fungus. Genomic analysis indicated that the genes of all the four peptides are intronless. Our studies expand the families of antimicrobial peptides from scorpions.

  14. [Snakes, scorpions and other poisonous creatures: prophylaxis and emergency medicine].

    PubMed

    Mebs, D

    2006-06-29

    Most cases of poisoning by animals are caused by snakes, spiders or scorpions. In addition to"first aid" such as calming the victim and immobilization of the bitten limb, other measures include monitoring vital functions and rapid transportation to hospital as dictated by the symptoms presenting, and, where indicated, injection of an antiserum (identification of the animal concerned). On no account should the bite wound be cut or attempts made to suck out the venom. While the sting of a scorpion or a spider bite often do not lead to severe complications in adults, a brush with a poisonous snake may be much more serious.

  15. Classification of Na channel receptors specific for various scorpion toxins.

    PubMed

    Wheeler, K P; Watt, D D; Lazdunski, M

    1983-04-01

    1. The specific binding to rat brain synaptosomes of a radiolabelled derivative of toxin II from the scorpion Centruroides suffusus suffusus could be prevented by toxins III and IV, but not by toxin V or variants 1-3, from the venom of Centruroides sculpturatus. 2. The specific binding of a similar derivative of toxin II from Androctonus australis Hector was not affected by any of the toxins from Centruroides sculpturatus. 3. There is biochemical evidence for only two distinct classes of Na channel receptors specific for known scorpion toxins.

  16. Hey! A Scorpion Stung Me!

    MedlinePlus

    ... dangerous scorpion from one that is harmless, all scorpion stings must be treated by a doctor. Capture the ... you to the doctor. Knowing the type of scorpion that caused the sting may make treatment easier. What a Doctor Will ...

  17. Deep intraspecific divergences in the medically relevant fat-tailed scorpions (Androctonus, Scorpiones).

    PubMed

    Coelho, P; Sousa, P; Harris, D J; van der Meijden, A

    2014-06-01

    The genus Androctonus, commonly known as fat-tailed scorpions, contains 22 species distributed from Togo and Mauritania in the west, North Africa, through the Middle East and to as far east as India. With 13 species, a substantial amount of this genus' diversity occurs in North Africa, which is a major hotspot of scorpion sting incidents. Androctonus are among the most medically relevant animals in North Africa. Since venom composition within species is known to vary regionally, the improvement of therapeutic management depends on a correct assessment of the existing regional specific and sub-specific variation. In this study, we assessed the phylogeographical patterns in six species of Androctonus scorpions from North Africa using mitochondrial DNA markers. We sequenced COX1, 12S, 16S and ND1 genes from 110 individuals. Despite lacking basal resolution in the tree, we found taxonomical and geographically coherent clades. We discovered deep intraspecific variation in the widespread Androctonus amoreuxi and Androctonus australis, which consisted of several well-supported clades. Genetic distances between some of these clades are as high as those found between species. North African A. australis have a deep split in Tunisia around the Chott el-Djerid salt-lake. A novel split between A. amoreuxi scorpions was found in Morocco. We also found deep divergences in Androctonus mauritanicus, corresponding to areas attributed to invalidated subspecies. In addition we uncovered a clade of specimens from coastal south Morocco, which could not be ascribed to any know species using morphological characters. Based on these findings we recommend a reassessment of venom potency and anti-venom efficacy between these deep intraspecific divergent clades.

  18. 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.

  19. Spatial Distribution of Scorpion Sting in a High-Risk Area of Southern Iran.

    PubMed

    Shahi, Mehran; Moosavy, Seyed Hamid; Hanafi-Bojd, Ahamd Ali; Navidpour, Shahrokh; Zare, Shahram; Madani, Abdolhossein; Rafinejad, Javad

    2016-06-16

    Scorpion sting is a public health problem in south and southwestern parts of Iran, with about 36,000 cases recorded annually. This study aimed to find the spatial distribution of scorpions and their stings in Bandar Abbas County. Monthly scorpion sting cases at the village level were obtained and used for mapping. Scorpions were collected from 14 collection sites using a UV lamp at night and searching under stones during the day time. During the study period, a total of 3,971 cases of scorpion sting were recorded, most of them were found in mountainous areas and affected individuals aged 25-44 yrs. In total, 18 scorpion species belonging to 10 genera were collected and identified. The peak of scorpion sting cases occurred from July to September. The northern part of the mountainous areas had a richer species composition. Hemiscorpius persicus and Hemiscorpius gaillardi were collected for the first time in the area. There were 22 scorpion species in the area across studies; among them, 10 were most dangerous. Hemiscorpius genus is the main etiologic agent in Bandar Abbas County. Mapping dangerous species allows the health system to provide relevant anti-scorpion venom serum accordingly and more cost-effectively.

  20. 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.

  1. Epidemiology of Scorpionism in Iran during 2009

    PubMed Central

    Rafizadeh, Sina; Rafinejad, Javad; Rassi, Yavar

    2013-01-01

    Background: Scorpion sting is a major health problem in Iran. The aim of current study was to measure the incidence rates of scorpion stings, mortality, recovery, and affected age groups. The results of treatment with and without anti venom also were considered in the entire country during 2009. Methods: All the data were collected from emergency section of different hospitals and then were analyzed by related software. The responsibility of such data collection and surveillance is related to the Department of Violence and Injury, Ministry of Health and Medical Education of Iran. Results: A total incidence of 59.5/100000 was found for the 12-month period. During the study period the most and the least cases were reported from Khuzestan and Mazandaran Provinces with incidence of 541 and 0 per 100000 respectively. Totally 40220 anti venom vials were used, i.e., the ratio of 91 vial/ 100 affected cases. The stings occur mainly in rural areas (57.7%). Young people with the age group of 15–24 years old were the most victims of stings. The mortality and recovery rates of cases who had received anti venom less than 6 h of stings were calculated as 0.01% and 99.9% respectively. Conclusion: The high incidence of scorpion stings in Iran especially in Khuzestan suggests the necessity of preventive programmes for decreasing the incidence. Such programmes could start by community educating in the high prevalent areas. In addition prompt and local treatment is particularly important for infants and pre-school children. PMID:23785696

  2. 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.

  3. 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.

  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. Serrumab: a novel human single chain-fragment antibody with multiple scorpion toxin-neutralizing capacities.

    PubMed

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Peigneur, Steve; Arantes, Eliane Candiani; Tytgat, Jan; Barbosa, José Elpidio

    2014-01-01

    In Brazil, scorpion envenomation is an important public health problem. The yellow scorpion, Tityus serrulatus (Ts), is considered the most dangerous species in the country, being responsible for the most severe clinical cases of envenomation. Currently, the administration of serum produced in horses is recognized and used as a treatment for accidents with scorpions. However, horse herds' maintenance is costly and the antibodies are heterologous, which can cause anaphylaxis and Serum Sickness. In the present work, a human monoclonal fragment antibody, Serrumab, has been analysed. Toxin neutralizing effects of Serrumab were evaluated using a two-electrode voltage-clamp technique. The results show that Serrumab presented a high neutralizing effect against Ts β-toxins (Ts1, 43.2% and Ts2, 68.8%) and none or low neutralizing effect against α-toxins (Ts3, 0% and Ts5, 10%). Additional experiments demonstrated that Serrumab was also able to neutralize the action of toxins from other scorpion genus (Css II, 45.96% and Lqh III, 100%/β- and α-toxins, respectively). This work indicated that Serrumab is able to neutralize many toxins in Ts venom, and could being considered as a neutralizing antibody for formulating a human anti-scorpion serum in Brazil. Additionally, this work demonstrated that Serrumab could neutralize different toxins from distinct scorpion genus. All these results reinforce the idea that Serrumab is a scFv antibody with multiple neutralizing capacities and a promising candidate for inclusion in scorpion anti-venoms against different genera.

  6. Serum level of scorpion toxins, electrolytes and electrocardiogram alterations in Mexican children envenomed by scorpion sting.

    PubMed

    Osnaya-Romero, N; Acosta-Saavedra, L C; Goytia-Acevedo, R; Lares-Asseff, I; Basurto-Celaya, G; Perez-Guille, G; Possani, L D; Calderón-Aranda, E S

    2016-11-01

    The scorpion Centruroides limpidus limpidus (C.l.l.) is endemic in México, producing hundreds of accidents in humans; children being one of the most susceptible targets. Few studies reported that severe envenoming by scorpion venom induces cardiac damage and electrolytes abnormalities in children, but the relationship of envenoming severity and toxic blood levels is unknown. The aim of this study was to determine the relationship among clinical status of envenoming, serum electrolyte, electrocardiographic abnormalities, and serum toxin levels in 44 children stung by scorpion over a period of 6 months in the State of Morelos, Mexico. The patients were said to be asymptomatic, when they presented just local symptoms, and were said to be symptomatic when showing local symptoms and at least one systemic symptom. The clinical status was evaluated at the admission at the emergency room of the Hospital, and 30 min after the administration of polyspecific F(ab')2 anti-scorpion therapy to symptomatic children. Forty-one percent of the children were asymptomatic and 59% symptomatic. Potassium and sodium imbalance and an elongation of the QT interval were detected; the rate of hypokalemia was higher in symptomatic than on asymptomatic children (50% and 6%, respectively). Hypokalemia persisted in 19% in symptomatic patients, whereas sodium reached normal levels 30 min after anti-venom therapy. The hypokalemia statistically correlated with elongation of the QT interval. The concentration of the toxic components of C.l.l in serum was significantly higher in symptomatic than asymptomatic children, and the serum levels of the toxic component significantly decreased to undetectable levels after the application of anti-venom therapy. Despite the small size of the sample, this study establishes that severity of envenoming was statistically related to potassium imbalance in serum, QT interval and the concentration of toxic components in serum, which decreased at undetectable levels

  7. Temperature dependence of water loss rates in scorpions and its effect on the distribution of Buthotus judaicus (Buthidae) in Israel.

    PubMed

    Gefen, Eran; Ar, Amos

    2006-05-01

    Scorpions of the family Buthidae have been shown to be more desiccation resistant in comparison with sympatric Scorpionidae species. This has been attributed to the surface-dwelling existence of the former, which unlike most other scorpion species do not avoid environmental extremes by burrowing. Still, within Buthidae, the mesic Buthotus judaicus showed better osmoregulatory capacities than the xeric Leiurus quinquestriatus, largely as a result of its high resistance to water loss. However, B. judaicus exhibited poor ability to regulate its haemolymph osmolarity at 37 degrees C. In this study we report a sharp increase in water loss rates of B. judaicus at the 30-35 degrees C temperature range compared to that measured for L. quinquestriatus, which could explain the poor osmoregulatory performance of the former at higher ambient temperatures. The increase in water loss rates of B. judaicus at high temperatures is not coupled with a similar increase in respiratory rate, suggesting an increase in cuticular permeability. We suggest that this increase in cuticular permeability, which may result from a relatively low critical transition temperature, contributes to limiting the distribution of B. judaicus to habitats of moderate environmental conditions.

  8. Scorpion sting: update.

    PubMed

    Bawaskar, Himmatrao Saluba; Bawaskar, Pramodini Himmatrao

    2012-01-01

    Scorpion envenomation is an important public health hazard in tropical and sub-tropical regions. Envenomation by scorpions can result in a wide range of clinical effects, including, cardiotoxicity, neurotoxicity and respiratory dysfunction. Out of 1500 scorpion species known to exist, about 30 are of medical importance. Although a variety of different scorpion species exist, majority of them produce similar cardiovascular effects. Scientists and clinicians have studied patho-physiology of scorpion envenomation by critical observations of clinical, neurotransmitters studies, radioisotope studies, echocardiography and haemodynamic patterns. Regimen including scorpion antivenom, vasodilators, intensive care management have been tried to alleviate the systemic effects of envenoming. In spite of advances in patho-physiology and therapy the mortality remains high in rural areas due to lack of access to medical facilities, moreover the medical attendee from developing tropical countries may not be aware of the advances in the treatment of scorpion sting. Since the advent of scorpion Antivenom, vasodilators, dobutamine and intensive care facilities, the fatality due to severe scorpion sting has been significantly reduced in areas where these treatment modalities are used.

  9. Scorpion toxin peptide action at the ion channel subunit level.

    PubMed

    Housley, David M; Housley, Gary D; Liddell, Michael J; Jennings, Ernest A

    2016-10-10

    This review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a diverse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 individual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Hemprich's long-eared bat (Otonycteris hemprichii) as a predator of scorpions: whispering echolocation, passive gleaning and prey selection.

    PubMed

    Holderied, Marc; Korine, Carmi; Moritz, Thorsten

    2011-05-01

    Over 70% of the droppings of the gleaning bat Otonycteris hemprichii can contain scorpion fragments. Yet, some scorpions found in its desert habitat possess venom of the highest known toxicity, rendering them a very dangerous prey. In this study, we describe how O. hemprichii catches and handles scorpions, quantify its flight and echolocation behaviour in the field, investigate what sensory modality it uses to detect scorpions, and test whether it selects scorpions according to their size or toxicity. We confirmed that O. hemprichi is a whispering bat (approx. 80 dB peSPL) with short, multi-harmonic calls. In a flight room we also confirmed that O. hemprichii detects scorpions by their walking noises. Amplitudes of such noises were measured and they reach the flying bat at or below the level of echoes of the loess substrate. Bats dropped straight onto moving scorpions and were stung frequently even straight in their face. Stings did not change the bats' behaviour and caused no signs of poisoning. Scorpions were eaten including poison gland and stinger. Bats showed no preference neither for any of the scorpion species nor their size suggesting they are generalist predators with regard to scorpions.

  11. A biomechanical view on stinger diversity in scorpions.

    PubMed

    van der Meijden, Arie; Kleinteich, Thomas

    2017-04-01

    Scorpions have elongated metasomas that bear a telson, which is used as a stinger for venom injection. There is a remarkable diversity in the use of the stinger among scorpions, comprising defensive behavior, prey subjugation and mating. This diversity could be reflected by the shape of the telson, as different stinging behaviors will result in very different functional demands. Here we explored the diversity of telson shapes in scorpions by providing morphological measurements, such as curvature and tip angle, as well as by testing stingers under load using finite element analysis (FEA). FEA models were loaded with forces scaled to the surface area of the models, to allow comparison of the relative strain energy based on shape alone. Load force angle was rotated to identify the optimal stinging angle based on the lowest strain energy. Aculeus length and mean aculeus height correlated with minimal strain energy. Optimal stinging angle correlated with tip angle, and differed from the tip angle by about 28.4 ± 6.22 °. We found that species that are more venomous have long aculei (stinger barbs) with a larger radius of curvature. FEA models of these longer aculei showed basal stress concentrations, indicating a potential greater risk of basal breakage due to shape alone. Telsons with shorter and thicker aculeus shapes showed stress concentrations at the tip only. Despite these marked differences in shape, we found no difference in the scaled strain energy between groups of species that are more venomous and less venomous groups of species. These results show that scorpion stingers may be biomechanically optimized, and this may indicate different usage of the stinger in different species. © 2016 Anatomical Society.

  12. 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

  13. 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.

  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.

  15. Scorpion sting envenomation in children in southeast Turkey.

    PubMed

    Bosnak, Mehmet; Ece, Aydin; Yolbas, Ilyas; Bosnak, Vuslat; Kaplan, Metin; Gurkan, Fuat

    2009-01-01

    Scorpion sting envenomation is a life-threatening emergency and a common public health problem in many regions of the world, particularly in children. Children are at greater risk of developing severe cardiac, respiratory, and neurological complications. The aims of this study were to evaluate demographic, clinical, laboratory, treatment, and outcome characteristics for pediatric patients with scorpion sting envenomation in southeast Turkey and to describe features that may be predictive of the need for pediatric intensive care unit (PICU) care. A total of 52 charts of children (mean age: 7.7 +/- 2.8 years; age range: 1.5-15 years) presenting with scorpion sting envenomation to a single hospital in southeastern Turkey were investigated. General characteristics of the children, species of the scorpions, anatomic site of the sting, clinical and laboratory findings, treatment approaches, complications, and outcomes were recorded. Twenty-four stings (46.2%) were inflicted by Androctonus crassicauda, 1 (1.9%) by Leiurus quinquestriatus, and the sources of the other stings were not known. Thirty-one patients (59.6%) were admitted from rural areas. Admission from a rural area was a significant risk factor for severe envenomation. Foot-leg was the most frequently stung part of the body (48%). The greatest number of stings occurred in the summer (78.8%). Cold extremities and tachycardia were the most frequently seen clinical findings (38.4% for both). Twenty patients (38.5%) had signs of serious envenomation and required admission to the PICU. Hemoglobin, white blood cell count, activated prothrombin time, aspartate aminotransferase, alanine aminotransferase, and creatine phosphokinase levels were higher in severely envenomed children compared to levels in those with mild-moderate stings. Antivenom was given at a primary or secondary health center before arrival to our hospital in 44 (84.6%) patients, without any apparent difference in the number of patients presenting with

  16. Scorpion sheds 'tail' to escape: consequences and implications of autotomy in scorpions (Buthidae: Ananteris).

    PubMed

    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.

  17. Antitoxin activity of plants used in Mexican traditional medicine against scorpion poisoning.

    PubMed

    Jiménez-Ferrer, J E; Pérez-Terán, Y Y; Román-Ramos, R; Tortoriello, J

    2005-01-01

    Scorpions, especially in urban areas of tropical and subtropical regions, present a common risk of poisoning. In Mexico, scorpion envenomation is considered a public health problem. Despite the frequency of scorpion sting cases, there are to date no uniform criteria for their treatment. In Mexican traditional medicine, different plant species have been widely used as a remedy for treating scorpion poisoning. The aim of this work was to evaluate the effect of Bouvardia ternifolia, Aristolochia elegans and Vitex mollis extracts on Centruroides limpidus limpidus venom lethality in mice, and to determine their antagonist activity on guinea pig ileum. The hexane and methanol extract from B. ternifolia modified the LD50 of C. limpidus limpidus venom from 0.750 +/- 0.08 to 1.64 +/- 0.19 and 1.16 +/- 0.14 mg/kg, respectively. The extracts of A. elegans produced lower antitoxic activity, while extracts of V. mollis did not show any protection. On in vitro test, addition of B. ternifolia and A. elegans extracts strongly inhibited, in a concentration-dependent manner, the ileum contractions induced by venom. In general, the results demonstrated the effectiveness of these two plant species in modifying the lethality of C. limpidus limpidus venom in mice.

  18. [Tityus asthenes scorpion stings: epidemiological, clinical and toxicological aspects].

    PubMed

    Gómez, Juan P; Quintana, Juan C; Arbeláez, Patricia; Fernández, Jorge; Silva, Juan F; Barona, Jacqueline; Gutiérrez, Juan C; Díaz, Abel; Otero, Rafael

    2010-01-01

    Scorpion stings are a public health problem in many countries. However, in Colombia, very few epidemiological, clinical or toxicological studies have been undertaken. Ecological and epidemiological aspects were related to the prevalence of scorpion stings by Tityus asthenes. The clinical features of envenomization were described in patients and in an experimental animal model. The study was conducted in four localities of Mutatá and Urabá Counties in the province of Antioquia, Colombia. The sample consisted of 1,593 (929 urban, 664 rural) of the 5,305 exposed people, inhabitating 324 households (188 urban (58%); 136 rural (42%) of 1,448 houses total in the study area. An interview survey was performed in every selected family for a more realistic estimate of sting prevalence. Additionally, a prospective study was directed toward patients presenting scorpion stings at care at the local hospital over an 18-month period. The probability was 12.9 times greater of finding T. asthenes inside or around houses in places near to forest and high agrarian plantations (odds ratio = 13). Eighty scorpion stings were reported in the retrospective study (4.1% prevalence [95% CI 3.3-4.8%] ), but only 14 of the patients (17.5%) sought care in the local hospital (an 82.5% underreportage). Seventy percent of the stings occurred in rural places; 50% occurred in the locality of Caucheras, with an attack rate of 10.6%. The overall household infestation rate was 269% (95% CI 22.9-30.8%) and an area dispersion ratio of 100%. Signs of systemic envenomization occurred mainly in children (67%). The 50% lethal dose of T. asthenes venom was 121.6 µg for 18-20 g Swiss Webster rats (95% CI 103.7-139.6). Immunodetection of T. asthenes and Centruroides gracilis/C.margantatus venoms in the experimental animals was possible when were tested by Western blot against Alacramyn (Instituto Bioclón, México) and Soro antiaracnídico (Instituto Butantan, Brasil) antivenoms. Scorpion interspecific

  19. A checklist of the scorpions of Ecuador (Arachnida: Scorpiones), with notes on the distribution and medical significance of some species.

    PubMed

    Brito, Gabriel; Borges, Adolfo

    2015-01-01

    Ecuador harbors one of the most diverse Neotropical scorpion faunas, hereby updated to 47 species contained within eight genera and five families, which inhabits the "Costa" (n = 17), "Sierra" (n = 34), "Oriente" (n = 16) and "Insular" (n = 2) biogeographical regions, corresponding to the western coastal, Andean, Amazonian, and the Galápagos archipelago regions, respectively. The genus Tityus Koch, in the family Buthidae, responsible for severe/fatal accidents elsewhere in northern South America and the Amazonia, is represented in Ecuador by 16 species, including T. asthenes, which has caused fatalities in Colombia and Panama, and now in the Ecuadorian provinces of Morona Santiago and Sucumbíos. Underestimation of the medical significance of scorpion envenoming in Ecuador arises from the fact that Centruroides margaritatus (Gervais) (family Buthidae) and Teuthraustes atramentarius Simon (family Chactidae), whose venoms show low toxicity towards vertebrates, frequently envenom humans in the highly populated Guayas and Pichincha provinces. This work also updates the local scorpion faunal endemicity (74.5 %) and its geographical distribution, and reviews available medical/biochemical information on each species in the light of the increasing problem of scorpionism in the country. A proposal is hereby put forward to classify the Ecuadorian scorpions based on their potential medical importance.

  20. Behavior, Ecology and Toxicity of Venomous Marine Fishes.

    DTIC Science & Technology

    1977-12-31

    u ltrastructure of the venom apparatus of the stingrays and scorpion fishes ’~~nd~ .. I# )”the chemistry and pharmacolo~~~~~~M~~ ~~~~~~ o of stingray

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

    PubMed

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

    2015-11-17

    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.

  2. 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

  3. Combating of scorpion bite with Pakistani medicinal plants having ethno-botanical evidences as antidote.

    PubMed

    Nasim, Muhammad Jawad; Asad, Muhammad Hassham Hassan Bin; Sajjad, Ashif; Khan, Shujaat Ali; Mumtaz, Amara; Farzana, Kalsoom; Rashid, Zarmina; Murtaza, Ghulam

    2013-01-01

    Although the majority of serious cases in the world are concerned with snake bite envenomation, but those which are caused by scorpion stings are also famous for causing extreme pain. The present view is an attempt to enlist scientifically ignored medicinal plants of Pakistan exhibiting anti-scorpion venom activity. In this review data of 35 medicinal plants is collected with their families, parts used, distribution in Pakistan, and major constituents present in plant. Amaranthaceae, Astraceae and Euphorbiaceae represent 3 species. Anacardiaceae, Asclepidaceae and Liliaceae represent 2 species. Araceae, Capparidaceae, Ceasalpinaceae, Cyperaceae, Labiatae, Lamiaceae, Meliaceae, Menispermaceae, Oleaceae, Oxalidaceae, Pinaceae, Polygonaceae, Rhamnaceae, Rubiaceae, Solanaceae, Valerianaceae and Zingiberaceae represented single medicinal plant with anti scorpion potential. According to literature, all parts are used in anti scorpion envenomination. Leaves exhibit 30%, whole plant 9%, fruit, bark and seeds 8% anti scorpion activity. Bulb and stems show 5% contribution in this respect and twigs, resins, inflorescence, latex and flowers express 3% potential. This article may assist the researchers to bring innovation in natural product field for scorpion bite envenomation. However, these medicinal plants are still requiring pharmacological and phytochemical investigation in order to be claimed as effective in scorpion bite envenomation.

  4. Antibacterial activity of the venom of Heterometrus xanthopus

    PubMed Central

    Ahmed, Umair; Mujaddad-ur-Rehman, Malik; Khalid, Nauman; Fawad, Sardar Atiq; Fatima, Anees

    2012-01-01

    Heterometrus xanthopus (Scorpion) is one of the most venomous and ancient arthropods. Its venom contains anti-microbial peptides like hadrurin, scorpine, Pandinin 1, and Pandinin 2 that are able to effectively kill multidrug-resistant pathogens. The present study was conducted to evaluate the anti-bacterial activity of H. xanthopus venom. Six Gram-positive and Gram-negative bacterial strains were tested against 1/100, 1/10, and 1/1 fractions of distilled water diluted and crude venom. 1/100 and 1/10 dilutions were not successful in any of the six bacterial strains studied while the 1/1 dilution was effective on Bacillus subtilis ATCC 6633, Salmonella typhimurium ATCC 14028, and Pseudomonas aeruginosa ATCC 27853 with highest zone of inhibition were obtained on B. subtilis. Crude venom was effective against Enterococcus faecalis ATCC 14506, B. subtilis, S. typhimurium, and P. aeruginosa. The most effective results were observed on B. subtilis. PMID:23087515

  5. Antibacterial activity of the venom of Heterometrus xanthopus.

    PubMed

    Ahmed, Umair; Mujaddad-Ur-Rehman, Malik; Khalid, Nauman; Fawad, Sardar Atiq; Fatima, Anees

    2012-01-01

    Heterometrus xanthopus (Scorpion) is one of the most venomous and ancient arthropods. Its venom contains anti-microbial peptides like hadrurin, scorpine, Pandinin 1, and Pandinin 2 that are able to effectively kill multidrug-resistant pathogens. The present study was conducted to evaluate the anti-bacterial activity of H. xanthopus venom. Six Gram-positive and Gram-negative bacterial strains were tested against 1/100, 1/10, and 1/1 fractions of distilled water diluted and crude venom. 1/100 and 1/10 dilutions were not successful in any of the six bacterial strains studied while the 1/1 dilution was effective on Bacillus subtilis ATCC 6633, Salmonella typhimurium ATCC 14028, and Pseudomonas aeruginosa ATCC 27853 with highest zone of inhibition were obtained on B. subtilis. Crude venom was effective against Enterococcus faecalis ATCC 14506, B. subtilis, S. typhimurium, and P. aeruginosa. The most effective results were observed on B. subtilis.

  6. 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

  7. 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.

  8. Emerging options for the management of scorpion stings.

    PubMed

    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.

  9. 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

  10. Small Packages, Big Returns: Uncovering the Venom Diversity of Small Invertebrate Conoidean Snails.

    PubMed

    Gorson, J; Holford, M

    2016-11-01

    Venomous organisms used in research were historically chosen based on size and availability. This opportunity-driven strategy created a species bias in which snakes, scorpions, and spiders became the primary subjects of venom research. Increasing technological advancements have enabled interdisciplinary studies using genomics, transcriptomics, and proteomics to expand venom investigation to animals that produce small amounts of venom or lack traditional venom producing organs. One group of non-traditional venomous organisms that have benefitted from the rise of -omic technologies is the Conoideans. The Conoidean superfamily of venomous marine snails includes, the Terebridae, Turridae (s.l), and Conidae. Conoidea venom is used for both predation and defense, and therefore under strong selection pressures. The need for conoidean venom peptides to be potent and specific to their molecular targets has made them important tools for investigating cellular physiology and bioactive compounds that are beneficial to improving human health. A convincing case for the potential of Conoidean venom is made with the first commercially available conoidean venom peptide drug Ziconotide (Prialt®), an analgesic derived from Conus magus venom that is used to treat chronic pain in HIV and cancer patients. Investigation of conoidean venom using -omics technology provides significant insights into predator-driven diversification in biodiversity and identifies novel compounds for manipulating cellular communication, especially as it pertains to disease and disorders. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.

  11. ADAMTS-13 deficiency following Hemiscorpius lepturus scorpion sting.

    PubMed

    Valavi, Ehsan; Ansari, Mohammad Javad Alemzadeh; Hoseini, Sudabeh

    2011-07-01

    Hemiscorpius lepturus is a lethal scorpion with potentially cytotoxic venom. Various degrees of local and systemic toxicity have been observed after its envenomation ranging from local erythema to disseminated intravascular coagulation, renal failure and severe pulmonary hemorrhage. In this case report, we report on a seven-year-old patient who developed the hemolytic uremic syndrome (HUS) after being stung by the scorpion H. lepturus. This condition is characterized by microangiopathic hemolytic anemia, thrombocytopenia, increased serum levels of lactate dehydrogenase and uremia. We evaluated the causes of HUS and found that the levels of C3, C4, CH50 and H factors were normal, but the activity of Von Willebrand factor cleaving protease was decreased (less than 5% of the normal activity). The patient improved after administering therapy with plasma exchange.

  12. A chimeric scorpion alpha-toxin displays de novo electrophysiological properties similar to those of alpha-like toxins.

    PubMed

    Bouhaouala-Zahar, Balkiss; Benkhalifa, Rym; Srairi, Najet; Zenouaki, Ilhem; Ligny-Lemaire, Caroline; Drevet, Pascal; Sampieri, François; Pelhate, Marcel; El Ayeb, Mohamed; Ménez, André; Karoui, Habib; Ducancel, Frédéric

    2002-06-01

    BotXIV and LqhalphaIT are two structurally related long chain scorpion alpha-toxins that inhibit sodium current inactivation in excitable cells. However, while LqhalphaIT from Leiurus quinquestriatus hebraeus is classified as a true and strong insect alpha-toxin, BotXIV from Buthus occitanus tunetanus is characterized by moderate biological activities. To assess the possibility that structural differences between these two molecules could reflect the localization of particular functional topographies, we compared their sequences. Three structurally deviating segments located in three distinct and exposed loops were identified. They correspond to residues 8-10, 19-22, and 38-43. To evaluate their functional role, three BotXIV/LqhalphaIT chimeras were designed by transferring the corresponding LqhalphaIT sequences into BotXIV. Structural and antigenic characterizations of the resulting recombinant chimera show that BotXIV can accommodate the imposed modifications, confirming the structural flexibility of that particular alpha/beta fold. Interestingly, substitution of residues 8-10 yields to a new electrophysiological profile of the corresponding variant, partially comparable to that one of alpha-like scorpion toxins. Taken together, these results suggest that even limited structural deviations can reflect functional diversity, and also that the structure-function relationships between insect alpha-toxins and alpha-like scorpion toxins are probably more complex than expected.

  13. 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

  14. 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).

  15. Inactivation of complement by Loxosceles reclusa spider venom.

    PubMed

    Gebel, H M; Finke, J H; Elgert, K D; Cambell, B J; Barrett, J T

    1979-07-01

    Zymosan depletion of serum complement in guinea pigs rendered them highly resistant to lesion by Loxosceles reclusa spider venom. Guinea pigs deficient in C4 of the complement system are as sensitive to the venom as normal guinea pigs. The injection of 35 micrograms of whole recluse venom intradermally into guinea pigs lowered their complement level by 35.7%. Brown recluse spider venom in concentrations as slight as 0.02 micrograms protein/ml can totally inactivate one CH50 of guinea pig complement in vitro. Bee, scorpion, and other spider venoms had no influence on the hemolytic titer of complement. Fractionation of recluse spider venom by Sephadex G-200 filtration separated the complement-inactivating property of the venom into three major regions which could be distinguished on the basis of heat stability as well as size. None was neutralized by antivenom. Polyacrylamide gel electrophoresis of venom resolved the complement inactivators into five fractions. Complement inactivated by whole venom or the Sephadex fractions could be restored to hemolytic activity by supplements of fresh serum but not by heat-inactivated serum, pure C3, pure C5, or C3 and C5 in combination.

  16. Chemical Punch Packed in Venoms Makes Centipedes Excellent Predators*

    PubMed Central

    Yang, Shilong; Liu, Zhonghua; Xiao, Yao; Li, Yuan; Rong, Mingqiang; Liang, Songping; Zhang, Zhiye; Yu, Haining; King, Glenn F.; Lai, Ren

    2012-01-01

    Centipedes are excellent predatory arthropods that inject venom to kill or immobilize their prey. Although centipedes have long been known to be venomous, their venoms remain largely unexplored. The chemical components responsible for centipede predation and the functional mechanisms are unknown. Twenty-six neurotoxin-like peptides belonging to ten groups were identified from the centipede venoms, Scolopendra subspinipes mutilans L. Koch by peptidomics combined with transcriptome analysis, revealing the diversity of neurotoxins. These neurotoxins each contain two to four intramolecular disulfide bridges, and in most cases the disulfide framework is different from that found in neurotoxins from the venoms of spiders, scorpions, marine cone snails, sea anemones, and snakes (5S animals). Several neurotoxins contain potential insecticidal abilities, and they are found to act on voltage-gated sodium, potassium, and calcium channels, respectively. Although these neurotoxins are functionally similar to the disulfide-rich neurotoxins found in the venoms of 5S animals in that they modulate the activity of voltage-gated ion channels, in almost all cases the primary structures of the centipede venom peptides are unique. This represents an interesting case of convergent evolution in which different venomous animals have evolved different molecular strategies for targeting the same ion channels in prey and predators. Moreover, the high level of biochemical diversity revealed in this study suggests that centipede venoms might be attractive subjects for prospecting and screening for peptide candidates with potential pharmaceutical or agrochemical applications. PMID:22595790

  17. Categorization of venoms according to bonding properties: An immunological overview.

    PubMed

    Ibrahim, Nihal M; El-Kady, Ebtsam M; Asker, Mohsen S

    2016-02-01

    In this report, we present a study on the antigenic cross-reactivity of various venoms from the most dangerous Egyptian snakes and scorpions belonging to families Elapidae, Viperidae and Buthidae. The study was carried out with special reference to bonding properties between venoms and antivenoms and their involvement in the formation of specific and/or cross-reactive interactions. The homologous polyclonal antivenoms showed high reactivity to the respective venoms and cross-reacted with varying degrees to other non-homologous venoms. Assorting the antivenoms according to their susceptibility to dissociation by different concentrations of NH4SCN revealed that most of the antibodies involved in homologous venom-antivenom interactions were highly avid; building up strong venom-antivenom bonding. Whereas cross-reactions due to heterologous interactions were mediated by less avid antibodies that ultimately led to the formation of venom-antivenom bonding of different power strengths depending on the antigenic similarity and hence on the phylogenetic relationship of the tested venom. A new parameter evaluating high and low avid interactions, designated as H/L value, for each antigen-antibody bonding was initiated and used as an indicator of bonding strength between different venom-antivenom partners. H/L values were many folds higher than 1 for homologous and closely related venoms, 1 or around 1 for cross-reactive venoms, whereas venoms from unrelated remote sources recorded H/L values far less than 1. Using well defined polyclonal antivenoms, H/L value was successfully used to assign eight unknown venoms to their animal families and the results were confirmed by species-specific ELISA and immunoblotting assays. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. A novel human recombinant antibody fragment capable of neutralizing Mexican scorpion toxins.

    PubMed

    Riaño-Umbarila, Lidia; Olamendi-Portugal, Timoteo; Morelos-Juárez, Citlalli; Gurrola, Georgina B; Possani, Lourival D; Becerril, Baltazar

    2013-12-15

    Using phage display and directed evolution, our group has progressed in the construction of a second family of human single chain variable fragments (scFv) which bind to scorpion toxins dangerous to mammals. It was observed that scFv C1 only bound initially to toxin Cn2, which constitutes 6.8% of whole venom from the scorpion Centruroides noxius Hoffman. Only a few amino acid changes were necessary to extend its recognition to other similar toxins and without affecting the recognition for its primary antigen (Cn2 toxin). One variant of scFv C1 (scFv 202F) was selected after two cycles of directed evolution against Cll1 toxin, the second major toxic component from the venom of the Mexican scorpion Centruroides limpidus limpidus Karsh (0.5% of the whole venom). scFv 202F is also capable of recognizing Cn2 toxin. Despite not having the highest affinity for toxins Cll1 (KD = 25.1 × 10(-9) M) or Cn2 (KD = 8.1 × 10(-9) M), this antibody fragment neutralized one LD50 of each one of these toxins. Additionally, scFv 202F moderately recognized Cll2 toxin which constitutes 1.5% of the venom from C. limpidus. Based on our previous experience, we consider that these results are promising; consequently, we continue working on generating new optimized variants from scFv C1 that could be part of a recombinant scorpion anti-venom from human origin, that might reach the market in the near future.

  19. Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms

    PubMed Central

    2013-01-01

    Background Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector (Aah) and Androctonus amoreuxi (Aam). Results Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (β adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming. Conclusion These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom. PMID:23849182

  20. Severity of Scorpion Stings in the Western Brazilian Amazon: A Case-Control Study

    PubMed Central

    Queiroz, Amanda M.; Sampaio, Vanderson S.; Mendonça, Iran; Fé, Nelson F.; Sachett, Jacqueline; Ferreira, Luiz Carlos L.; Feitosa, Esaú; Wen, Fan Hui; Lacerda, Marcus; Monteiro, Wuelton

    2015-01-01

    Background Scorpion stings are a major public health problem in Brazil, with an increasing number of registered cases every year. Affecting mostly vulnerable populations, the phenomenon is not well described and is considered a neglected disease. In Brazil, the use of anti-venom formulations is provided free of charge. The associate scorpion sting case is subject to compulsory reporting. This paper describes the epidemiology and identifies factors associated with severity of scorpions stings in the state of Amazonas, in the Western Brazilian Amazon. Methodology/Principal Findings This study included all cases of scorpion stings in the state of Amazonas reported to the Brazilian Diseases Surveillance System from January 1, 2007 to December 31, 2014. A case-control study was conducted to identify factors associated with scorpions sting severity. A total of 2,120 cases were reported during this period. The mean incidence rate in the Amazonas was 7.6 per 100,000 inhabitants/year. Scorpion stings showed a large spatial distribution in the state and represent a potential occupational health problem for rural populations. There was a positive correlation between the absolute number of cases and the altimetric river levels in the Central (p<0.001; Rs = 0.479 linear) and Southwest (p = 0.032; linear Rs = 0.261) regions of the state. Cases were mostly classified as mild (68.6%), followed by moderate (26.8%), and severe (4.6%). The overall lethality rate was 0.3%. Lethality rate among children ≤10 years was 1.3%. Age <10 years [OR = 2.58 (95%CI = 1.47–4.55; p = 0.001)], stings occurring in the rural area [OR = 1.97 (95%CI = 1.18–3.29; p = 0.033) and in the South region of the state [OR = 1.85 (95%CI = 1.17–2.93; p = 0.008)] were independently associated with the risk of developing severity. Conclusions/Significance Scorpion stings show an extensive distribution in the Western Brazilian Amazon threatening especially rural populations, children ≤10 in particular. Thus

  1. Envenomation caused by Rhopalurus amazonicus Lourenço, 1986 (Scorpiones, Buthidae) in Pará State, Brazil.

    PubMed

    Fuentes-Silva, Deyanira; Santos-Jr, Alfredo P; Oliveira, Joacir Stolarz

    2014-01-01

    Scorpions, mainly those belonging to the genus Tityus cause many deaths and injuries in Brazil, with tens of thousands of envenomations notified every year. However, injuries involving other scorpion species are scarcely registered. Among the sixteen species of the genus Rhopalurus, Thorell, 1876, described up to date, nine are found in this country, with only a confirmed case of human envenomation provoked by R. agamemnon Koch, 1839. The present case reports, for the first time, a case of scorpion sting in a human victim involving Rhopalurus amazonicus, endemic species of the west region of the Pará state, Amazon, Brazil. The symptoms of envenomation were local pain and paresthesia. This study contributes to develop the knowledge on venomous scorpions, particularly those that may cause envenomations in this region.

  2. [Quod medicina aliis, aliis est acre venenum**--venoms as a source of anticancer agents].

    PubMed

    Kucińska, Małgorzata; Ruciński, Piotr; Murias, Marek

    2013-01-01

    Natural product derived from plants and animals were used in folk medicine for centuries. The venoms produced by animals for hunting of self-defence are rich in bioactive compounds with broad spectrum of biological activity. The papers presents the most promising compounds isolated from venoms of snakes, scorpions and toads. For these compounds both: mechanism of anticancer activity as well as possibilities of clinical use are presented.

  3. The Acetylcholine Receptor and Its Ionic Channel as Targets for Drugs and Toxins

    DTIC Science & Technology

    1981-12-10

    twitch (Tsai et al., 1980). R•e- sting membrane potential and passive electrical properties were..Z1ttle-i. affected by PCP. At high concentrations of...unaffected by tetrodotoxin and cevLne. Under conditions of this assay, neither crude Leiurus quinquestriatus scorpion venom nor purified sea anemone

  4. Cloning and characterization of a novel calcium channel toxin-like gene BmCa1 from Chinese scorpion Mesobuthus martensii Karsch.

    PubMed

    Zhijian, Cao; Yun, Xie; Chao, Dai; Shunyi, Zhu; Shijin, Yin; Yingliang, Wu; Wenxin, Li

    2006-06-01

    Many studies have been carried on peptides and genes encoding scorpion toxins from the venom of Mesobuthus martensii Karsch (synonym: Buthus martensii Karsch, BmK), such as Na+, K+ and Cl- channel modulators. In this study, a novel calcium channel toxin-like gene BmCa1 was isolated and characterized from the venom of Mesobuthus martensii Karsch. First, a partial cDNA sequence of the Ca2+ channel toxin-like gene was identified by random sequencing method from a venomous gland cDNA library of Mesobuthus martensii Karsch. The full-length sequence of BmCa1 was then obtained by 5'RACE technique. The peptide deduced from BmCa1 precursor nucleotide sequence contains a 27-residue signal peptide and a 37-residue mature peptide. Although BmCa1 and other scorpion toxins are different at the gene and protein primary structure levels, BmCa1 has the same precursor nucleotide organization and cysteine arrangement as that of the first subfamily members of calcium channel scorpion toxins. Genomic DNA sequence of BmCa1 was also cloned by PCR. Sequence analysis showed that BmCa1 gene consists of three exons separated by two introns of 72 bp and 1076 bp in length, respectively. BmCa1 is the first calcium channel toxin-like gene cloned from the venom of Mesobuthus martensii Karsch and potentially represents a novel class of calcium channel toxins in scorpion venoms.

  5. Animal venom studies: Current benefits and future developments.

    PubMed

    Utkin, Yuri N

    2015-05-26

    Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom of these animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and

  6. Modern trends in animal venom research - omics and nanomaterials.

    PubMed

    Utkin, Yuri N

    2017-02-26

    Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times. The development of new methods in mass spectrometry and sequencing have allowed such characterizations of venom, encompassing the identification of new toxins present in venoms at extremely low concentrations to changes in metabolism of prey organisms after envenomation. In particular, this type of comprehensive research has become possible due to the development of the various omics technologies: Proteomics, peptidomics, transcriptomics, genomics and metabolomics. As in other research fields, these omics technologies ushered in a revolution for venom studies, which is now entering the era of big data. Nanotechnology is a very new branch of technology and developing at an extremely rapid pace. It has found application in many spheres and has not bypassed the venom studies. Nanomaterials are quite promising in medicine, and most studies combining venoms and nanomaterials are dedicated to medical applications. Conjugates of nanoparticles with venom components have been proposed for use as drugs or diagnostics. For example, nanoparticles conjugated with chlorotoxin - a toxin in scorpion venom, which has been shown to bind specifically to glioma cells - are considered as potential glioma-targeted drugs, and conjugates of neurotoxins with fluorescent semiconductor nanoparticles or quantum dots may be used to detect endogenous targets expressed in live cells. The data on application of omics and

  7. Animal venom studies: Current benefits and future developments

    PubMed Central

    Utkin, Yuri N

    2015-01-01

    Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom of these animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and

  8. Modern trends in animal venom research - omics and nanomaterials

    PubMed Central

    Utkin, Yuri N

    2017-01-01

    Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times. The development of new methods in mass spectrometry and sequencing have allowed such characterizations of venom, encompassing the identification of new toxins present in venoms at extremely low concentrations to changes in metabolism of prey organisms after envenomation. In particular, this type of comprehensive research has become possible due to the development of the various omics technologies: Proteomics, peptidomics, transcriptomics, genomics and metabolomics. As in other research fields, these omics technologies ushered in a revolution for venom studies, which is now entering the era of big data. Nanotechnology is a very new branch of technology and developing at an extremely rapid pace. It has found application in many spheres and has not bypassed the venom studies. Nanomaterials are quite promising in medicine, and most studies combining venoms and nanomaterials are dedicated to medical applications. Conjugates of nanoparticles with venom components have been proposed for use as drugs or diagnostics. For example, nanoparticles conjugated with chlorotoxin - a toxin in scorpion venom, which has been shown to bind specifically to glioma cells - are considered as potential glioma-targeted drugs, and conjugates of neurotoxins with fluorescent semiconductor nanoparticles or quantum dots may be used to detect endogenous targets expressed in live cells. The data on application of omics and

  9. Bugs as drugs, part two: worms, leeches, scorpions, snails, ticks, centipedes, and spiders.

    PubMed

    Cherniack, E Paul

    2011-03-01

    In this second of a two-part series analyzing the evidence for the use of organisms as medicine, the use of a number of different "bugs" (worms, leeches, snails, ticks, centipedes, and spiders) is detailed. Several live organisms are used as treatments: leeches for plastic surgery and osteoarthritis and the helminths Trichuris suis and Necator americanus for inflammatory bowel disease. Leech saliva is the source of a number of anticoagulants, including the antithrombin agent hirudin and its synthetic analogues, which have been approved for human use. Predatory arthropods, such as certain species of snails, spiders, scorpions, centipedes, and ticks provide a trove of potential analgesic peptides in their venom. A synthetic analogue of a snail venom peptide, ziconotide, has been approved for human use and is used as an alternative to opioids in severe pain cases. Arthropods, such as ticks, have venom that contains anticoagulants and centipede venom has a protein that corrects abnormalities in lipid metabolism.

  10. A K⁺ channel blocking peptide from the Cuban scorpion Rhopalurus garridoi.

    PubMed

    Rodríguez-Ravelo, Rodolfo; Restano-Cassulini, Rita; Zamudio, Fernando Z; Coronas, Fredy I V; Espinosa-López, Georgina; Possani, Lourival D

    2014-03-01

    A proteomic analysis of the venom obtained from the Cuban scorpion Rhopalurus garridoi was performed. Venom was obtained by electrical stimulation, separated by high performance liquid chromatography, and the molecular masses of their 50 protein components were identified by mass spectrometry. A peptide of 3940 Da molecular mass was obtained in pure form and its primary structure determined. It contains 37 amino acid residues, including three disulfide bridges. Electrophysiological experiments showed that this peptide is capable of blocking reversibly K(+)-channels hKv1.1 with a Kd close to 1 μM, but is not effective against hKv1.4, hERG1 and EAG currents, at the same concentration. This is the first protein component ever isolated from this species of scorpion and was assigned the systematic number α-KTx 2.14.

  11. Preparation of a polyvalent antivenom against various Mexican scorpion Centruroides species.

    PubMed

    Garcia y Perez, G; Martin, M F; Rochat, H

    1988-01-01

    Antisera were obtained from rabbits injected with four different immunogens from the Mexican scorpion Centruroides suffusus suffusus i.e. the crude venom, a telson extract, a toxic fraction obtained from this telson extract by gel filtration and the same toxic fraction subjected to acetylation. The neutralizing capacity of these antisera are compared: it appears that a telson extract can be used instead of the crude venom to produce an efficient antiserum. The immunological properties of ground telsons obtained from three other species of the Mexican scorpion Centruroides (Centruroides noxius, Centruroides limpidus limpidus, Centruroides limpidus tecomanus) are studied with the antisera raised against Centruroides suffusus suffusus immunogens: an almost total cross-neutralization is observed.

  12. Electrophysiological Characterization of the Antarease Metalloprotease from Tityus serrulatus Venom

    PubMed Central

    Zornetta, Irene; Scorzeto, Michele; Mendes Dos Reis, Pablo Victor; De Lima, Maria E.; Montecucco, Cesare; Megighian, Aram; Rossetto, Ornella

    2017-01-01

    Scorpions are among the oldest venomous living organisms and the family Buthidae is the largest and most medically relevant one. Scorpion venoms include many toxic peptides, but recently, a metalloprotease from Tityus serrulatus called antarease was reported to be capable of cleaving VAMP2, a protein involved in the neuroparalytic syndromes of tetanus and botulism. We have produced antarease and an inactive metalloprotease mutant in a recombinant form and analyzed their enzymatic activity on recombinant VAMP2 in vitro and on mammalian and insect neuromuscular junction. The purified recombinant antarease paralyzed the neuromuscular junctions of mice and of Drosophila melanogaster whilst the mutant was inactive. We were unable to demonstrate any cleavage of VAMP2 under conditions which leads to VAMP proteolysis by botulinum neurotoxin type B. Antarease caused a reduced release probability, mainly due to defects upstream of the synaptic vesicles fusion process. Paired pulse experiments indicate that antarease might proteolytically inactivate a voltage-gated calcium channel. PMID:28264432

  13. Electrophysiological Characterization of the Antarease Metalloprotease from Tityus serrulatus Venom.

    PubMed

    Zornetta, Irene; Scorzeto, Michele; Mendes Dos Reis, Pablo Victor; De Lima, Maria E; Montecucco, Cesare; Megighian, Aram; Rossetto, Ornella

    2017-02-27

    Scorpions are among the oldest venomous living organisms and the family Buthidae is the largest and most medically relevant one. Scorpion venoms include many toxic peptides, but recently, a metalloprotease from Tityus serrulatus called antarease was reported to be capable of cleaving VAMP2, a protein involved in the neuroparalytic syndromes of tetanus and botulism. We have produced antarease and an inactive metalloprotease mutant in a recombinant form and analyzed their enzymatic activity on recombinant VAMP2 in vitro and on mammalian and insect neuromuscular junction. The purified recombinant antarease paralyzed the neuromuscular junctions of mice and of Drosophila melanogaster whilst the mutant was inactive. We were unable to demonstrate any cleavage of VAMP2 under conditions which leads to VAMP proteolysis by botulinum neurotoxin type B. Antarease caused a reduced release probability, mainly due to defects upstream of the synaptic vesicles fusion process. Paired pulse experiments indicate that antarease might proteolytically inactivate a voltage-gated calcium channel.

  14. The Mediterranean scorpion Mesobuthus gibbosus (Scorpiones, Buthidae): transcriptome analysis and organization of the genome encoding chlorotoxin-like peptides

    PubMed Central

    2014-01-01

    Background Transcrof toxin genes of scorpion species have been published. Up to this moment, no information on the gene characterization of M. gibbosus is available. Results This study provides the first insight into gene expression in venom glands from M. gibbosus scorpion. A cDNA library was generated from the venom glands and subsequently analyzed (301 clones). Sequences from 177 high-quality ESTs were grouped as 48 Mgib sequences, of those 48 sequences, 40 (29 “singletons” and 11 “contigs”) correspond with one or more ESTs. We identified putative precursor sequences and were grouped them in different categories (39 unique transcripts, one with alternative reading frames), resulting in the identification of 12 new toxin-like and 5 antimicrobial precursors (transcripts). The analysis of the gene families revealed several new components categorized among various toxin families with effect on ion channels. Sequence analysis of a new KTx precursor provides evidence to validate a new KTx subfamily (α-KTx 27.x). A second part of this work involves the genomic organization of three Meg-chlorotoxin-like genes (ClTxs). Genomic DNA sequence reveals close similarities (presence of one same-phase intron) with the sole genomic organization of chlorotoxins ever reported (from M. martensii). Conclusions Transcriptome analysis is a powerful strategy that provides complete information of the gene expression and molecular diversity of the venom glands (telson). In this work, we generated the first catalogue of the gene expression and genomic organization of toxins from M. gibbosus. Our result represents a relevant contribution to the knowledge of toxin transcripts and complementary information related with other cell function proteins and venom peptide transcripts. The genomic organization of the chlorotoxin genes may help to understand the diversity of this gene family. PMID:24746279

  15. Computational Studies of Venom Peptides Targeting Potassium Channels

    PubMed Central

    Chen, Rong; Chung, Shin-Ho

    2015-01-01

    Small peptides isolated from the venom of animals are potential scaffolds for ion channel drug discovery. This review article mainly focuses on the computational studies that have advanced our understanding of how various toxins interfere with the function of K+ channels. We introduce the computational tools available for the study of toxin-channel interactions. We then discuss how these computational tools have been fruitfully applied to elucidate the mechanisms of action of a wide range of venom peptides from scorpions, spiders, and sea anemone. PMID:26633507

  16. A New Assay for the Detection of Loxosceles Species (Brown Recluse) Spider Venom

    PubMed Central

    Gomez, Hernan F.; Krywko, Diann M.; Stoecker, William V.

    2011-01-01

    Study objective Dermal lesions from unrelated arthropod species and medical causes appear similar to Loxosceles species (brown recluse spider) bites. This may result in delayed diagnosis and treatment. We developed a sensitive Loxosceles species venom enzyme-linked immunosorbent assay (ELISA) and characterized the specificity of the assay by evaluating antigenic cross-reactivity from a variety of North American arthropod venoms. Methods North American arthropod (14 spiders, 2 scorpions, and 1 bee) venoms were studied. Three venom amounts (diluted in 100 μL of ELISA buffer) were assayed: 16,000 ng, 2,000 ng, and 40 ng. The latter quantity was selected because this is the observed maximum amount of venom we detect when inoculating dermis with amounts likely to be deposited by a spider bite. The larger venom amounts are overwhelming quantities designed to test the limits of the assay for arthropod venom cross-reactivity. Similar amounts of Loxosceles species venom and bovine albumin served as positive and negative controls, respectively. Results At the lowest amount of venom tested (40 ng), the ELISA detected only the Loxosceles species positive control. When 2,000 ng was assayed, only Scytodes fusca and Kukulcania hibernalis arachnid venoms (in addition to Loxosceles species) cross-reacted to the assay. Finally, at 16,000 ng, the ELISA assay modestly detected Diguetia canities, Heteropoda venatoria, Tegenaria agrestis, Plectreurys tristes, Dolomedes tenebrosus, and Hadrurus arizonensis arachnid venoms. Conclusion Cross-reactivity was observed in 8 of 17 North American arthropod venoms when large venom amounts were assayed with a Loxosceles species ELISA. By using a relevant quantity of venom, 40 ng, the assay was specific for Loxosceles species venom. The venom specificity of the ELISA may allow clinical application in Loxosceles species endemic regions of North America. PMID:11973553

  17. Neurotoxic and Cytotoxic Effects of Venom from Different Populations of the Egyptian Scorpio Maurus Palmatus

    USDA-ARS?s Scientific Manuscript database

    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 i...

  18. Three new antimicrobial peptides from the scorpion Pandinus imperator.

    PubMed

    Zeng, Xian-Chun; Zhou, Lingli; Shi, Wanxia; Luo, Xuesong; Zhang, Lei; Nie, Yao; Wang, Jinwei; Wu, Shifen; Cao, Bin; Cao, Hanjun

    2013-07-01

    Three novel cysteine-free venom peptides, which were referred to as Pantinin-1, Pantinin-2 and Pantinin-3, respectively, have been identified from the scorpion Pandinus imperator by cDNA cloning strategy. The precursor of each peptide consists of a signal peptide, a mature peptide with no disulfide bridges, and an acidic propeptide with a typical processing signal. Each of the three peptides is an α-helical, cationic and amphipathic molecule with 13 or 14 amino acid residues. Their amino acid sequences are homologous to those of some 13-mer antimicrobial peptides isolated from scorpions. Antimicrobial assay showed that all the three peptides possess relatively strong activities against Gram-positive bacteria and a fungus, but have very weak antimicrobial activities against Gram-negative bacteria. Toxicity assay showed that the three peptides exhibit very low or mild hemolytic activities against human red blood cells. It is interesting to see that Pantinin-3 is able to potently inhibit the growth of vancomycin-resistant Enterococcus (VRE) S13, a pathogen that can cause a number of human infections; this suggests that Pantinin-3 has great potential to be applied in the treatment of VRE infections. Our findings gain new insights into the structure/function relationships of the small linear cationic antimicrobial peptides from scorpions, and provide new templates for designing of antimicrobial agents targeting antibiotic-resistant pathogenic bacteria.

  19. Insights into Antimicrobial Peptides from Spiders and Scorpions

    PubMed Central

    Wang, Xiuqing; Wang, Guangshun

    2015-01-01

    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

  20. Scorpionism in Ecuador: First report of severe and fatal envenoming cases from northern Manabí by Tityus asthenes Pocock.

    PubMed

    Borges, Adolfo; Morales, Melva; Loor, Wilmer; Delgado, Miguel

    2015-10-01

    The presence in rural areas of western Ecuador of scorpions in the genus Tityus capable of producing pediatric mortality is hereby evidenced. The medical significance of scorpions in Ecuador has been underestimated partly because of the clinically unimportant stings delivered by Centruroides margaritatus and Teuthraustes atramentarius, which have venom with low toxicity to vertebrates. Five intra-domiciliary cases of scorpion envenoming in victims aged between 1.9 and 16 years old, including one fatality, are reported from rural settings in forest areas of Chone (n = 2) and Flavio Alfaro (n = 3) counties, northern Manabí province, western Ecuador. Three cases were graded as Class II (moderate) and two in Class III (severe) envenoming. Manifestations showed characteristic autonomic nervous system hyper-stimulation and the fatality (a 1.9-year-old boy from Flavio Alfaro) was due to cardio-respiratory failure. Marked leukocytosis in four of the cases (21,800-31,800 cells/mm(3)), with notable neutrophilia (58-82%), suggests induction of a venom-mediated systemic inflammatory response-like syndrome. Specimens responsible for cases in Flavio Alfaro County, including the fatality, were classified as Tityus asthenes Pocock, accountable for severe scorpionism in Colombia. These findings demand implementation of control and therapeutic measures in affected areas in Ecuador, including evaluation of available scorpion antivenoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. 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). Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Isolation and Characterization of CvIV4: A Pain Inducing α- Scorpion Toxin

    PubMed Central

    Rowe, Ashlee H.; Xiao, Yucheng; Scales, Joseph; Linse, Klaus D.; Rowe, Matthew P.; Cummins, Theodore R.; Zakon, Harold H.

    2011-01-01

    Background Among scorpion species, the Buthidae produce the most deadly and painful venoms. However, little is known regarding the venom components that cause pain and their mechanism of action. Using a paw-licking assay (Mus musculus), this study compared the pain-inducing capabilities of venoms from two species of New World scorpion (Centruroides vittatus, C. exilicauda) belonging to the neurotoxin-producing family Buthidae with one species of non-neurotoxin producing scorpion (Vaejovis spinigerus) in the family Vaejovidae. A pain-inducing α-toxin (CvIV4) was isolated from the venom of C. vittatus and tested on five Na+ channel isoforms. Principal Findings C. vittatus and C. exilicauda venoms produced significantly more paw licking in Mus than V. spinigerus venom. CvIV4 produced paw licking in Mus equivalent to the effects of whole venom. CvIV4 slowed the fast inactivation of Nav1.7, a Na+ channel expressed in peripheral pain-pathway neurons (nociceptors), but did not affect the Nav1.8-based sodium currents of these neurons. CvIV4 also slowed the fast inactivation of Nav1.2, Nav1.3 and Nav1.4. The effects of CvIV4 are similar to Old World α-toxins that target Nav1.7 (AahII, BmK MI, LqhIII, OD1), however the primary structure of CvIV4 is not similar to these toxins. Mutant Nav1.7 channels (D1586A and E1589Q, DIV S3–S4 linker) reduced but did not abolish the effects of CvIV4. Conclusions This study: 1) agrees with anecdotal evidence suggesting that buthid venom is significantly more painful than non-neurotoxic venom; 2) demonstrates that New World buthids inflict painful stings via toxins that modulate Na+ channels expressed in nociceptors; 3) reveals that Old and New World buthids employ similar mechanisms to produce pain. Old and New World α-toxins that target Nav1.7 have diverged in sequence, but the activity of these toxins is similar. Pain-inducing toxins may have evolved in a common ancestor. Alternatively, these toxins may be the product of convergent

  3. Phylogenomic resolution of scorpions reveals multilevel discordance with morphological phylogenetic signal.

    PubMed

    Sharma, Prashant P; Fernández, Rosa; Esposito, Lauren A; González-Santillán, Edmundo; Monod, Lionel

    2015-04-07

    Scorpions represent an iconic lineage of arthropods, historically renowned for their unique bauplan, ancient fossil record and venom potency. Yet, higher level relationships of scorpions, based exclusively on morphology, remain virtually untested, and no multilocus molecular phylogeny has been deployed heretofore towards assessing the basal tree topology. We applied a phylogenomic assessment to resolve scorpion phylogeny, for the first time, to our knowledge, sampling extensive molecular sequence data from all superfamilies and examining basal relationships with up to 5025 genes. Analyses of supermatrices as well as species tree approaches converged upon a robust basal topology of scorpions that is entirely at odds with traditional systematics and controverts previous understanding of scorpion evolutionary history. All analyses unanimously support a single origin of katoikogenic development, a form of parental investment wherein embryos are nurtured by direct connections to the parent's digestive system. Based on the phylogeny obtained herein, we propose the following systematic emendations: Caraboctonidae is transferred to Chactoidea new superfamilial assignment: ; superfamily Bothriuroidea revalidated: is resurrected and Bothriuridae transferred therein; and Chaerilida and Pseudochactida are synonymized with Buthida new parvordinal synonymies: .

  4. Phylogenomic resolution of scorpions reveals multilevel discordance with morphological phylogenetic signal

    PubMed Central

    Sharma, Prashant P.; Fernández, Rosa; Esposito, Lauren A.; González-Santillán, Edmundo; Monod, Lionel

    2015-01-01

    Scorpions represent an iconic lineage of arthropods, historically renowned for their unique bauplan, ancient fossil record and venom potency. Yet, higher level relationships of scorpions, based exclusively on morphology, remain virtually untested, and no multilocus molecular phylogeny has been deployed heretofore towards assessing the basal tree topology. We applied a phylogenomic assessment to resolve scorpion phylogeny, for the first time, to our knowledge, sampling extensive molecular sequence data from all superfamilies and examining basal relationships with up to 5025 genes. Analyses of supermatrices as well as species tree approaches converged upon a robust basal topology of scorpions that is entirely at odds with traditional systematics and controverts previous understanding of scorpion evolutionary history. All analyses unanimously support a single origin of katoikogenic development, a form of parental investment wherein embryos are nurtured by direct connections to the parent's digestive system. Based on the phylogeny obtained herein, we propose the following systematic emendations: Caraboctonidae is transferred to Chactoidea new superfamilial assignment; superfamily Bothriuroidea revalidated is resurrected and Bothriuridae transferred therein; and Chaerilida and Pseudochactida are synonymized with Buthida new parvordinal synonymies. PMID:25716788

  5. Pulmonary edema following scorpion envenomation: mechanisms, clinical manifestations, diagnosis and treatment.

    PubMed

    Bahloul, Mabrouk; Chaari, Anis; Dammak, Hassen; Samet, Mohamed; Chtara, Kamilia; Chelly, Hedi; Ben Hamida, Chokri; Kallel, Hatem; Bouaziz, Mounir

    2013-01-10

    Scorpion envenomation is common in tropical and subtropical regions. Cardio-respiratory manifestations, mainly cardiogenic shock and pulmonary edema, are the leading causes of death after scorpion envenomation. The mechanism of pulmonary edema remains unclear and contradictory conclusions were published. However, most publications confirm that pulmonary edema has been attributed to acute left ventricular failure. Cardiac failure can result from massive release of catecholamines, myocardial damage induced by the venom or myocardial ischemia. Factors usually associated with the diagnosis of pulmonary edema were young age, tachypnea, agitation, sweating, or the presence of high plasma protein concentrations. Treatment of scorpion envenomation has two components: antivenom administration and supportive care. The latter mainly targets hemodynamic impairment and cardiogenic pulmonary edema. In Latin America, and India, the use of Prazosin is recommended for treatment of pulmonary edema because pulmonary edema is associated with arterial hypertension. However, in North Africa, scorpion leads to cardiac failure with systolic dysfunction with normal vascular resistance and dobutamine was recommended. Dobutamine infusion should be used as soon as we have enough evidence suggesting the presence of pulmonary edema, since it has been demonstrated that scorpion envenomation can result in pulmonary edema secondary to acute left ventricular failure. In severe cases, mechanical ventilation can be required.

  6. Biochemical and enzymatic changes after black scorpion Heterometrus fastigiousus Couzijn envenomation in experimental albino mice.

    PubMed

    Chaubey, Mukesh Kumar; Upadhyay, Ravi Kant

    2008-10-01

    The toxic effects of Asian black scorpion Heterometrus fastigiousus (Family, Scorpionidae) venom were determined in albino mice (NIH strain). Venom was isolated and fractioned by Sepharose CL-6B column chromatography. The toxicity of fractioned venom was determined in albino mice by subcutaneous envenomation. The LD(50) of venom was found to be 15 mg kg(-1) body weight and range of molecular weight of venom proteins responsible for toxicity was found from 9.5-63 kDs. The effects of fractioned venom on different biochemical and enzymatic parameters in blood serum and gastrocnemius muscle tissue of albino mice were determined after experimental envenomation. An increase in serum levels of glucose, free amino acids, uric acid, pyruvic acid and total protein was observed while a decrease in the cholesterol level in serum was observed after 4 h of envenomation. Increase in alkaline phosphatase (ALP), acid phosphatase (ACP), lactic dehydrogenase (LDH) and glutamate-pyruvate transaminase (GPT) enzyme activity in serum was observed. Glycogen content in liver, atria, ventricle, rectus abdominus and gastrocnemius muscle was decreased after experimental envenomation. Activity of ALP, ACP, LDH, GPT, AChE and Na+K+ATPase enzymes in gastrocnemius muscle tissue of envenomed albino mice was studied. Inhibition in ALP, AChE and Na+K+ATPase enzyme activity and increase in ACP, LDH and GPT enzyme activity was observed in gastrocnemius muscle after scorpion envenomation. In vitro studies with AChE and Na+K+ATPase enzymes indicated that enzymatic activity of AChE was inhibited competitively by fractioned venom in gastrocnemius muscle.

  7. Effects of Animal Venoms and Toxins on Hallmarks of Cancer.

    PubMed

    Chaisakul, Janeyuth; Hodgson, Wayne C; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components.

  8. Effects of Animal Venoms and Toxins on Hallmarks of Cancer

    PubMed Central

    Chaisakul, Janeyuth; Hodgson, Wayne C.; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

  9. Convergent evolution in the antennae of a cerambycid beetle, Onychocerus albitarsis, and the sting of a scorpion.

    PubMed

    Berkov, Amy; Rodríguez, Nelson; Centeno, Pedro

    2008-03-01

    Venom-injecting structures have arisen independently in unrelated arthropods including scorpions, spiders, centipedes, larval owlflies and antlions, and Hymenoptera (wasps, ants, and bees). Most arthropods use venom primarily as an offensive weapon to subdue prey, and only secondarily in defense against enemies. Venom is injected by biting with fangs or stinging with a specialized hypodermic structure used exclusively for the delivery of venom (usually modified terminal abdominal segments). A true sting apparatus, previously known only in scorpions and aculeate wasps, is now known in a third group. We here report the first known case of a cerambycid beetle using its antennae to inject a secretion that causes cutaneous and subcutaneous inflammation in humans. Scanning electron microscopy revealed that the terminal antennal segment of Onychocerus albitarsis (Pascoe) has two pores opening into channels leading to the tip through which the secretion is delivered. This is a novel case of convergent evolution: The delivery system is almost identical to that found in the stinger of a deadly buthid scorpion.

  10. Convergent evolution in the antennae of a cerambycid beetle, Onychocerus albitarsis, and the sting of a scorpion

    NASA Astrophysics Data System (ADS)

    Berkov, Amy; Rodríguez, Nelson; Centeno, Pedro

    2008-03-01

    Venom-injecting structures have arisen independently in unrelated arthropods including scorpions, spiders, centipedes, larval owlflies and antlions, and Hymenoptera (wasps, ants, and bees). Most arthropods use venom primarily as an offensive weapon to subdue prey, and only secondarily in defense against enemies. Venom is injected by biting with fangs or stinging with a specialized hypodermic structure used exclusively for the delivery of venom (usually modified terminal abdominal segments). A true sting apparatus, previously known only in scorpions and aculeate wasps, is now known in a third group. We here report the first known case of a cerambycid beetle using its antennae to inject a secretion that causes cutaneous and subcutaneous inflammation in humans. Scanning electron microscopy revealed that the terminal antennal segment of Onychocerus albitarsis (Pascoe) has two pores opening into channels leading to the tip through which the secretion is delivered. This is a novel case of convergent evolution: The delivery system is almost identical to that found in the stinger of a deadly buthid scorpion.

  11. Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif

    PubMed Central

    Smith, Jennifer J.; Hill, Justine M.; Little, Michelle J.; Nicholson, Graham M.; King, Glenn F.; Alewood, Paul F.

    2011-01-01

    The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails. Over a decade ago it was proposed that the ICK motif is an elaboration of an ancestral two-disulfide fold coined the disulfide-directed β-hairpin (DDH). Here we report the isolation, characterization, and structure of a novel toxin [U1-liotoxin-Lw1a (U1-LITX-Lw1a)] from the venom of the scorpion Liocheles waigiensis that is the first example of a native peptide that adopts the DDH fold. U1-LITX-Lw1a not only represents the discovery of a missing link in venom protein evolution, it is the first member of a fourth structural fold to be adopted by scorpion-venom peptides. Additionally, we show that U1-LITX-Lw1a has potent insecticidal activity across a broad range of insect pest species, thereby providing a unique structural scaffold for bioinsecticide development. PMID:21670253

  12. Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif.

    PubMed

    Smith, Jennifer J; Hill, Justine M; Little, Michelle J; Nicholson, Graham M; King, Glenn F; Alewood, Paul F

    2011-06-28

    The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails. Over a decade ago it was proposed that the ICK motif is an elaboration of an ancestral two-disulfide fold coined the disulfide-directed β-hairpin (DDH). Here we report the isolation, characterization, and structure of a novel toxin [U(1)-liotoxin-Lw1a (U(1)-LITX-Lw1a)] from the venom of the scorpion Liocheles waigiensis that is the first example of a native peptide that adopts the DDH fold. U(1)-LITX-Lw1a not only represents the discovery of a missing link in venom protein evolution, it is the first member of a fourth structural fold to be adopted by scorpion-venom peptides. Additionally, we show that U(1)-LITX-Lw1a has potent insecticidal activity across a broad range of insect pest species, thereby providing a unique structural scaffold for bioinsecticide development.

  13. A Combinational Strategy upon RNA Sequencing and Peptidomics Unravels a Set of Novel Toxin Peptides in Scorpion Mesobuthus martensii

    PubMed Central

    Luan, Ning; Shen, Wang; Liu, Jie; Wen, Bo; Lin, Zhilong; Yang, Shilong; Lai, Ren; Liu, Siqi; Rong, Mingqiang

    2016-01-01

    Scorpion venom is deemed to contain many toxic peptides as an important source of natural compounds. Out of the two hundred proteins identified in Mesobuthus martensii (M. martensii), only a few peptide toxins have been found so far. Herein, a combinational approach based upon RNA sequencing and Liquid chromatography-mass spectrometry/mass spectrometry (LC MS/MS) was employed to explore the venom peptides in M. martensii. A total of 153 proteins were identified from the scorpion venom, 26 previously known and 127 newly identified. Of the novel toxins, 97 proteins exhibited sequence similarities to known toxins, and 30 were never reported. Combining peptidomic and transcriptomic analyses, the peptide sequence of BmKKx1 was reannotated and four disulfide bridges were confirmed within it. In light of the comparison of conservation and variety of toxin amino acid sequences, highly conserved and variable regions were perceived in 24 toxins that were parts of two sodium channel and two potassium channel toxins families. Taking all of this evidences together, the peptidomic analysis on M. martensii indeed identified numerous novel scorpion peptides, expanded our knowledge towards the venom diversity, and afforded a set of pharmaceutical candidates. PMID:27782050

  14. Androctonus australis hector venom contributes to the interaction between neuropeptides and mast cells in pulmonary hyperresponsiveness.

    PubMed

    Chaïr-Yousfi, Imène; Laraba-Djebari, Fatima; Hammoudi-Triki, Djelila

    2015-03-01

    Lung injury and respiratory distress syndrome are frequent symptoms observed in the most severe cases of scorpion envenomation. The uncontrolled transmigration of leukocyte cells into the lung interstitium and alveolar space and pulmonary edema may be the cause of death. Mast cells can release various inflammatory mediators known to be involved in the development of lung edema following scorpion venom injection. The present study was designed to determine the evidence of neurokinin 1 (NK1) receptor and the involvement of mast cell activation to induce pulmonary edema and to increase vascular permeability after Androctonus australis hector (Aah) venom administration. To this end, mast cells were depleted using compound 48/80 (C48/80). Furthermore, the involvement of tachykinin NK1 receptors expressed on mast cell membranes was elucidated by their blocking with an antagonist. On the other hand, the ability of Aah venom to increase vascular permeability and to induce edema was also assessed by measuring the amount of Evans blue dye (EBD) extravasation in bronchoalveolar lavage (BAL) fluid and in the lungs of mice. Pulmonary edema, as assessed by the levels of EBD extravasation, was completely inhibited in compound 48/80-treated animals. Depletion by stimuli non-immunological C48/80 component markedly reduced induced inflammatory response following the venom administration. The mast cells seem to play an important role in the development of lung injury and the increase of vascular permeability in mice following the subcutaneous administration of Aah scorpion venom through the NK1 receptor.

  15. Pediatric electrocardiograph abnormalities following Centruroides limpidus tecomanus scorpion envenomation.

    PubMed

    Diaz, P; Chowell, G; Ceja, G; D'Auria, T C; Lloyd, R C; Castillo-Chavez, C

    2005-01-01

    Scorpionism is an endemic public health problem in Mexico [Hoffmann, C.C., 1936. La distribucion geografica de los alacranes peligrosos en la Republica Mexicana. Bol. Inst. Hygiene Mex. 2, 321; Hoffmann, C.C., Nieto, D.R., 1939. Segunda contribucion al conocimiento de los alacranes mexicanos. Anal. Inst. Biol. 10, 83-92; Mazzoti, L., Bravo-Becherelle, M.A., 1963. Scorpionism in the Mexican Republic. In: Keegan, H.L., McFarlane, W.V. (Eds.), Venomous and Poissonous Animals and Noxious Plants of the Pacific Area. Pergamon Press, London, pp. 119-131; Monroy-Velasco, J., 1961. Alacranes venenosos de Mexico. Rev. Mex. Cien. Med. Biol., Mex. 1, 1-23; Diaz-Najera, A., 1975. Listas y datos de distribucion geografica de los alacranes de Mexico. Rev. Inv. Salud. Publica. (Mex.) 35, 1; Velasco-Castrejon, O., Lara-Aguilera, R., Alatorre, H., 1976. Aspectos epidemiologicos y clinicos de la picadura de alacran en una area hiperendemica. Rev. Inv. Salud Publica. (Mex.) 36, 93-103; Dehesa-Davila, M., Possani, L.D., 1994. Scorpionism and serotherapy in Mexico. Toxicon 32 (9), 1015-1018]. In this prospective study, we assess cardiovascular disorders in children via electrocardiographic (ECG) recordings following envenomation by scorpion species Centruroides limpidus tecomanus found in the state of Colima, Mexico. We analyzed 113 cases between the ages of 5 and 14 years. Among the most frequent symptoms presented included local pain (99.1%) and paresthesia (75.2%), pruritus (36.3%), sialorrhoea (35.4%), and nystagmus (24.8%). Cardiovascular disorders were observed in 39.8% of cases, 71% of which were rhythm abnormalities. We find a significant association between the frequency of ECG alterations and age, whereby 8-9-year-old children are more likely to experience ECG alterations when compared with other tested age groups.

  16. Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals

    PubMed Central

    Mourão, Caroline B.F.; Schwartz, Elisabeth F.

    2013-01-01

    The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine pancreatic trypsin inhibitor (BPTI)-like protease inhibitors, which strongly inhibit trypsin and chymotrypsin. In this review we present the protease inhibitors (PIs) described to date from marine venomous animals, such as from sea anemone extracts and Conus venom, as well as their counterparts in terrestrial venomous animals, such as snakes, scorpions, spiders, Anurans, and Hymenopterans. More emphasis was given to the Kunitz-type inhibitors, once they are found in all these organisms. Their biological sources, specificity against different proteases, and other molecular blanks (being also K+ channel blockers) are presented, followed by their molecular diversity. Whereas sea anemone, snakes and other venomous animals present mainly Kunitz-type inhibitors, PIs from Anurans present the major variety in structure length and number of Cys residues, with at least six distinguishable classes. A representative alignment of PIs from these venomous animals shows that, despite eventual differences in Cys assignment, the key-residues for the protease inhibitory activity in all of them occupy similar positions in primary sequence. The key-residues for the K+ channel blocking activity was also compared. PMID:23771044

  17. Recruitment and diversification of an ecdysozoan family of neuropeptide hormones for black widow spider venom expression

    PubMed Central

    McCowan, Caryn; Garb, Jessica E.

    2014-01-01

    Venoms have attracted enormous attention because of their potent physiological effects and dynamic evolution, including the convergent recruitment of homologous genes for venom expression. Here we provide novel evidence for the recruitment of genes from the Crustacean Hyperglycemic Hormone (CHH) and arthropod Ion Transport Peptide (ITP) superfamily for venom expression in black widow spiders. We characterized latrodectin peptides from venom gland cDNAs from the Western black widow spider (Latrodectus hesperus), the brown widow (L. geometricus) and cupboard spider (Steatoda grossa). Phylogenetic analyses of these sequences with homologs from other spider, scorpion and wasp venom cDNAs, as well as CHH/ITP neuropeptides, show latrodectins as derived members of the CHH/ITP superfamily. These analyses suggest that CHH/ITP homologs are more widespread in spider venoms, and were recruited for venom expression in two additional arthropod lineages. We also found that the latrodectin 2 gene and nearly all CHH/ITP genes include a phase 2 intron in the same position, supporting latrodectin’s placement within the CHH/ITP superfamily. Evolutionary analyses of latrodectins suggest episodes of positive selection along some sequence lineages, and positive and purifying selection on specific codons, supporting its functional importance in widow venom. We consider how this improved understanding of latrodectin evolution informs functional hypotheses regarding its role in black widow venom as well as its potential convergent recruitment for venom expression across arthropods. PMID:24316130

  18. Recruitment and diversification of an ecdysozoan family of neuropeptide hormones for black widow spider venom expression.

    PubMed

    McCowan, Caryn; Garb, Jessica E

    2014-02-25

    Venoms have attracted enormous attention because of their potent physiological effects and dynamic evolution, including the convergent recruitment of homologous genes for venom expression. Here we provide novel evidence for the recruitment of genes from the Crustacean Hyperglycemic Hormone (CHH) and arthropod Ion Transport Peptide (ITP) superfamily for venom expression in black widow spiders. We characterized latrodectin peptides from venom gland cDNAs from the Western black widow spider (Latrodectus hesperus), the brown widow (Latrodectus geometricus) and cupboard spider (Steatoda grossa). Phylogenetic analyses of these sequences with homologs from other spider, scorpion and wasp venom cDNAs, as well as CHH/ITP neuropeptides, show latrodectins as derived members of the CHH/ITP superfamily. These analyses suggest that CHH/ITP homologs are more widespread in spider venoms, and were recruited for venom expression in two additional arthropod lineages. We also found that the latrodectin 2 gene and nearly all CHH/ITP genes include a phase 2 intron in the same position, supporting latrodectin's placement within the CHH/ITP superfamily. Evolutionary analyses of latrodectins suggest episodes of positive selection along some sequence lineages, and positive and purifying selection on specific codons, supporting its functional importance in widow venom. We consider how this improved understanding of latrodectin evolution informs functional hypotheses regarding its role in black widow venom as well as its potential convergent recruitment for venom expression across arthropods. Copyright © 2014. Published by Elsevier B.V.

  19. Echocardiologic evaluation and follow-up of cardiovascular complications in children with scorpion sting in coastal South India.

    PubMed

    Kumar, Chandra Mohan; Prasad, S V Naveen

    2015-01-01

    Scorpion stings are a common emergency in India and many other tropical countries. In India, the red scorpions are more prevalent, and their venom is more likely to cause myocardial dysfunctions. There are very few studies conducted on this problem. The following study was done in Andhra Pradesh and aimed to identify cardiovascular complications of scorpion stings in children with a follow-up of 6 months. Prospective observational study. Children admitted with scorpion sting in a tertiary care hospital between December 2009 and November 2010 and followed-up till May 2011. Scorpion stings account for 1 in every 36 admissions. Maximum cases were in 0-3 years age group. Electrocardiogram changes were seen in 76% cases and myocarditis in 42% cases. Echocardiography revealed decreased ejection fraction (EF), transient mitral regurgitation and wall motion abnormalities were observed. Average EF improved from 16% on day 1 to 47.94% and 59% on day 5 and 14 respectively, which was highly statistically significant. By the end of 1 month, all the survivors had normal EF and no residual cardiac dysfunction was observed at 6 months. Scorpion stings, a common and fatal medical emergency in India, produce echocardiographic changes without any long term residual damage on myocardial activity.

  20. Toxic peptides and genes encoding toxin gamma of the Brazilian scorpions Tityus bahiensis and Tityus stigmurus.

    PubMed

    Becerril, B; Corona, M; Coronas, F I; Zamudio, F; Calderon-Aranda, E S; Fletcher, P L; Martin, B M; Possani, L D

    1996-02-01

    Seven toxic peptides from the venom of Tityus bahiensis and Tityus stigmurus was isolated and sequenced, five of them to completion. The most abundant peptide from each of these two species of scorpion was 95% identical with that of toxin gamma from the venom of Tityus serrulatus. They were consequently named gamma-b and gamma-st respectively. The genes encoding these new gamma-like peptides were cloned and sequenced by utilizing oligonucleotides synthesized according to known cDNA sequences of toxin gamma, and amplified by PCR on templates of DNA purified from both T. bahiensis and T. stigmurus. They contain an intron of approx. 470 bp. Possible mechanisms of processing and expressing these peptides are discussed, in view of the fact that glycine is the first residue of the N-terminal sequence of T. stigmurus, whereas lysine is the residue at position 1 of toxin gamma from T. serrulatus and T. bahiensis. In addition, chemical characterization of the less abundant toxic peptides showed the presence of at least four distinct families of peptides in all three species of the genus Tityus studied. There is a large degree of similarity among peptides from different venoms of the same family. By using specific horse and rabbit antisera, the venoms of T. bahiensis, T. serrulatus and T. stigmurus were compared. They showed an extended degree of cross-reactivity. Thus these three species of scorpion have similar toxic components, the genes of which are similarly organized, processed and expressed.

  1. Toxic peptides and genes encoding toxin gamma of the Brazilian scorpions Tityus bahiensis and Tityus stigmurus.

    PubMed Central

    Becerril, B; Corona, M; Coronas, F I; Zamudio, F; Calderon-Aranda, E S; Fletcher, P L; Martin, B M; Possani, L D

    1996-01-01

    Seven toxic peptides from the venom of Tityus bahiensis and Tityus stigmurus was isolated and sequenced, five of them to completion. The most abundant peptide from each of these two species of scorpion was 95% identical with that of toxin gamma from the venom of Tityus serrulatus. They were consequently named gamma-b and gamma-st respectively. The genes encoding these new gamma-like peptides were cloned and sequenced by utilizing oligonucleotides synthesized according to known cDNA sequences of toxin gamma, and amplified by PCR on templates of DNA purified from both T. bahiensis and T. stigmurus. They contain an intron of approx. 470 bp. Possible mechanisms of processing and expressing these peptides are discussed, in view of the fact that glycine is the first residue of the N-terminal sequence of T. stigmurus, whereas lysine is the residue at position 1 of toxin gamma from T. serrulatus and T. bahiensis. In addition, chemical characterization of the less abundant toxic peptides showed the presence of at least four distinct families of peptides in all three species of the genus Tityus studied. There is a large degree of similarity among peptides from different venoms of the same family. By using specific horse and rabbit antisera, the venoms of T. bahiensis, T. serrulatus and T. stigmurus were compared. They showed an extended degree of cross-reactivity. Thus these three species of scorpion have similar toxic components, the genes of which are similarly organized, processed and expressed. PMID:8611151

  2. Design and expression of recombinant toxins from Mexican scorpions of the genus Centruroides for production of antivenoms.

    PubMed

    Jiménez-Vargas, J M; Quintero-Hernández, V; González-Morales, L; Ortiz, E; Possani, L D

    2017-03-15

    This manuscript describes the design of plasmids containing the genes coding for four main mammalian toxins of scorpions from the genus Centruroides (C.) of Mexico. The genes that code for toxin 2 of C. noxius (Cn2), toxin 2 from C. suffusus (Css2) and toxins 1 and 2 from C. limpidus (Cll1 and Cll2) were included into individual plasmids carrying the genetic construction for expression of fusion proteins containing a leader peptide (pelB) that directs the expressed protein to the bacterial periplasm, a carrier protein (thioredoxin), the cleavage site for enterokinase, the chosen toxin and a poly-histidine tag (6xHis-tag) for purification of the hybrid protein by immobilized metal ion affinity chromatography after expression in Escherichia coli strain BL21 (DE3). The purified hybrid proteins containing the recombinant toxins (abbreviated Thio-EK-Toxin) were used for immunization of three independent groups of ten mice and four rabbits. Challenging the first group of mice, immunized with recombinant Thio-EK-Css2, with three median lethal doses (LD50) of C. suffusus soluble venom resulted in the survival of all the test animals without showing intoxication symptoms. All control mice (none immunized) died. Similar results were obtained with mice previously immunized with Thio-EK-Cn2 and challenged with C. noxius venom. The third group of mice immunized with both Thio-EK-Cll1 and Thio-EK-Cll2 showed an 80% survival ratio when challenged with only one LD50 of C. limpidus venom, all showing symptoms of intoxication. The sera from rabbits immunized with a combination of the four recombinant toxins were collected separately and used to assess their neutralization capacity in vitro (pre-incubating the serum with the respective scorpion venom and injecting the mixture into mice), using six mice for each serum/venom combination tested. The venoms from the six most dangerous scorpion species of Mexico were assayed: C. noxius, C. suffusus, C. limpidus, C. elegans, C

  3. BjalphaIT: a novel scorpion alpha-toxin selective for insects--unique pharmacological tool.

    PubMed

    Arnon, Tal; Potikha, Tamara; Sher, Daniel; Elazar, Menashe; Mao, Wenfu; Tal, Tzachy; Bosmans, Frank; Tytgat, Jan; Ben-Arie, Nissim; Zlotkin, Eliahu

    2005-03-01

    Long-chain neurotoxins derived from the venom of the Buthidae scorpions, which affect voltage-gated sodium channels (VGSCs) can be subdivided according to their toxicity to insects into insect-selective excitatory and depressant toxins (beta-toxins) and the alpha-like toxins which affect both mammals and insects. In the present study by the aid of reverse-phase HPLC column chromatography, RT-PCR, cloning and various toxicity assays, a new insect selective toxin designated as BjalphaIT was isolated from the venom of the Judean Black Scorpion (Buthotus judaicus), and its full primary sequence was determined: MNYLVVICFALLLMTVVESGRDAYIADNLNCAYTCGSNSYCNTECTKNGAVSGYCQWLGKYGNACWCINLPDKVPIRIPGACR (leader sequence is underlined). Despite its lack of toxicity to mammals and potent toxicity to insects, BjalphaIT reveals an amino acid sequence and an inferred spatial arrangement that is characteristic of the well-known scorpion alpha-toxins highly toxic to mammals. BjalphaITs sharp distinction between insects and mammals was also revealed by its effect on sodium conductance of two cloned neuronal VGSCs heterloguously expressed in Xenopus laevis oocytes and assayed with the two-electrode voltage-clamp technique. BjalphaIT completely inhibits the inactivation process of the insect para/tipE VGSC at a concentration of 100 nM, in contrast to the rat brain Na(v)1.2/beta1 which is resistant to the toxin. The above categorical distinction between mammal and insect VGSCs exhibited by BjalphaIT enables its employment in the clarification of the molecular basis of the animal group specificity of scorpion venom derived neurotoxic polypeptides and voltage-gated sodium channels.

  4. A single-point mutation enhances dual functionality of a scorpion toxin.

    PubMed

    Wang, Xueli; Gao, Bin; Zhu, Shunyi

    2016-01-01

    Scorpion venom represents a tremendous, hitherto partially explored peptide library that has been proven to be useful not only for understanding ion channels but also for drug design. MeuTXKα3 is a functionally unknown scorpion toxin-like peptide. Here we describe new transcripts of this gene arising from alternative polyadenylation and its biological function as well as a mutant with a single-point substitution at site 30. Native-like MeuTXKα3 and its mutant were produced in Escherichia coli and their toxic function against Drosophila Shaker K(+) channel and its mammalian counterparts (rKv1.1-rKv1.3) were assayed by two-electrode voltage clamp technique. The results show that MeuTXKα3 is a weak toxin with a wide-spectrum of activity on both Drosophila and mammalian K(+) channels. The substitution of a proline at site 30 by an asparagine, an evolutionarily conserved functional residue in the scorpion α-KTx family, led to an increased activity on rKv1.2 and rKv1.3 but a decreased activity on the Shaker channel without changing the potency on rKv1.1, suggesting a key role of this site in species selectivity of scorpion toxins. MeuTXKα3 was also active on a variety of bacteria with lethal concentrations ranging from 4.66 to 52.01μM and the mutant even had stronger activity on some of these bacterial species. To the best of our knowledge, this is the first report on a bi-functional short-chain peptide in the lesser Asian scorpion venom. Further extensive mutations of MeuTXKα3 at site 30 could help improve its K(+) channel-blocking and antibacterial functions.

  5. Hey! A Scorpion Stung Me!

    MedlinePlus

    ... arachnid family, which also includes mites, ticks , and spiders. Scorpions are about 3 inches long (about the ... A Bee Stung Me! Hey! A Black Widow Spider Bit Me! Hey! A Mosquito Bit Me! Hey! ...

  6. Arthropod venoms: a vast arsenal of insecticidal neuropeptides.

    PubMed

    Schwartz, Elisabeth F; Mourão, Caroline B F; Moreira, Karla G; Camargos, Thalita S; Mortari, Márcia R

    2012-01-01

    Arthropods are the most diverse animal group on the planet, and occupy almost all ecological niches. Venomous arthropods are a rich source of bioactive compounds evolved for prey capture and defense against predators and/or microorganisms. These highly potent chemical arsenals represent an available source for new insecticidal compounds as they act selectively on their molecular targets. These toxins affect the invertebrate nervous system and, until the moment, several insecticidal compounds belonging to the class of peptides or polyamine-like compounds have been purified and characterized from the venom of arachnids and hymenopterans. This review focuses on invertebrate-specific peptide neurotoxins that have been isolated from the venom ofspiders, scorpions, centipedes, ants, and wasps, discussing their potential in pest control and as invaluable tools in neuropharmacology.

  7. Lung compliance, plasma electrolyte levels and acid-base balance are affected by scorpion envenomation in anesthetized rats under mechanical ventilation.

    PubMed

    Andrade, Marcus V; Caramez, Maria Paula R; Abreu, Elnara Marcia N N; Dolnikoff, Marisa; Omar, Erick D; Velasco, Irineu T; Cunha-Melo, José R

    2004-05-01

    To determine the effects of Tityus serrulatus scorpion toxin on lung compliance and resistance, ionic equilibrium and acid-base balance over time in anesthetized and mechanically ventilated rats, we measured air flow, tracheal and esophageal pressure. Lung volume was obtained by electronic integration of airflow signal. Arterial blood samples were collected through a catheter at baseline (before) and 5, 15, 30 and 60 min after scorpion toxin injection for arterial blood gases, bicarbonate, and alkali reserve levels as well as for, sodium, potassium, magnesium, glucose, lactate, hematocrit, and osmolality analysis. Injection of the gamma fraction of the T. serrulatus scorpion venom in rats under mechanical ventilatory support leads to a continuous decrease in lung compliance secondary to pulmonary edema, but no change in airway resistance. The changes in arterial blood gases characterizing metabolic acidosis were accompanied by an increase in arterial lactate and glucose values, suggesting a scorpion toxin-induced lactic acidosis, in association with poor tissue perfusion (hypotension and low cardiac output). Moreover, scorpion toxin injection resulted in hyperosmolality, hyperkalemia, hypermagnesemia and an increase in hematocrit. The experiments have shown a clinically relevant animal model to study severe scorpion envenoming and may help to better understand the scorpion envenoming syndrome.

  8. The importance of early bedside echocardiography in children with scorpion envenomation.

    PubMed

    Sofer, Shaul; Zucker, Nili; Bilenko, Natalya; Levitas, Aviva; Zalzstein, Eli; Amichay, Doron; Cohen-Lahav, Merav; Bernstein, Tamar

    2013-06-01

    Scorpion sting may cause myocardial injury and heart failure (HF). Clinical signs of failure may develop several hours or even days after the sting, while electrocardiography (ECG) and blood examination soon after the sting may be normal. We sought to examine whether normal echocardiographic (echo) examination performed shortly after hospital arrival would exclude subsequent HF. We also sought to check if blood troponin and natriuretic peptide values measured shortly after arrival may predict or exclude subsequent HF. Natriuretic peptide activities have not been measured in scorpion sting victims. We also wanted to check if HF occurs in envenomated young infants. In a 3-year prospective study we looked at the demographic, clinical, laboratory, ECG, and echo data of all patients with general envenomation who arrived at the emergency department (ED) after scorpion sting. Clinical, laboratory, ECG, and echo results on arrival and 24 h after arrival were checked and compared between groups of patients with normal and abnormal echo on arrival. We then looked for differences in clinical course, therapy, and outcome between groups. The study included 98 children aged 80 days to 19 years (median 53.1 months), 25 were below the age of 2 years. Envenomation by the "yellow scorpion"Leiurus quinquestriatus was suspected in 74 cases. Median time between sting and ED arrival was 80 min. Echo was performed on arrival in 93 of the 98 patients, (in 5 occasions it was not performed or not recorded) 74 were normal and 19 were abnormal. Abnormal echo included hypokinesia and low fractional shortening and ejection fraction of the left ventricle. Clinical signs, abnormal ECG, and laboratory results were not discriminative between groups on arrival. Mean troponin T was higher in patients with abnormal echo, but within normal range in 13 of the 19 patients with abnormal echo and above normal in 2 of the 74 patients with normal echo-missing sensitivity and specificity. Mean N-terminal pro

  9. Mortality and antibody responses of mice to three successive episodes of experimental scorpion (Centruroides limpidus limpidus) envenomation and immunological rescue.

    PubMed

    Padilla, Alejandro; Govezensky, Tzipe; Possani, Lourival D; Larralde, Carlos

    2005-08-01

    Mortality rates of mice and their levels of anti-venom and anti-F(ab')2 antibodies were assessed after three episodes of subcutaneous envenomations with or without treatment with horse F(ab')2. Soluble venom from the Mexican scorpion Centruroides limpidus limpidus was used for these experiments. Repetition of episodes did not induce different mortality rates in untreated mice. F(ab')2 rescued about 85% of the mice in the first two episodes and 66% in the third, without distinction of gender or ostensible side-effects: a suggestion of selection of the most resistant mice. Surviving mice produced in vitro neutralizing antibodies to the scorpion venom and also antibodies to F(ab')2, when injected alone but more so if combined: a possible immunological adjuvant or alarm effect of the venom or of the cascading physiopathology of envenomation. In the few surviving mice, both anti-venom and anti-F(ab')2 antibodies increased significantly after the first envenomation but not thereafter, showing no correlation with mortality rates: a suggestion of their clinical irrelevance, the few hard-to kill mice appeared to resist envenomation by mechanisms other than antibody response. Injection of F(ab')2 alone induced production of detectable anti-venom antibodies in a few mice and injection of venom alone induced that of anti-F(ab')2 antibodies, perhaps due to trace amounts of venom in the high affinity fraction of F(ab')2 and to anti-idiotypic antibodies or polyclonal activity in the envenomation episode, respectively.

  10. Rapid sensitive analysis of cysteine rich peptide venom components.

    PubMed

    Ueberheide, Beatrix M; Fenyö, David; Alewood, Paul F; Chait, Brian T

    2009-04-28

    Disulfide-rich peptide venoms from animals such as snakes, spiders, scorpions, and certain marine snails represent one of nature's great diversity libraries of bioactive molecules. The various species of marine cone shells have alone been estimated to produce >50,000 distinct peptide venoms. These peptides have stimulated considerable interest because of their ability to potently alter the function of specific ion channels. To date, only a small fraction of this immense resource has been characterized because of the difficulty in elucidating their primary structures, which range in size between 10 and 80 aa, include up to 5 disulfide bonds, and can contain extensive posttranslational modifications. The extraordinary complexity of crude venoms and the lack of DNA databases for many of the organisms of interest present major analytical challenges. Here, we describe a strategy that uses mass spectrometry for the elucidation of the mature peptide toxin components of crude venom samples. Key to this strategy is our use of electron transfer dissociation (ETD), a mass spectrometric fragmentation technique that can produce sequence information across the entire peptide backbone. However, because ETD only yields comprehensive sequence coverage when the charge state of the precursor peptide ion is sufficiently high and the m/z ratio is low, we combined ETD with a targeted chemical derivatization strategy to increase the charge state of cysteine-containing peptide toxins. Using this strategy, we obtained full sequences for 31 peptide toxins, using just 7% of the crude venom from the venom gland of a single cone snail (Conus textile).