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Sample records for lethal venom effect

  1. Comparative study on the ability of IgG and F(ab')2 antivenoms to neutralize lethal and myotoxic effects induced by Micrurus nigrocinctus (coral snake) venom

    OpenAIRE

    León Montero, Guillermo; Stiles, Bradley G.; Alape Girón, Alberto; Rojas Céspedes, Gustavo; Gutiérrez, José María

    1999-01-01

    A comparative study was performed on the ability of IgG and F(ab')2 antivenoms to neutralize lethal and myotoxic activities of Micrurus nigrocinctus venom. Both antivenoms were adjusted to a similar neutralizing potency in experiments where venom and antivenoms were preincubated prior to injection. No significant differences were observed between IgG and F(ab')2 antivenoms concerning neutralization of lethal effect in rescue experiments, i.e., when antivenom was administered intravenously aft...

  2. Tityus serrulatus venom--A lethal cocktail.

    Science.gov (United States)

    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.

  3. Does toxic defence in Nycticebus spp. relate to ectoparasites? The lethal effects of slow loris venom on arthropods.

    Science.gov (United States)

    Grow, Nanda B; Wirdateti; Nekaris, K A I

    2015-03-01

    The venom produced by slow lorises (Nycticebus spp.) is toxic both intra- and inter-specifically. In this study we assessed the ecoparasite repellent properties of their venom. We tested venom from two Indonesian slow loris species: Nycticebus javanicus and Nycticebus coucang. Arthropods directly exposed to brachial gland secretions mixed with saliva from both species were immediately impaired or exhibited reduced activity (76%), and often died as a result (61%). We found no significant difference in the result of 60-min trials between N. coucang and N. javanicus [X(2)(1, n = 140) = 2.110, p = 0.3482]. We found evidence that the degree of lethality of the venom varies according to the arthropod taxa to which it is exposed. While most maggots (84%) were initially impaired from the venom after 10 min, maggots died after a 1 h trial 42% of the time. In contrast, at the end of 1 h trial, spiders died 78% of the time. For all arthropods, the average time to death from exposure was less than 25 min (M = 24.40, SD = 22.60). Ectoparasites including ticks, members of the arachnid order, are known to transmit pathogens to hosts and may be an intended target of the toxic secretions. Our results suggest that one function of slow loris venom is to repel parasites that affect their fitness, and that their topical anointing behaviour may be an adaptive response to ectoparasites. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Standardization of anti-lethal toxin potency test of antivenoms prepared from two different Agkistrodon halys venoms

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    K. H. Lee

    2006-01-01

    Full Text Available In Korea, antivenoms for the treatment of patients bitten by venomous snakes have been imported from Japan or China. Although there is cross-reactivity between these antibodies and venoms from snakes indigenous to Korea (e.g. Agkistrodon genus, protection is not optimal. Antivenoms specifically prepared to neutralize Korean snake venoms could be more effective, with fewer side effects. To this end, we established an infrastructure to develop national standards and created a standardized method to evaluate the efficacy of two horse-derived antivenoms using mouse lethal toxin test. Additionally, we determined the antivenoms neutralizing activity against lethal doses (LD50 of Agkistrodon halys (from Japan and Jiangzhe Agkistrodon halys (from China venoms. We also performed cross-neutralization tests using probit analysis on each pairing of venom and antivenom in order to check the possibility of using Jiangzhe A. halys venom as a substitute for A. halys venom, the current standard. Slope of A. halys venom with A. halys antivenom was 10.2 and that of A. halys venom with Jiangzhe A. halys antivenom was 9.6. However, Slope of Jiangzhe A. halys venom with A. halys antivenom was 4.7 while that of Jiangzhe A. halys venom with Jiangzhe A. halys antivenom was 11.5. Therefore, the significant difference in slope patterns suggests that Jiangzhe A. halys venom cannot be used as a substitute for the standard venom to test the anti-lethal toxin activity of antivenoms (p<0.05.

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

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    ErsenAydın Yağmur

    2015-10-01

    Full Text Available 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.

  6. Venomics, lethality and neutralization of Naja kaouthia (monocled cobra) venoms from three different geographical regions of Southeast Asia.

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    Tan, Kae Yi; Tan, Choo Hock; Fung, Shin Yee; Tan, Nget Hong

    2015-04-29

    Previous studies showed that venoms of the monocled cobra, Naja kaouthia from Thailand and Malaysia are substantially different in their median lethal doses. The intraspecific venom variations of N. kaouthia, however, have not been fully elucidated. Here we investigated the venom proteomes of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V) through reverse-phase HPLC, SDS-PAGE and tandem mass spectrometry. The venom proteins comprise 13 toxin families, with three-finger toxins being the most abundant (63-77%) and the most varied (11-18 isoforms) among the three populations. NK-T has the highest content of neurotoxins (50%, predominantly long neurotoxins), followed by NK-V (29%, predominantly weak neurotoxins and some short neurotoxins), while NK-M has the least (18%, some weak neurotoxins but less short and long neurotoxins). On the other hand, cytotoxins constitute the main bulk of toxins in NK-M and NK-V venoms (up to 45% each), but less in NK-T venom (27%). The three venoms show different lethal potencies that generally reflect the proteomic findings. Despite the proteomic variations, the use of Thai monovalent and Neuro polyvalent antivenoms for N. kaouthia envenomation in the three regions is appropriate as the different venoms were neutralized by the antivenoms albeit at different degrees of effectiveness. Biogeographical variations were observed in the venom proteome of monocled cobra (Naja kaouthia) from Malaysia, Thailand and Vietnam. The Thai N. kaouthia venom is particularly rich in long neurotoxins, while the Malaysian and Vietnamese specimens were predominated with cytotoxins. The differentially expressed toxin profile accounts for the discrepancy in the lethal dose of the venom from different populations. Commercially available Thai antivenoms (monovalent and polyvalent) were able to neutralize the three venoms at different effective doses, hence supporting their uses in the three regions. While dose adjustment according to

  7. Neutralizing properties of Musa paradisiaca L. (Musaceae) juice on phospholipase A2, myotoxic, hemorrhagic and lethal activities of crotalidae venoms.

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    Borges, M H; Alves, D L F; Raslan, D S; Piló-Veloso, D; Rodrigues, V M; Homsi-Brandeburgo, M I; de Lima, M E

    2005-04-08

    The use of plants as medicine has been referred to since ancient peoples, perhaps as early as Neanderthal man. Plants are a source of many biologically active products and nowadays they are of great interest to the pharmaceutical industry. The study of how people of different culture use plants in particular ways has led to the discovery of important new medicines. In this work, we verify the possible activity of Musa paradisiaca L. (Musaceae) against the toxicity of snake venoms. Musa paradisiaca, an important source of food in the world, has also been reported to be popularly used as an anti-venom. Interaction of Musa paradisiaca extract (MsE) with snake venom proteins has been examined in this study. Phospholipase A2 (PLA2), myotoxic and hemorrhagic activities, including lethality in mice, induced by crotalidae venoms were significantly inhibited when different amounts of MsE were mixed with these venoms before assays. On the other hand, mice that received MsE and venoms without previous mixture or by separated routes were not protected against venom toxicity. Partial chemical characterization of MsE showed the presence of polyphenols and tannins and they are known to non-specifically inactivate proteins. We suggest that these compounds can be responsible for the in vitro inhibition of the toxic effects of snake venoms. In conclusion, according to our results, using mice as experimental model, MsE does not show protection against the toxic effects of snake venoms in vivo, but if was very effective when the experiments were done in vitro.

  8. The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom: pathophysiological mechanisms, prophylactic analgesia, and a surrogate in vitro assay.

    Science.gov (United States)

    Chacón, Francisco; Oviedo, Andrea; Escalante, Teresa; Solano, Gabriela; Rucavado, Alexandra; Gutiérrez, José María

    2015-01-01

    The potency of antivenoms is assessed by analyzing the neutralization of venom-induced lethality, and is expressed as the Median Effective Dose (ED50). The present study was designed to investigate the pathophysiological mechanisms responsible for lethality induced by the venom of Bothrops asper, in the experimental conditions used for the evaluation of the neutralizing potency of antivenoms. Mice injected with 4 LD50s of venom by the intraperitoneal route died within ∼25 min with drastic alterations in the abdominal organs, characterized by hemorrhage, increment in plasma extravasation, and hemoconcentration, thus leading to hypovolemia and cardiovascular collapse. Snake venom metalloproteinases (SVMPs) play a predominat role in lethality, as judged by partial inhibition by the chelating agent CaNa2EDTA. When venom was mixed with antivenom, there was a venom/antivenom ratio at which hemorrhage was significantly reduced, but mice died at later time intervals with evident hemoconcentration, indicating that other components in addition to SVMPs also contribute to plasma extravasation and lethality. Pretreatment with the analgesic tramadol did not affect the outcome of the neutralization test, thus suggesting that prophylactic (precautionary) analgesia can be introduced in this assay. Neutralization of lethality in mice correlated with neutralization of in vitro coagulant activity in human plasma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Snake Venom As An Effective Tool Against Colorectal Cancer.

    Science.gov (United States)

    Uzair, Bushra; Atlas, Nagina; Malik, Sidra Batool; Jamil, Nazia; Salaam, Temitope Ojuolape; Rehman, Mujaddad Ur; Khan, Barkat Ali

    2018-06-13

    Cancer is considered one of the most predominant causes of morbidity and mortality all over the world and colorectal cancer is the most common fatal cancers, triggering the second cancer related death. Despite progress in understanding carcinogenesis and development in chemotherapeutics, there is an essential need to search for improved treatment. More than the half a century, cytotoxic and cytostatic agents have been examined as a potential treatment of cancer, among these agents; remarkable progresses have been reported by the use of the snake venom. Snake venoms are secreting materials of lethal snakes are store in venomous glands. Venoms are composite combinations of various protein, peptides, enzymes, toxins and non proteinaceous secretions. Snake venom possesses immense valuable mixtures of proteins and enzymes. Venoms have potential to combat with the cancerous cells and produce positive effect. Besides the toxicological effects of venoms, several proteins of snake venom e.g. disintegrins, phospholipases A2, metalloproteinases, and L-amino acid oxidases and peptides e.g. bradykinin potentiators, natriuretic, and analgesic peptides have shown potential as pharmaceutical agents, including areas of diagnosis and cancer treatment. In this review we have discussed recent remarkable research that has involved the dynamic snake venoms compounds, having anticancer bustle especially in case of colorectal cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Effects of gamma radiation on bee venom: preliminary studies

    International Nuclear Information System (INIS)

    Costa, H.; Boni-Mitake, M.; Souza, C.F.; Rogero, J.R.

    1999-01-01

    Africanized honeybees are very common insects in Brazil and frequently cause accidents followed by important immunological reactions and even deaths. Their venoms are composed of a complex mixture of substances of general biological actions. several works utilizing ionizing radiation showed that it is able to modify protein structures, and successfully detoxify snake venoms toxins, although maintaining its immunological properties. The main objective of this paper was to study the effects of gamma radiation on bee venom, regarding some biochemical and toxicological aspects. Africanized Apis melllifera whole venom (2 mg/ml) in 0.15 M Na Cl solution was irradiated with 2 kGy in a 60 Co source. Preliminary studies has been carried out in order to identify some biochemical changes after irradiation. Concerning this, irradiated and native venom were submitted to a molecular exclusion chromatography (Sephadex G-100), UV absorption spectrum and protein concentration analysis. It could be seen that irradiated bee venom spectrum presented differences when compared to native bee venom, suggesting that some structural alterations has occurred. Protein concentration and chromatography profiles were not changes after irradiation. In order to evaluate the toxicity a lethality assay (L D 50 ) has been performed with both venoms, and irradiated venom showed to be less toxic than native one. (author)

  11. Effects of gamma radiation on bee venom: preliminary studies

    Energy Technology Data Exchange (ETDEWEB)

    Costa, H.; Boni-Mitake, M.; Souza, C.F.; Rogero, J.R. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Div. de Radiobiologia

    1999-11-01

    Africanized honeybees are very common insects in Brazil and frequently cause accidents followed by important immunological reactions and even deaths. Their venoms are composed of a complex mixture of substances of general biological actions. several works utilizing ionizing radiation showed that it is able to modify protein structures, and successfully detoxify snake venoms toxins, although maintaining its immunological properties. The main objective of this paper was to study the effects of gamma radiation on bee venom, regarding some biochemical and toxicological aspects. Africanized Apis melllifera whole venom (2 mg/ml) in 0.15 M Na Cl solution was irradiated with 2 kGy in a {sup 60} Co source. Preliminary studies has been carried out in order to identify some biochemical changes after irradiation. Concerning this, irradiated and native venom were submitted to a molecular exclusion chromatography (Sephadex G-100), UV absorption spectrum and protein concentration analysis. It could be seen that irradiated bee venom spectrum presented differences when compared to native bee venom, suggesting that some structural alterations has occurred. Protein concentration and chromatography profiles were not changes after irradiation. In order to evaluate the toxicity a lethality assay (L D{sub 50}) has been performed with both venoms, and irradiated venom showed to be less toxic than native one. (author) 23 refs., 3 figs., 1 tab.

  12. Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom

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    S. F. Barros

    1998-01-01

    Full Text Available We have provided evidence that: (a lethality of mice to crude Bothrops venom varies according the isogenic strain (A/J > C57Bl/6 > A/Sn > BALB/c > C3H/ HePas > DBA/2 > C3H/He; (bBALB/c mice (LD50=100.0 μg were injected i.p. with 50 μg of venom produced IL-6, IL-10, INF-γ, TNF-α and NO in the serum. In vitro the cells from the mice injected and challenged with the venom only released IL-10 while peritoneal macrophages released IL-10, INF-γ and less amounts of IL-6; (c establishment of local inflammation and necrosis induced by the venom, coincides with the peaks of TNF-α, IFN-γ and NO and the damage was neutralized when the venom was incubated with a monoclonal antibody against a 60 kDa haemorrhagic factor. These results suggest that susceptibility to Bothrops a trox venom is genetically dependent but MHC independent; that IL-6, IL10, TNF-α, IFN-γ and NO can be involved in the mediation of tissue damage; and that the major venom component inducers of the lesions are haemorrhagins.

  13. The protective effect of Mucuna pruriens seeds against snake venom poisoning.

    Science.gov (United States)

    Tan, Nget Hong; Fung, Shin Yee; Sim, Si Mui; Marinello, Enrico; Guerranti, Roberto; Aguiyi, John C

    2009-06-22

    The seed, leaf and root of Mucuna pruriens have been used in traditional medicine for treatments of various diseases. In Nigeria, the seed is used as oral prophylactics for snakebite. To study the protective effects of Mucuna pruriens seed extract against the lethalities of various snake venoms. Rats were pre-treated with Mucuna pruriens seed extract and challenged with various snake venoms. The effectiveness of anti-Mucuna pruriens (anti-MPE) antibody to neutralize the lethalities of snake venoms was investigated by in vitro neutralization. In rats, MPE pre-treatment conferred effective protection against lethality of Naja sputatrix venom and moderate protection against Calloselasma rhodostoma venom. Indirect ELISA and immunoblotting studies showed that there were extensive cross-reactions between anti-MPE IgG and venoms from many different genera of poisonous snakes, suggesting the involvement of immunological neutralization in the protective effect of MPE pre-treatment against snake venom poisoning. In vitro neutralization experiments showed that the anti-MPE antibodies effectively neutralized the lethalities of Asiatic cobra (Naja) venoms, but were not very effective against other venoms tested. The anti-MPE antibodies could be used in the antiserum therapy of Asiatic cobra (Naja) bites.

  14. Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In Vivo Lethal Dose Assay

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    Daniela Cajado-Carvalho

    2017-11-01

    Full Text Available Scorpion stings are the main cause of human envenomation in Brazil and, for the treatment of victims, the World Health Organization (WHO recommends the use of antivenoms. The first step to achieve effective antivenom is to use a good quality venom pool and to evaluate it, with LD50 determination as the most accepted procedure. It is, however, time-consuming and requires advanced technical training. Further, there are significant ethical concerns regarding the number of animals required for testing. Hence, we investigated the correspondence between LD50 results, in vitro assays, and a strong correlation with proteolytic activity levels was observed, showing, remarkably, that proteases are potential toxicity markers for Tityus serrulatus venom. The comparison of reversed-phase chromatographic profiles also has a potential application in venoms’ quality control, as there were fewer neurotoxins detected in the venom with high LD50 value. These results were confirmed by mass spectrometry analysis. Therefore, these methods could precede the LD50 assay to evaluate the venom excellence by discriminating—and discarding—poor-quality batches, and, consequently, with a positive impact on the number of animals used. Notably, proposed assays are fast and inexpensive, being technically and economically feasible in Tityus serrulatus venom quality control to produce effective antivenoms.

  15. Histopathological effects of lethal and sub-lethal concentrations of ...

    African Journals Online (AJOL)

    The histopathological effects of lethal and sub-lethal concentrations of glyphosate on African catfish Clarias gariepinus were investigated. C. gariepinus juveniles were assessed in a static renewal bioassay for 96 hours (acute toxicity) and 28 days (chronic toxicity) using varying concentrations (0.0 mg/l 20.0 mg/l, 30.0 mg/l, ...

  16. The effects of Bee Venom and Sweet Bee Venom to the preadipocyte proliferation and lipolysis of adipocyte, localized fat accumulation

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    Min-Ki Kim

    2007-12-01

    Full Text Available Objectives : The purpose of this study was to investigate the effects of Bee Venom and Sweet Bee Venom to the primary cultured preadipocyte, adipocytes, and localized fat tissue. Methods : Decreased preadipocyte proliferation and decreased lipogenesis are mechanisms to reduce obesity. So, preadipocytes and adipocytes were performed on cell cultures using Sprague-Dawley Rats and treated with 0.01-1mg/㎖ Bee Venom and Sweet Bee Venom. And porcine skin including fat tissue after treated Bee Venom and Sweet Bee Venom according to the dosage dependent variation are investigated the histologic changes after injection of these Pharmacopuncture. Result : Following results were obtained from the preadipocyte proliferation and lipolysis of adipocyte and histologic investigation of fat tissue. 1. Bee Venom and Sweet Bee Venom showed the effect of decreased preadipocyte proliferation depend on concentration. 2. Bee Venom and Sweet Bee Venom showed the effect of decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH significantly. 3. Bee Venom was not showed the effect of lipolysis, but Sweet Bee Venom was increased in low dosage and decreased in high dosage. 4. Investigated the histologic changes in porcine fat tissue after treated Bee Venom and Sweet Bee Venom, we knew that these Pharmacopuncture was activated nonspecific lysis of cell membranes depend on concentration. Conclusion : These results suggest that Bee Venom and Sweet Bee Venom efficiently induces decreased proliferation of preadipocyte and lipolysis in adipose tissue

  17. Inhibitory Effect of Plant Manilkara subsericea against Biological Activities of Lachesis muta Snake Venom

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    Eduardo Coriolano De Oliveira

    2014-01-01

    Full Text Available Snake venom is composed of a mixture of substances that caused in victims a variety of pathophysiological effects. Besides antivenom, literature has described plants able to inhibit injuries and lethal activities induced by snake venoms. This work describes the inhibitory potential of ethanol, hexane, ethyl acetate, or dichloromethane extracts and fractions from stem and leaves of Manilkara subsericea against in vivo (hemorrhagic and edema and in vitro (clotting, hemolysis, and proteolysis activities caused by Lachesis muta venom. All the tested activities were totally or at least partially reduced by M. subsericea. However, when L. muta venom was injected into mice 15 min first or after the materials, hemorrhage and edema were not inhibited. Thus, M. subsericea could be used as antivenom in snakebites of L. muta. And, this work also highlights Brazilian flora as a rich source of molecules with antivenom properties.

  18. Some Neuropharmacological Effects of the Crude Venom Extract of ...

    African Journals Online (AJOL)

    This study reports some neuropharmacological effects of the crude venom extract of Conus musicus (family Conidae) in mice using various experimental models. The crude venom was found to significantly increase tail flick reaction time in mice. The effects of the venom on the central nervous system were studied by ...

  19. Anti-arthritic effects of microneedling with bee venom gel

    OpenAIRE

    Mengdi Zhao; Jie Bai; Yang Lu; Shouying Du; Kexin Shang; Pengyue Li; Liu Yang; Boyu Dong; Ning Tan

    2016-01-01

    Objective: To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel. Methods: In this study, the sodium urate and LPS were used on rats and mice to construct the model. Bee venom gel–microneedle combination effect on the model is to determine the role of microneedle gel permeation by observing inflammation factors. Results: Compared with the model group, the bee venom gel–microneedle combination group can r...

  20. Systemic effects induced by the venom of the snake Bothrops caribbaeus in a murine model.

    Science.gov (United States)

    Herrera, Cristina; Rucavado, Alexandra; Warrell, David A; Gutiérrez, José María

    2013-03-01

    Snakebite envenoming by Bothrops caribbaeus, an endemic viperid from the Lesser Antillean island of Saint Lucia, is clinically characterized by local tissue damage and systemic thrombosis that can lead to cerebral, myocardial or pulmonary infarctions and venous thromboses. Systemic effects (lethality, pulmonary hemorrhage, thrombocytopenia and coagulopathy) induced by intravenous (i.v.) administration of B. caribbaeus venom were studied in mice. The role of snake venom metalloproteinases (SVMPs) in these systemic alterations was assessed by inhibition with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa(2)EDTA). A snake C-type lectin-like (snaclec) and a type P-III hemorrhagic SVMP were isolated and characterized from this venom, and the effect of venom and the isolated snaclec on human platelet aggregation was studied in vitro. Results indicate that SVMPs play an important role in the overall toxicity of B. caribbaeus venom, being responsible for systemic hemorrhage and lethality, but not thrombocytopenia, whereas the isolated snaclec is involved in the thrombocytopenic effect. Both venom and snaclec induce platelet aggregation/agglutination. Moreover, the snaclec binds directly to glycoprotein Ib (GPIb) and induces agglutination in washed fixed platelets. On the other hand, B. caribbaeus venom hydrolyzed fibrinogen in vitro and induced a partial drop of fibrinogen levels with an increase in fibrin/fibrinogen degradation products (FDP) levels in vivo. The negative result for D-dimer (DD) in plasma is consistent with the lack of microscopic evidence of pulmonary thrombosis and endothelial cell damage. Likewise, no increments in plasma sE-selectin levels were detected. The absence of thrombosis in this murine model suggests that this effect may be species-specific. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Protective Effect of the Plant Extracts of Erythroxylum sp. against Toxic Effects Induced by the Venom of Lachesis muta Snake

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    Eduardo Coriolano de Oliveira

    2016-10-01

    Full Text Available Snake venoms are composed of a complex mixture of active proteins that induce toxic effects, such as edema, hemorrhage, and death. Lachesis muta has the highest lethality indices in Brazil. In most cases, antivenom fails to neutralize local effects, leading to disabilities in victims. Thus, alternative treatments are under investigation, and plant extracts are promising candidates. The objective of this work was to investigate the ability of crude extracts, fractions, or isolated products of Erythroxylum ovalifolium and Erythroxylum subsessile to neutralize some toxic effects of L. muta venom. All samples were mixed with L. muta venom, then in vivo (hemorrhage and edema and in vitro (proteolysis, coagulation, and hemolysis assays were performed. Overall, crude extracts or fractions of Erythroxylum spp. inhibited (20%–100% toxic effects of the venom, but products achieved an inhibition of 4%–30%. However, when venom was injected into mice before the plant extracts, hemorrhage and edema were not inhibited by the samples. On the other hand, an inhibition of 5%–40% was obtained when extracts or products were given before venom injection. These results indicate that the extracts or products of Erythroxylum spp. could be a promising source of molecules able to treat local toxic effects of envenomation by L. muta venom, aiding in the development of new strategies for antivenom treatment.

  2. Experimental Study on the comparison of antibacterial and antioxidant effects between the Bee Venom and Sweet Bee Venom

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    Joong chul An

    2006-12-01

    Full Text Available Objectives : This study was conducted to compare antibacterial activities and free radical scavenging activity between the Bee Venom and Sweet Bee Venom in which the allergy-causing enzyme is removed. Methods : To evaluate antibacterial activities of the test samples, gram negative E. coli and gram positive St. aureus were compared using the paper disc method. For comparison of the antioxidant effects, DPPH (1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay and Thiobarbituric Acid Reactive Substances (TBARS assay were conducted. Results : 1. Antibacterial activity against gram negative E. coli was greater in the Sweet Bee Venom group than the Bee Venom group. 2. Antibacterial activity against gram positive St. aureus was similar between the Bee Venom and Sweet Bee Venom groups. 3. DPPH free radical scavenging activity of the Bee Venom group showed 2.8 times stronger than that of the Sweet Bee Venom group. 4. Inhibition of lipid peroxidation of the Bee Venom group showed 782 times greater than that of the Sweet Bee Venom group. Conclusions : The Bee Venom group showed outstanding antibacterial activity against gram positive St. aureus, and allergen-removed Sweet Bee Venom group showed outstanding antibacterial activity against both gram negative E. coli and gram positive St. aureus. For antioxidant effects, the Bee Venom was superior over the Sweet Bee Venom and the superiority was far more apparent for lipid peroxidation.

  3. Biological effects of Naja haje crude venom on the hepatic and renal tissues of mice

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    Amany A. Tohamy

    2014-07-01

    Full Text Available Snake venoms are known to cause different metabolic disorders, altering cellular and enzymatic activities in animals and releasing pharmacological substances. In this study, the lethality as well as biochemical and histopathological effect of Egyptian cobra (Naja haje; N. haje crude venom at a sublethal dose have been investigated on liver and kidney of male mice. Venom injected intramuscularly in mice with 1/2 LD50 (approximately 0.0115 μg/g body weight of mice and the animals were sacrificed 6 days post injection. Results indicated that the injection of crude venom of the N. haje induced a significant disturbance in liver and kidney functions. In addition, results revealed that N. haje venom has a potent oxidative activity by increasing the level of reactive oxygen species with concomitant significant increase in hydrogen peroxide, lipid peroxidation, carbonyl protein and nitric oxide levels in hepatic and renal tissues. This activity was extended to decrease non-enzymatic and enzymatic antioxidant defense components such as glutathione, superoxide dismutase and catalase. Additionally, the biochemical alternations induced in hepatic and renal tissues were associated with significant alternations in the histological architecture of liver and kidney of injected mice. From this study, we can conclude that such injury could be considered among the factors that lead to death caused by N. haje venom.

  4. Biochemical and histopathological effects of the stonefish (Synanceia verrucosa) venom in rats.

    Science.gov (United States)

    Khalil, Ahmad M; Wahsha, Mohammad A; Abu Khadra, Khalid M; Khalaf, Maroof A; Al-Najjar, Tariq H

    2018-02-01

    The Reef Stonefish (Synanceia verrucosa) is one of the most dangerous venomous fish known, and has caused occasional human fatalities. The present study was designed to examine some of the pathological effects of the venom from this fish in Sprague Dawley rats. Crude venom was extracted from venom glands of the dorsal spines of stonefish specimens collected from coral reefs in the Gulf of Aqaba (in the northeastern branch of the Red Sea). The rats were given intramuscular injections of the venom and acute toxicity and effect on selected serum marker enzymes as well as normal architecture of vital organs were evaluated. The rat 24 h LD50 was 38 μg/kg body weight. The serum biochemical markers; alanine transaminase (ALT), lactate dehydrogenase (LDH) and creatine kinase (CK) increased after 6 h of administration of a sub lethal dose of the venom and remained significantly raised at 24 h. Amylase levels also significantly increased after venom injection. The venom caused histological damage manifested as an interstitial hemorrhage, inflammatory cell infiltration, and necrosis. The demonstrated rises in the levels of different critical biochemical parameters in the serum may have led to the observed abnormal morphological changes in these organs. These results may account for some of the clinical manifestations observed in victims of stonefish envenomation. Thus, the presented data provide further in vivo evidence of the stonefish toxic effects that may threaten human life and call for the need for special measures to be considered. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. The effects of Bee Venom and Sweet Bee Venom to the preadipocyte proliferation and lipolysis of adipocyte, localized fat accumulation

    OpenAIRE

    Min-Ki Kim; Si Hyeong, Lee; Jo Young Shin; Kang San Kim; Nam Guen Cho; Ki Rok Kwon; Tae Jin Rhim

    2007-01-01

    Objectives : The purpose of this study was to investigate the effects of Bee Venom and Sweet Bee Venom to the primary cultured preadipocyte, adipocytes, and localized fat tissue. Methods : Decreased preadipocyte proliferation and decreased lipogenesis are mechanisms to reduce obesity. So, preadipocytes and adipocytes were performed on cell cultures using Sprague-Dawley Rats and treated with 0.01-1mg/㎖ Bee Venom and Sweet Bee Venom. And porcine skin including fat tissue after treated Bee Ve...

  6. Anti-arthritic effects of microneedling with bee venom gel

    Directory of Open Access Journals (Sweden)

    Mengdi Zhao

    2016-10-01

    Conclusions: Bee venom can significantly suppress the occurrence of gouty arthritis inflammation in rats and mice LPS inflammatory reaction. Choose the 750 μm microneedle with 10N force on skin about 3 minutes, bee venom can play the optimal role, and the anti-inflammatory effect is obvious. Microneedles can promote the percutaneous absorption of the active macromolecules bee venom gel.

  7. Effect of Diterpenes Isolated of the Marine Alga Canistrocarpus cervicornis against Some Toxic Effects of the Venom of the Bothrops jararaca Snake

    Directory of Open Access Journals (Sweden)

    Thaisa Francielle Souza Domingos

    2015-02-01

    Full Text Available Snake venoms are composed of a complex mixture of active proteins and peptides which induce a wide range of toxic effects. Envenomation by Bothrops jararaca venom results in hemorrhage, edema, pain, tissue necrosis and hemolysis. In this work, the effect of a mixture of two secodolastane diterpenes (linearol/isolinearol, previously isolated from the Brazilian marine brown alga, Canistrocarpus cervicornis, was evaluated against some of the toxic effects induced by B. jararaca venom. The mixture of diterpenes was dissolved in dimethylsulfoxide and incubated with venom for 30 min at room temperature, and then several in vivo (hemorrhage, edema and lethality and in vitro (hemolysis, plasma clotting and proteolysis assays were performed. The diterpenes inhibited hemolysis, proteolysis and hemorrhage, but failed to inhibit clotting and edema induced by B. jararaca venom. Moreover, diterpenes partially protected mice from lethality caused by B. jararaca venom. The search for natural inhibitors of B. jararaca venom in C. cervicornis algae is a relevant subject, since seaweeds are a rich and powerful source of active molecules which are as yet but poorly explored. Our results suggest that these diterpenes have the potential to be used against Bothropic envenomation accidents or to improve traditional treatments for snake bites.

  8. Study of gamma radiation from 60Co effects on Apis mellifera venom: biochemical, pharmacological and immunological aspects

    International Nuclear Information System (INIS)

    Costa, Helena

    2001-01-01

    Africanized honeybees are very common insects in Brazil and frequently cause accidents followed by important immunological reactions and even deaths. Their venoms are composed of a complex mixture of substances of general biological actions. Ionizing radiation is able to modify molecular structures affecting the biological properties of proteins. It decreases toxic and enzymatic activities and so, it appears promising as a venom detoxification tool. The main objective of this work was to study the effects of gamma radiation on bee venom, regarding biochemical, pharmacological and immunological aspects. Africanized Apis mellifera whole venom (2 mg/ml) in 0.15 M NaCl solution was irradiated with 2 kGy in a 60 Co source. Native and irradiated bee venoms were submitted to high performance size exclusion chromatography (Tosohaas G2000SW column), high performance reversed phase chromatography in a C-18 column under water/acetonitrile gradient, SDS-PAGE. For both venoms studies have been carried out in UV absorption spectrum, protein concentration, hemolytic activity, and PLA 2 activity analysis, lethality assay (LD 50 ). Biodistribution studies was carried out after labelling native and irradiated bee venom with 99m Tc. The results showed that gamma radiation did not change the protein concentration nor its immunogenicity, although it could be observed that irradiated bee venom UV spectrum and SDS-PAGE profile presented differences when compared to native bee venom. This suggests that some structural alterations in bee venom components could have occurred after irradiation. HPLC-RP profiles showed that gamma radiation could have caused conformational changes, such as unfolding of molecule chains, changing their hydrophobic groups exposuring. The hemolytic and the PLA 2 activities of irradiated bee venom were smaller than the native ones. The gamma radiation diminished the toxicity of bee venom, but did not abolish its bioactivity, like hemolysis. Biodistribution studies

  9. Embriotoxic effects of maternal exposure to Tityus serrulatus scorpion venom

    Directory of Open Access Journals (Sweden)

    A. A. S. Barão

    2008-01-01

    Full Text Available Tityus serrulatus is the most venomous scorpion in Brazil; however, it is not known whether its venom causes any harm to the offspring whose mothers have received it. This study investigates whether the venom of T. serrulatus may lead to deleterious effects in the offspring, when once administered to pregnant rats at a dose that causes moderate envenomation (3mg/kg. The venom effects were studied on the 5th and on the 10th gestation day (GD5 and GD10. The maternal reproductive parameters of the group that received the venom on GD5 showed no alteration. The group that received the venom on GD10 presented an increase in post-implantation losses. In this group, an increase in the liver weight was also observed and one-third of the fetuses presented incomplete ossification of skull bones. None of the groups that received the venom had any visceral malformation or delay in the fetal development of their offspring. The histopathological analysis revealed not only placentas and lungs but also hearts, livers and kidneys in perfect state. Even having caused little effect on the dams, the venom may act in a more incisive way on the offspring, whether by stress generation or by a direct action.

  10. Comparison between IgG and F(ab′)2 polyvalent antivenoms: neutralization of systemic effects induced by Bothrops asper venom in mice, extravasation to muscle tissue, and potential for induction of adverse reactions

    OpenAIRE

    León Montero, Guillermo; Monge Monge, María; Rojas Umaña, Ermila; Lomonte, Bruno; Gutiérrez, José María

    2001-01-01

    Whole IgG and F(ab′)2 equine-derived polyvalent (Crotalinae) antivenoms, prepared from the same batch of hyperimmune plasma, were compared in terms of neutralization of the lethal and defibrinating activities induced by Bothrops asper venom, their ability to reach the muscle tissue compartment in envenomated mice, and their potential for the induction of adverse reactions. Both preparations were adjusted to the same potency against the lethal effect of B. asper venom in experiments involving ...

  11. Use of gamma irradiated viper venom as the toxoid against viper venom poisoning in mice and rabbits

    International Nuclear Information System (INIS)

    Hati, A.K.; Mandal, M.; Hati, R.N.; Das, S.

    1995-01-01

    The present paper deals with detoxification of the crude viper (Vipera russelli) venom by gamma irradiation and its effective immunogenic role in Balb/C mice, used as a toxoid. The successful immunization of rabbits with irradiated viper venom toxoid is also reported. Certain biochemical changes of the venom due to radiation exposure and neutralization capacity of the immune sera against phosphodiesterase and protease activity of the crude viper venom have also been studied. The neutralizing potency of Russell's viper venom (RVV) toxoid anti venom (anti venom raised in rabbits against γ-irradiated RVV toxoid adsorbed on aluminium phosphate), in comparison with a commercial bivalent anti venom (as a standard reference) with reference to haemorrhagic, necrotic and lethal effects of Russell's viper envenomation are reported. 25 refs

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

    Science.gov (United States)

    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

  13. Antivenom potential of ethanolic extract of Cordia macleodii bark against Naja venom

    OpenAIRE

    Pranay Soni; Surendra H. Bodakhe

    2014-01-01

    Objective: To evaluate the antivenom potential of ethanolic extract of bark of Cordia macleodii against Naja venom induced pharmacological effects such as lethality, hemorrhagic lesion, necrotizing lesion, edema, cardiotoxicity and neurotoxicity. Methods: Wistar strain rats were challenged with Naja venom and treated with the ethanolic extract of Cordia macleodii bark. The effectiveness of the extract to neutralize the lethalities of Naja venom was investigated as recommended by WHO. Re...

  14. Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom

    Science.gov (United States)

    2013-01-01

    Background Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms “double sensitization” or “double positivity” cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients. Objective We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients. Methods Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests. Results Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15). Conclusions Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the

  15. Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom

    Science.gov (United States)

    Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Aguiyi, John C.

    2012-01-01

    Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value. PMID:21785646

  16. Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra Venom

    Directory of Open Access Journals (Sweden)

    Shin Yee Fung

    2012-01-01

    Full Text Available Mucuna pruriens Linn. (velvet bean has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value.

  17. Efficacy of tannins from Mimosa pudica and tannic acid in neutralizing cobra (Naja kaouthia venom

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    FY Sia

    2011-01-01

    Full Text Available In the present study, the effectiveness of Mimosa pudica tannins (MPT in neutralizing the lethality of Naja kaouthia venom was compared with commercially derived tannins. Preincubation of MPT with N. kaouthia venom maintained 100% survival of mice after 24 hours. The mouse group in which there was no preincubation, no protection against the effects of the venom was observed. M. pudica tannin was found to be more effective in neutralizing the lethality of N. kaouthia venom when compared to commercial tannic acid. Two protein spots were missing in the two-dimensional gel electrophoresis (2-DE of the MPT treated mouse indicating the down-regulation of venom proteins. The results from this study indicated that tannins obtained from M. pudica are better than tannic acid in neutralizing the lethality of N. kaouthia venom in vitro. However, further investigations are required to establish that M. pudica has potential for treating N. kaouthia snakebites.

  18. Effect of gamma irradiation on toxicity and immunogenicity of Androctonus australis hector venom

    International Nuclear Information System (INIS)

    Abib, L.; Laraba-Djebari, F.

    2003-01-01

    An investigation was made of the radiosensitivity of the toxic and immunological properties of Androctonus australis hector venom. This venom was irradiated with two doses of gamma rays (1 and 2 kGy) from a 60 Co source. The results showed that venom toxicity was abolished for the two radiation doses (1 and 2 kGy) with, respectively, 10 and 25 times its initial LD50 value. However, irradiated venoms were immunogenic, and the antibodies elicited by them were able to recognize the native venom by enzyme-linked immunosorbent assay. Antisera raised against these toxoids (1 and 2 kGy) had a higher neutralizing capacity and immunoreactivity against all components of native venom than did the antiserum produced against the native venom. The antiserum of rabbits immunized with 2-kGy-irradiated venom was more efficient than 1-kGy-irradiated toxoid antiserum. Indeed, in vivo protection assays showed that the mice immunized with 2-kGy-irradiated venom resisted lethal doses (i.p.) of A. australis hector venom. (author)

  19. Comparative studies of the venom of a new Taipan species, Oxyuranus temporalis, with other members of its genus.

    Science.gov (United States)

    Barber, Carmel M; Madaras, Frank; Turnbull, Richard K; Morley, Terry; Dunstan, Nathan; Allen, Luke; Kuchel, Tim; Mirtschin, Peter; Hodgson, Wayne C

    2014-07-02

    Taipans are highly venomous Australo-Papuan elapids. A new species of taipan, the Western Desert Taipan (Oxyuranus temporalis), has been discovered with two specimens housed in captivity at the Adelaide Zoo. This study is the first investigation of O. temporalis venom and seeks to characterise and compare the neurotoxicity, lethality and biochemical properties of O. temporalis venom with other taipan venoms. Analysis of O. temporalis venom using size-exclusion and reverse-phase HPLC indicated a markedly simplified "profile" compared to other taipan venoms. SDS-PAGE and agarose gel electrophoresis analysis also indicated a relatively simple composition. Murine LD50 studies showed that O. temporalis venom is less lethal than O. microlepidotus venom. Venoms were tested in vitro, using the chick biventer cervicis nerve-muscle preparation. Based on t90 values, O. temporalis venom is highly neurotoxic abolishing indirect twitches far more rapidly than other taipan venoms. O. temporalis venom also abolished responses to exogenous acetylcholine and carbachol, indicating the presence of postsynaptic neurotoxins. Prior administration of CSL Taipan antivenom (CSL Limited) neutralised the inhibitory effects of all taipan venoms. The results of this study suggest that the venom of the O. temporalis is highly neurotoxic in vitro and may contain procoagulant toxins, making this snake potentially dangerous to humans.

  20. The Comparison of Effectiveness between Bee Venom and Sweet Bee Venom Therapy on Low back pain with Radiating pain

    OpenAIRE

    Lee Tae-ho; Hwang Hee-sang; Chang So-young; Cha Jung-ho; Jung Ki-hoon; Lee Eun-young; Roh Jeongdu

    2007-01-01

    Objective : The aim of this study is to investigate if Sweet Bee Venom therapy has the equal effect in comparison with Bee Venom Therapy on Low back pain with Radiation pain. Methods : Clinical studies were done 24 patients who were treated low back pain with radiation pain to Dept. of Acupuncture & Moxibusition, of Oriental Medicine Se-Myung University from April 1, 2007 to September 30, 2007. Subjects were randomly divided into two groups ; Bee Venom treated group(Group A, n=10), Sweet B...

  1. Experimental Study on the comparison of antibacterial and antioxidant effects between the Bee Venom and Sweet Bee Venom

    OpenAIRE

    Joong chul An; Ki Rok Kwon; Eun Hee Lee; Bae Chun Cha

    2006-01-01

    Objectives : This study was conducted to compare antibacterial activities and free radical scavenging activity between the Bee Venom and Sweet Bee Venom in which the allergy-causing enzyme is removed. Methods : To evaluate antibacterial activities of the test samples, gram negative E. coli and gram positive St. aureus were compared using the paper disc method. For comparison of the antioxidant effects, DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging assay and Thiobarbituric Ac...

  2. Testing the "toxin hypothesis of allergy": Mast cells, IgE, and innate and acquired immune responses to venoms*

    Science.gov (United States)

    Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J.

    2015-01-01

    Summary Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell’s viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic Th2 immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. PMID:26210895

  3. Effects of Puff-Adder Venom on Coagulation, Fibrinolysis and ...

    African Journals Online (AJOL)

    The in vitro and in vivo haematological effects of puffadder (Bitis arietans) venom in the baboon (Papio ursinus) with regard to its effect on coagulation, fibrinolysis and platelet aggregation were studied. There is a delay in the intrinsic coagulation mechanism with fibrinolysis and in vitro fibrinogenolysis. Normal human ...

  4. Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) against Russell's viper venom: characterization of piperine as active principle.

    Science.gov (United States)

    Shenoy, P A; Nipate, S S; Sonpetkar, J M; Salvi, N C; Waghmare, A B; Chaudhari, P D

    2013-05-20

    Piper longum L. fruits have been traditionally used against snakebites in north-eastern and southern region of India. To examine the ability of ethanolic extract of fruits of Piper longum L., Piperaceae (PLE) and piperine, one of the main active principles of Piper longum, to inhibit the Russell's viper (Doboia russelii, Viperidae) snake venom activities. Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) and piperine against Russell's viper venom was studied in embryonated fertile chicken eggs, mice and rats by using various models as follows: inhibition of venom lethal action, inhibition of venom haemorrhagic action (in vitro), inhibition of venom haemorrhagic action (in vivo), inhibition of venom necrotizing action, inhibition of venom defibrinogenating action, inhibition of venom induced paw edema, inhibition of venom induced mast cell degranulation, creatine kinase assay and assay for catalase activity. PLE was found to inhibit the venom induced haemorrhage in embryonated fertile chicken eggs. Administration of PLE and piperine significantly (p<0.01) inhibited venom induced lethality, haemorrhage, necrosis, defibrinogenation and inflammatory paw edema in mice in a dose dependent manner. PLE and piperine also significantly (p<0.01) reduced venom induced mast cell degranulation in rats. Venom induced decrease in catalase enzyme levels in mice kidney tissue and increase in creatine kinase enzyme levels in mice serum were significantly (p<0.01) reversed by administration of both PLE and piperine. PLE possesses good anti-snake venom properties and piperine is one of the compounds responsible for the effective venom neutralizing ability of the plant. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Effects of gamma radiation on snake venoms

    International Nuclear Information System (INIS)

    Nascimento, N.; Spencer, P.J.; Andrade, H.F.; Guarnieri, M.C.; Rogero, J.R.

    1998-01-01

    Ionizing radiation is able to detoxify several venoms, including snake venoms, without affecting significantly their immunogenic properties. In order to elucidate this phenomena, we conceived a comparative pharmacological study between native and irradiated (2,000 Gy) crotoxin, the main toxin of the South American rattlesnake Crotalus durissus terrificus. Crotoxin was isolated and purified by molecular exclusion chromatography, pI precipitation and, subsequently submitted to irradiation. Gel filtration of the irradiated toxin resulted in some high molecular weight aggregates formation. Crotoxin toxicity decreased two folds after irradiation, as determined by LD 50 in mice. Native and irradiated crotoxin biodistribution ocurred in the same general manner, with renal elimination. However, in contrast to irradiated crotoxin, the native form was initially retained in kidneys. A later concentration (2-3 hr) appeared in phagocytic mononuclear cells rich organs (liver and spleen) and neural junction rich organs (muscle and brain)

  6. Evaluation of the effect of gamma rays on the venom of Vipera lebetina by biochemical study

    International Nuclear Information System (INIS)

    Bennacef-Heffar, N.; Laraba-Djebari, F.

    2003-01-01

    Snake bites represent a serious public health problem in many areas of the world. In Algeria, two widespread snakes are Vipera lebetina and Cerastes cerastes. Vipera lebetina venom causes local hemorrhage and necrosis, and it may lead to permanent limb loss. The principal causes of mortality after snakebites are acute renal failure and hemorrhage, which occur not only locally, at the site of the bite, but also systemically, contributing to the cardiovascular shock characteristic of severe envenomation. Gamma radiation has been shown to be effective for attenuating venom toxicity. Vipera lebetina venom was irradiated with two doses of gamma rays (1 and 2 kGy) from a 60 Co source, and the venom's toxic, enzymatic, and structural properties were analyzed. Intraperitoneal injection of the irradiated venoms (100-500 μg/20 g mouse body mass) revealed a significant decrease of the toxicity. Irradiated venoms with 1 and 2 kGy doses were four and nine times less toxic, respectively, than the native venom. A biochemical characterization of in vitro enzymatic activities was performed. Vipera lebetina displayed in vitro caseinolytic, amidolytic, esterasic, coagulant, and phospholipase A 2 activities. Caseinolytic, amidolytic, esterasic, and coagulative activities were reduced for the irradiated venoms; only phospholipase A 2 activity was abolished in the irradiated venom with a dose of 2 kGy. The native and irradiated venoms were separated by gel filtration and electrophoresis. Chromatographic and electrophoretic profiles were drastically changed as compared with the native venom. Vipera lebetina venom detoxified by gamma rays was used for active immunization, and the presence of antibody in the immune sera was detected by ELISA. The immunogenic properties were preserved and the antisera obtained with the irradiated venoms could cross-react. Antisera were able to neutralize the toxic effect of V. lebetina native venom. These results indicate that irradiation of V. lebetina

  7. Revisiting Notechis scutatus venom: on shotgun proteomics and neutralization by the "bivalent" Sea Snake Antivenom.

    Science.gov (United States)

    Tan, Choo Hock; Tan, Kae Yi; Tan, Nget Hong

    2016-07-20

    Recent advances in proteomics enable deep profiling of the compositional details of snake venoms for improved understanding on envenomation pathophysiology and immunological neutralization. In this study, the venom of Australian tiger snake (Notechis scutatus) was trypsin-digested in solution and subjected to nano-ESI-LCMS/MS. Applying a relative quantitative proteomic approach, the findings revealed a proteome comprising 42 toxin subtypes clustered into 12 protein families. Phospholipases A2 constitute the most abundant toxins (74.5% of total venom proteins) followed by Kunitz serine protease inhibitors (6.9%), snake venom serine proteases (5.9%), alpha-neurotoxins (5.6%) and several toxins of lower abundance. The proteome correlates with N. scutatus envenoming effects including pre-synaptic and post-synaptic neurotoxicity and consumptive coagulopathy. The venom is highly lethal in mice (intravenous median lethal dose=0.09μg/g). BioCSL Sea Snake Antivenom, raised against the venoms of beaked sea snake (Hydrophis schistosus) and N. scutatus (added for enhanced immunogenicity), neutralized the lethal effect of N. scutatus venom (potency=2.95mg/ml) much more effectively than the targeted H.schistosus venom (potency=0.48mg/ml). The combined venom immunogen may have improved the neutralization against phospholipases A2 which are abundant in both venoms, but not short-neurotoxins which are predominant only in H. schistosus venom. A shotgun proteomic approach adopted in this study revealed the compositional details of the venom of common tiger snake from Australia, Notechis scutatus. The proteomic findings provided additional information on the relative abundances of toxins and the detection of proteins of minor expression unreported previously. The potent lethal effect of the venom was neutralized by bioCSL Sea Snake Antivenom, an anticipated finding due to the fact that the Sea Snake Antivenom is actually bivalent in nature, being raised against a mix of venoms of the

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

    Directory of Open Access Journals (Sweden)

    SuhandanAdigüzel Van-Zoelen

    2015-10-01

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

  9. The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo

    Directory of Open Access Journals (Sweden)

    Miriéle Cristina Ferraz

    2015-01-01

    Full Text Available We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL, but only partial blockade (~30% in EPSTA (3.6 mg/kg, i.m. after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations. Preincubation of venom with betulin (200 μg/mL markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite.

  10. The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo

    Science.gov (United States)

    Ferraz, Miriéle Cristina; de Oliveira, Jhones Luiz; de Oliveira Junior, Joel Reis; Cogo, José Carlos; dos Santos, Márcio Galdino; Franco, Luiz Madaleno; Puebla, Pilar; Ferraz, Helena Onishi; Ferraz, Humberto Gomes; da Rocha, Marisa Maria Teixeira; Hyslop, Stephen

    2015-01-01

    We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL), but only partial blockade (~30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations). Preincubation of venom with betulin (200 μg/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite. PMID:26633987

  11. Bee Venom (Apis Mellifera an Effective Potential Alternative to Gentamicin for Specific Bacteria Strains Bee Venom an Effective Potential for Bacteria

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    Hossein Zolfagharian

    2016-09-01

    Full Text Available Objectives: Mellitine, a major component of bee venom (BV, Apis mellifera, is more active against gram positive than gram negative bacteria. Moreover, BV has been reported to have multiple effects, including antibacterial, antivirus, and anti-inflammation effects, in various types of cells. In addition, wasp venom has bee

  12. Effect of Venom from the Jellyfish Nemopilema nomurai on the Silkworm Bombyx mori L.

    Science.gov (United States)

    Yu, Huahua; Li, Rongfeng; Chen, Xiaolin; Yue, Yang; Xing, Ronge; Liu, Song; Li, Pengcheng

    2015-09-24

    The silkworm Bombyx mori L. (B. mori) has a significant impact on the economy by producing more than 80% of the globally produced raw silk. The exposure of silkworm to pesticides may cause adverse effects on B. mori, such as a reduction in the production and quality of silk. This study aims to assay the effect of venom from the jellyfish Nemopilema nomurai on growth, cuticle and acetylcholinesterase (AChE) activity of the silkworm B. mori by the leaf dipping method. The experimental results revealed that the four samples caused neither antifeeding nor a lethal effect on B. mori. The sample SFV inhibited B. mori growth after 6 days of treatment in a dose-dependent manner. The samples SFV, DSFV and Fr-1 inhibited the precipitation and synthesis of chitin in the cuticle after 12 and 14 days of treatment. In the case of the four samples, the AChE was significantly improved after 14 days of treatment.

  13. Animal venoms as antimicrobial agents.

    Science.gov (United States)

    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. Comparison of the effect of Crotalus simus and Crotalus durissus ruruima venoms on the equine antibody response towards Bothrops asper venom: implications for the production of polyspecific snake antivenoms.

    Science.gov (United States)

    Dos-Santos, Maria Cristina; Arroyo, Cynthia; Solano, Sergio; Herrera, María; Villalta, Mauren; Segura, Alvaro; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo

    2011-02-01

    Antivenoms are preparations of immunoglobulins purified from the plasma of animals immunized with snake venoms. Depending on the number of venoms used during the immunization, antivenoms can be monospecific (if venom from a single species is used) or polyspecific (if venoms from several species are used). In turn, polyspecific antivenoms can be prepared by purifying antibodies from the plasma of animals immunized with a mixture of venoms, or by mixing antibodies purified from the plasma of animals immunized separately with single venom. The suitability of these strategies to produce polyspecific antibothropic-crotalic antivenoms was assessed using as models the venoms of Bothrops asper, Crotalus simus and Crotalus durissus ruruima. It was demonstrated that, when used as co-immunogen, C. simus and C. durissus ruruima venoms exert a deleterious effect on the antibody response towards different components of B. asper venom and in the neutralization of hemorrhagic and coagulant effect of this venom when compared with a monospecific B. asper antivenom. Polyspecific antivenoms produced by purifying immunoglobulins from the plasma of animals immunized with venom mixtures showed higher antibody titers and neutralizing capacity than those produced by mixing antibodies purified from the plasma of animals immunized separately with single venom. Thus, despite the deleterious effect of Crotalus sp venoms on the immune response against B. asper venom, the use of venom mixtures is more effective than the immunization with separate venoms for the preparation of polyspecific bothropic-crotalic antivenoms. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. [Effects of venom from Sclerodermus sichuanensis Xiao on pupa of Tenebrio molitor].

    Science.gov (United States)

    Zhuo, Zhi-Hang; Yang, Wei; Qin, Huan; Yang, Chun-Ping; Yang, Hua; Xu, Dan-Ping

    2013-11-01

    To explore the regulatory mechanisms of parasitism of Sclerodermus sichuanensis on Tenebrio molitor, the methods of natural parasitism and venom injection were adopted to investigate the effects of the venom from S. sichuanensis on the pupa of T. molitor in the parasitic process. Under venom injection, the paralytic degree of the pupa had a positive correlation with the concentration of injected venom, and the number of recovered pupa had a negative correlation with the injected venom concentration. The T. molitor pupa was in slight and reversible paralysis when injected with 0.01 VRE (venom reservoir equivalent) of venom, and in non-reversible and complete paralysis when 0.2 VRE was injected. The pupa died massively and appeared a wide range of melanization when injected with soil bacterial suspension alone, but the melanization delayed and the mortality declined significantly when the mixed liquor of bacterium and venom was injected. The bacteriostasis of the venom on Staphylococcus aureus was significantly stronger than that on Escherichia coli. Within a definite range of temperature, the paralytic activity decreased significantly with increasing temperature, the bacteriostasis on S. aureus increased significantly, while that on E. coli was opposite. This study showed that the venom from S. sichuanensis had the effects of paralysis, bacteriostasis, inhibiting exuviations, and delaying melanization.

  16. Functional and proteomic comparison of Bothrops jararaca venom from captive specimens and the Brazilian Bothropic Reference Venom.

    Science.gov (United States)

    Farias, Iasmim Baptista de; Morais-Zani, Karen de; Serino-Silva, Caroline; Sant'Anna, Sávio S; Rocha, Marisa M T da; Grego, Kathleen F; Andrade-Silva, Débora; Serrano, Solange M T; Tanaka-Azevedo, Anita M

    2018-03-01

    Snake venom is a variable phenotypic trait, whose plasticity and evolution are critical for effective antivenom production. A significant reduction of the number of snake donations to Butantan Institute (São Paulo, Brazil) occurred in recent years, and this fact may impair the production of the Brazilian Bothropic Reference Venom (BBRV). Nevertheless, in the last decades a high number of Bothrops jararaca specimens have been raised in captivity in the Laboratory of Herpetology of Butantan Institute. Considering these facts, we compared the biochemical and biological profiles of B. jararaca venom from captive specimens and BBRV in order to understand the potential effects of snake captivity upon the venom composition. Electrophoretic analysis and proteomic profiling revealed few differences in venom protein bands and some differentially abundant toxins. Comparison of enzymatic activities showed minor differences between the two venoms. Similar cross-reactivity recognition pattern of both venoms by the antibothropic antivenom produced by Butantan Institute was observed. Lethality and neutralization of lethality for B. jararaca venom from captive specimens and BBRV showed similar values. Considering these results we suggest that the inclusion of B. jararaca venom from captive specimens in the composition of BBRV would not interfere with the quality of this reference venom. Snakebite envenomation is a neglected tropical pathology whose treatment is based on the use of specific antivenoms. Bothrops jararaca is responsible for the majority of snakebites in South and Southeastern Brazil. Its venom shows individual, sexual, and ontogenetic variability, however, the effect of animal captivity upon venom composition is unknown. Considering the reduced number of wild-caught snakes donated to Butantan Institute in the last decades, and the increased life expectancy of the snakes raised in captivity in the Laboratory of Herpetology, this work focused on the comparative

  17. Effects of Brazilian scorpion venoms on the central nervous system.

    Science.gov (United States)

    Nencioni, Ana Leonor Abrahão; Neto, Emidio Beraldo; de Freitas, Lucas Alves; Dorce, Valquiria Abrão Coronado

    2018-01-01

    In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus , T. bahiensis , T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus , T. silvestres, T. brazilae , T. confluens , T. costatus , T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms - such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock - are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis . Little information is available regarding the other Brazilian Tityus species.

  18. A Study on the Effects of Bee Venom Aqua-Acupuncture on Writhing Reflex

    OpenAIRE

    Jeong Sun-Hee; Koh Hyung-kyun; Park Dong-Suk

    2000-01-01

    Introduction:In spite of the use of Bee Venom aqua-acupuncture in the clinics, the scientific evaluation on effects is not enough. Bee Venom aqua-acupuncture is used according to the stimulation of acupuncture point and the chemical effects of Bee Venom. The aims of this study is to investigate the analgegic effects of the Bee Venom aqua-acupuncture, through the change of writhing reflex Materials and Methods:Pain animal model was used acetic acid method. The changes of writhing reflex of ...

  19. Hematological parameters on the effect of the jellyfish venom Cassiopea andromeda in animal models

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    Iraj Nabipour

    2017-04-01

    Full Text Available For the first time, we previously recorded an enormous population of the Cassiopea andromeda jellyfish that had increased dramatically from Bushehr coasts of Iran. The sub-acute toxicity of the jellyfish venom in rat organs was correspondingly carried out. The data presented in this paper relate to the in vivo and in vitro hematological effects of this venomous species of jellyfish venom.

  20. Intraspecific Variation of Centruroides Edwardsii Venom from Two Regions of Colombia

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    Sebastián Estrada-Gómez

    2014-07-01

    Full Text Available We report the first description studies, partial characterization, and intraspecific difference of Centruroides edwardsii, Gervais 1843, venom. C. edwardsii from two Colombian regions (Antioquia and Tolima were evaluated. Both venoms showed hemolytic activity, possibly dependent of enzymatic active phospholipases, and neither coagulant nor proteolytic activities were observed. Venom electrophoretic profile showed significant differences between C. edwardsii venom from both regions. A high concentration of proteins with molecular masses between 31 kDa and 97.4 kDa, and an important concentration close or below 14.4 kDa were detected. RP-HPLC retention times between 38.2 min and 42.1 min, showed bands close to 14.4 kDa, which may correspond to phospholipases. RP-HPLC venom profile showed a well conserved region in both venoms between 7 and 17 min, after this, significant differences were detected. From Tolima region venom, 50 well-defined peaks were detected, while in the Antioquia region venom, 55 well-defined peaks were detected. Larvicidal activity was only detected in the C. edwardsii venom from Antioquia. No antimicrobial activity was observed using complete venom or RP-HPLC collected fractions of both venoms. Lethally activity (carried out on female albino swiss mice was detected at doses over 19.2 mg/kg of crude venom. Toxic effects included distress, excitability, eye irritation and secretions, hyperventilation, ataxia, paralysis, and salivation.

  1. The effects of hybridization on divergent venom phenotypes: Characterization of venom from Crotalus scutulatus scutulatus × Crotalus oreganus helleri hybrids.

    Science.gov (United States)

    Smith, Cara Francesca; Mackessy, Stephen P

    2016-09-15

    Hybridization between divergent species can be analyzed to elucidate expression patterns of distinct parental characteristics, as well as to provide information about the extent of reproductive isolation between species. A known hybrid cross between two rattlesnakes with highly divergent venom phenotypes provided the opportunity to examine occurrence of parental venom characteristics in the F1 hybrids as well as ontogenetic shifts in the expression of these characters as the hybrids aged. Although venom phenotypes of adult rattlesnake venoms are known for many species, the effect of hybridization on phenotype inheritance is not well understood, and effects of hybridization on venom ontogeny have not yet been investigated. The current study investigates both phenomena resulting from the hybridization of a male snake with type I degradative venom, Crotalus oreganus helleri (Southern Pacific Rattlesnake), and a female snake with type II highly toxic venom, Crotalus scutulatus scutulatus (Mojave Rattlesnake). SDS-PAGE, enzymology, Western blot and reversed phase HPLC (RP-HPLC) were used to characterize the venom of the C. o. helleri male, the C. s. scutulatus female and their two hybrid offspring as they aged. In general, Crotalus o. helleri × C. s. scutulatus hybrid venoms appeared to exhibit overlapping parental venom profiles, and several different enzyme activity patterns. Both hybrids expressed C. o. helleri father-specific myotoxins as well as C. s. scutulatus mother-specific Mojave toxin. Snake venom metalloprotease activity displayed apparent sex-influenced expression patterns, while hybrid serine protease activities were intermediate to parental activities. The C. s. scutulatus × C. o. helleri hybrid male's venom profile provided the strongest evidence that type I and type II venom characteristics are expressed simultaneously in hybrid venoms, as this snake contained distinctive characteristics of both parental species. However, the possibility of

  2. A Study on the Effects of Bee Venom Aqua-Acupuncture on Writhing Reflex

    Directory of Open Access Journals (Sweden)

    Jeong Sun-Hee

    2000-07-01

    Full Text Available Introduction:In spite of the use of Bee Venom aqua-acupuncture in the clinics, the scientific evaluation on effects is not enough. Bee Venom aqua-acupuncture is used according to the stimulation of acupuncture point and the chemical effects of Bee Venom. The aims of this study is to investigate the analgegic effects of the Bee Venom aqua-acupuncture, through the change of writhing reflex Materials and Methods:Pain animal model was used acetic acid method. The changes of writhing reflex of the mice which were derived pain by injecting acetic acid into the abdomen, after stimulating Bee Venom aqua-acupuncture on Chungwan(CV12 and non acupuncture point on the backside were measured. Results:1. It showed that the writhing reflex were appeared on the groups which injected acetic acid only, and saline-acetic acid group(sample I, but not on the group bee venom-saline group(sample II. 2. The change of writhing reflex by Chungwan(CV12 Bee Venom aqua-acupuncture showed significant decrease in the order of Chungwan(CV12 Bee Venom aqua-acupuncture group III(2.5×10-3g/kg, II(2.5×10-4g/kg, and I(2.5×10-5g/kg, compared with control group. There were significant decrease of number of writhing reflex in 5~10, 10~15 and 15~20 minutes intervals of Chung wan(CV12 Bee Venom aqua-acupuncture group I, and in 0~5, 5~10, 10~15 and 15~20 minutes intervals of II and III, compared with control group. 3. The change of writhing reflex by non acupuncture point Bee Venom aqua-acupuncture showed significant decrease in the 0~5 and 5~10 minutes intervals and the total number of writhing reflex in 2.5×10-4g/kg group, compared with control group 4. The effects of writhing reflex of Chungwan(CV12 Bee Venom aqua-acupuncture group showed significant decrease, compared with non acupuncture point Bee Venom aqua-acupuncture group. Conclusion:This study shows that the Bee Venom aqua-acupuncture on Chungwan(CV12 decreases the numbers of writhing reflex. As the

  3. Snake venomics of Crotalus tigris: the minimalist toxin arsenal of the deadliest Nearctic rattlesnake venom. Evolutionary Clues for generating a pan-specific antivenom against crotalid type II venoms [corrected].

    Science.gov (United States)

    Calvete, Juan J; Pérez, Alicia; Lomonte, Bruno; Sánchez, Elda E; Sanz, Libia

    2012-02-03

    We report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7-8 gene products from 6 toxin families; the presynaptic β-neurotoxic heterodimeric PLA(2), Mojave toxin, and two serine proteinases comprise, respectively, 66 and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1-2 PIII-SVMPs each represent 0.1-5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A-subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend toward neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by pedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, Crotalus horridus , Crotalus oreganus helleri, Crotalus scutulatus scutulatus, and Sistrurus catenatus catenatus indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South and North American Crotalus species.

  4. The effect of Hemiscorpius lepturus venom on pathologic changes of Rat organs

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    rohollah Dehghani

    2004-11-01

    Conclusion: The heiscorpius lepturus venom has some effects on skin injury or ulcer and pathologic changes in liver, kidney and spleen of rats. The study of skin injuries and pathologic changes in different organs on human cases in Biopsy and Autopsy can lead to diagnosis of the effect of this venom on human being and consequently suitable cure for the injured.

  5. Comparison of Treatment Effects and Allergic responses to stiff neck between Sweet Bee Venom and Bee Venom Pharmacopuncture (A pilot study, Double blind, Randomized Controlled Clinical Trail

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    Kyoung-hee Lee

    2008-12-01

    Full Text Available Objective : The purpose of this study is to investigate the difference of treatment effects and allergic responses to stiff neck between Bee Venom Pharmacopuncture and Sweet Bee Venom Pharmacopuncture. Methods : Forty one patients who felt stiff neck were randomly divided into two groups, a Bee Venom Pharmacopuncture group(group Ⅰ and a Sweet Bee Venom Pharmacopuncture group(group Ⅱ. Evaluations of the treatment effects were made before and after a treatment using Visual Analog Scale(VAS, Neck Disability Index(NDI, Clinical Evaluation Grade(CEG. The comparison of allergic responses was measured with VAS. The obtained data were analyzed and compared with SPSS. Results : The group Ⅰ and group Ⅱ showed significant improvement(p<0.05 according to the VAS, NDI, CEG. And the differences between the two groups were insignificant according to VAS, NDI, CEG. But allergic responses such as localized edema, localized itching were significantly lower in group Ⅱ than group Ⅰ. Conclusions : It seems that there are no big different treatment effects between the two groups. Sweet Bee Venom Pharmacopuncture appears to be more effective measurement against allergic reactions than the Bee Venom Pharmacopuncture. Further studies are needed for the comparison of Bee Venom Pharmacopuncture and Sweet Bee Venom Pharmacopuncture.

  6. Optimization of antiscorpion venom production

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    O. Ozkan

    2006-01-01

    Full Text Available The present study was carried out to produce highly efficient antivenom from a small number of telsons in a short time. Venom solution was prepared through maceration of telsons from Androctonus crassicauda (Olivier, 1807 collected in the Southeastern Anatolia Region, Turkey. Lethal dose 50% (LD50 of the venom solution injected into mice was 1 ml/kg (95% confidence interval; 0.8-1.3, according to probit analysis. Different adjuvants (Freund's Complete Adjuvant, Freund's Incomplete Adjuvant, and 0.4% aluminium phosphate, at increasing doses and combined with venom, were subcutaneously injected into horses on days 0, 14, 21, 28, 35, and 42 of the experiment. Antivenom was collected from the immunized horses on days 45, 48, and 51 using the pepsin digestive method. The antivenom effective dose 50% (ED50 in mice was 0.5 ml (95% confidence interval; 0.40-0.58, according to probit analysis. It was concluded that 0.5 ml antivenom neutralized a venom dose 35-fold higher than the venom LD50. Thus, highly potent antivenom could be produced from about 238 telsons in 51 days.

  7. Study of gamma radiation from {sup 60}Co effects on Apis mellifera venom: biochemical, pharmacological and immunological aspects; Estudo dos efeitos da radiacao gama de {sup 60}Co na peconha de Apis mellifera: aspectos bioquimicos, farmacologicos e imunologicos

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Helena

    2001-07-01

    Africanized honeybees are very common insects in Brazil and frequently cause accidents followed by important immunological reactions and even deaths. Their venoms are composed of a complex mixture of substances of general biological actions. Ionizing radiation is able to modify molecular structures affecting the biological properties of proteins. It decreases toxic and enzymatic activities and so, it appears promising as a venom detoxification tool. The main objective of this work was to study the effects of gamma radiation on bee venom, regarding biochemical, pharmacological and immunological aspects. Africanized Apis mellifera whole venom (2 mg/ml) in 0.15 M NaCl solution was irradiated with 2 kGy in a {sup 60}Co source. Native and irradiated bee venoms were submitted to high performance size exclusion chromatography (Tosohaas G2000SW column), high performance reversed phase chromatography in a C-18 column under water/acetonitrile gradient, SDS-PAGE. For both venoms studies have been carried out in UV absorption spectrum, protein concentration, hemolytic activity, and PLA{sub 2} activity analysis, lethality assay (LD{sub 50}). Biodistribution studies was carried out after labelling native and irradiated bee venom with {sup 99m}Tc. The results showed that gamma radiation did not change the protein concentration nor its immunogenicity, although it could be observed that irradiated bee venom UV spectrum and SDS-PAGE profile presented differences when compared to native bee venom. This suggests that some structural alterations in bee venom components could have occurred after irradiation. HPLC-RP profiles showed that gamma radiation could have caused conformational changes, such as unfolding of molecule chains, changing their hydrophobic groups exposuring. The hemolytic and the PLA{sub 2} activities of irradiated bee venom were smaller than the native ones. The gamma radiation diminished the toxicity of bee venom, but did not abolish its bioactivity, like hemolysis

  8. Adrenergic and cholinergic activity contributes to the cardiovascular effects of lionfish (Pterois volitans) venom.

    Science.gov (United States)

    Church, Jarrod E; Hodgson, Wayne C

    2002-06-01

    The aim of the present study was to further investigate the cardiovascular activity of Pterois volitans crude venom. Venom (0.6-18 microg protein/ml) produced dose- and endothelium-dependent relaxation in porcine coronary arteries that was potentiated by atropine (10nM), but significantly attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (NOLA; 0.1mM), by prior exposure of the tissue to stonefish antivenom (SFAV, 3 units/ml, 10 min), or by removal of extracellular Ca(2+). In rat paced left atria, venom (10 microg protein/ml) produced a decrease, followed by an increase, in contractile force. Atropine (0.5 microM) abolished the decrease in force and potentiated the increase. Propranolol (5 microM) did not affect the decrease in force but significantly attenuated the increase. In spontaneously beating right atria, venom (10 microg protein/ml) produced an increase in rate that was significantly attenuated by propranolol (5 microM). Prior incubation with SFAV (0.3 units/microg protein, 10 min) abolished both the inotropic and chronotropic responses to venom. In the anaesthetised rat, venom (100 micro protein/kg, i.v.) produced a pressor response, followed by a sustained depressor response. Atropine (1mg/kg, i.v.) potentiated the pressor response. The further addition of prazosin (50 microg/kg, i.v.) restored the original response to venom. Prior administration of SFAV (100 units/kg, i.v., 10 min) significantly attenuated the in vivo response to venom. It is concluded that P. volitans venom produces its cardiovascular effects primarily by acting on muscarinic cholinergic receptors and adrenoceptors. As SFAV neutralised many of the effects of P. volitans venom, we suggest that the two venoms share a similar component(s). Copright 2002 Elsevier Science Ltd.

  9. The Antinociceptive Effects of Iranian Cobra Snake Venom using Formalin Test

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    Zahra Hadi Chegeni

    2015-06-01

    Full Text Available Abstract Background: There have been numerous reports of snake venoms being employed as analgesics in attempts to relieve severe pain associated with cancer, immune dysfunction and viral infections. This study investigates the antinociceptive effects of iranian cobra snake venom (Naja naja oxiana in comparison with morphine and lidocain on laboratorial femal mice. Materials and Methods: This study has been done on 48 NMRI female mice of 18-20 g in weight. Antinociceptive activeity of snake venom was evaluated by formalin test. In this test, the animals were divided into 6 groups (each group consisting of 8 mice: Sham, positive Control (receiving morphine at dose of 5 mg/kg, and receiving lidocain at dose of 20 mg/kg, and experimental groups receiving venom at doses of 1, 3 and 4/5 µg/mice. In all groups, the formalin test was recorded for 60 min after administration of venom and drugs in mice. Data were analyzed using one-way ANOVA and Tukey test. Results: The results showed that the venom of Naja naja oxiana decreased nociception meaningfully in both acute and chronic phases. We also showed that this venom revealed even a better analgesic activity in comparison with morphine and lidocain. Conclusion: This study showed that the antinociceptive effect of the venom was mediated through central nervous system and peripheral mechanisms. Although details of the mechanism remain unclear, and further studies should be considered to demonstrate its therapeutic effects.

  10. Biological and molecular properties of yellow venom of the Amazonian coral snake Micrurus surinamensis.

    Science.gov (United States)

    Oliveira, Fabiana da Rocha; Noronha, Maria das Dores Nogueira; Lozano, Jorge Luis Lopez

    2017-01-01

    The coral snake Micrurus surinamensis, which is widely distributed throughout Amazonia, has a neurotoxic venom. It is important to characterize the biological and molecular properties of this venom in order to develop effective antitoxins. Toxins from the venom of M. surinamensis were analyzed by two-dimensional polyacrylamide gel electrophoresis and their neurotoxic effects in vivo were evaluated. Most proteins in the venom had masses < 14kDa, low phospholipase A2 activity, and no proteolytic activity. The toxins inhibited the coagulation cascade. The venom had neurotoxic effects in mice, with a median lethal dose upon intravenous administration of 700 µg/kg. Immunogenic studies revealed abundant cross-reactivity of antielapidic serum with 14kDa toxins and limited cross-reactivity with toxins < 10kDa. These results indicate that antielapidic serum against M. surinamensis venom has weak potency (0.35mg/ml) in mice.

  11. The protective effect of bee venom on fibrosis causing inflammatory diseases.

    Science.gov (United States)

    Lee, Woo-Ram; Pak, Sok Cheon; Park, Kwan-Kyu

    2015-11-16

    Bee venom therapy is a treatment modality that may be thousands of years old and involves the application of live bee stings to the patient's skin or, in more recent years, the injection of bee venom into the skin with a hypodermic needle. Studies have proven the effectiveness of bee venom in treating pathological conditions such as arthritis, pain and cancerous tumors. However, there has not been sufficient review to fully elucidate the cellular mechanisms of the anti-inflammatory effects of bee venom and its components. In this respect, the present study reviews current understanding of the mechanisms of the anti-inflammatory properties of bee venom and its components in the treatment of liver fibrosis, atherosclerosis and skin disease.

  12. Effects of the Bee Venom Herbal Acupuncture on the Neurotransmitters of the Rat Brain Cortex

    Directory of Open Access Journals (Sweden)

    Hyoung-Seok Yun

    2001-02-01

    Full Text Available In order to study the effects of bee venom Herbal Acupuncture on neurotransmitters in the rat brain cortex, herbal acupuncture with bee venom group and normal saline group was performed at LI4 bilaterally of the rat. the average optical density of neurotransmitters from the cerebral cortex was analysed 30 minutes after the herbal aqupuncture, by the immunohistochemistry. The results were as follows: 1. The density of NADPH-diaphorase in bee venom group was increased significantly at the motor cortex, visual cortex, auditory cortex, cingulate cortex, retrosplenial cortex and perirhinal cortex compared to the normal saline group. 2. The average optical density of vasoactive intestinal peptide in bee venom group had significant changes at the insular cortex, retrosplenial cortex and perirhinal cortex, compared to the normal saline group. 3. The average optical density of neuropeptide-Y in bee venom group increased significantly at the visual cortex and cingulate cortex, compared to the normal saline group.

  13. Rabbit IgG antibodies against Phospholipase A2 from Crotalus durissus terrificus neutralize the lethal activity of the venom Los anticuerpos IgG de conejos anti-fosfolipasa A2 de Crotalus durissus terrificus neutralizan la actividad letal del veneno

    Directory of Open Access Journals (Sweden)

    Juan P. Rodríguez

    2006-12-01

    Full Text Available Crotalus durissus terrificus (C.d.t. (South American rattlesnake venom possesses myotoxic and neurotoxic activities, both of which are also expressed by crotoxin, the principal toxin of this venom. Crotoxin contains a basic phospholipase A2 (PLA2 and a non toxic acidic protein, crotapotin. We have produced and investigated the ability of IgG antibodies raised in rabbits against PLA2 to neutralize the lethality of the whole venom. PLA2 was isolated by gel filtration chromatography (Sephadex G-75. Specific antibodies were obtained by subcutaneous and intramuscular inoculation of PLA2 (700 µg with Freund adjuvant. Groups of six mice (20 + 2 g were inoculated with 0.5 ml i.p. of C. d. t. venom (4 µg or a mixture of venom that had been preincubated with the desired volume of IgG antibodies. Mortality, recorded 24 and 48 h after inoculation, showed that IgG anti-PLA2 were more effective than anticrotalic serum in neutralizing the lethal activity. These results demonstrate that it could be possible to obtain an anti-venom made by specific antibodies with a high level of protection against the lethal component of C.d.t. venom, and/or the inclusion of these antibodies as a supplement in heterologous anti-venoms.El veneno de Crotalus durissus terrificus (C.d.t. (Cascabel de Sud América posee actividad miotóxica y neurotóxica, actividades que también exhibe el complejo crotoxina, principal componente tóxico de este veneno. El complejo crotoxina está constituido por una fosfolipasa A2 básica (PLA2 y una proteína acídica no tóxica, el crotapotín. En este trabajo se estudió la capacidad neutralizante de anticuerpos IgG anti-PLA2 sobre la letalidad inducida por el veneno entero. El antígeno PLA2, fue aislado por cromatografía de filtración en gel (Sephadex G-75. Se inocularon conejos machos por vía subcutánea e intramuscular, con 700 µg de PLA2 y adyuvante para la obtención de anticuerpos específicos. La capacidad neutralizante del

  14. Antivenom potential of ethanolic extract of Cordia macleodii bark against Naja venom.

    Science.gov (United States)

    Soni, Pranay; Bodakhe, Surendra H

    2014-05-01

    To evaluate the antivenom potential of ethanolic extract of bark of Cordia macleodii against Naja venom induced pharmacological effects such as lethality, hemorrhagic lesion, necrotizing lesion, edema, cardiotoxicity and neurotoxicity. Wistar strain rats were challenged with Naja venom and treated with the ethanolic extract of Cordia macleodii bark. The effectiveness of the extract to neutralize the lethalities of Naja venom was investigated as recommended by WHO. At the dose of 400 and 800 mg/kg ethanolic extract of Cordia macleodii bark significantly inhibited the Naja venom induced lethality, hemorrhagic lesion, necrotizing lesion and edema in rats. Ethanolic extract of Cordia macleodii bark was effective in neutralizing the coagulant and defibrinogenating activity of Naja venom. The cardiotoxic effects in isolated frog heart and neurotoxic activity studies on frog rectus abdominus muscle were also antagonized by ethanolic extract of Cordia macleodii bark. It is concluded that the protective effect of extract of Cordia macleodii against Naja venom poisoning may be mediated by the cardiotonic, proteolysin neutralization, anti-inflammatory, antiserotonic and antihistaminic activity. It is possible that the protective effect may also be due to precipitation of active venom constituents.

  15. Neutralization of lethality and proteolytic activities of Malayan pit viper (Calloselasma rhodostoma) venom with North American Virginia opossum (Didelphis virginiana) serum.

    Science.gov (United States)

    Pornmanee, Piboon; Sánchez, Elda E; López, Gonzalo; Petsom, Amorn; Khow, Orawan; Pakmanee, Narumol; Chanhome, Lawan; Sangvanich, Polkit; Pérez, John C

    2008-07-01

    Malayan pit viper (Calloselasma rhodostoma) envenomation is a major health problem in South East Asia. During envenomation, venom components mainly affect the hemostatic system. The sera from the North American Virginia opossums (Didelphis virginiana) were able to neutralize the venom of the Malayan pit viper. These natural inhibitors could be explored as potential therapeutics against envenomations of a variety of venomous snake species in different geographical habitats.

  16. Irradiated cobra (Naja naja) venom for biomedical applications

    International Nuclear Information System (INIS)

    Kankonkar, S.R.; Kankonkar, R.C.; Gaitonde, B.B.

    1975-01-01

    Ionizing radiation is known to cause damage to proteins in aqueous solutions in a selective manner, thereby producing remarkable changes in their properties. Since venoms are very rich in proteins, it was felt that they would also show such changes upon irradiation. It was of interest to know if one could get rid of the toxicity and retain the immunogenicity of the venom by suitable choice of radiation dose and strength of venom solution. If so, the method could be profitably exploited for the rapid preparation of venom toxoid and this could be expected to have many applications in the biological sciences. Accordingly, laboratory investigations were undertaken on the effect of gamma radiation on cobra (Naja naja) venom. To avoid drastic changes, solutions of cobra venom having low protein content were irradiated with gamma radiation from a cobalt-60 source. The results obtained with 0.01 to 1.0% venom solutions are found to be encouraging. The solutions did not manifest any toxicity in mice. For the immunogenicity test, guinea pigs were immunized with varying doses of the irradiated cobra venom and the immunized guinea pigs were found to survive when challenged with as big a dose as 10 MLD (i.e. minimum lethal dose, approximately 1 mg). The paper describes the experimental details and the results of the observations. (author)

  17. Neutralizing effects of polyvalent antivenom on severe inflammatory response induced by Mesobuthus eupeus scorpion venom

    Directory of Open Access Journals (Sweden)

    Zayerzadeh1 E.

    2014-11-01

    Full Text Available This study evaluated the effects of Mesobuthus eupeus (Me scorpion venom on inflammatory response following injection. Additionally, the present study examined whether immunotherapy at specific time intervals would be effective on inflammatory response after Me venom inoculation. Animals were divided randomly into four groups: the first group received LD50 of venom and the second and third groups of animals; immunotherapy was performed in different time intervals and fourth group was considered as control group. Me venom inoculation is caused respiratory perturbations such as respiratory distress, respiration with open mouth, crepitation and finally respiratory arrest. Me inoculation is resulted in increased pro-inflammatory cytokines including TNF-α and IL-1. Venom injection also induced inflammatory response, characterized by significant increase in serum white blood cells and neutrophils at 30, 60 and 180 min following envenomation. Simultaneous administration of antivenom and venom prevented entirely clinical sings, cytokines and hematological changes. Delayed immunotherapy gradually ameliorated clinical features, cytokines changes and hematological abnormalities related to the envenomation. In conclusion, our observations indicate injection of M. eupeus scorpion venom induces severe inflammatory response which can be one of the causes of clinical complications. Additionally, immunotherapy beyond 1 h after envenomation with appropriate dose and route in victims with severe inflammatory response related to the M.eupeus scorpion envenomation is beneficial.

  18. Effect of Trimeresurus albolabris (green pit viper) venom on mean ...

    African Journals Online (AJOL)

    An in vitro study was conducted by mixing small amounts of green pit viper venom with blood and observing changes. At a concentration of 10 mg crude venom, red blood cells (RBC) osmotic fragility slightly increased. RBC morphology changed to spherical shape which was compatible with what was observed in scanning ...

  19. Effect of lethal and sub-lethal concentrations of tobacco (Nicotiana ...

    African Journals Online (AJOL)

    Lethal and sub-lethal bioassays on Clarias gariepinus were conducted to evaluate the toxicity of tobacco (Nicotiana tobaccum) leaf dust on weight gain and haematological indices of Clarias gariepinus (mean weight 10.5±0.70g) in glass aquaria with aeration system. The concentrations used during the lethal exposure are: ...

  20. Therapeutic Effects of Bee Venom on Immunological and Neurological Diseases.

    Science.gov (United States)

    Hwang, Deok-Sang; Kim, Sun Kwang; Bae, Hyunsu

    2015-06-29

    Bee Venom (BV) has long been used in Korea to relieve pain symptoms and to treat inflammatory diseases, such as rheumatoid arthritis. The underlying mechanisms of the anti-inflammatory and analgesic actions of BV have been proved to some extent. Additionally, recent clinical and experimental studies have demonstrated that BV and BV-derived active components are applicable to a wide range of immunological and neurodegenerative diseases, including autoimmune diseases and Parkinson's disease. These effects of BV are known to be mediated by modulating immune cells in the periphery, and glial cells and neurons in the central nervous system. This review will introduce the scientific evidence of the therapeutic effects of BV and its components on several immunological and neurological diseases, and describe their detailed mechanisms involved in regulating various immune responses and pathological changes in glia and neurons.

  1. Neutralization of Apis mellifera bee venom activities by suramin.

    Science.gov (United States)

    El-Kik, Camila Z; Fernandes, Fabrício F A; Tomaz, Marcelo Amorim; Gaban, Glauco A; Fonseca, Tatiane F; Calil-Elias, Sabrina; Oliveira, Suellen D S; Silva, Claudia L M; Martinez, Ana Maria Blanco; Melo, Paulo A

    2013-06-01

    In this work we evaluated the ability of suramin, a polysulfonated naphthylurea derivative, to antagonize the cytotoxic and enzymatic effects of the crude venom of Apis mellifera. Suramin was efficient to decrease the lethality in a dose-dependent way. The hemoconcentration caused by lethal dose injection of bee venom was abolished by suramin (30 μg/g). The edematogenic activity of the venom (0.3 μg/g) was antagonized by suramin (10 μg/g) in all treatment protocols. The changes in the vascular permeability caused by A. mellifera (1 μg/g) venom were inhibited by suramin (30 μg/g) in the pre- and posttreatment as well as when the venom was preincubated with suramin. In addition, suramin also inhibited cultured endothelial cell lesion, as well as in vitro myotoxicity, evaluated in mouse extensor digitorum longus muscle, which was inhibited by suramin (10 and 25 μM), decreasing the rate of CK release, showing that suramin protected the sarcolemma against damage induced by components of bee venom (2.5 μg/mL). Moreover, suramin inhibited the in vivo myotoxicity induced by i.m. injection of A. mellifera venom in mice (0.5 μg/g). The analysis of the area under the plasma CK vs. time curve showed that preincubation, pre- and posttreatment with suramin (30 μg/g) inhibited bee venom myotoxic activity in mice by about 89%, 45% and 40%, respectively. Suramin markedly inhibited the PLA2 activity in a concentration-dependent way (1-30 μM). Being suramin a polyanion molecule, the effects observed may be due to the interaction of its charges with the polycation components present in A. mellifera bee venom. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. The pharmacological effect of Bothrops neuwiedii pauloensis (jararaca-pintada snake venom on avian neuromuscular transmission

    Directory of Open Access Journals (Sweden)

    C.R. Borja-Oliveira

    2003-05-01

    Full Text Available The neuromuscular effects of Bothrops neuwiedii pauloensis (jararaca-pintada venom were studied on isolated chick biventer cervicis nerve-muscle preparations. Venom concentrations of 5-50 µg/ml produced an initial inhibition and a secondary increase of indirectly evoked twitches followed by a progressive concentration-dependent and irreversible neuromuscular blockade. At venom concentrations of 1-20 µg/ml, the responses to 13.4 mM KCl were inhibited whereas those to 110 µM acetylcholine alone and cumulative concentrations of 1 µM to 10 mM were unaffected. At venom concentrations higher than 50 µg/ml, there was pronounced muscle contracture with inhibition of the responses to acetylcholine, KCl and direct stimulation. At 20-24ºC, the venom (50 µg/ml produced only partial neuromuscular blockade (30.7 ± 8.0%, N = 3 after 120 min and the initial inhibition and the secondary increase of the twitch responses caused by the venom were prolonged and pronounced and the response to KCl was unchanged. These results indicate that B.n. pauloensis venom is neurotoxic, acting primarily at presynaptic sites, and that enzyme activity may be involved in this pharmacological action.

  3. The effects of low-level laser on muscle damage caused by Bothrops neuwiedi venom

    Directory of Open Access Journals (Sweden)

    DM Dourado

    2008-01-01

    Full Text Available The present study aimed to assess the effects of low-level laser (660 nm on myonecrosis caused by the insertion of Bothrops neuwiedi venom in the gastrocnemius muscle of rats. Male Wistar rats were divided into three groups (n = 24 each: Group S (0.9% saline solution; Group V (venom and Group VLLL (venom plus low-level laser. These categories were subdivided into four additional groups (n = 6 based on the euthanasia timing (3 hours, 24 hours, 3 days and 7 days. The groups V and VLLL were inoculated with 100 µL of concentrated venom (40 µg/mL in the gastrocnemius muscle. The muscle was irradiated using a gallium-aluminum-arsenide laser (GaAlAs at 35 mW power and 4 J/cm² energy density for 3 hours, 24 hours, 3 days or 7 days after venom inoculation. To evaluate the myotoxic activity of the venom, CK activity was measured and the muscle was histologically analyzed. The low-level laser reduced venom-induced CK activity in the groups euthanized at 3 hours, 24 hours and 3 days (p < 0.0001. Histological analysis revealed that low-level laser reduced neutrophilic inflammation as well as myofibrillar edema, hemorrhage and myonecrosis following B. neuwiedi envenomation. These results suggest that low-level laser can be useful as an adjunct therapy following B. neuwiedi envenomation.

  4. The effects of low-level laser on muscle damage caused by Bothrops neuwiedi venom

    Energy Technology Data Exchange (ETDEWEB)

    Dourado, D.M.; Matias, R.; Almeida, M.F.; Paula, K.R. de; Carvalho, P.T.C. [University for the Development of the State and of the Region of Pantanal (UNIDERP), Campo Grande, MS (Brazil). Lab. of Experimental Histopathology]. E-mail: ccfi@uniderp.br; Vieira, R.P. [University of Sao Paulo (USP), SP (Brazil). School of Medicine. Dept. of Pathology and Physical Therapy; Oliveira, L.V.F. [Nove de Julho University (UNINOVE), Sao Paulo, SP (Brazil). Masters Program in Rehabilitation Sciences

    2008-07-01

    The present study aimed to assess the effects of low-level laser (660 nm) on myonecrosis caused by the insertion of Bothrops neuwiedi venom in the gastrocnemius muscle of rats. Male Wistar rats were divided into three groups (n = 24 each): Group S (0.9% saline solution); Group V (venom) and Group VLLL (venom plus low-level laser). These categories were subdivided into four additional groups (n = 6) based on the euthanasia timing (3 hours, 24 hours, 3 days and 7 days). The groups V and VLLL were inoculated with 100 {mu}L of concentrated venom (40 {mu}g/mL) in the gastrocnemius muscle. The muscle was irradiated using a gallium-aluminum-arsenide laser (GaAlAs) at 35 mW power and 4 J/cm{sup 2} energy density for 3 hours, 24 hours, 3 days or 7 days after venom inoculation. To evaluate the myotoxic activity of the venom, CK activity was measured and the muscle was histologically analyzed. The low-level laser reduced venom-induced CK activity in the groups euthanized at 3 hours, 24 hours and 3 days (p < 0.0001). Histological analysis revealed that low-level laser reduced neutrophilic inflammation as well as myofibrillar edema, hemorrhage and myonecrosis following B. neuwiedi envenomation. These results suggest that low-level laser can be useful as an adjunct therapy following B. neuwiedi envenomation. (author)

  5. The effects of low-level laser on muscle damage caused by Bothrops neuwiedi venom

    International Nuclear Information System (INIS)

    Dourado, D.M.; Matias, R.; Almeida, M.F.; Paula, K.R. de; Carvalho, P.T.C.; Vieira, R.P.; Oliveira, L.V.F.

    2008-01-01

    The present study aimed to assess the effects of low-level laser (660 nm) on myonecrosis caused by the insertion of Bothrops neuwiedi venom in the gastrocnemius muscle of rats. Male Wistar rats were divided into three groups (n = 24 each): Group S (0.9% saline solution); Group V (venom) and Group VLLL (venom plus low-level laser). These categories were subdivided into four additional groups (n = 6) based on the euthanasia timing (3 hours, 24 hours, 3 days and 7 days). The groups V and VLLL were inoculated with 100 μL of concentrated venom (40 μg/mL) in the gastrocnemius muscle. The muscle was irradiated using a gallium-aluminum-arsenide laser (GaAlAs) at 35 mW power and 4 J/cm 2 energy density for 3 hours, 24 hours, 3 days or 7 days after venom inoculation. To evaluate the myotoxic activity of the venom, CK activity was measured and the muscle was histologically analyzed. The low-level laser reduced venom-induced CK activity in the groups euthanized at 3 hours, 24 hours and 3 days (p < 0.0001). Histological analysis revealed that low-level laser reduced neutrophilic inflammation as well as myofibrillar edema, hemorrhage and myonecrosis following B. neuwiedi envenomation. These results suggest that low-level laser can be useful as an adjunct therapy following B. neuwiedi envenomation. (author)

  6. Evaluation of the effects of photooxidized Echis carinatus venom on learning, memory and stress

    Directory of Open Access Journals (Sweden)

    C. M. Reddy

    2006-01-01

    Full Text Available Snake venoms are a mixture of complex proteins, which have many physical and pharmacological properties. Photochemical detoxification has been suggested to generate photooxidized Echis carinatus venom product (POECVP. Antigenically-active photooxidized species of Echis carinatus venom could be obtained by exposing the venom to ultraviolet radiation (UVR in the presence of methylene blue. The aim of the present study was to evaluate the effects of POECVP on learning, memory and stress in rats. Detoxification of the photooxidized venom was evident since the POECVP-treated group had longer survival time than the group of mice treated with Echis carinatus venom product (ECVP following intraperitoneal and intracerebral injections. Photooxidized Echis carinatus venom product showed antidepressant activity by prolonging sleep onset and shortening the duration of pentobarbitone-induced hypnosis in mice. In single and chronic dose studies with rats, we observed that POECVP significantly decreased the time needed to reach food in T-maze, shortened transfer latency in elevated plus-maze, and decreased immobility time in forced swim test. We concluded that although there is a possibility of employing POECVP in the treatment of depressive and chronic degenerative illnesses as a nonherbal and nonsynthetic alternative for patients not responding to the available therapy, further investigation is still needed.

  7. Effects of 60Co gamma radiation on toxicity and hemorrhagic, myonecrotic, and edema-forming activities of Cerastes cerastes venom

    International Nuclear Information System (INIS)

    Abib, H.; Laraba-Djebari, F.

    2003-01-01

    Antisera are used as effective antidotes against the local effects of snake bites. To improve antisera production and extend the life of surrogates used to produce antibodies, the chronic effects of venom toxicity must be reduced. The present study evaluated the effectiveness of gamma irradiation to reduce the local effects associated with viperid snake bites by evaluating in NMRI mice the toxicity and edematic, hemorrhagic, and myonecrotic activities of native and irradiated Cerastes cerastes venoms. These results indicated that the toxicity of irradiated venoms (1 and 2 kGy) decreased as compared with that of native venom. The edematic and hemorrhagic activities were also reduced in the detoxified samples, particularly with the 2-kGy radiation dose. Furthermore, the creatine phosphokinase (CPK) activity was significantly increased in the serum and decreased in the myocardium after envenomation with native venom, but no significant enzymatic changes were observed in mice envenomated with irradiated venom. Histopathologic evaluation showed that native venom caused severe degenerative changes in the myocardium. In the case of 2-kGy-irradiated venom, no tissue alterations were observed. These results indicate that irradiation of venom with a 2-kGy dose may offer an effective method for reducing the chronic toxic effects of venom in immunized animals. (author)

  8. Intraspecies variation in the venom of the rattlesnake Crotalus simus from Mexico: different expression of crotoxin results in highly variable toxicity in the venoms of three subspecies.

    Science.gov (United States)

    Castro, Edgar Neri; Lomonte, Bruno; del Carmen Gutiérrez, María; Alagón, Alejandro; Gutiérrez, José María

    2013-07-11

    The composition and toxicological profile of the venom of the rattlesnake Crotalus simus in Mexico was analyzed at the subspecies and individual levels. Venoms of the subspecies C. s. simus, C. s. culminatus and C. s. tzabcan greatly differ in the expression of the heterodimeric neurotoxin complex 'crotoxin', with highest concentrations in C. s. simus, followed by C. s. tzabcan, whereas the venom of C. s. culminatus is almost devoid of this neurotoxic PLA2. This explains the large variation in lethality (highest in C. s. simus, which also exerts higher myotoxicity). Coagulant activity on plasma and fibrinogen occurs with the venoms of C. s. simus and C. s. tzabcan, being absent in C. s. culminatus which, in turn, presents higher crotamine-like activity. Proteomic analysis closely correlates with toxicological profiles, since the venom of C. s. simus has high amounts of crotoxin and of serine proteinases, whereas the venom of C. s. culminatus presents higher amounts of metalloproteinases and crotamine. This complex pattern of intraspecies venom variation provides valuable information for the diagnosis and clinical management of envenoming by this species in Mexico, as well as for the preparation of venom pools for the production and quality control of antivenoms. This study describes the variation in venom composition and activities of the three subspecies of Crotalus simus from Mexico. Results demonstrate that there is a notorious difference in these venoms, particularly regarding the content of the potent neurotoxic phospholipase A2 complex 'crotoxin'. In addition, other differences were observed regarding myotoxic and coagulant activities, and expression of the myotoxin 'crotamine'. These findings have implications in, at least, three levels: (a) the adaptive role of variations in venom composition; (b) the possible differences in the clinical manifestations of envenomings by these subspecies in Mexico; and (c) the design of venom mixtures for the preparation of

  9. Optimization and preliminary characterization of venom isolated from 3 medically important jellyfish: the box (Chironex fleckeri), Irukandji (Carukia barnesi), and blubber (Catostylus mosaicus) jellyfish.

    Science.gov (United States)

    Wiltshire, C J; Sutherland, S K; Fenner, P J; Young, A R

    2000-01-01

    To optimize venom extraction and to undertake preliminary biochemical studies of venom from the box jellyfish (Chironex fleckeri), the Irukandji jellyfish (Carukia barnesi), and the blubber jellyfish (Catostylus mosaicus). Lyophilized crude venoms from box jellyfish tentacles and whole Irukandji jellyfish were prepared in water by homogenization, sonication, and rapid freeze thawing. A second technique, consisting of grinding samples with a glass mortar and pestle and using phosphate-buffered saline, was used to prepare crude venom from isolated nematocysts of the box jellyfish, the bells of Irukandji jellyfish, and the oral lobes of blubber jellyfish. Venoms were compared by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot test. Toxicity of some venoms was determined by intravenous median lethal dose assay in mice. Different venom extraction techniques produced significantly different crude venoms for both box and Irukandji jellyfish. Irukandji and blubber venom SDS-PAGE protein profiles were established for the first time. Analysis of Western blot tests revealed that box jellyfish antivenin reacted specifically with the venom of each jellyfish. Toxicity was found in Irukandji jellyfish venom derived by use of the mortar-and-pestle method, but not in the lyophilized venom. Glass mortar-and-pestle grinding and use of an appropriate buffer was found to be a simple and suitable method for the preparation of venom from each jellyfish species studied. This study contributes to biochemical investigations of jellyfish venoms, particularly the venom of the Irukandji jellyfish, for which there are, to our knowledge, no published studies. It also highlights the importance of optimizing venom extraction as the first step toward understanding the complex biological effects of jellyfish venoms.

  10. The Effects of Anthrax Lethal Toxin on Host Barrier Function

    Directory of Open Access Journals (Sweden)

    David M. Frucht

    2011-06-01

    Full Text Available The pathological actions of anthrax toxin require the activities of its edema factor (EF and lethal factor (LF enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA. LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs, but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects.

  11. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: a double-edged sword.

    Science.gov (United States)

    Chen, Jun; Lariviere, William R

    2010-10-01

    Bee venom injection as a therapy, like many other complementary and alternative medicine approaches, has been used for thousands of years to attempt to alleviate a range of diseases including arthritis. More recently, additional theraupeutic goals have been added to the list of diseases making this a critical time to evaluate the evidence for the beneficial and adverse effects of bee venom injection. Although reports of pain reduction (analgesic and antinociceptive) and anti-inflammatory effects of bee venom injection are accumulating in the literature, it is common knowledge that bee venom stings are painful and produce inflammation. In addition, a significant number of studies have been performed in the past decade highlighting that injection of bee venom and components of bee venom produce significant signs of pain or nociception, inflammation and many effects at multiple levels of immediate, acute and prolonged pain processes. This report reviews the extensive new data regarding the deleterious effects of bee venom injection in people and animals, our current understanding of the responsible underlying mechanisms and critical venom components, and provides a critical evaluation of reports of the beneficial effects of bee venom injection in people and animals and the proposed underlying mechanisms. Although further studies are required to make firm conclusions, therapeutic bee venom injection may be beneficial for some patients, but may also be harmful. This report highlights key patterns of results, critical shortcomings, and essential areas requiring further study. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. Neutralization of bitis parviocula (Ethiopian mountain adder venom by the south african institute of medical research (SAIMR antivenom

    Directory of Open Access Journals (Sweden)

    Elda E. Sánchez

    2011-08-01

    Full Text Available BACKGROUND: The Ethiopian mountain adder (Bitis parviocula is a viperid known only from a few locations in southwestern Ethiopia. METHODS: a total of 30 µg of B. arietans and B. parviocula venoms were run on a 10-20% Tricine gel. To assay lethality dose fifty (LD50, five groups of eight mice for each venom were used. Hemorrhagic activity for crude venom was tested. Fibrinogenolytic activity of crude venom was measured using (2.5 mg/mL of fibrinogen solution and (0.03 mg/mL of crude venom. Gelatinase activity of the venom was tested on a Kodak X-OMAT TM film. Crude venoms of B. parviocula and B. arietans were tested for their abilities to affect clotting time, clotting rate and platelet function on whole human blood. RESULTS: The (SAIMR antivenom was confirmed in this study to neutralize the lethal activity of venom from Bitis parviocula. The ED50s of SAIMR antivenom on B. parviocula and B. arietans neutralized half of 18.2 and 66.7 mg of venom, respectively. The hemorrhagic activities (MHDs of B. parviocula and B. arietans were 0.88 and 1.7 µg, respectively. Bitis arietans and B. parviocula venoms degradated α and β chains at different times. The γ chains remained unaffected. Bitis parviocula venom did not exhibit gelatinase activity, while B. arietans had a MGD of 6.9 µg. At 3 mg/mL, the crude venoms of B. parviocula and B. arietans did not significantly affect clotting time or clotting rate. CONCLUSIONS: The SAIMR antivenom is very effective in neutralizing the venom of B. parviocula and should be considered in treating envenomations by these snakes.

  13. Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models.

    Science.gov (United States)

    Maduwage, Kalana P; Scorgie, Fiona E; Lincz, Lisa F; O'Leary, Margaret A; Isbister, Geoffrey K

    2016-01-01

    Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma. Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 μg/ml), D. russelli (0.4 and 0.1 μg/ml), E. carinatus (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 μg/ml) venom. Cow, rat, pig and guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human. Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Effective lethal mutagenesis of influenza virus by three nucleoside analogs.

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    Pauly, Matthew D; Lauring, Adam S

    2015-04-01

    Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. All three drugs were active against a panel of seasonal H3N2 and laboratory-adapted H1N1 strains. We found that each drug increased the frequency of mutations in influenza virus populations and decreased the virus' specific infectivity, indicating a mutagenic mode of action. We were able to drive viral populations to extinction by passaging influenza virus in the presence of each drug, indicating that complete lethal mutagenesis of influenza virus populations can be achieved when a sufficient mutational burden is applied. Population-wide resistance to these mutagenic agents did not arise after serial passage of influenza virus populations in sublethal concentrations of drug. Sequencing of these drug-passaged viral populations revealed genome-wide accumulation of mutations at low frequency. The replicative capacity of drug-passaged populations was reduced at higher multiplicities of infection, suggesting the presence of defective interfering particles and a possible barrier to the evolution of resistance. Together, our data suggest that lethal mutagenesis may be a particularly effective therapeutic approach with a high genetic barrier to resistance for influenza virus. Influenza virus is an RNA virus that causes significant morbidity and mortality during annual epidemics. Novel therapies for RNA viruses are needed due to the ease with which these viruses evolve resistance to existing therapeutics. Lethal mutagenesis is a broad-spectrum strategy that exploits the high mutation rate and the low

  15. Effects of Co60 gamma radiation on the immunogenic and antigenic properties of Bothrops jararacussu venom

    International Nuclear Information System (INIS)

    Spencer, Patrick J.; Nascimento, Nanci do; Rogero, Jose R.

    1997-01-01

    Ionizing radiation has been successfully employed to attenuate animals toxins and venoms for immunizing antisera producing animals. However, the radiation effects on antigenicity and immunogenecity have not yet been elucidated. In the present work, we investigated the effects of gamma rays on the antigenic and immunogenicity have not yet been elucidated. In the present work, we investigated the effects of gamma rays on the antigenic and immunogenic behaviour of Bothrops jararacussu venon. Venom samples (2mg/ml in 150 mM NaCl) were irradiated with 500, 1000 and 2000 Gy of 60 Co gamma rays. These samples were submitted to antigen capture ELISA on plates coated with commercial bothropic antiserum. Results suggest a loss of reactivity of the 1000 and 2000 Gy irradiated samples. Antibodies against native and 2000 Gy irradiated venoms were produced in rabbits. Both sera able to bind native venom with a slightly higher titer for anti-irradiated serum. These data suggest that radiation promoted structural modification on the antigen molecules. However since the antibodies produced against irradiated antivenom were able to recognize native venom, there must have been preservation of some antigenic determinants. It has already been demosntrated that irradiation of proteins leads to structural modifications and unfolding of the molecules. Our data suggest that irradiation led to conformational epitopes destruction with preservation of linear epitopes and that the response against irradiated venom may be attributed to these linear antigenic determinants. (author). 8 refs., 3 figs

  16. New proline-rich oligopeptides from the venom of African adders: Insights into the hypotensive effect of the venoms.

    Science.gov (United States)

    Kodama, Roberto T; Cajado-Carvalho, Daniela; Kuniyoshi, Alexandre K; Kitano, Eduardo S; Tashima, Alexandre K; Barna, Barbara F; Takakura, Ana Carolina; Serrano, Solange M T; Dias-Da-Silva, Wilmar; Tambourgi, Denise V; Portaro, Fernanda V

    2015-06-01

    The snakes from the Bitis genus are some of the most medically important venomous snakes in sub Saharan Africa, however little is known about the composition and effects of these snake venom peptides. Considering that the victims with Bitis genus snakes have exacerbate hypotension and cardiovascular disorders, we investigated here the presence of angiotensin-converting enzyme modulators on four different species of venoms. The peptide fractions from Bitis gabonica gabonica, Bitis nasicornis, Bitis gabonica rhinoceros and Bitis arietans which showed inhibitory activity on angiotensin-converting enzyme were subjected to mass spectrometry analysis. Eight proline-rich peptides were synthetized and their potencies were evaluated in vitro and in vivo. The MS analysis resulted in over 150 sequences, out of which 32 are new proline-rich oligopeptides, and eight were selected for syntheses. For some peptides, inhibition assays showed inhibitory potentials of cleavage of angiotensin I ten times greater when compared to bradykinin. In vivo tests showed that all peptides decreased mean arterial pressure, followed by tachycardia in 6 out of 8 of the tests. We describe here some new and already known proline-rich peptides, also known as bradykinin-potentiating peptides. Four synthetic peptides indicated a preferential inhibition of angiotensin-converting enzyme C-domain. In vivo studies show that the proline-rich oligopeptides are hypotensive molecules. Although proline-rich oligopeptides are known molecules, we present here 32 new sequences that are inhibitors of the angiotensin-converting enzyme and consistent with the symptoms of the victims of Bitis spp, who display severe hypotension. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Effect of low level doses of fast neutrons on the activity of the snake venom

    International Nuclear Information System (INIS)

    Hanafy, Magda S.; Amin, Aida M.

    1998-01-01

    In this work, the effect of low level doses of fast neutrons from 252 Cf on snake venom (Cerastes cerastes) was studied through measurements of biophysical and haematological changes. The absorption spectrum (200-700 nm) of haemoglobin (Hb) collected from the blood of rats after 3 and 24 hours post injection with irradiated and non-irradiated snake venom with neutron fluences of 3x10 6 , 2.8x10 7 and 3X10 8 n/cm 2 was measured. The results indicated that injection of animals with either non- irradiated or irradiated venom ( with different neutron fluences) resulted into the decrease of the absorption band intensities of Hb. These changes in the properties of the characteristic band showed to be a marker for irradiated venom and is dose dependent. It was concluded that neutron irradiation of the venom leads to the decrease of its toxicity and, consequently, to the increase of the chance of repair mechanism in livings. Obvious changes of most haematological erythrocytic values of Hb, packed cell volume (PCV), red blood counts (RBC), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCHb) and mean corpuscular haemoglobin concentration (MCHC) were observed in the blood of the rats injected with non-irradiated venom (as a first group) and those injected with the irradiated venom (as a second group). The microcytic haemolytic anemia was more acute in the first group than in the second one which showed lesser extent. It is concluded from this study that low level doses of fast neutrons could postpone and lower acute haematological action induced by the venom. (authors)

  18. The renal effects and initial characterization of venom from Philodryas nattereri Steindachner, 1870

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    Marinetes Dantas de Aquino Nery

    2014-01-01

    Full Text Available The venom of the snake Philodryas nattereri is a mixture of proteins and toxic peptides with several important local and systemic actions, which are similar to those occurring in Bothrops snake bites. The mechanisms involved in the local and systemic actions of this venom are unknown. The aims of the work were to initial characterization of P. nattereri venom and investigate the effects of the poison in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin–Darby canine kidney. The P. nattereri venom is composed majority of proteins (86.3% and this poison promoted changes in all the evaluated renal parameters, mainly decreasing renal perfusion pressure (PP and renal vascular resistance (RVR and increasing urine flow (UF and glomerular filtration rate (GFR. The most relevant result was that this venom was highly detrimental to the renal tubules independent of the PP reduction, which was shown by a decrease in sodium (Na+, potassium (K+ and chloride (Cl− electrolyte transport in the studied concentrations. The glomeruli and tubules contain protein bodies and blood extravasation, which were observed by histological analysis. The venom of P. nattereri reduced viability of the MDCK cells only at high concentrations (50 and 100 μg/mL with an IC50 of 169.5 μg/mL.

  19. Effect of Iranian Honey bee (Apis Mellifera Venom on Blood Glucose and Insulin in Diabetic Rats

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    Seyyedeh Mahbubeh Mousavi

    2012-12-01

    Full Text Available Background: Diabetes is an important disease. This disease is a metabolic disorder characterized by hyperglycemia resulting from perturbation in insulin secretion, insulin action or both. Honey bee venom contains a wide range of polypeptide agents. The principle components of bee venom are mellitin and phospholipase A2. These components increase insulin secretion from the β-cells of pancreas. This study was conducted to show the hypoglycemic effect of honey bee venom on alloxan induced diabetic male rats.Methods: Eighteen adult male rats weighting 200±20 g were placed into 3 randomly groups: control, alloxan monohy­drate-induced diabetic rat and treated group that received honey bee venom daily before their nutrition for four months. Forty eight hours after the last injection, blood was collected from their heart, serum was dissented and blood glucose, insulin, triglyceride and total cholesterol were determined.Results: Glucose serum, triglyceride and total cholesterol level in treated group in comparison with diabetic group was significantly decreased (P< 0.01. On the other hand, using bee venom causes increase in insulin serum in com­parison with diabetic group (P< 0.05.Conclusion: Honeybee venom (apitoxin can be used as therapeutic option to lower blood glucose and lipids in dia­betic rats.

  20. The Comparison of Effective between Acupuncture and Bee Venom Acupuncture on the Treatment of Acute Lumbar Herniation of Intervertebral Disc

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    Chang So-Young

    2006-06-01

    Full Text Available Objective : Herniation of Intervertebral Disc(HIVD is the most common disease causing low back pain. Acupuncture and Bee Venom Acupuncture has been used for treatment of HIVD. This study is to investigate the effective of Bee Venom Acupuncture for HIVD. Methods : We researched 18 patients who were diagnosed by CT and MRI as having HIVD, and treated them Acupuncture only or Acupuncture and Bee Venom Acupuncture. We compared the VAS and ROM angle of two groups. Results & Conclusions : 1. In admission date, no significant improvement between Acupuncture group and Bee Venom Acupuncture group 2. In variation of flexion and extension, Bee Venom Acupuncture group shows statistically significant improvement 3. In VAS, Bee Venom Acupuncture group shows statistically significant improvement for 1 week and discharge day

  1. Antiadhesive and cytotoxic effect of Iranian Vipera lebetina snake venom on lung epithelial cancer cells.

    Science.gov (United States)

    Oghalaie, Akbar; Kazemi-Lomedasht, Fatemeh; Zareinejad, Mohammad Reza; Shahbazzadeh, Delavar

    2017-01-01

    Cancer is one of the major health problems worldwide. Hence, finding potent therapeutics from natural sources seems necessary. Snake venom of Vipera lebetina contains potential component with anticancer activities such as antiproliferation, migration, invasion, adhesion, and angiogenesis effect. Evaluation of cytotoxic and antiadhesive effect of V. lebetina venom on lung epithelial cancer tumor cell (TC-1) was the main aim of this study. Here, we purified snake venom of V. lebetina by fast protein liquid chromatography (FPLC) using Sephacryl S-200 hr column. The fractions collected and evaluated by SDS-PAGE analysis. The cytotoxicity and antiadhesive effect of crude venom and fractions on TC-1 cells were demonstrated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and adhesion assay, respectively. Our results showed six fractions in FPLC diagram. V. lebetina crude venom and fractions showed dose-dependent cytotoxic effect on TC-1 cells. Fractions 2 and 5 showed high cytotoxic effect with high IC50 value (IC50 = 6 μg/ml for fraction 2 and IC50 = 7.3 μg/ml for fraction 5). Fractions 2 and 5 selected for analysis antiadhesive effect on TC-1 cells. Furthermore, our results showed that both fractions 2 and 5 had antiadhesive effect on TC-1 cells. Because of potent cytotoxic and antiadhesive effect of V. lebetina fractions on lung epithelial cancer cell line, it could be promising tools for further analysis as anticancer therapeutic development.

  2. Antiadhesive and cytotoxic effect of Iranian Vipera lebetina snake venom on lung epithelial cancer cells

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    Akbar Oghalaie

    2017-01-01

    Full Text Available Background: Cancer is one of the major health problems worldwide. Hence, finding potent therapeutics from natural sources seems necessary. Snake venom of Vipera lebetina contains potential component with anticancer activities such as antiproliferation, migration, invasion, adhesion, and angiogenesis effect. Evaluation of cytotoxic and antiadhesive effect of V. lebetina venom on lung epithelial cancer tumor cell (TC-1 was the main aim of this study. Materials and Methods: Here, we purified snake venom of V. lebetina by fast protein liquid chromatography (FPLC using Sephacryl S-200 hr column. The fractions collected and evaluated by SDS-PAGE analysis. The cytotoxicity and antiadhesive effect of crude venom and fractions on TC-1 cells were demonstrated using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and adhesion assay, respectively. Results: Our results showed six fractions in FPLC diagram. V. lebetina crude venom and fractions showed dose-dependent cytotoxic effect on TC-1 cells. Fractions 2 and 5 showed high cytotoxic effect with high IC50 value (IC50 = 6 μg/ml for fraction 2 and IC50 = 7.3 μg/ml for fraction 5. Fractions 2 and 5 selected for analysis antiadhesive effect on TC-1 cells. Furthermore, our results showed that both fractions 2 and 5 had antiadhesive effect on TC-1 cells. Conclusion: Because of potent cytotoxic and antiadhesive effect of V. lebetina fractions on lung epithelial cancer cell line, it could be promising tools for further analysis as anticancer therapeutic development.

  3. Effects of bee venom against Propionibacterium acnes-induced inflammation in human keratinocytes and monocytes.

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    Kim, Jung-Yeon; Lee, Woo-Ram; Kim, Kyung-Hyun; An, Hyun-Jin; Chang, Young-Chae; Han, Sang-Mi; Park, Yoon-Yub; Pak, Sok Cheon; Park, Kwan-Kyu

    2015-06-01

    Propionibacterium acnes (P. acnes) cause inflammatory acne and play an important role in the pathogenesis of acne by inducing inflammatory mediators. P. acnes contributes to the inflammatory responses of acne by activating inflammatory cells, keratinocytes and sebocytes to secrete pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-8. Bee venom has traditionally been used in the treatment of certain immune-related diseases. However, there has not yet been a robust trial to prove the therapeutic effect of bee venom in skin inflammation. The aim of the present study was to investigate anti-inflammatory properties of bee venom in skin inflammation induced by P. acnes using keratinocytes (HaCaT) and monocytes (THP-1). P. acnes is known to stimulate the production of pro-inflammatory cytokines such as IL-1, IL-8, IL-12 and TNF-α. In the present study, the production of interferon-γ (IFN-γ), IL-1β, IL-8 and TNF-α was increased by P. acnes treatment in HaCaT and THP-1 cells. By contrast, bee venom effectively inhibited the secretion of IFN-γ, IL-1β, IL-8 and TNF-α. Furthermore, P. acnes treatment activated the expression of IL-8 and toll-like receptor 2 (TLR2) in HaCaT cells. However, bee venom inhibited the expression of IL-8 and TLR2 in heat-killed P. acnes. Based on these results, it is concluded that bee venom has an effective anti-inflammatory activity against P. acnes in HaCaT and THP-1 cells. Therefore, we suggest that bee venom is an alternative treatment to antibiotic therapy of acne.

  4. Effects of Mucuna pruriens protease inhibitors on Echis carinatus venom.

    Science.gov (United States)

    Hope-Onyekwere, Nnadozie Stanley; Ogueli, Godwin Ifeanyi; Cortelazzo, Alessio; Cerutti, Helena; Cito, Annarita; Aguiyi, John C; Guerranti, Roberto

    2012-12-01

    The medicinal plant Mucuna pruriens, with reputed anti-snake venom properties has been reported to contain a kunitz-type trypsin inhibitor. This study was undertaken to further evaluate the protease inhibitory potential of gpMuc, a multiform glycoprotein, and other protein fractions from M. pruriens seeds against trypsin, chymotrypsin, Echis carinatus snake venom, ecarin and thrombin. The results showed that gpMuc inhibited both trypsin and chymotrypsin activities and was thermally stable, maintaining its trypsin inhibitory activity at temperatures of up to 50°C. Its structural conformation was also maintained at pH ranges of 4-7. Immunoreactivity study confirms that it contains protease-recognizing epitope on one of its isoforms. The whole protein extract of M. pruriens seeds inhibited prothrombin activation by ecarin and whole E. carinatus venom, and also thrombin-like activity using chromogenic assay. Copyright © 2012 John Wiley & Sons, Ltd.

  5. The Effects of Bee Venom on PLA2 and Calcium Concentration in Raw 264.7 Cells

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    Jong-Il Yun

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate the effect of Bee Venom on the lipopolysaccharide, sodium nitroprusside and hydrogen peroxide induced expression phospholipase A2 and calcium concentration in RAW 264.7 cells, a murine macrophage cell line. Methods : The expression of phospholipase A2 was determined by western blotting with corresponding antibodies, and the generation of intracellular calcium concentration was investigated by delta scan system in RAW 264.7 cells. Results : 1. Compared with control, expressions of lipopolysaccharide-induced phospholipase A2 were decreased significantly by 1 ㎍/㎕ of bee venom and decreased by 0.5, 5 ㎍/㎕ of bee venom. 2. Compared with control, expressions of sodium nitroprusside-induced phospholipase A2 were decreased significantly by 5 ㎍/㎕ of bee venom but increased by 0.5, 5 ㎍/㎕ of bee venom. 3. Compared with control, expressions of hydrogen peroxide-induced phospholipase A2 were decreased significaltly by 1 ㎍/㎕ of bee venom and decreased by 0.5 ㎍/㎕ of bee venom but increased by 5 ㎍/㎕ of bee venom. 4. Compared with control, lipopolysaccharide, sodium nitroprusside and hydrogen peroxide- induced intracellular calcium concentrations were decreased by 0.5, 1, 5 ㎍/㎕ of bee venom and by indomethacin

  6. Clinical Studies of Sweet Bee Venom to The Effect of Abdominal Fat Accumulation

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    Lim, Chung-San

    2008-06-01

    Full Text Available Objective The purpose of this study was to investigate the effects of Sweet Bee Venom to the abdominal fat accumulation clinically. Methods The 20 healthy women volunteers who showed the notice of this study by the home page of Sangji University were treated with Sweet Bee Venom(SBV during twenty times. To investigate the effects of Sweet Bee Venom of the abdominal fat accumulation, abdominal CT, LFT, Thermography, BMI, Inbody 3.0 etc. were performed during clinical trials. And statistical analysis was carried out the data of 10 volunteers who performed all the schedule of this study. Results Following results were obtained from the clinical studies Sweet Bee Venom showed the effect of decreased the body weight, thickness of abdominal skin and fat layer, BMI, and increased abdominal heat, but they are not showed statistical significant. Conclusions These results suggest that treatment Sweet Bee Venom on the abdomen was effective to decrease fat tissue but for the treatment of obesity was performed with right diet program and exercise.

  7. A Pharmacological Examination of the Cardiovascular Effects of Malayan Krait (Bungarus candidus Venoms

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    Janeyuth Chaisakul

    2017-03-01

    Full Text Available Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated the in vivo and in vitro cardiovascular effects of B. candidus venoms from Southern (BC-S and Northeastern (BC-NE Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms. B. candidus venoms (50 µg/kg–100 µg/kg, i.v. caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II prior to a small decrease in blood pressure (phase III. Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.. The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v. or atropine (5 mg/kg, i.v.. BC-S and BC-NE venoms (0.1 µg/kg–100 µg/ml induced concentration-dependent relaxation (EC50 = 8 ± 1 and 13 ± 3 µg/mL, respectively in endothelium-intact aorta. The concentration–response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM, or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused by B. candidus venoms may be due to a combination of vascular mediators (i.e., NO and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.

  8. Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

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    Carlos Eduardo Tosta

    1983-03-01

    Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.

  9. Effects of irradiated Bothropstoxin-1 and Bothrops jararacussu crude venom on the immune system

    International Nuclear Information System (INIS)

    Caproni, Priscila

    2009-01-01

    Ionizing radiation has been successfully employed to modify the immunological properties of biomolecules and has been proven to be a powerful tool to attenuate snake venoms toxicity without affecting and even increasing their immunogenic properties. Very promising results were obtained when crude animal venoms, as well as isolated toxins, were treated with 60 Co gamma rays, yielding toxoids with good immunogenicity, however, little is known about the modifications that irradiated molecules undergo and even less about the immunological response that such antigens elicit. At the present work, we have evaluated the effects on immune system of B10.PL and BALB/c mice of Bothrops jararacussu crude venom and isolated bothropstoxin-1 (Bthx-1), before and after gamma radiation exposition. According to our data, irradiation process promoted structural modifications on both isolated toxin and crude venom, characterized by higher molecular weight protein (aggregates and oligomers) formation. Irradiated samples were immunogenic and the antibodies elicited by them were able to recognize the native toxin in ELISA. These results indicate that irradiation of toxic proteins can promote significant modifications in their structures, but still retain many of the original antigenic and immunological properties. Also, our data indicate that the irradiated protein induced higher titers of IgG2b, suggesting that Th1 cells were predominantly involved. Results from Western blot assay showed that antibodies raised against irradiated bothropstoxin-1 recognize both native isolated toxin or crude venom. Cytotoxicity assay showed that irradiated toxin and crude venom were less toxic than their native counterpart. Thus, the viability of the macrophages cultured in the presence of irradiated Bthx-1 or crude venom was higher if compared with their native forms. LDH Assay showed that irradiated Bthx-1 promotes less muscular damage than the native form. Our data confirm a potential use of ionizing

  10. Antitoxin activity of Mimosa pudica root extracts against Naja naja and Bangarus caerulus venoms

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    Subramani Meenatchisundaram

    2009-06-01

    Full Text Available Aqueous extract of dried roots of Mimosa pudica was tested for inhibitory activity on lethality, phospholipase activity, edema forming activity, fibrinolytic activity and hemorrhagic activity of Naja naja and Bangarus caerulus venoms. The aqueous extract displayed a significant inhibitory effect on the lethality, phospholipase activity, edema forming activity, fibrinolytic activity and hemorrhagic activity. About 0.14 mg and 0.16 mg of M. pudica extracts were able to completely neutralize the lethal activity of 2LD50 of Naja naja and Bangarus caerulus venoms respectively. The present finding suggests that aqueous extract of M. pudica root possesses compounds, which inhibit the activity of Naja naja and Bangarus caerulus venoms.

  11. Antitoxin activity of Mimosa pudica root extracts against Naja naja and Bangarus caerulus venoms

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    Subramani Meenatchisundaram, Selvin Priyagrace, Ramasamy Vijayaraghavan, Ambikapathi Velmurugan, Govindarajan Parameswari, Antonysamy Michael

    2009-12-01

    Full Text Available Aqueous extract of dried roots of Mimosa pudica was tested for inhibitory activity on lethality, phospholipase activity, edema forming activity, fibrinolytic activity and hemorrhagic activity of Naja naja and Bangarus caerulus venoms. The aqueous extract displayed a significant inhibitory effect on the lethality, phospholipase activity, edema forming activity, fibrinolytic activity and hemorrhagic activity. About 0.14 mg and 0.16 mg of M. pudica extracts were able to completely neutralize the lethal activity of 2LD50 of Naja naja and Bangarus caerulus venoms respectively. The present finding suggests that aqueous extract of M. pudica root possesses compounds, which inhibit the activity of Naja naja and Bangarus caerulus venoms.

  12. Molecular Biological Study of Anti-cancer Effects of Bee Venom Aqua-acupuncture

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    Park Chan-Yol

    2000-07-01

    Full Text Available To study anti-cancer effect and molecular biological mechanism of bee venom for aqua-acupuncture, the effects of bee venom on cell viability and apoptosis were analyzed using MTT assay, tryphan blue assay, [3H]thymidine release assay, flow cytometric analysis, and activity of caspase-3 protease activity assay. To explore whether anti-cancer effects of bee venom are associated with the transcriptional control of gene expression, quantitative RT-PCR analysis of apoptosis-related genes was performed. The obtained results are summarized as follows: 1. The MTT assay demonstrated that cell viability was decreased by bee venom in a dose-dependant manner. 2. Significant induction of apoptosis was identified using tryphan blue assay, [3H]thymidine release assay, and flow cytometric analysis of sub G1 fraction. 3. In analysis of caspase-3 protease activity, the activity had increased significantly, in a dose-dependant manner. 4. Quantitative RT-PCR analysis of the apoptosis-related genes showed that Bcl-2 and Bcl-XL were down-regulated whereas Bax was up-regulated by bee venom treatment.

  13. Chemical and radiation induced late dominant lethal effects in mice

    International Nuclear Information System (INIS)

    Favor, J.; Crenshaw, J.W. Jr.; Soares, E.R.

    1978-01-01

    Although theoretically expected, experimental data to date have not shown dominant lethal expression to occur throughout the developmental period. Specifically, late post-implantation effects have not been demonstrated. The authors routinely use an experimental technique in which parental females mated to mutagenically treated males are allowed to give birth and wean their litter, and their uterine horns are then inspected for uterine scars indicative of live and dead embryos. In a number of experiments in which males were mutagenically treated with either chemicals or X-irradiation, a discrepancy was observed between the number of live embryos as determined by the scar technique and the number of live observed at birth, suggesting the possibility of embryonic losses at a late stage in development. Initial analyses showed that mutagenic treatment increased the percentage of these late losses. These differences were statistically significant in 2 of 3 analyses. Factors affecting statistical significance and an understanding of dominant lethal mutations are discussed. (Auth.)

  14. Prolonged analgesic effect of PLGA-encapsulated bee venom on formalin-induced pain in rats.

    Science.gov (United States)

    Jeong, Injae; Kim, Beom-Soo; Lee, Hyejung; Lee, Kang-Min; Shim, Insop; Kang, Sung-Keel; Yin, Chang-Shick; Hahm, Dae-Hyun

    2009-10-01

    To enhance the medicinal activity of bee venom (BV) acupuncture, bee venom was loaded into biodegradable poly(D,L-lactide-co-glycolide) nanoparticles (BV-PLGA-NPs) by a water-in-oil-in-water-emulsion/solvent-evaporation technique. Rat formalin tests were performed after subcutaneous injection of BV-PLGA-NPs to the Zusanli acupuncture point (ST36) at 0.5, 1, 2, 6, 12, 24, and 48 h before plantar injection of 2% formalin. BV-PLGA-NPs treatment showed comparable analgesic activity to typical BV acupuncture during the late phase, compared with saline-treated controls, and the analgesic effect lasted for 12h. PLGA-encapsulation was also effective in alleviating the edema induced by allergens in bee venom. These results indicate that PLGA-encapsulation provided a more prolonged effect of BV acupuncture treatment, while maintaining a comparable therapeutic effect.

  15. Clinical effectiveness of hymenoptera venom immunotherapy: a prospective observational multicenter study of the European academy of allergology and clinical immunology interest group on insect venom hypersensitivity.

    Science.gov (United States)

    Ruëff, Franziska; Przybilla, Bernhard; Biló, Maria Beatrice; Müller, Ulrich; Scheipl, Fabian; Seitz, Michael J; Aberer, Werner; Bodzenta-Lukaszyk, Anna; Bonifazi, Floriano; Campi, Paolo; Darsow, Ulf; Haeberli, Gabrielle; Hawranek, Thomas; Küchenhoff, Helmut; Lang, Roland; Quercia, Oliviero; Reider, Norbert; Schmid-Grendelmeier, Peter; Severino, Maurizio; Sturm, Gunter Johannes; Treudler, Regina; Wüthrich, Brunello

    2013-01-01

    Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.

  16. Clinical effectiveness of hymenoptera venom immunotherapy: a prospective observational multicenter study of the European academy of allergology and clinical immunology interest group on insect venom hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Franziska Ruëff

    Full Text Available BACKGROUND: Treatment failure during venom immunotherapy (VIT may be associated with a variety of risk factors. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC and of other parameters with the frequency of VIT failure during the maintenance phase. METHODS: In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154 or patient self-reporting of the outcome of a field sting (n = 203. Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. RESULTS: 22 patients (6.2% developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3 of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. INTERPRETATION: It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.

  17. Gamma radiation effect on biological activity and enzymatic properties of snake venoms

    International Nuclear Information System (INIS)

    Herrera, E.; Yarleque, A.; Campos, S.; Zavaleta, A.

    1986-01-01

    The effect of gamma radiation, from Co-60, on the biological activity and on some enzymatic activities, present in the venoms of Lachesis muta and Bothrops atrox, using samples of dried venom that had been irradiated at a dose of 0.1, 0.5 and 1.0 Mrad have been studied. Variations in the degree of hemorrhage and local necrosis were observed in albino mice injected subcutaneously with venoms of both types. The reduction of the biological activity was greater for the local hemorrhagic effect and was dependent on the doses of irradiation. The specific activity of various enzymes, present in both venoms, is affected by the gamma radiation, at a dose of 0.1 Mrad the order of increasing inactivation being: exonuclease (4%), phospholipase (24%), caseinolytic enzyme (20%), tamesterase (33%), a thrombine-like enzyme (40%), fibrinolytic enzyme (41%), 5'-nucleotidase (50%) and endonuclease (55%). The enzymatic inactivation was augmented by 0.5 and 1.0 Mrad, without maintaining an arithmetic relation. The enzyme of major resistance to the radiation was exonuclease, whereas 5'-nucleotidase and endonuclease were the most sensitive. No significant changes were observed in the spectrum of UV absorbtion (range 260 to 290 nm) nor in the contents of L-tyrosine in the irradiated venoms

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bjoern Marcus von Reumont

    2014-12-01

    Full Text Available 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.

  20. Snake venom L-amino acid oxidases: an overview on their antitumor effects

    Science.gov (United States)

    2014-01-01

    The L-amino acid oxidases (LAAOs) constitute a major component of snake venoms and have been widely studied due to their widespread presence and various effects, such as apoptosis induction, cytotoxicity, induction and/or inhibition of platelet aggregation, hemorrhage, hemolysis, edema, as well as antimicrobial, antiparasitic and anti-HIV activities. The isolated and characterized snake venom LAAOs have become important research targets due to their potential biotechnological applications in pursuit for new drugs of interest in the scientific and medical fields. The current study discusses the antitumor effects of snake venom LAAOs described in the literature to date, highlighting the mechanisms of apoptosis induction proposed for this class of proteins. PMID:24940304

  1. Effects of venom immunotherapy on serum level of CCL5/RANTES in patients with Hymenoptera venom allergy.

    Science.gov (United States)

    Gawlik, Radoslaw; Glück, Joanna; Jawor, Barbara; Rogala, Barbara

    2015-01-01

    Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Venom immunotherapy is a recommended treatment of insect allergy with still the mechanism not being completely understood. We decided to assess the serum CCL5/RANTES level in patients who experienced severe anaphylactic reaction to Hymenoptera venom and to find out changes in the course of immunotherapy. Twenty patients (9 men, 11 women, mean age: 31.91 ± 7.63 years) with history of anaphylactic reaction after insect sting were included into the study. Diagnosis was made according to sIgE and skin tests. All of them were enrolled into rush venom immunotherapy with bee or wasp venom extracts (Pharmalgen, ALK-Abello, Horsholm, Denmark). Serum levels of CCL5/RANTES were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN). CCL5/RANTES serum concentration are higher in insect venom allergic patients than in healthy controls (887.5 ± 322.77 versus 387.27 ± 85.11 pg/ml). Serum concentration of CCL5/RANTES in insect venom allergic patient was significantly reduced in the course of allergen immunotherapy already after 6 days of vaccination (887.5 ± 322.77 versus 567.32 ± 92.16 pg/ml). CCL5/RANTES serum doesn't correlate with specific IgE. Chemokine CCL5/RANTES participates in allergic inflammation induced by Hymenoptera venom allergens. Specific immunotherapy reduces chemokine CCL5/RANTES serum level already after initial days of venom immunotherapy.

  2. Study of 60 Co gamma radiation effects on the biochemical, biological and immunological properties of the Bothrops jararaca venom

    International Nuclear Information System (INIS)

    Guarnieri, M.C.

    1992-01-01

    Gamma radiation, by including different modifications on the toxic, enzymatic and immunological activities of proteins, could be an useful implement for detoxification of snake venoms. The present work was done to study the mechanism of action and effects of gamma rays on the Bothrops jararaca venom, determining the radiation dose that attenuates the toxic and enzymatic activities maintaining the immunological properties of venom, and also the most important free radicals on this process. The results of immuno diffusion, immunoblotting, immunoprecipitation, immunization of mice and rabbits, and neutralization tests, showed the maintenance of antigenic and immunogenic properties and decrease of neutralizing capacity of antibodies induced by 3,000 and 4,000 Gy irradiated venom. Since the immunological properties were the most radioresistant, it was possible to determine the dose of 2,000 Gy, as the ideal radiation dose in the treatment of venoms aiming the improvement of the immunization schedule to obtain bothropic antisera. (author). 164 refs, 19 tabs, 54 figs

  3. In vivo evaluation of homeostatic effects of Echis carinatus snake venom in Iran

    Science.gov (United States)

    2013-01-01

    Background The venom of the family Viperidae, including the saw-scaled viper, is rich in serine proteinases and metalloproteinases, which affect the nervous system, complementary system, blood coagulation, platelet aggregation and blood pressure. One of the most prominent effects of the snake venom of Echis carinatus (Ec) is its coagulation activity, used for killing prey. Materials and methods Subfractions F1A and F1B were isolated from Ec crude venom by a combination of gel chromatography (Sephadex G-75) and ion exchange chromatography on a DEAE-Sepharose (DE-52). These subfractions were then intravenously (IV) injected into NIH male mice. Blood samples were taken before and after the administration of these subfractions. Times for prothrombin, partial thromboplastin and fibrinogen were recorded. Results and conclusions Comparison of the prothrombin time before and after F1A and F1B administrations showed that time for blood coagulation after injection is shorter than that of normal blood coagulation and also reduced coagulation time after Ec crude venom injection. This difference in coagulation time shows the intense coagulation activity of these subfractions that significantly increase the coagulation cascade rate and Causes to quick blood coagulation. The LD50 of the Ec crude venom was also determined to be 11.1 μg/mouse. Different crude venom doses were prepared with physiological serum and injected into four mice. Comparison of the prothrombin times after injection of subfractions F1A and F1B showed that the rate of mouse blood coagulation increases considerably. Comparing the partial thromboplastin times after injecting these subfractions with this normal test time showed that the activity rate of intrinsic blood coagulation system rose sharply in mice. Finally, by comparing the fibrinogen time after subfraction injections and normal test time, we can infer intense activation of coagulation cascade and fibrin production. PMID:23848979

  4. Effectiveness of acupuncture and bee venom acupuncture in idiopathic Parkinson's disease.

    Science.gov (United States)

    Cho, Seung-Yeon; Shim, So-Ra; Rhee, Hak Young; Park, Hi-Joon; Jung, Woo-Sang; Moon, Sang-Kwan; Park, Jung-Mi; Ko, Chang-Nam; Cho, Ki-Ho; Park, Seong-Uk

    2012-09-01

    This study aimed to explore the effectiveness of both acupuncture and bee venom acupuncture as adjuvant therapies for idiopathic Parkinson's disease. We recruited 43 adults with idiopathic Parkinson's disease who had been on a stable dose of antiparkinsonian medication for at least 1 month. They were randomly assigned to 1 of 3 groups: acupuncture, bee venom acupuncture, or control. All participants were assessed using the Unified Parkinson's Disease Rating Scale, the Parkinson's Disease Quality of Life Questionnaire, the Beck Depression Inventory, the Berg Balance Scale, and the time and number of steps required to walk 30 m. Treatment groups underwent stimulation of 10 acupuncture points using acupuncture or bee venom acupuncture twice a week for 8 weeks. The initial assessment was repeated at the completion of treatment. The control group did not receive any treatment. Participants in the bee venom acupuncture group showed significant improvement on the Unified Parkinson's Disease Rating Scale (total score, as well as parts II and III individually), the Berg Balance Scale, and the 30 m walking time. When compared to the control group, the bee venom acupuncture group experienced significantly greater improvement on the Unified Parkinson's Disease Rating Scale. In the acupuncture group, the Unified Parkinson's Disease Rating Scale (part III and total scores) and the Beck Depression Inventory showed significant improvement. The control group showed no significant changes in any outcome after 8 weeks. In this pilot study, both acupuncture and bee venom acupuncture showed promising results as adjuvant therapies for Parkinson's disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. In vivo evaluation of homeostatic effects of Echis carinatus snake venom in Iran

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    Salmanizadeh Hossein

    2013-02-01

    Full Text Available Abstract Background The venom of the family Viperidae, including the saw-scaled viper, is rich in serine proteinases and metalloproteinases, which affect the nervous system, complementary system, blood coagulation, platelet aggregation and blood pressure. One of the most prominent effects of the snake venom of Echis carinatus (Ec is its coagulation activity, used for killing prey. Materials and methods Subfractions F1A and F1B were isolated from Ec crude venom by a combination of gel chromatography (Sephadex G-75 and ion exchange chromatography on a DEAE-Sepharose (DE-52. These subfractions were then intravenously (IV injected into NIH male mice. Blood samples were taken before and after the administration of these subfractions. Times for prothrombin, partial thromboplastin and fibrinogen were recorded. Results and conclusions Comparison of the prothrombin time before and after F1A and F1B administrations showed that time for blood coagulation after injection is shorter than that of normal blood coagulation and also reduced coagulation time after Ec crude venom injection. This difference in coagulation time shows the intense coagulation activity of these subfractions that significantly increase the coagulation cascade rate and Causes to quick blood coagulation. The LD50 of the Ec crude venom was also determined to be 11.1 μg/mouse. Different crude venom doses were prepared with physiological serum and injected into four mice. Comparison of the prothrombin times after injection of subfractions F1A and F1B showed that the rate of mouse blood coagulation increases considerably. Comparing the partial thromboplastin times after injecting these subfractions with this normal test time showed that the activity rate of intrinsic blood coagulation system rose sharply in mice. Finally, by comparing the fibrinogen time after subfraction injections and normal test time, we can infer intense activation of coagulation cascade and fibrin production.

  6. Antitoxin activity of aqueous extract of Cyclea peltata root against Naja naja venom.

    Science.gov (United States)

    Sivaraman, Thulasi; Sreedevi, N S; Meenatchisundaram, S; Vadivelan, R

    2017-01-01

    Snakebites are a significant and severe global health problem. Till date, anti-snake venom serum is the only beneficial remedy existing on treating the snakebite victims. As antivenom was reported to induce early or late adverse reactions to human beings, snake venom neutralizing potential for Cyclea peltata root extract was tested for the present research by ex vivo and in vivo approaches on Naja naja toxin. Ex vivo evaluation of venom toxicity and neutralization assays was carried out. The root extracts from C. peltata were used to evaluate the Ex vivo neutralization tests such as acetylcholinesterase, protease, direct hemolysis assay, phospholipase activity, and procoagulant activity. Gas chromatography-mass spectrometry (GC-MS) analysis from root extracts of C. peltata was done to investigate the bioactive compounds. The in vivo calculation of venom toxicity (LD 50 ) of N. naja venom remained to be 0.301 μg. C. peltata root extracts were efficiently deactivated the venom lethality, and effective dose (ED 50 ) remained to be 7.24 mg/3LD 50 of N. naja venom. C. peltata root extract was found effective in counteracting all the lethal effects of venom. GC-MS analysis of the plant extract revealed the presence of antivenom compounds such as tetradecanoic and octadecadienoic acid which have neutralizing properties on N. naja venom. The result from the ex vivo and in vivo analysis indicates that C. peltata plant root extract possesses significant compounds such as tetradecanoic acid hexadecanoic acid, heptadecanoic acid, and octadecadienoic acid which can counteract the toxins present in N. naja .

  7. Sulfated Galactan from Palisada flagellifera Inhibits Toxic Effects of Lachesis muta Snake Venom

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    Ana Cláudia Rodrigues da Silva

    2015-06-01

    Full Text Available In Brazil, snakebites are a public health problem and accidents caused by Lachesis muta have the highest mortality index. Envenomation by L. muta is characterized by systemic (hypotension, bleeding and renal failure and local effects (necrosis, pain and edema. The treatment to reverse the evolution of all the toxic effects is performed by injection of antivenom. However, such therapy does not effectively neutralize tissue damage or any other local effect, since in most cases victims delay seeking appropriate medical care. In this way, alternative therapies are in demand, and molecules from natural sources have been exhaustively tested. In this paper, we analyzed the inhibitory effect of a sulfated galactan obtained from the red seaweed Palisada flagellifera against some toxic activities of L. muta venom. Incubation of sulfated galactan with venom resulted in inhibition of hemolysis, coagulation, proteolysis, edema and hemorrhage. Neutralization of hemorrhage was also observed when the galactan was administered after or before the venom injection; thus mimicking a real in vivo situation. Moreover, the galactan blocked the edema caused by a phospholipase A2 isolated from the same venom. Therefore, the galactan from P. flagellifera may represent a promising tool to treat envenomation by L. muta as a coadjuvant for the conventional antivenom.

  8. A novel neurotoxin from venom of the spider, Brachypelma albopilosum.

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    Yunhua Zhong

    Full Text Available Spiders have evolved highly selective toxins for insects. There are many insecticidal neurotoxins in spider venoms. Although a large amount of work has been done to focus on neurotoxicity of spider components, little information, which is related with effects of spider toxins on tumor cell proliferation and cytotoxicity, is available for Brachypelma albopilosum venom. In this work, a novel spider neurotoxin (brachyin was identified and characterized from venoms of the spider, Brachypelma albopilosum. Brachyin is composed of 41 amino acid residues with the sequence of CLGENVPCDKDRPNCCSRYECLEPTGYGWWYASYYCYKKRS. There are six cysteines in this sequence, which form three disulfided bridges. The serine residue at the C-terminus is amidated. Brachyin showed strong lethal effects on American cockroaches (Periplaneta americana and Tenebrio molitor (common mealbeetle. This neurotoxin also showed significant analgesic effects in mice models including abdominal writhing induced by acetic acid and formalin-induced paw licking tests. It was interesting that brachyin exerted marked inhibition on tumor cell proliferation.

  9. Preparación toxoide a partir de la fracción hemorrágica del veneno de Bothrops asper (serpiente de América Central y del Sur) (Toxoid preparation from hemorrhagic fraction of the venom from Bothrops asper (snake from Central and South America).

    Science.gov (United States)

    Rodríguez-Acosta, A; Aguilar, I; Girón, M E

    1993-01-01

    A technique is described for preparing a toxoid from the hemorrhagic fraction of the Bothrops asper venom. This method conserves a high degree of immunogenicity although it eliminates lethal effects. None of the animals vaccinated with the toxoid from this fraction had hemorrhagic lesions after they were injected the venom from the hemorrhagic fraction.

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

    Science.gov (United States)

    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...

  11. Diversity of Micrurus Snake Species Related to Their Venom Toxic Effects and the Prospective of Antivenom Neutralization

    Science.gov (United States)

    Tanaka, Gabriela D.; Furtado, Maria de Fátima D.; Portaro, Fernanda C. V.; Sant'Anna, Osvaldo Augusto; Tambourgi, Denise V.

    2010-01-01

    immunization scheme, with the inclusion of other venoms in the antigenic mixture, should occur in order to generate effective therapeutic coral snake antivenom. PMID:20231886

  12. Involvement of Nitric Oxide on Bothropoides insularis Venom Biological Effects on Murine Macrophages In Vitro.

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    Ramon R P P B de Menezes

    Full Text Available Viperidae venom has several local and systemic effects, such as pain, edema, inflammation, kidney failure and coagulopathy. Additionally, bothropic venom and its isolated components directly interfere on cellular metabolism, causing alterations such as cell death and proliferation. Inflammatory cells are particularly involved in pathological envenomation mechanisms due to their capacity of releasing many mediators, such as nitric oxide (NO. NO has many effects on cell viability and it is associated to the development of inflammation and tissue damage caused by Bothrops and Bothropoides venom. Bothropoides insularis is a snake found only in Queimada Grande Island, which has markedly toxic venom. Thus, the aim of this work was to evaluate the biological effects of Bothropoides insularis venom (BiV on RAW 264.7 cells and assess NO involvement. The venom was submitted to colorimetric assays to identify the presence of some enzymatic components. We observed that BiV induced H2O2 production and showed proteolytic and phospholipasic activities. RAW 264.7 murine macrophages were incubated with different concentrations of BiV and then cell viability was assessed by MTT reduction assay after 2, 6, 12 and 24 hours of incubation. A time- and concentration-dependent effect was observed, with a tendency to cell proliferation at lower BiV concentrations and cell death at higher concentrations. The cytotoxic effect was confirmed after lactate dehydrogenase (LDH measurement in the supernatant from the experimental groups. Flow cytometry analyses revealed that necrosis is the main cell death pathway caused by BiV. Also, BiV induced NO release. The inhibition of both proliferative and cytotoxic effects with L-NAME were demonstrated, indicating that NO is important for these effects. Finally, BiV induced an increase in iNOS expression. Altogether, these results demonstrate that B. insularis venom have proliferative and cytotoxic effects on macrophages, with

  13. Late radiation effects in animals surviving lethal irradiation

    International Nuclear Information System (INIS)

    Dimitrov, L.A.

    1974-01-01

    Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergence of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine desintegrations which lead to a disturbed supply of the vessels and afterwards to their sclerosis. Some of the described late radiation effects were also observed in biological controls as festures of ageing while in irradiated animals they were manifested in an earlier period. After application of optimal amounts radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival

  14. Venoms of South Asian hump-nosed pit vipers (Genus: Hypnale cause muscarinic effects in BALB/c mice

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    A Silva

    2014-03-01

    Full Text Available Although clinical, in-vivo and in-vitro studies suggest the necrotic, haemorrhagic, pro-coagulant and nephrotoxic effects of South Asian Hump nosed pit vipers, reports on neurotoxic properties are limited to a single in-vitro study. Using BALB/c mice, for the first time, here we demonstrate the signs of envenoming suggestive of possible muscarinic effects of the venoms of all three Hypnale species. Further, we demonstrate that the muscarinic effects are occurred at lower venom doses by H. hypnale venom, compared to H. nepa and H. zara.

  15. The beneficial effects of honeybee-venom serum on facial wrinkles in humans

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    Han SM

    2015-10-01

    Full Text Available Sang Mi Han,1 In Phyo Hong,1 Soon Ok Woo,1 Sung Nam Chun,2 Kwan Kyu Park,3 Young Mee Nicholls,4 Sok Cheon Pak5 1Department of Agricultural Biology, National Academy of Agricultural Science, Wanju, 2Dong Sung Pharmaceuticals Co Ltd, Seoul, 3Department of Pathology, School of Medicine, Catholic University of Daegu, Daegu, South Korea; 4Manuka Doctor Ltd, Auckland, New Zealand; 5School of Biomedical Sciences, Charles Sturt University, Bathurst, NSW, Australia Abstract: Facial wrinkles are an undesirable outcome caused by extrinsic photodamage and intrinsic aging processes. Currently, no effective strategies are known to prevent facial wrinkles. We assessed the beneficial effects of bee-venom serum on the clinical signs of aging skin. Our results show that bee-venom serum treatment clinically improved facial wrinkles by decreasing total wrinkle area, total wrinkle count, and average wrinkle depth. Therefore, bee-venom serum may be effective for the improvement of skin wrinkles. Keywords: bee venom, wrinkle, area, count, depth

  16. IN VITRO INHIBITORY EFFECTS OF GAMMA RADIATION ON NAJA NIGRICOLLIS SNAKE VENOM INDUCED HEP-2 CELL INJURY

    International Nuclear Information System (INIS)

    ABOUELELLA, A.M.

    2008-01-01

    Naja nigricollis venom was irradiated with four different doses of gamma rays; 1, 5, 20 and 50 kGy, from 6 0C o source. The ability of gamma rays to attenuate the cytotoxic effects of N. nigricollis venom was investigated on HEp-2 cell line. The cell necrosis was measured by lactate dehydrogenase (LDH) and malondialdehyde (MDA) while cell apoptosis was measured by DNA fragmentation, nitric oxide (NO) synthesis, mitochondrial cytochrome-C release and cleavage of both caspase-3 and PARP-1. The results showed that gamma irradiation reduced significantly the necrotic effects of N. nigricollis venom in almost all irradiation doses of venom, especially at 1 and 50 kGy. DNA fragmentation showed decreased apoptotic effects after exposing of snake venom to gamma radiation. Venom exposed to 1 kGy showed the highest decrease in the NO (47.5±2.4 M) while the 50kGy showed the highest decrease in the MDA release (11.75 ±0.6 nmol/ml). The mitochondrial cytochrome-C was released after treatment with all radiation doses while caspase-3 was cleaved in only the cells incubated with radiated venom of 5 and 20 kGy which were consistent with the results of PARP-1 cleavage at the same radiation doses

  17. Lethal and Sub-lethal Effects of Four Insecticides on the Aphidophagous Coccinellid Adalia bipunctata (Coleoptera: Coccinellidae).

    Science.gov (United States)

    Depalo, Laura; Lanzoni, Alberto; Masetti, Antonio; Pasqualini, Edison; Burgio, Giovanni

    2017-12-05

    Conventional insecticide assays, which measure the effects of insecticide exposure on short-term mortality, overlook important traits, including persistence of toxicity or sub-lethal effects. Therefore, such approaches are especially inadequate for prediction of the overall impact of insecticides on beneficial arthropods. In this study, the side effects of four modern insecticides (chlorantraniliprole, emamectin benzoate, spinosad, and spirotetramat) on Adalia bipunctata (L.) (Coleoptera: Coccinellidae) were evaluated under laboratory conditions by exposition on treated potted plants. In addition to investigation of acute toxicity and persistence of harmful activity in both larvae and adults of A. bipunctata, demographic parameters were evaluated, to provide a comprehensive picture of the nontarget effects of these products. Field doses of the four insecticides caused detrimental effects to A. bipunctata; but in different ways. Overall, spinosad showed the best toxicological profile among the products tested. Emamectin benzoate could be considered a low-risk insecticide, but had high persistence. Chlorantraniliprole exhibited lethal effects on early instar larvae and adults, along with a long-lasting activity, instead spirotetramat showed a low impact on larval and adult mortality and can be considered a short-lived insecticide. However, demographic analysis demonstrated that chlorantraniliprole and spirotetramat caused sub-lethal effects. Our findings highlight that sole assessment of mortality can lead to underestimation of the full impact of pesticides on nontarget insects. Demographic analysis was demonstrated to be a sensitive method for detection of the sub-lethal effects of insecticides on A. bipunctata, and this approach should be considered for evaluation of insecticide selectivity. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Potential Environmental and Ecological Effects of Global Climate Change on Venomous Terrestrial Species in the Wilderness.

    Science.gov (United States)

    Needleman, Robert K; Neylan, Isabelle P; Erickson, Timothy

    2018-06-01

    Climate change has been scientifically documented, and its effects on wildlife have been prognosticated. We sought to predict the overall impact of climate change on venomous terrestrial species. We hypothesize that given the close relationship between terrestrial venomous species and climate, a changing global environment may result in increased species migration, geographical redistribution, and longer seasons for envenomation, which would have repercussions on human health. A retrospective analysis of environmental, ecological, and medical literature was performed with a focus on climate change, toxinology, and future modeling specific to venomous terrestrial creatures. Species included venomous reptiles, snakes, arthropods, spiders, and Hymenoptera (ants and bees). Animals that are vectors of hemorrhagic infectious disease (eg, mosquitos, ticks) were excluded. Our review of the literature indicates that changes to climatic norms will have a potentially dramatic effect on terrestrial venomous creatures. Empirical evidence demonstrates that geographic distributions of many species have already shifted due to changing climatic conditions. Given that most terrestrial venomous species are ectotherms closely tied to ambient temperature, and that climate change is shifting temperature zones away from the equator, further significant distribution and population changes should be anticipated. For those species able to migrate to match the changing temperatures, new geographical locations may open. For those species with limited distribution capabilities, the rate of climate change may accelerate faster than species can adapt, causing population declines. Specifically, poisonous snakes and spiders will likely maintain their population numbers but will shift their geographic distribution to traditionally temperate zones more often inhabited by humans. Fire ants and Africanized honey bees are expected to have an expanded range distribution due to predicted warming trends

  19. Effects of gamma radiation on Crotalus durissus terrificus venom

    International Nuclear Information System (INIS)

    Murata, Y.

    1988-01-01

    A poll of crotomine positive Crotalus durissus terrificus venom was dissolved in 0.15 M NaCl and the supernatant irradiated using 60 CO. Doses of 100,250,750,1000,1500 and 2000 Cy were used at a dose rate of 1.190Gy/h. The presence of free SH, casein hydrolytic degradation, SDS-PAGE and molecular exclusion chromatography analysis together with LD 50 determination in mice were studied. The antigenic properties of samples were investigated by immunodiffision and immunoprecipitation. (M.A.C.) [pt

  20. Evaluation of effects of photooxidized Vespa orientalis venom on memory and learning in rats

    Directory of Open Access Journals (Sweden)

    H Mukund

    2011-01-01

    Full Text Available Wasp venom is mixture of complex proteins that have several physical and pharmacological properties. The photochemical detoxification of Vespa orientalis venom is expected to generate photooxidized venom sac extract (PVSE. Antigenically active PVSE is obtained by exposing the venom sac extract (VSE of Vespa orientalis to ultraviolet radiation in the presence of methylene blue. The aim of the present work was to evaluate the effect of PVSE on learning and memory of rats. Detoxification of PVSE was evident since treated mice had longer survival time than the group of mice treated with VSE. Photooxidized VSE of V. orientalis revealed enhancement on learning and memory by shortening the time to reach food (TRF in T-maze. In a 28-day study with rats, we observed that PVSE significantly decreased transfer latency (TL in elevated plus maze (EPM, significantly increased step down latency (SDL, diminished step down errors (SDE and time spent in shock zone (TSS in step down avoidance test. Thus, we concluded that although there is a possibility of employing PVSE in the treatment of Alzheimer, dementia or neurodegenerative illness as a non-herbal and non-synthetic alternative for patients who do not respond to available therapy, further investigation is still required.

  1. Effects of Androctonus crassicauda (Olivier, 1807 (Scorpiones: Buthidae venom on rat metabolism

    Directory of Open Access Journals (Sweden)

    O. Ozkan

    2008-01-01

    Full Text Available Scorpions are venomous arthropods of the Arachnida class and are considered relatives of spiders, ticks and mites. There is not any study about the biochemical effects of Androctonus crassicauda (Olivier, 1807 venom. Therefore, in the present study, we aimed at evaluating the toxicity of the venom from A. crassicauda, which is responsible for a number of deaths of infants, children and adults in tropical and subtropical countries. For this purpose, rats (n=35 were divided into seven groups of five animals each; venom solutions (250µg/kg were subcutaneously injected into rats; blood samples were taken from each animal at various times; and serum biochemical parameters were measured (levels of total proteins, total bilirubin, albumin, globulin, urea, creatinine, uric acid, glucose, cholesterol, triglycerides, sodium, chlorine, potassium and calcium, and the activity of the enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase. Serum levels of glucose, cholesterol, aspartate aminotransferase, alanine aminotransferase and uric acid increased in envenomed animals, compared to controls. There was a statistically positive correlation between Na+ and Cl- ions.

  2. Computational Studies of Snake Venom Toxins

    OpenAIRE

    Paola G. Ojeda; David Ramírez; Jans Alzate-Morales; Julio Caballero; Quentin Kaas; Wendy González

    2017-01-01

    Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics t...

  3. Late radiation effects in animals surviving lethal irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Dimitrov, L A

    1974-01-01

    Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergency of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine disintegrations. Some of the described late radiation effects were also observed in biological controls as features of ageing. After application of radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival till 30th day, DNA and protein metabolism, immune reactions) of the lethally irradiated animals.

  4. Snake venomics of the Lesser Antillean pit vipers Bothrops caribbaeus and Bothrops lanceolatus: correlation with toxicological activities and immunoreactivity of a heterologous antivenom.

    Science.gov (United States)

    Gutiérrez, José María; Sanz, Libia; Escolano, José; Fernández, Julián; Lomonte, Bruno; Angulo, Yamileth; Rucavado, Alexandra; Warrell, David A; Calvete, Juan J

    2008-10-01

    The venom proteomes of the snakes Bothrops caribbaeus and Bothrops lanceolatus, endemic to the Lesser Antillean islands of Saint Lucia and Martinique, respectively, were characterized by reverse-phase HPLC fractionation, followed by analysis of each chromatographic fraction by SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of tryptic peptides. The venoms contain proteins belonging to seven ( B. caribbaeus) and five ( B. lanceolatus) types of toxins. B. caribbaeus and B. lanceolatus venoms contain phospholipases A 2, serine proteinases, l-amino acid oxidases and zinc-dependent metalloproteinases, whereas a long disintegrin, DC-fragments and a CRISP molecule were present only in the venom of B. caribbaeus, and a C-type lectin-like molecule was characterized in the venom of B. lanceolatus. Compositional differences between venoms among closely related species from different geographic regions may be due to evolutionary environmental pressure acting on isolated populations. The venoms of these two species differed in the composition and the relative abundance of their component toxins, but they exhibited similar toxicological and enzymatic profiles in mice, characterized by lethal, hemorrhagic, edema-forming, phospholipase A 2 and proteolytic activities. The venoms of B. caribbaeus and B. lanceolatus are devoid of coagulant and defibrinogenating effects and induce only mild local myotoxicity in mice. The characteristic thrombotic effect described in human envenomings by these species was not reproduced in the mouse model. The toxicological profile observed is consistent with the abundance of metalloproteinases, PLA 2s and serine proteinases in the venoms. A polyvalent (Crotalinae) antivenom produced in Costa Rica was able to immunodeplete approximately 80% of the proteins from both B. caribbaeus and B. lanceolatus venoms, and was effective in neutralizing the lethal, hemorrhagic, phospholipase

  5. Three days rush venom immunotherapy in bee allergy: safe, inexpensive and instantaneously effective.

    Science.gov (United States)

    Goldberg, Arnon; Yogev, Ayala; Confino-Cohen, Ronit

    2011-01-01

    Rush venom immunotherapy (VIT) is highly effective in vespid venom allergy, but comparable data regarding bee venom (BV) allergy are sparse. We evaluated its safety, efficacy and cost in BV-allergic patients. Conventional or rush VIT were offered to all patients with systemic reaction to insect sting. Rush VIT was also given to hyperreactive patients who failed to reach the maintenance dose with conventional VIT due to multiple systemic reactions. In BV-allergic patients, honeybee sting challenge was performed within 1 week after reaching the maintenance dose. 179 patients, some of them allergic to more than one venom, received 246 rush VIT courses. Bee VIT was administered to 132 patients (73.7%); 173 patients (96.6%) reached the maintenance dose. The incidence of systemic reactions was 29.6%. They were more common in VIT with BV than with vespid venoms (31.1 and 16.3%, respectively, p = 0.01). After excluding the hyperreactive subgroup (n = 20), this difference was not significant (23.7 and 16%, respectively, p = 0.19). Despite the high incidence of systemic reactions (15 of 20, 75%) among hyperreactive patients, 17 patients (85%) achieved the maintenance dose. Sting challenges resulted in systemic reaction in 4 of 8 (50%) hyperreactive patients and in 2 of 47 (4.3%) ordinary patients. The cost of rush VIT was 41% of that of conventional VIT. Rush VIT with BV is safe, instantaneously effective, less expensive and enables most patients with previous failures of conventional VIT to reach the maintenance dose. Copyright © 2011 S. Karger AG, Basel.

  6. IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity.

    Science.gov (United States)

    Starkl, Philipp; Marichal, Thomas; Gaudenzio, Nicolas; Reber, Laurent Lionel; Sibilano, Riccardo; Tsai, Mindy; Galli, Stephen Joseph

    2016-01-01

    Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom. We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain. We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV. A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional FcεRI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom. These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. A Clinical Study on the Effects of Sweet Bee Venom Herbal Acupuncture for Patients with Whiplash Injury

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    Beom-Yong Song

    2007-12-01

    Full Text Available Objectives : The aim of this study is to investigate the effect of Sweet Bee Venom herbal acupuncture for patients with acute whiplash injury by Traffic Accident. Methods : This clinical study was carried out 25 cases of acute whiplash injury patients which had been treatment in Woosuk oriental hospital from March, 2007 to September, 2007. Sweet bee venom herbal acupuncture(N=15 and normal saline(N=10 injected on the acupoints that were cervical area. I checked the VAS for the pain and ROM(range of motion of the cervical. these were checked 3 times. one was before treatments, another was after 3 times treatments with sweet bee venom herbal acupuncture and normal saline injection, and the other was after 5 times treatments with sweet bee venom herbal acupuncture and normal saline injection. Results : VAS score was significantly improved after 5 times treatments with the sweet bee venom herbal acupuncture compared to normal saline I.M. on the acupoints that was cervical area. There were significant changes in the sweet bee venom herbal acupuncture group with VAS and ROM check. Conclusions : This study suggests that sweet bee venom herbal acupuncture can improve symptoms in patients with acute whiplash injury by traffic accident.

  8. Inhibitory effects of ascorbic acid, vitamin E, and vitamin B-complex on the biological activities induced by Bothrops venom.

    Science.gov (United States)

    Oliveira, Carlos Henrique de Moura; Assaid Simão, Anderson; Marcussi, Silvana

    2016-01-01

    Natural compounds have been widely studied with the aim of complementing antiophidic serum therapy. The present study evaluated the inhibitory potential of ascorbic acid and a vitamin complex, composed of ascorbic acid, vitamin E, and all the B-complex vitamins, on the biological activities induced by snake venoms. The effect of vitamins was evaluated on the phospholipase, proteolytic, coagulant, and fibrinogenolytic activities induced by Bothrops moojeni (Viperidae), B. jararacussu, and B. alternatus snake venoms, and the hemagglutinating activity induced by B. jararacussu venom. The vitamin complex (1:5 and 1:10 ratios) totally inhibited the fibrinogenolytic activity and partially the phospholipase activity and proteolytic activity on azocasein induced by the evaluated venoms. Significant inhibition was observed in the coagulation of human plasma induced by venoms from B. alternatus (1:2.5 and 1:5, to vitamin complex and ascorbic acid) and B. moojeni (1:2.5 and 1:5, to vitamin complex and ascorbic acid). Ascorbic acid inhibited 100% of the proteolytic activities of B. moojeni and B. alternatus on azocasein, at 1:10 ratio, the effects of all the venoms on fibrinogen, the hemagglutinating activity of B. jararacussu venom, and also extended the plasma coagulation time induced by all venoms analyzed. The vitamins analyzed showed relevant in vitro inhibitory potential over the activities induced by Bothrops venoms, suggesting their interaction with toxins belonging to the phospholipase A2, protease, and lectin classes. The results can aid further research in clarifying the possible mechanisms of interaction between vitamins and snake enzymes.

  9. Peptidomimetic hydroxamate metalloproteinase inhibitors abrogate local and systemic toxicity induced by Echis ocellatus (saw-scaled) snake venom.

    Science.gov (United States)

    Arias, Ana Silvia; Rucavado, Alexandra; Gutiérrez, José María

    2017-06-15

    The ability of two peptidomimetic hydroxamate metalloproteinase inhibitors, Batimastat and Marimastat, to abrogate toxic and proteinase activities of the venom of Echis ocellatus from Cameroon and Ghana was assessed. Since this venom largely relies for its toxicity on the action of zinc-dependent metalloproteinases (SVMPs), the hypothesis was raised that toxicity could be largely eliminated by using SVMP inhibitors. Both hydroxamate molecules inhibited local and pulmonary hemorrhagic, in vitro coagulant, defibrinogenating, and proteinase activities of the venoms in conditions in which venom and inhibitors were incubated prior to the test. In addition, the inhibitors prolonged the time of death of mice receiving 4 LD 50 s of venom by the intravenous route. Lower values of IC 50 were observed for in vitro and local hemorrhagic activities than for systemic effects. When experiments were performed in conditions that simulated the actual circumstances of snakebite, i.e. by administering the inhibitor after envenoming, Batimastat completely abrogated local hemorrhage if injected immediately after venom. Moreover, it was also effective at inhibiting lethality and defibrinogenation when venom and inhibitor were injected by the intraperitoneal route. Results suggest that these, and possibly other, metalloproteinase inhibitors may become an effective adjunct therapy in envenomings by E. ocellatus when administered at the anatomic site of venom injection rapidly after the bite. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. The Effect of Bee Venom on COX-2, P38, ERK and JNK in RAW 264.7 Cells

    Directory of Open Access Journals (Sweden)

    Jae-Young Sim

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate the effect of Bee Venom on the lipopolysaccharide(LPS, sodium nitroprusside(SNP, hydrogen peroxide(H2O2-induced expressions of cyclooxygenase-2(COX-2, p38, jun N-terminal Kinase(JNK and extra-signal response kinase(ERK in RAW 264.7 cells, a murine macrophage cell line. Methods : The expressions of COX-2, p38, JNK and ERK were determined by western blotting with corresponding antibodies.\\ Results : 1. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited significantly LPS and SNP-induced expression of COX-2 compared with control, respectively. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited insignificantly H2O2-induced expression of COX-2 compared with control, respectively. 2. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited significantly LPS, SNP and H2O2-induced expression of p38 compared with control, respectively. 3. The 1 and 5 ㎍/㎖ of bee venom inhibited significantly SNP-induced expression of JNK compared with control, respectively. All of bee venom inhibited insignificantly LPS and H2O2-induced expression of JNK compared with control, respectively. 4. The 5 ㎍/㎖ of bee venom inhibited significantly SNP-induced expression of ERK, the 0.5 ㎍/㎖ of bee venom increased significantly H2O2-induced expression of ERK compared with control. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited insignificantly LPS-induced expression of ERK compared with control, respectively.

  11. Biochemical and biological characterization of Bothriechis schlegelii snake venoms from Colombia and Costa Rica.

    Science.gov (United States)

    Prezotto-Neto, José P; Kimura, Louise F; Alves, André F; Gutiérrez, José María; Otero, Rafael; Suárez, Ana M; Santoro, Marcelo L; Barbaro, Katia C

    2016-12-01

    Snakebites inflicted by the arboreal viperid snake Bothriechis schlegelii in humans are characterized by pain, edema, and ecchymosis at the site of the bite, rarely with blisters, local necrosis, or defibrination. Herein, a comparative study of Bothriechis schlegelii snake venoms from Colombia (BsCo) and Costa Rica (BsCR) was carried out in order to compare their main activities and to verify the efficacy of Bothrops antivenom produced in Brazil to neutralize them. Biochemical (SDS-PAGE and zymography) and biological parameters (edematogenic, lethal, hemorrhagic, nociceptive, and phospholipase A 2 activities) induced by BsCo and BsCR snake venoms were evaluated. The presence of antibodies in Bothrops antivenom that recognize BsCo and BsCR snake venoms by enzyme-linked immunosorbent assay and Western blotting, as well as the ability of this antivenom to neutralize the toxic activities were also verified. SDS-PAGE showed differences between venoms. Distinctive caseinolytic and hyaluronidase patterns were detected by zymography. BsCo and BsCR showed similar phospholipase A 2 activity. Strong cross-reactivity between BsCo and BsCR was detected using Bothrops antivenom with many components located between 150 and 35 kDa. BsCR was more edematogenic and almost fourfold more hemorrhagic than BsCo, and both venoms induced nociception. BsCR (LD 50 5.60 mg/kg) was more lethal to mice than BsCo (LD 50 9.24 mg/kg). Bothrops antivenom was effective in the neutralization of lethal and hemorrhagic activities of BsCo and BsCR and was partially effective in the neutralization of edematogenic and nociceptive activities. In conclusion, geographic distribution influences the composition and activities of Bothriechis schlegelii venoms. Bothrops antivenom cross-reacted with these venoms and was partially effective in neutralizing some toxic activities of BsCo and BsCR.

  12. Studies on Impact of Irradiation Treatment on Certain Pharmacological and Biochemical Responses of Naja nigricollis Snake Venom

    International Nuclear Information System (INIS)

    Abd El Hamid, F.Y.A.

    2015-01-01

    Snakebite is a serious medical problem worldwide, especially in the tropics. In Egypt, the Black-neck Spitting Cobra; Naja nigricollis is one of the most venomous snakes distributed in the south part of Egypt. The lethality as well as the immunological, biochemical and histological effects of Naja nigricollis venom at a sublethal dose has been investigated before and after exposure to gamma radiation (1.5 KGy and 3 KGy). The toxicity of irradiated venom decreased as compared to that of the native one. There was no change in the antigenic reactivity between both native and irradiated venom. The effect of ½ LD 50 of native or irradiated (1.5 KGy) was studied on the activities of heart enzymes: CPK, CK-MB, LDH and AST after (1, 2, 4, 24 hours) of envenomation. The present study showed that snake venom envenomation caused significant (p ≤ 0.05) elevation in serum CPK, CK-MB, LDH and AST levels. In contrast, the 1.5 KGy gamma-irradiated venom recorded no significant changes compared to that of normal rats. Histopathological study of heart confirmed these findings. The 1.5 KGy and 3 KGy gamma irradiation decrease the phospholipase activity of the venom. Anticoagulant activity was prominent when re calcification time was tested on human plasma using each venom (native, γ- irradiated venoms) as a test solution. Naja nigricollis venom detoxified by gamma irradiation (1.5 KGy or 3 KGy) was used as toxoid for active immunization of rabbits following a short schedule of immunization with complete Freund's adjuvant. Effective neutralization of venom toxin by immune sera of rabbits was observed.

  13. Protective effects of Mucuna pruriens seed extract pretreatment against cardiovascular and respiratory depressant effects of Calloselasma rhodostoma (Malayan pit viper) venom in rats.

    Science.gov (United States)

    Fung, S Y; Tan, N H; Sim, S M

    2010-12-01

    The protective effects of Mucuna pruriens seed extract (MPE) against the cardio-respiratory depressant and neuromuscular paralytic effects induced by injection of Calloselasma rhodostoma (Malayan pit viper) venom in anaesthetized rats were investigated. While MPE pretreatment did not reverse the inhibitory effect of the venom on the gastrocnemius muscle excitability, it significantly attenuated the venom-induced cardio-respiratory depressant effects (p < 0.05). The protection effects may have an immunological mechanism, as indicated by the presence of several proteins in the venom that are immunoreactive against anti-MPE. However, we cannot rule out the possibility that the pretreatment may exert a direct, non-immunological protective action against the venom.

  14. In vivo studies on detoxifying actions of aqueous bark extract of Prosopis cineraria against crude venom from Indian cobra (Naja naja)

    OpenAIRE

    Thirunavukkarasu Sivaraman; Sivarathri Siva Rajesh; Veerayan Elango

    2013-01-01

    Detoxification effect of aqueous, methanol and petroleum ether extracts of medicinal plants such as Aristolochia bracteolata, Mucuna pruriens, Prosopis cineraria and Rauvolfia tetraphylla was systematically screened against lethality of crude venom of Naja naja using Swiss albino mice as animal models. We have herein demonstrated that aqueous bark extract of P. cineraria has substantial anti-venom potential vis-à-vis other extracts used in the present study. The aqueous extract at the dose of...

  15. Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent.

    Science.gov (United States)

    Park, Joonsoo; Kwon, Osung; An, Hyun-Jin; Park, Kwan Kyu

    2018-04-01

    Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified. This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect. Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies. The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl ( p =0.026) and 40 mg/100 µl ( p =0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl ( p =0.000) and 300 µl/100 µl ( p =0.030). The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.

  16. Lethal effect of glucose load on malignant cells

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Yarmonenko, S.P.; Kozubek, S.

    1987-01-01

    Ehrlich ascites tumor (EAT) cells were treated with glucose load under anoxic conditions (for 15 or 60 min) and/or with γ radiation (20 Gy). The efficiency of the treatment was judged from the tumorigenic activity of EAT cell inocula. The markedly increased efficiency of the combined treatment of EAT cells using glucose load in anoxia and γ radiation is due to the additive action of both agents. The glucose load in anoxia leads to extensive desintegration of tumor cells. Further, the lethal effect of various pH values on EAT cells was investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect was investigated by determining the tumorigenic activity of EAT cells tested in vivo in mice and by determining the radiosensitivity of treated EAT cells. The results allowed us to conclude that the same values of pH lead to the same effect on EAT cells independently of the way by which the given pH value was reached. (author). 5 figs., 2 tabs., 12 refs

  17. Toxicological effect of herbicides (diuron and bentazon) on snake venom and electric eel acetylcholinesterase.

    Science.gov (United States)

    Ahmed, Mushtaq; Latif, Nadia; Khan, Rehmat Ali; Ahmad, Akhlaq

    2012-08-01

    The toxicological effects of the active ingredients of the herbicides diuron and bentazon on the activity of acetylcholinesterase (AChE) of krait (Bungarus sindanus) venom and electric eel (Electrophorus electricus) were studied. The diuron and entazon caused non-competitive inhibition of AChE from both species. For the venom AChE, the calculated IC50 for diuron and bentazon were found to be 3.25 and 0.14 μM, while for eel AChE, the respective IC50 values were 3.6 and 0.135 μM. In comparison, bentazon was a more potent inhibitor than diuron of AChE from both species. The insecticide lindane did not have any inhibitory effect on AChE activity in either species, even when tested at high concentrations (200-800 μM).

  18. Integrative characterization of the venom of the coral snake Micrurus dumerilii (Elapidae) from Colombia: Proteome, toxicity, and cross-neutralization by antivenom.

    Science.gov (United States)

    Rey-Suárez, Paola; Núñez, Vitelbina; Fernández, Julián; Lomonte, Bruno

    2016-03-16

    In Colombia, nearly 2.8% of the 4200 snakebite accidents recorded annually are inflicted by coral snakes (genus Micrurus). Micrurus dumerilii has a broad distribution in this country, especially in densely populated areas. The proteomic profile of its venom was here studied by a bottom-up approach combining RP-HPLC, SDS-PAGE and MALDI-TOF/TOF. Venom proteins were assigned to eleven families, the most abundant being phospholipases A2 (PLA2; 52.0%) and three-finger toxins (3FTx; 28.1%). This compositional profile shows that M. dumerilii venom belongs to the 'PLA2-rich' phenotype, in the recently proposed dichotomy for Micrurus venoms. Enzymatic and toxic venom activities correlated with protein family abundances. Whole venom induced a conspicuous myotoxic, cytotoxic and anticoagulant effect, and was mildly edematogenic and proteolytic, whereas it lacked hemorrhagic activity. Some 3FTxs and PLA2s reproduced the lethal effect of venom. A coral snake antivenom to Micrurus nigrocinctus demonstrated significant cross-recognition of M. dumerilii venom proteins, and accordingly, ability to neutralize its lethal effect. The combined compositional, functional, and immunological data here reported for M. dumerilii venom may contribute to a better understanding of these envenomings, and support the possible use of anti-M. nigrocinctus coral snake antivenom in their treatment. Coral snakes represent a highly diversified group of elapids in the New World, with nearly 70 species within the genus Micrurus. Owing to their scarce yields, the biochemical composition and toxic activities of coral snake venoms have been less well characterized than those of viperid species. In this work, an integrative view of the venom of M. dumerilii, a medically relevant coral snake from Colombia, was obtained by a combined proteomic, functional, and immunological approach. The venom contains proteins from at least eleven families, with a predominance of phospholipases A2 (PLA2), followed by three

  19. Effects of ionizing radiation on crotoxin (toxin of Crotalus durissus terrificus venom): molecular studies

    International Nuclear Information System (INIS)

    Souza Filho, J.N. de.

    1988-01-01

    It is know that the ionizing radiation is able to change significantly the biological and antigenic response of a toxin depending of the dose and irradiation's conditions, probable by structural alterations caused by radiation. In this work, the crotoxin, principal neurotoxin of the South American rattlesnake venom, was isolated using molecular exclusion chromatography with Sephadex G-75 and follwed by precipitation on the isoelectric point. Fractions in the concentration of 2 mg of protein/m1 0.85% NaCl were irradiated in a source of sup(60)Co GAMMACELL with dose rate of 1100 Gy/h using doses of 250, 500, 1000, 1500 and 2000 Gy. It was determinated for these samples, the proteic concentration (Lowry's method), the content sulphydryl (Ellman's method), the profile electrophoretic (SDS-PAGE), the toxicity by lethal dose 50% in mice and the antigenic response using crotalic antiserum by the diffusion imunoassay (Ouchterlony's method). The results showed the formation of aggregates and loss of protein in solution by precipitation. In the dose of 1000 Gy and higher it was possible to observe the presence of sulphydryl groups indicating the breakage of S-S bridges. The lethal dose 50% increased 2 times for the dose of 1000 Gy and 3.5 times for 1500 Gy shoding a detoxication. By the other hand, the antigenic response seems to be still intact at doses up to 1000 Gy. (author)

  20. Respiratory Effects of Sarafotoxins from the Venom of Different Atractaspis Genus Snake Species

    Directory of Open Access Journals (Sweden)

    Stéphanie Malaquin

    2016-07-01

    Full Text Available Sarafotoxins (SRTX are endothelin-like peptides extracted from the venom of snakes belonging to the Atractaspididae family. A recent in vivo study on anesthetized and ventilated animals showed that sarafotoxin-b (SRTX-b, extracted from the venom of Atractaspis engaddensis, decreases cardiac output by inducing left ventricular dysfunction while sarafotoxin-m (SRTX-m, extracted from the venom of Atractaspis microlepidota microlepidota, induces right ventricular dysfunction with increased airway pressure. The aim of the present experimental study was to compare the respiratory effects of SRTX-m and SRTX-b. Male Wistar rats were anesthetized, tracheotomized and mechanically ventilated. They received either a 1 LD50 IV bolus of SRTX-b (n = 5 or 1 LD50 of SRTX-m (n = 5. The low-frequency forced oscillation technique was used to measure respiratory impedance. Airway resistance (Raw, parenchymal damping (G and elastance (H were determined from impedance data, before and 5 min after SRTX injection. SRTX-m and SRTX-b injections induced acute hypoxia and metabolic acidosis with an increased anion gap. Both toxins markedly increased Raw, G and H, but with a much greater effect of SRTX-b on H, which may have been due to pulmonary edema in addition to bronchoconstriction. Therefore, despite their structural analogy, these two toxins exert different effects on respiratory function. These results emphasize the role of the C-terminal extension in the in vivo effect of these toxins.

  1. Rush immunotherapy for wasp venom allergy seems safe and effective in patients with mastocytosis.

    Science.gov (United States)

    Verburg, M; Oldhoff, J M; Klemans, R J B; Lahey-de Boer, A; de Bruin-Weller, M S; Röckmann, H; Sanders, C; Bruijnzeel-Koomen, C A F M; Pasmans, S G M A; Knulst, A C

    2015-11-01

    Patients with mastocytosis and wasp venom allergy (WA) may benefit from venom immunotherapy (VIT). However, fatal insect sting reactions have been described in mastocytosis patients despite previous immunotherapy. We investigated the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. To investigate the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. We describe nine patients with cutaneous mastocytosis and WA who received VIT. Cutaneous mastocytosis was confirmed by histopathology and systemic mastocytosis was diagnosed according to World Health Organization criteria. VIT was given according to a rush protocol. Given the difference in safety and efficacy of VIT in patients with WA and honeybee venom allergy, we reviewed the literature for VIT with the focus on WA patients with mastocytosis and addressed the difference between patients with cutaneous versus systemic mastocytosis. Nine patients had WA and mastocytosis, of whom six had cutaneous mastocytosis, two combined cutaneous and systemic mastocytosis and one systemic mastocytosis. All patients received rush IT with wasp venom. Most patients had only mild local side effects, with no systemic side effects during the course of VIT. One patient had a systemic reaction upon injection on one occasion, during the updosing phase, with dyspnoea and hypotension, but responded well to treatment. Immunotherapy was continued after temporary dose adjustment without problems. Two patients with a previous anaphylactic reaction were re-stung, without any systemic effects. VIT is safe in cutaneous mastocytosis patients with WA, while caution has to be made in case of systemic mastocytosis. VIT was effective in the patients who were re-stung.

  2. Antisnake Venom Activity of Hibiscus aethiopicus L. against Echis ocellatus and Naja n. nigricollis

    Directory of Open Access Journals (Sweden)

    S. S. Hasson

    2010-01-01

    Full Text Available The objective of the study is to investigate whether the Hibiscus aethiopicus L. plant has neutralization activity against venoms of two clinically important snakes. The H. aethiopicus was dried and extracted with water. Different assays were performed to evaluate the plant's acute toxicity and its anti-snake venom activities. The results showed that H. aethiopicus extract alone had no effect on the viability of C2C12 muscle cells, but significantly (P<.05 protected muscle cells against the toxic effects of E. ocellatus venom at 55, 150, and 300 μg/mL. The maximum protective effect of the extract was exhibited at 75 μg/mL. The extract significantly (P<.001 inhibited the cytotoxic effects of E. ocellatus venom at 300 μg/mL. All rabbits (n=10 and guinea pigs (n=10 were alive after the two weeks of given the lethal dosage 16 g/Kg of the H. aethiopicus extract herbal solution. No abnormal behaviour was observed of both groups of animals. All guinea pigs (n=3 treated with venoms alone (5 mg/kg died. However, all guinea pigs (n=21 treated with venom (5 mg/kg and the extract (400 to 1000 mg/kg survived. Guinea pigs (n=3 treated with Naja n. nigricollis venom alone (2.5 mg/kg and guinea pigs (n=21 venom with the extract (400 to 1000 mg/kg died. The H. aethiopicus completely (100% blocked the haemorrhagic activity of E. ocellatus in the egg embryo at 3.3 mg/mL of extract. These findings suggest that H. aethiopicus may contain an endogenous inhibitor of venom-induced haemorrhage.

  3. Anti snake Venom Activity of Hibiscus aethiopicus L. against Echis ocellatus and Naja n. nigricollis

    International Nuclear Information System (INIS)

    Hasson, S.S.; Al-Jabri, A.A.; Al-Balushi, M.S.; Hasson, S.S.; Sallam, T.A.; Mothana, R.A.A.

    2010-01-01

    The objective of the study is to investigate whether the Hibiscus aethiopicus L. plant has neutralization activity against venoms of two clinically important snakes. The H. aethiopicus was dried and extracted with water. Different assays were performed to evaluate the plant's acute toxicity and its anti-snake venom activities. The results showed that H. aethiopicus extract alone had no effect on the viability of C 2 C 12 muscle cells, but significantly (P<.05) protected muscle cells against the toxic effects of E. ocellatus venom at 55, 150, and 300 μg/ mL. The maximum protective effect of the extract was exhibited at 75μg/mL. The extract significantly (P<.001) inhibited the cytotoxic effects of E. ocellatus venom at 300?μg/mL. All rabbits (n=10) and guinea pigs (n=10) were alive after the two weeks of given the lethal dosage 16g/Kg of the H. aethiopicus extract herbal solution. No abnormal behaviour was observed of both groups of animals. All guinea pigs (n=3) treated with venoms alone (5 mg/kg) died. However, all guinea pigs (n=21) treated with venom (5 mg/kg) and the extract (400 to 1000 mg/kg) survived. Guinea pigs (n=3) treated with Naja n. nigricollis venom alone (2.5 mg/kg) and guinea pigs (n=21) venom with the extract (400 to 1000 mg/kg) died. The H. aethiopicus completely (100%) blocked the haemorrhagic activity of E. ocellatus in the egg embryo at 3.3mg/ mL of extract. These findings suggest that H. aethiopicus may contain an endogenous inhibitor of venom-induced haemorrhage.

  4. Effect of toxin-g from Tityus serrulatus scorpion venom on gastric emptying in rats

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    F. Bucaretchi

    1999-04-01

    Full Text Available The effect of toxin-g from Tityus serrulatus scorpion venom on the gastric emptying of liquids was studied in 176 young adult male Wistar rats (2-3 months of age divided into subgroups of 8 animals each. Toxin-g was injected iv at doses of 25, 37.5, 50 or 100 µg/kg and the effect on gastric emptying was assessed 30 min and 8 h later. A time-course study was also performed by injecting 50 µg of toxin-g /kg and measuring the effect on gastric emptying at times 0.25, 0.5, 1, 2, 4, 8, 24 and 48 h post-venom. Each envenomed animal was paired with its saline control and all received a saline test meal solution containing phenol red (60 µg/ml as a marker. Ten minutes after administering the test meal by gavage the animals were sacrificed and gastric retention was determined by measuring the residual marker concentration of the test meal. A significant delay in gastric emptying, at 30 min and 8 h post-venom, was observed only after 50 and 100 µg of toxin-g /kg compared to control values. The responses to these two doses were significantly different after 8 h post-venom. Toxin-g (50 µg/kg significantly delayed the gastric emptying of liquids at all times studied, with a peak response at 4 h after toxin administration compared to control values. These results indicate that the iv injection of toxin-g may induce a rapid, intense and sustained inhibition of gastric emptying 0.25 to 48 h after envenomation.

  5. Venomics-Accelerated Cone Snail Venom Peptide Discovery

    Science.gov (United States)

    Himaya, S. W. A.

    2018-01-01

    Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads. PMID:29522462

  6. Venomics-Accelerated Cone Snail Venom Peptide Discovery

    Directory of Open Access Journals (Sweden)

    S. W. A. Himaya

    2018-03-01

    Full Text Available Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads.

  7. Lethal and Sublethal Effects of Fenpropathrin on the Biological Performance of Scolothrips longicornis (Thysanoptera: Thripidae)

    DEFF Research Database (Denmark)

    Pakyari, Hajar; Enkegaard, Annie

    2013-01-01

    Determination of negative nontarget effects of pesticides on beneficial organisms by measuring only lethal effects is likely to underestimate effects of sublethal doses. In this study, the sublethal effects of fenpropathrin on the predatory thrips Scolothrips longicornis Priesner (Thysanoptera: T...

  8. Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Monique Silva Martines

    Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

  9. Effects of snake venom from Saudi cobras and vipers on hormonal levels in peripheral blood.

    Science.gov (United States)

    Abdel-Galil, Khidir A; Al-Hazimi, Awdah M

    2004-08-01

    Knowledge about the effects of snake venoms on endocrine glands in the Kingdom of Saudi Arabia (KSA) is meager. The aim of the present study is to investigate the acute and chronic envenomation from 4 snakes out of 8 species of Saudi Cobras and Vipers on the tissues of endocrine glands and peripheral hormonal levels in male rats. The peripheral blood levels of 4 hormones mainly testosterone, cortisol, insulin and thyroxin were investigated in male Wistar rats following acute and chronic treatment of the rats with poisonous snake venoms at the Department of Physiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia between September 2000 to May 2001. Using radio immunoassay for hormonal analysis, a rise in testosterone levels in peripheral blood was obtained following acute treatment, which is due to the effect of the venoms on vascular permeability and increased blood flow. In contrast, the chronic treatment with venoms resulted in a delayed effect on vascular permeability and testicular degeneration resulting in a decreased blood flow and a significant drop in testosterone concentration. Cortisol levels were no different from the controls during acute treatment but it demonstrates gradual rise following chronic treatment to withstand the stress imposed on the animals. Similar results were obtained for insulin, which showed normal values with acute treatment but decreased levels of chronic treatment suggesting insulin insufficiently. Likewise, the thyroxin levels were decreased with chronic treatment suggesting a toxic effect of the poison on the rich blood supply of the thyroid follicles with a subsequent decrease in blood flow to the tissues and therefore, decreased thyroid hormone levels. The effects of venom toxicity on testosterone levels were either normal or stimulatory with acute treatment or inhibitory with chronic treatment depending on the vascular blood flow and testicular degeneration. Cortisol levels were normal at

  10. Differential Effects of Naja naja atra Venom on Immune Activity

    Directory of Open Access Journals (Sweden)

    Jian-Qun Kou

    2014-01-01

    Full Text Available Previous studies reported that Naja naja atra venom (NNAV inhibited inflammation and adjuvant arthritis. Here we investigated the role of NNAV in regulation of immune responses in mice. Oral administration of NNAV to normal mice showed significant increase in natural killer cell activity, B lymphocyte proliferation stimulated by lipopolysaccharides, and antibody production in response to sheep red blood cells. Meanwhile, NNAV markedly decreased T lymphocyte proliferation stimulated by concanavalin A, arrested the cell cycle at G0/G1 phase, and suppressed CD4 and CD8 T cell divisions. Furthermore, NNAV inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reaction. This modulation of immune responses may be partly attributed to the selective increase in Th1 and Th2 cytokines (IFN-γ, IL-4 secretion and inhibition of Th17 cytokine (IL-17 production. In dexamethasone-induced immunosuppressed mice, NNAV restored the concentration of serum IgG and IgM, while decreasing the percentage of CD4 and CD8 T-cell subsets. These results indicate that NNAV enhances the innate and humoral immune responses while inhibiting CD4 Th17 and CD8 T cell actions, suggesting that NNAV could be a potential therapeutic agent for autoimmune diseases.

  11. Effect of pretreatment with venom of Apis mellifera bees on the yield of gamma-ray induced chromosome aberrations in human blood lymphocytes

    International Nuclear Information System (INIS)

    Varanda, E.A.; Takahashi, C.S.

    1993-01-01

    Venom of the honey bee Apis mellifera induced a protective effect against the induction of dicentric chromosomes by gamma radiation (2.0 Gy) in human peripheral blood lymphocytes when the cultures were treated with 0.00015 μl venom/1 ml medium 6 h before irradiation. In cultures to which the venom was added immediately before irradiation with 0.25, 1.0 and 2.0 Gy, no significant differences in number of dicentric chromosomes induced was observed when compared to cultures submitted to irradiation only. The venom did not induce clastogenic effects nor did it increase the frequency of sister chromatid exchanges. (author)

  12. Indirect effects of non-lethal predation on bivalve activity and sediment reworking

    NARCIS (Netherlands)

    Maire, O.; Merchant, J.N.; Bulling, M.; Teal, L.R.; Gremare, A.; Duchene, J.C.; Solan, M.

    2010-01-01

    Deposit-feeders are the dominant bioturbators of aquatic sediments, where they profoundly impact biogeochemical processes, but they are also vulnerable to both lethal and non-lethal predation by a large variety of predators. In this study, we performed a series of experiments to test the effects of

  13. Activity evaluation from different native or irradiated with 60 Co gamma rays snake venoms and their inhibitory effect on Leishmania (Leishmania) amazonensis

    International Nuclear Information System (INIS)

    Lourenco, Cecilia de Oliveira

    2000-01-01

    Cutaneous leishmaniasis is a disease, caused by Leishmania parasites, that occurs frequently in tropical and sub-tropical regions of the world. Skin lesions that could results in disfiguring aspect characterize it. The treatment is based on few drugs as antimony salts or pentamidine that are toxic with increasing resistance by the parasite. Alternative forms of disease treatment are in constant search, including natural components as snake venoms. Previous studies demonstrate that some components of snake venoms have an inhibitory effect against those parasites, including Leishmania species. Although snake venoms presented high toxicity, several methods have been described to detoxify most or some of their toxic components, with favorable results by the use of gamma irradiation. In this report we tested several native and irradiated snake venoms for inhibitory effect against Leishmania (Leishmania) amazonensis parasite and LLCMK 2 mammalian cells, with enzymatic tests and electrophoresis. There are significant activity in Acanthophis antarcticus, Agkistrodon bilineatus, Bothrops moojeni, Bothrops jararaca, Hoplocephalus stephensi, Naja melanoleuca, Naja mossambica, Pseudechis australis, Pseudechis colletti, Pseudechis guttatus and Pseudechis porphyriacus, venom being inactive Pseudonaja textilis, Notechis ater niger, Notechis scutatus. Oxyuranus microlepidotus and Oxyuranus scutellatus venoms. After 2 KGy of 60 Co irradiation most venom loses significantly their activity. Venoms with antileishmanial activity presented L-amino acid oxidase (L-AO) activity and showed common protein with a molecular weight about 60kDa in SDS-PAGE. These results indicate that L-AO activity in those venoms are probably related with antileishmanial effect. (author)

  14. Proteomics and antivenomics of Papuan black snake (Pseudechis papuanus) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms.

    Science.gov (United States)

    Pla, Davinia; Bande, Benjamin W; Welton, Ronelle E; Paiva, Owen K; Sanz, Libia; Segura, Álvaro; Wright, Christine E; Calvete, Juan J; Gutiérrez, José María; Williams, David J

    2017-01-06

    The Papuan black snake (Pseudechis papuanus Serpentes: Elapidae) is endemic to Papua New Guinea, Indonesian Papua and Australia's Torres Strait Islands. We have investigated the biological activity and proteomic composition of its venom. The P. papuanus venom proteome is dominated by a variety (n≥18) of PLA 2 s, which together account for ~90% of the venom proteins, and a set of low relative abundance proteins, including a short-neurotoxic 3FTx (3.1%), 3-4 PIII-SVMPs (2.8%), 3 cysteine-rich secretory proteins (CRISP; 2.3%) 1-3 l-amino acid oxidase (LAAO) molecules (1.6%). Probing of a P. papuanus cDNA library with specific primers resulted in the elucidation of the full-length nucleotide sequences of six new toxins, including vespryn and NGF not found in the venom proteome, and a calglandulin protein involved in toxin expression with the venom glands. Intravenous injection of P. papuanus venom in mice induced lethality, intravascular haemolysis, pulmonary congestion and oedema, and anticoagulation after intravenous injection, and these effects are mainly due to the action of PLA 2 s. This study also evaluated the in vivo preclinical efficacy of Australian black snake and polyvalent Seqirus antivenoms. These antivenoms were effective in neutralising the lethal, PLA 2 and anticoagulant activities of P. papuanus venom in mice. On the other hand, all of the Seqirus antivenoms tested using an antivenomic approach exhibited strong immunorecognition of all the venom components. These preclinical results suggest that Australian Seqirus 1 antivenoms may provide paraspecific protection against P. papuanus venom in humans. The toxicological profile and proteomic composition of the venom of the Papuan black snake, Pseudechis papuanus, a large diurnal snake endemic to the southern coast of New Guinea and a handful of close offshore islands, were investigated. Intravenous injection of P. papuanus venom in mice induced intravascular hemolysis, pulmonary congestion and edema

  15. Electric shocks are ineffective in treatment of lethal effects of rattlesnake envenomation in mice.

    Science.gov (United States)

    Johnson, E K; Kardong, K V; Mackessy, S P

    1987-01-01

    Electrical shocks, even crudely delivered from 'stun guns' and gasoline engine spark plugs, have been reported to be effective in the treatment of snake bite. We thus applied similar electric shocks to mice artificially injected with reconstituted rattlesnake venom at various LD50 multiples. Those envenomated mice treated with electric shock survived no better than the controls. We thus found no evidence that electric shocks crudely administered had any life saving effect in mice.

  16. Occurrence of a tetrodotoxin-like compound in the eggs of the venomous blue-ringed octopus (Hapalochlaena maculosa).

    Science.gov (United States)

    Sheumack, D D; Howden, M E; Spence, I

    1984-01-01

    A lethal toxin was isolated and partly purified from the eggs of the blue-ringed octopus, Hapalochlaena maculosa. Examination of the toxin by thin layer chromatography, isoelectric focusing and its effects upon the compound nerve action potentials of the toad sciatic nerve gave results that were indistinguishable from those displayed by authentic tetrodotoxin, the toxin present in the venom glands of the octopus.

  17. Venom of the Coral Snake Micrurus clarki: Proteomic Profile, Toxicity, Immunological Cross-Neutralization, and Characterization of a Three-Finger Toxin

    Directory of Open Access Journals (Sweden)

    Bruno Lomonte

    2016-05-01

    Full Text Available Micrurus clarki is an uncommon coral snake distributed from the Southeastern Pacific of Costa Rica to Western Colombia, for which no information on its venom could be found in the literature. Using a ‘venomics’ approach, proteins of at least nine families were identified, with a moderate predominance of three-finger toxins (3FTx; 48.2% over phospholipase A2 (PLA2; 36.5%. Comparison of this venom profile with those of other Micrurus species suggests that it may represent a more balanced, ‘intermediate’ type within the dichotomy between 3FTx- and PLA2-predominant venoms. M. clarki venom was strongly cross-recognized and, accordingly, efficiently neutralized by an equine therapeutic antivenom against M. nigrocinctus, revealing their high antigenic similarity. Lethal activity for mice could be reproduced by a PLA2 venom fraction, but, unexpectedly, not by fractions corresponding to 3FTxs. The most abundant venom component, hereby named clarkitoxin-I, was identified as a short-chain (type I 3FTx, devoid of lethal effect in mice, whose target remains to be defined. Its amino acid sequence of 66 residues shows high similarity with predicted sequences of venom gland transcripts described for M. fulvius, M. browni, and M. diastema.

  18. The effects of Western Diamondback Rattlesnake (Crotalus atrox) venom on the production of antihemorrhagins and/or antibodies in the Virginia opossum (Didelphis virginiana).

    Science.gov (United States)

    McKeller, Morgan R; Pérez, John C

    2002-04-01

    Opossums are animals that are naturally resistant to the proteolytic effects of Crotalid venoms. Opossums possess proteinase inhibitors in their sera that bind to and neutralize hemorrhagic and other proteolytic activity in many snake venoms. The proteinase inhibitors are not antibodies since they have different molecular weights (60kDa) and pI (4.2). The purpose of this study was to determine if opossums were capable of producing antibodies against venom and/or increasing the production of proteinase inhibitors (specifically antihemorrhagins). Five different venom immunization protocols were used to determine the effects of the venom in the opossums. The dosages ranged from 1mg of venom per immunization to 350mg/kg body weight of venom per immunization. The antihemorrhagic response was increased, but there is no evidence to suggest that an opossum can produce antibodies against venom. The lack of an antibody response is most likely due to the natural proteinase inhibitors clearing the venom from the opossum's body before an antibody response can occur.

  19. Anticonvulsant Effects of Fractions Isolated from Dinoponera quadriceps (Kempt Ant Venom (Formicidae: Ponerinae

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    Diana Aline Morais Ferreira Nôga

    2016-12-01

    Full Text Available Natural products, sources of new pharmacological substances, have large chemical diversity and architectural complexity. In this context, some toxins obtained from invertebrate venoms have anticonvulsant effects. Epilepsy is a neurological disorder that affects about 65 million people worldwide, and approximately 30% of cases are resistant to pharmacological treatment. Previous studies from our group show that the denatured venom of the ant Dinoponera quadriceps (Kempt protects mice against bicuculline (BIC-induced seizures and death. The aim of this study was to investigate the anticonvulsant activity of compounds isolated from D. quadriceps venom against seizures induced by BIC in mice. Crude venom was fractionated by high-performance liquid chromatography (HPLC resulting in six fractions referred to as DqTx1–DqTx6. A liquid chromatography-mass spectrometry (LC/MS analysis revealed a major 431 Da compound in fractions DqTx1 and DqTx2. Fractions DqTx3 and DqTx4 showed a compound of 2451 Da and DqTx5 revealed a 2436 Da compound. Furthermore, the DqTx6 fraction exhibited a major component with a molecular weight of 13,196 Da. Each fraction (1 mg/mL was microinjected into the lateral ventricle of mice, and the animals were observed in an open field. We did not observe behavioral alterations when the fractions were given alone. Conversely, when the fractions were microinjected 20 min prior to the administration of BIC (21.6 nM, DqTx1, DqTx4, and DqTx6 fractions increased the latency for onset of tonic-clonic seizures. Moreover, all fractions, except DqTx5, increased latency to death. The more relevant result was obtained with the DqTx6 fraction, which protected 62.5% of the animals against tonic-clonic seizures. Furthermore, this fraction protected 100% of the animals from seizure episodes followed by death. Taken together, these findings indicate that compounds from ant venom might be a potential source of new anticonvulsants molecules.

  20. Effect of lethality on the extinction and on the error threshold of quasispecies.

    Science.gov (United States)

    Tejero, Hector; Marín, Arturo; Montero, Francisco

    2010-02-21

    In this paper the effect of lethality on error threshold and extinction has been studied in a population of error-prone self-replicating molecules. For given lethality and a simple fitness landscape, three dynamic regimes can be obtained: quasispecies, error catastrophe, and extinction. Using a simple model in which molecules are classified as master, lethal and non-lethal mutants, it is possible to obtain the mutation rates of the transitions between the three regimes analytically. The numerical resolution of the extended model, in which molecules are classified depending on their Hamming distance to the master sequence, confirms the results obtained in the simple model and shows how an error catastrophe regime changes when lethality is taken in account. (c) 2009 Elsevier Ltd. All rights reserved.

  1. Impact of Hymenoptera venom allergy and the effects of specific venom immunotherapy on mast cell metabolites in sensitized children

    Directory of Open Access Journals (Sweden)

    Ewa Cichocka-Jarosz

    2014-06-01

    Full Text Available introduction and objective. Mast cells (MC are effector cells during severe systemic reactions (SR to Hymenoptera stings. Venom specific immunotherapy (VIT is the treatment of choice for prevention of SR to stings. Tryptase and prostaglandin D[sub]2[/sub] metabolites (PGD[sub]2[/sub] are the markers of MC activation. The study design was to 1. compare baseline values of serum tryptase concentration (BST and PGD[sub]2[/sub] metabolites in children with/without venom sensitization, 2. to evaluate an influence of rush VIT on MC markers in treated children. materials and methods. Sensitized group: 25 children with SR to Hymenoptera sting. Control group: 19 healthy children. Active treatment: 5-day-rush-VIT. BST was evaluated by ImmunoCAP, PGD[sub]2[/sub] metabolites in blood and urine by GC-NICI-MS. results. The baseline blood levels of MC markers were significantly higher, while urinary concentration of 9α,11β-PGF2 was significantly lower in the whole group of venom-sensitized children compared to controls. Severity of SR showed negative correlation with urinary PGD[sub]2[/sub] metabolites, while positive with plasma 9α,11β-PGF2 and BST concentration The highest sensitivity was obtained for plasma 9α,11β-PGF2 whereas the highest specificity for urinary PGD-M. conclusions. In children with IgE-mediated SR to Hymenoptera stings, elevation of baseline values of PGD2 metabolites in blood is accompanied by decreased excretion of its urinary metabolites. Assessment of stable PGD[sub]2 [/sub] metabolites might serve as an independent MC marker to identify allergic children. There is an association between urinary PGD[sub]2[/sub] metabolites and severity of the SR to Hymenoptera stings.

  2. Proteomic and functional analyses of the venom of Porthidium lansbergii lansbergii (Lansberg's hognose viper) from the Atlantic Department of Colombia.

    Science.gov (United States)

    Jiménez-Charris, Eliécer; Montealegre-Sanchez, Leonel; Solano-Redondo, Luis; Mora-Obando, Diana; Camacho, Erika; Castro-Herrera, Fernando; Fierro-Pérez, Leonardo; Lomonte, Bruno

    2015-01-30

    The venom of the Lansberg's hognose pitviper, Porthidium lansbergii lansbergii, a species found in the northern region of Colombia, is poorly known. Aiming to increase knowledge on Porthidium species venoms, its proteomic analysis and functional evaluation of in vitro and in vivo activities relevant to its toxicity were undertaken. Out of 51 protein components resolved by a combination of RP-HPLC and SDS-PAGE, 47 were assigned to 12 known protein families. In similarity with two previously characterized venoms from species within this genus, Porthidium nasutum and Porthidium ophryomegas, that of P. lansbergii lansbergii was dominated by metalloproteinases, although in lower proportion. A common feature of the three Porthidium venoms appears to be a high content of disintegrins. Proteins not previously observed in Porthidium venoms belong to the vascular endothelium growth factor, phosphodiesterase, and phospholipase B families. P. lansbergii lansbergii venom showed relatively weak lethal activity to mice, and induced a moderate local myotoxicity, but considerable hemorrhage. Its isolated VEGF component showed potent edema-inducing activity in the mouse footpad assay. Significant thrombocytopenia, but no other major hematological changes, were observed in envenomed mice. In vitro, this venom lacked coagulant effect on human plasma, and induced a potent inhibition of platelet aggregation which was reproduced by its purified disintegrin components. Phospholipase A2 and proteolytic activities were also demonstrated. Overall, the compositional and functional data herein described for the venom of P. lansbergii lansbergii may contribute to a better understanding of envenomings by this pitviper species, for which specific clinical information is lacking. Porthidium lansbergii lansbergii is estimated to be responsible for nearly 20% of snakebite envenoming cases at the Atlantic Department of Colombia, but the identity and functional properties of its venom components are

  3. Lethal and sub-lethal chronic effects of the herbicide diuron on seagrass.

    Science.gov (United States)

    Negri, Andrew P; Flores, Florita; Mercurio, Phil; Mueller, Jochen F; Collier, Catherine J

    2015-08-01

    Photosystem II herbicides from agricultural sources have been detected throughout nearshore tropical habitats including seagrass meadows. While PSII herbicides have been shown to inhibit growth in microalgae at low concentrations, the potential impacts of chronic low concentration exposures to seagrass health and growth have not been investigated. Here we exposed two tropical seagrass species Halodule uninervis and Zostera muelleri to elevated diuron concentrations (from 0.3 to 7.2μgl(-1)) over a 79-day period followed by a 2-week recovery period in uncontaminated seawater. PAM fluorometry demonstrated rapid effect of diuron on photosystem II (PSII) in both seagrass species at 0.3μgl(-1). This effect included significant inhibition of photosynthetic efficiency (ΔF/Fm') and inactivation of PSII (Fv/Fm) over the 11 week exposure period. Significant mortality and reductions in growth was only observed at the highest exposure concentration of 7.2μgl(-1) diuron. However, biochemical indicators demonstrated that the health of seagrass after this prolonged exposure was significantly compromised at lower concentrations. For example, the drop in C:N ratios (0.6μgl(-1)) and reduced δ(13)C (1.7μgl(-1)) in seagrass leaves indicated reduced C-assimilation from photosynthesis. Critically, the energetic reserves of the plants (as measured by starch content in the root-rhizome complex) were approximately halved following diuron exposure at and above 1.7μgl(-1). During the 2-week recovery period, the photosynthetic capacity of the seagrass improved with only plants from the highest diuron treatment still exhibiting chronic damage to PSII. This study shows that, although seagrass may survive prolonged herbicide exposures, concentrations ≥0.6μgl(-1) diuron equivalents cause measureable impacts on energetic status that may leave the plants vulnerable to other simultaneous stressors. For example, tropical seagrasses have been heavily impacted by reduced light from coastal

  4. Venom Evolution

    Indian Academy of Sciences (India)

    IAS Admin

    Therefore, the platypus sequence was studied to quantify the role of gene duplication in the evolution of venom. ... Platypus venom is present only in males and is used for asserting dominance over com- petitors during the ... Certain toxin gene families are known to re- peatedly evolve through gene duplications. The rapidly ...

  5. Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.

    Science.gov (United States)

    Gowtham, Yashonandana J; Kumar, M S; Girish, K S; Kemparaju, K

    2012-06-01

    Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation.

  6. Lethal and sub-lethal chronic effects of the herbicide diuron on seagrass

    Energy Technology Data Exchange (ETDEWEB)

    Negri, Andrew P., E-mail: a.negri@aims.gov.au [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); Flores, Florita [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); Mercurio, Phil [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); University of Queensland and National Research Centre for Environmental Toxicology, Coopers Plains, Queensland 4108 (Australia); Mueller, Jochen F. [University of Queensland and National Research Centre for Environmental Toxicology, Coopers Plains, Queensland 4108 (Australia); Collier, Catherine J. [Centre for Tropical Water & Aquatic Ecosystem Research (TropWATER), James Cook University, Cairns, Queensland 4870 (Australia)

    2015-08-15

    Highlights: • We performed chronic exposures of two seagrass species to the herbicide diuron. • Diuron affected photosystem II (PSII) at 0.3 μg l{sup −1} and growth at 7.2 μg l{sup −1}. • Biomarkers indicated that carbon-assimilation from photosynthesis dropped following 0.6 μg l{sup −1} diuron exposure. • Energetic reserves in the seagrass were halved at 1.7 μg l{sup −1} after 11 weeks. • Chronic exposure to diuron is likely to enhance the impacts of low light stress during flood plumes - Abstract: Photosystem II herbicides from agricultural sources have been detected throughout nearshore tropical habitats including seagrass meadows. While PSII herbicides have been shown to inhibit growth in microalgae at low concentrations, the potential impacts of chronic low concentration exposures to seagrass health and growth have not been investigated. Here we exposed two tropical seagrass species Halodule uninervis and Zostera muelleri to elevated diuron concentrations (from 0.3 to 7.2 μg l{sup −1}) over a 79-day period followed by a 2-week recovery period in uncontaminated seawater. PAM fluorometry demonstrated rapid effect of diuron on photosystem II (PSII) in both seagrass species at 0.3 μg l{sup −1}. This effect included significant inhibition of photosynthetic efficiency (ΔF/F{sub m}′) and inactivation of PSII (F{sub v}/F{sub m}) over the 11 week exposure period. Significant mortality and reductions in growth was only observed at the highest exposure concentration of 7.2 μg l{sup −1} diuron. However, biochemical indicators demonstrated that the health of seagrass after this prolonged exposure was significantly compromised at lower concentrations. For example, the drop in C:N ratios (0.6 μg l{sup −1}) and reduced δ{sup 13}C (1.7 μg l{sup −1}) in seagrass leaves indicated reduced C-assimilation from photosynthesis. Critically, the energetic reserves of the plants (as measured by starch content in the root-rhizome complex) were

  7. Lethal and sub-lethal chronic effects of the herbicide diuron on seagrass

    International Nuclear Information System (INIS)

    Negri, Andrew P.; Flores, Florita; Mercurio, Phil; Mueller, Jochen F.; Collier, Catherine J.

    2015-01-01

    Highlights: • We performed chronic exposures of two seagrass species to the herbicide diuron. • Diuron affected photosystem II (PSII) at 0.3 μg l −1 and growth at 7.2 μg l −1 . • Biomarkers indicated that carbon-assimilation from photosynthesis dropped following 0.6 μg l −1 diuron exposure. • Energetic reserves in the seagrass were halved at 1.7 μg l −1 after 11 weeks. • Chronic exposure to diuron is likely to enhance the impacts of low light stress during flood plumes - Abstract: Photosystem II herbicides from agricultural sources have been detected throughout nearshore tropical habitats including seagrass meadows. While PSII herbicides have been shown to inhibit growth in microalgae at low concentrations, the potential impacts of chronic low concentration exposures to seagrass health and growth have not been investigated. Here we exposed two tropical seagrass species Halodule uninervis and Zostera muelleri to elevated diuron concentrations (from 0.3 to 7.2 μg l −1 ) over a 79-day period followed by a 2-week recovery period in uncontaminated seawater. PAM fluorometry demonstrated rapid effect of diuron on photosystem II (PSII) in both seagrass species at 0.3 μg l −1 . This effect included significant inhibition of photosynthetic efficiency (ΔF/F m ′) and inactivation of PSII (F v /F m ) over the 11 week exposure period. Significant mortality and reductions in growth was only observed at the highest exposure concentration of 7.2 μg l −1 diuron. However, biochemical indicators demonstrated that the health of seagrass after this prolonged exposure was significantly compromised at lower concentrations. For example, the drop in C:N ratios (0.6 μg l −1 ) and reduced δ 13 C (1.7 μg l −1 ) in seagrass leaves indicated reduced C-assimilation from photosynthesis. Critically, the energetic reserves of the plants (as measured by starch content in the root-rhizome complex) were approximately halved following diuron exposure at and above

  8. Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida

    NARCIS (Netherlands)

    Rico, Andreu; Sabater, Consuelo; Castillo, María Ángeles

    2016-01-01

    The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure

  9. The Effects of Posture, Body Armor and Other Equipment on Rifleman Lethality

    National Research Council Canada - National Science Library

    Kramlich, Gary R., II

    2005-01-01

    ...? This study quantifies the effects of Soldier equipment on lethality through multi-factor logistic regression using data from range experiments with the 1st Brigade, 1st Infantry Division (Mechanized...

  10. The protective effects of Mucuna pruriens seed extract against histopathological changes induced by Malayan cobra (Naja sputatrix) venom in rats.

    Science.gov (United States)

    Fung, S Y; Tan, N H; Liew, S H; Sim, S M; Aguiyi, J C

    2009-04-01

    Seed of Mucuna pruriens (Velvet beans) has been prescribed by traditional medicine practitioners in Nigeria as a prophylactic oral antisnake remedy. In the present studies, we investigated the protective effects of M. pruriens seed extract (MPE) against histopathological changes induced by intravenous injection of Naja sputatrix (Malayan cobra) venom in rats pretreated with the seed extract. Examination by light microscope revealed that the venom induced histopathological changes in heart and blood vessels in liver, but no effect on brain, lung, kidney and spleen. The induced changes were prevented by pretreatment of the rats with MPE. Our results suggest that MPE pretreatment protects rat heart and liver blood vessels against cobra venom-induced damages.

  11. Inhibitory effects of bee venom and its components against viruses in vitro and in vivo.

    Science.gov (United States)

    Uddin, Md Bashir; Lee, Byeong-Hoon; Nikapitiya, Chamilani; Kim, Jae-Hoon; Kim, Tae-Hwan; Lee, Hyun-Cheol; Kim, Choul Goo; Lee, Jong-Soo; Kim, Chul-Joong

    2016-12-01

    Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A 2 (PLA 2 ), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3). Such antiviral properties were mainly explained by virucidal mechanism. Moreover, MLT protected mice which were challenged with lethal doses of pathogenic influenza A H1N1 viruses. Therefore, these results provides the evidence that BV and MLT could be a potential source as a promising antiviral agent, especially to develop as a broad spectrum antiviral agent.

  12. Coagulating Colubrids: Evolutionary, Pathophysiological and Biodiscovery Implications of Venom Variations between Boomslang (Dispholidus typus) and Twig Snake (Thelotornis mossambicanus).

    Science.gov (United States)

    Debono, Jordan; Dobson, James; Casewell, Nicholas R; Romilio, Anthony; Li, Bin; Kurniawan, Nyoman; Mardon, Karine; Weisbecker, Vera; Nouwens, Amanda; Kwok, Hang Fai; Fry, Bryan G

    2017-05-19

    Venoms can deleteriously affect any physiological system reachable by the bloodstream, including directly interfering with the coagulation cascade. Such coagulopathic toxins may be anticoagulants or procoagulants. Snake venoms are unique in their use of procoagulant toxins for predatory purposes. The boomslang ( Dispholidus typus ) and the twig snakes ( Thelotornis species) are iconic African snakes belonging to the family Colubridae. Both species produce strikingly similar lethal procoagulant pathologies. Despite these similarities, antivenom is only produced for treating bites by D. typus , and the mechanisms of action of both venoms have been understudied. In this study, we investigated the venom of D. typus and T. mossambicanus utilising a range of proteomic and bioactivity approaches, including determining the procoagulant properties of both venoms in relation to the human coagulation pathways. In doing so, we developed a novel procoagulant assay, utilising a Stago STA-R Max analyser, to accurately detect real time clotting in plasma at varying concentrations of venom. This approach was used to assess the clotting capabilities of the two venoms both with and without calcium and phospholipid co-factors. We found that T. mossambicanus produced a significantly stronger coagulation response compared to D. typus . Functional enzyme assays showed that T. mossambicanus also exhibited a higher metalloprotease and phospholipase activity but had a much lower serine protease activity relative to D. typus venom. The neutralising capability of the available boomslang antivenom was also investigated on both species, with it being 11.3 times more effective upon D. typus venom than T. mossambicanus . In addition to being a faster clotting venom, T. mossambicanus was revealed to be a much more complex venom composition than D. typus . This is consistent with patterns seen for other snakes with venom complexity linked to dietary complexity. Consistent with the external

  13. Coagulating Colubrids: Evolutionary, Pathophysiological and Biodiscovery Implications of Venom Variations between Boomslang (Dispholidus typus and Twig Snake (Thelotornis mossambicanus

    Directory of Open Access Journals (Sweden)

    Jordan Debono

    2017-05-01

    Full Text Available Venoms can deleteriously affect any physiological system reachable by the bloodstream, including directly interfering with the coagulation cascade. Such coagulopathic toxins may be anticoagulants or procoagulants. Snake venoms are unique in their use of procoagulant toxins for predatory purposes. The boomslang (Dispholidus typus and the twig snakes (Thelotornis species are iconic African snakes belonging to the family Colubridae. Both species produce strikingly similar lethal procoagulant pathologies. Despite these similarities, antivenom is only produced for treating bites by D. typus, and the mechanisms of action of both venoms have been understudied. In this study, we investigated the venom of D. typus and T. mossambicanus utilising a range of proteomic and bioactivity approaches, including determining the procoagulant properties of both venoms in relation to the human coagulation pathways. In doing so, we developed a novel procoagulant assay, utilising a Stago STA-R Max analyser, to accurately detect real time clotting in plasma at varying concentrations of venom. This approach was used to assess the clotting capabilities of the two venoms both with and without calcium and phospholipid co-factors. We found that T. mossambicanus produced a significantly stronger coagulation response compared to D. typus. Functional enzyme assays showed that T. mossambicanus also exhibited a higher metalloprotease and phospholipase activity but had a much lower serine protease activity relative to D. typus venom. The neutralising capability of the available boomslang antivenom was also investigated on both species, with it being 11.3 times more effective upon D. typus venom than T. mossambicanus. In addition to being a faster clotting venom, T. mossambicanus was revealed to be a much more complex venom composition than D. typus. This is consistent with patterns seen for other snakes with venom complexity linked to dietary complexity. Consistent with the

  14. Effects of Emollient Containing Bee Venom on Atopic Dermatitis: A Double-Blinded, Randomized, Base-Controlled, Multicenter Study of 136 Patients.

    Science.gov (United States)

    You, Chung Eui; Moon, Seok Hoon; Lee, Kwang Hoon; Kim, Kyu Han; Park, Chun Wook; Seo, Seong Joon; Cho, Sang Hyun

    2016-10-01

    Atopic dermatitis (AD) is a common, complex disease that follows a chronic relapsing course and significantly affects the quality of life of patients. Skin barrier dysfunction and inflammatory processes induce and aggravate this skin condition. Proper use of an emollient for hydration is a keystone of AD treatment. Bee venom is known to have anti-inflammatory effects and has been widely used in traditional medicine to treat various inflammatory disorders. To find out the beneficial effect of an emollient containing bee venom in the treatment of patients with AD. This study included 136 patients with AD who were randomized to receive either an emollient containing bee venom and silk-protein or a vehicle that was identical except for the bee venom for 4 weeks. The patients were instructed to apply the emollient twice daily on their entire body and not to use other medications, including topicals, during the course of the study. The eczema area and severity index (EASI) score, transepidermal water loss, and visual analogue scale (VAS) score of itching were evaluated at the first visit and after 2 and 4 weeks. The investigator global assessment was evaluated at 2 and 4 weeks after the application of emollient containing bee venom or vehicle. Patients applying emollient containing bee venom showed significantly lower EASI score and VAS value compared to patients applying emollient without bee venom. Emollient containing bee venom is a safe and effective option for patients with AD.

  15. Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations

    Science.gov (United States)

    Sardanyés, Josep; Simó, Carles; Martínez, Regina; Solé, Ricard V.; Elena, Santiago F.

    2014-04-01

    The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.

  16. The role of platelets in hemostasis and the effects of snake venom toxins on platelet function.

    Science.gov (United States)

    de Queiroz, Mayara Ribeiro; de Sousa, Bruna Barbosa; da Cunha Pereira, Déborah Fernanda; Mamede, Carla Cristine Neves; Matias, Mariana Santos; de Morais, Nadia Cristina Gomes; de Oliveira Costa, Júnia; de Oliveira, Fábio

    2017-07-01

    The human body has a set of physiological processes, known as hemostasis, which keeps the blood fluid and free of clots in normal vessels; in the case of vascular injury, this process induces the local formation of a hemostatic plug, preventing hemorrhage. The hemostatic system in humans presents complex physiological interactions that involve platelets, plasma proteins, endothelial and subendothelial structures. Disequilibrium in the regulatory mechanisms that control the growth and the size of the thrombus is one of the factors that favors the development of diseases related to vascular disorders such as myocardial infarction and stroke, which are among the leading causes of death in the western world. Interfering with platelet function is a strategy for the treatment of thrombotic diseases. Antiplatelet drugs are used mainly in cases related to arterial thrombosis and interfere in the formation of the platelet plug by different mechanisms. Aspirin (acetylsalicylic acid) is the oldest and most widely used antithrombotic drug. Although highly effective in most cases, aspirin has limitations compared to other drugs used in the treatment of homeostatic disorders. For this reason, research related to molecules that interfere with platelet aggregation are of great relevance. In this regard, snake venoms are known to contain a number of molecules that interfere with hemostasis, including platelet function. The mechanisms by which snake venom components inhibit or activate platelet aggregation are varied and can be used as tools for the diagnosis and the treatment of several hemostatic disorders. The aim of this review is to present the role of platelets in hemostasis and the mechanisms by which snake venom toxins interfere with platelet function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effect of Apis mellifera bee venom and gamma radiation on bone marrow cells of wistar rats treated in vivo

    International Nuclear Information System (INIS)

    Varanda, E.A.; Takahashi, C.S.; Soares, A.E.E.; Barreto, S.A.J.

    1992-01-01

    To determine whether the venom of Apis mellifera can exert a radioprotective effect, by reducing the frequency of chromosomal aberrations induced by radiation, five different experiments were performed on bone marrow cells of Wistar rats. Animals weighing about 100 g were injected intraperitoneally with different venom concentrations (1.0 or 0.5 μ1) 1 or 24 h before, or 30 min after being submitted to three or four Gy of gamma radiation, and sacrificed 24 h after the last treatment. (author)

  18. The Effect of Hemiscorpius lepturus (Scorpionida: Hemiscorpiidae Venom on Leukocytes and the Leukocyte Subgroups in Peripheral Blood of Rat

    Directory of Open Access Journals (Sweden)

    Mehri Ghafourian

    2016-01-01

    Full Text Available Background: The aim of this study was to investigate the effect of Hemiscorpius lepturus venom on leukocytes and the leukocyte subgroups in peripheral blood of rat.Methods: In this experimental study, sixty N-Mari rats were divided into three groups of 20 rats. Then the rats in each group were divided into four subgroups based on the blood sampling time that was 2, 6, 24 and 48 hours after the venom injection, respectively. The control group did not receive anything, however, the first and the second ex­perimental groups received 0.1 and 0.01mg/kg of venom, subcutaneously. In accordance with a designated four sam­pling times, the blood sampling was carried out in three groups. After RBC lysis, the leukocytes and leukocyte sub­populations were determined and counted using appropriate hematological standard methods.Results: The leukocyte and the neutrophil count at two (P<0.05, six (P<0.01 and 24 (P<0.05 hours after the venom injection showed a significant decline compared with the control group, this decrease was significant at the dose of 0.1 mg/kg until 48 hours after the venom injection (P<0.05. The lymphocyte count showed a significant decline throughout the all hours of the experiment, compared with the control group (P<0.05.Conclusion: Leukocytes are probably affected by the cytotoxicity effect of the H. lepturus venom in a dose-dependent manner. This could be a wakeup call for the medical staff to perform quick and accurate treatment in the least time possible.

  19. Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-κB.

    Science.gov (United States)

    Park, Mi Hee; Choi, Myoung Suk; Kwak, Dong Hoon; Oh, Ki-Wan; Yoon, Do Young; Han, Sang Bae; Song, Ho Sueb; Song, Min Jong; Hong, Jin Tae

    2011-06-01

    Bee venom has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of bee venom on the prostate cancer and their action mechanisms have not been reported yet. To determine the effect of bee venom and its major component, melittin on the prostate cancer cells, apoptosis is analyzed by tunnel assay and apoptotic gene expression. For xenograft studies, bee venom was administrated intraperitoneally twice per week for 4 weeks, and the tumor growth was measured and the tumor were analyzed by immunohistochemistry. To investigate whether bee venom and melittin can inactivate nuclear factor kappa B (NF-κB), we assessed NF-κB activity in vitro and in vivo. Bee venom (1-10 µg/ml) and melittin (0.5-2.5 µg/ml) inhibited cancer cell growth through induction of apoptotic cell death in LNCaP, DU145, and PC-3 human prostate cancer cells. These effects were mediated by the suppression of constitutively activated NF-κB. Bee venom and melittin decreased anti-apoptotic proteins but induced pro-apoptotic proteins. However, pan caspase inhibitor abolished bee venom and melittin-induced apoptotic cell death and NF-κB inactivation. Bee venom (3-6 mg/kg) administration to nude mice implanted with PC-3 cells resulted in inhibition of tumor growth and activity of NF-κB accompanied with apoptotic cell death. Therefore, these results indicated that bee venom and melittin could inhibit prostate cancer in in vitro and in vivo, and these effects may be related to NF-κB/caspase signal mediated induction of apoptotic cell death. Copyright © 2010 Wiley-Liss, Inc.

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

    Directory of Open Access Journals (Sweden)

    Mariana Angélica Oliveira Bitencourt

    2014-01-01

    Full Text Available 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.

  1. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

    International Nuclear Information System (INIS)

    Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya; An, Byeong Jun; Song, Ho Sueb; Han, Sang Bae; Kim, Jang Heub; Song, Min Jong; Hong, Jin Tae

    2012-01-01

    We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. -- Highlights: ► Some studies have showed that bee venom and/or melittin have anti-cancer effects. ► We found that bee venom and melittin inhibited cell growth in ovarian cancer cells. ► Bee venom and melittin induce apoptosis in SKOV3 and PA-1.

  2. Bee Venom Pharmacopuncture: An Effective Treatment for Complex Regional Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Jong-Min Kim

    2014-12-01

    Full Text Available Objectives: Treating complex regional pain syndrome (CRPS is difficult because it still does not have a recommended therapy. A 29-year-old man was diagnosed with CRPS after surgery on his 4th and 5th left toes 7 years ago. Though he had undergone diverse pain treatment, the symptoms persisted, so he visited Dunsan Korean Medicine Hospital of Daejeon University. This case report presents results on the effect of bee venom pharmacopuncture in treating patient with CRPS. Methods: Bee venom pharmacopuncture (BVP, 0.15 to 0.4 mL dosage, was administered at GB43. The treatment was applied each week for a total 14 times. The symptoms were evaluated using a numeric rating scale (NRS and the dosage of pain medicine. Results: On the first visit, he was taking an anticonvulsant, a trycyclic antidepressant, and an analgesic. On the NRS the worst pain in the toes received a score of 8. He also complained of severe pain and hypersensitivity when the 4th and the 5th toes were touched just slightly. Other complaint included dyspepsia, rash, and depression. After treatment, on the NRS, the score for toe pain was 0, and he no longer needed to take pain medication. During the 4-months follow-up period, he has remained without pain; neither have additional symptoms appeared nor adverse events occurred. Conclusion: BVP may have potential benefits for treating patients with CRPS.

  3. Mast cells and IgE in defense against venoms: Possible “good side” of allergy?

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    Stephen J. Galli

    2016-01-01

    Full Text Available Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This ‘bad side’ of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells, can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as “misdirected” type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, as well as against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance to reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice which survive an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcɛRI, and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances.

  4. Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia

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    V. Núñez

    2004-07-01

    Full Text Available We determined the neutralizing activity of 12 ethanolic extracts of plants against the edema-forming, defibrinating and coagulant effects of Bothrops asper venom in Swiss Webster mice. The material used consisted of the leaves and branches of Bixa orellana (Bixaceae, Ficus nymphaeifolia (Moraceae, Struthanthus orbicularis (Loranthaceae and Gonzalagunia panamensis (Rubiaceae; the stem barks of Brownea rosademonte (Caesalpiniaceae and Tabebuia rosea (Bignoniaceae; the whole plant of Pleopeltis percussa (Polypodiaceae and Trichomanes elegans (Hymenophyllaceae; rhizomes of Renealmia alpinia (Zingiberaceae, Heliconia curtispatha (Heliconiaceae and Dracontium croatii (Araceae, and the ripe fruit of Citrus limon (Rutaceae. After preincubation of varying amounts of each extract with either 1.0 µg venom for the edema-forming effect or 2.0 µg venom for the defibrinating effect, the mixture was injected subcutaneously (sc into the right foot pad or intravenously into the tail, respectively, to groups of four mice (18-20 g. All extracts (6.2-200 µg/mouse partially neutralized the edema-forming activity of venom in a dose-dependent manner (58-76% inhibition, with B. orellana, S. orbicularis, G. panamensis, B. rosademonte, and D. croatii showing the highest effect. Ten extracts (3.9-2000 µg/mouse also showed 100% neutralizing ability against the defibrinating effect of venom, and nine prolonged the coagulation time induced by the venom. When the extracts were administered either before or after venom injection, the neutralization of the edema-forming effect was lower than 40% for all extracts, and none of them neutralized the defibrinating effect of venom. When they were administered in situ (sc at the same site 5 min after venom injection, the neutralization of edema increased for six extracts, reaching levels up to 64% for C. limon.

  5. Ethnobotanic study of Randia aculeata (Rubiaceae in Jamapa, Veracruz, Mexico, and its anti-snake venom effects on mouse tissue

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    CA Gallardo-Casas

    2012-01-01

    Full Text Available In Mexico, medicinal plants are widely used. The use of Randia aculeata by healers against snakebites has never been scientifically tested in relation to possible effects on blood parameters and muscle tissue damage. Interviews were carried out in Jamapa, Veracuz, Mexico, with local residents to collect information about the traditional use of Randia aculeata. In this locality, seven pieces of fruit from the plant are mixed in a liter of alcohol, and then administered orally against snakebites. By using histological techniques and a murine model, we explored its cytoprotective properties against the effects of Crotalus simus and Bothrops asper venoms. Possible protections provided by the plant against tissue damage to skeletal and cardiac muscles and against the typical loss of red blood cells were analyzed. Randia aculeata caused an increase in microhematocrit and total hemoglobin, parameters that are often decremented in association with the loss of red blood cells, which is a characteristic effect of animal venom. Randia aculeata was also shown to protect against the lowering of platelet levels caused by Bothrops asper venom. Finally, Randia aculeata produced a partial inhibition of necrosis following administration of snake venom in skeletal and myocardial muscles. The present results provide solid evidence for the traditional use of Randia aculeata against snakebites, as demonstrated by protection against muscular tissue damage and the diminution of red blood cells.

  6. Mucuna pruriens Linn. seed extract pretreatment protects against cardiorespiratory and neuromuscular depressant effects of Naja sputatrix (Javan spitting cobra) venom in rats.

    Science.gov (United States)

    Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Marinello, Enrico; Guerranti, Roberto; Aguiyi, John Chinyere

    2011-04-01

    Mucuna pruriens has been used by native Nigerians as a prophylactic for snakebite. The protective effects of M. pruriens seed extract (MPE) were investigated against the pharmacological actions of N. sputatrix (Javan spitting cobra) venom in rats. The results showed that MPE-pretreatment protected against cardiorespiratory and, to a lesser extent, neuromuscular depressant effects of N. sputatrix venom. These may be explained at least in part by the neutralisation of the cobra venom toxins by anti-MPE antibodies elicited by the MPE pretreatment.

  7. Antibodies against Venom of the Snake Deinagkistrodon acutus.

    Science.gov (United States)

    Lee, Chi-Hsin; Lee, Yu-Ching; Liang, Meng-Huei; Leu, Sy-Jye; Lin, Liang-Tzung; Chiang, Jen-Ron; Yang, Yi-Yuan

    2016-01-01

    Snake venom protein from Deinagkistrodon acutus (DA protein), one of the major venomous species in Taiwan, causes hemorrhagic symptoms that can lead to death. Although horse-derived antivenin is a major treatment, relatively strong and detrimental side effects are seen occasionally. In our study, yolk immunoglobulin (IgY) was purified from eggs, and DA protein was recognized using Western blotting and an enzyme-linked immunosorbent assay (ELISA), similar to therapeutic horse antivenin. The ELISA also indicated that specific IgY antibodies were elicited after the fifth booster, plateaued, and lasted for at least 3 months. To generate monoclonal single-chain variable fragment (scFv) antibodies, we used phage display technology to construct two libraries with short or long linkers, containing 6.24 × 10(8) and 5.28 × 10(8) transformants, respectively. After four rounds of biopanning, the eluted phage titer increased, and the phage-based ELISA indicated that the specific clones were enriched. Nucleotide sequences of 30 individual clones expressing scFv were analyzed and classified into four groups that all specifically recognized the DA venom protein. Furthermore, based on mass spectrometry, the scFv-bound protein was deduced to be snake venom metalloproteinase proteins. Most importantly, both IgY and mixed scFv inhibited the lethal effect in mice injected with the minimum lethal dosage of the DA protein. We suggest that together, these antibodies could be applied to the development of diagnostic agents or treatments for snakebite envenomation in the future. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

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    Witchuda Danpaiboon

    2014-05-01

    Full Text Available Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase. N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

  9. Ophiophagus hannah venom: proteome, components bound by Naja kaouthia antivenin and neutralization by N. kaouthia neurotoxin-specific human ScFv.

    Science.gov (United States)

    Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

    2014-05-13

    Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5'-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins.

  10. Discovery of human scFvs that cross-neutralize the toxic effects of B. jararacussu and C. d. terrificus venoms.

    Science.gov (United States)

    Silva, Luciano C; Pucca, Manuela B; Pessenda, Gabriela; Campos, Lucas B; Martinez, Edson Z; Cerni, Felipe A; Barbosa, José E

    2018-01-01

    Accidents involving venomous snakes are a public health problem worldwide, causing a large number of deaths per year. In Brazil, the majority of accidents are caused by the Bothrops and Crotalus genera, which are responsible for approximately 80% of severe envenoming cases. The cross-neutralization of snake venoms by antibodies is an important issue for development of more effective treatments. Our group has previously reported the construction of human monoclonal antibody fragments towards Bothrops jararacussu and Crotalus durissus terrificus' venoms. This study aimed to select human single-chain variable fragments (scFvs) that recognize both bothropic and crotalic crude venoms following venoms neutralizing capacity in vitro and in vivo. The cross-reactivity of Cro-Bothrumabs were demonstrated by ELISA and in vitro and in vivo experiments showed that a combination of scFvs neutralizes in vitro toxic activities (e.g. indirect hemolysis and plasma-clotting) of crotalic and bothropic venoms as well as prolonged survival time of envenomed animals. Our results may contribute to the development of the first human polyvalent antivenom against Bothrops jararacussu and Crotalus durissus terrificus venoms, overcoming some undesirable effects caused by conventional serotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

    Science.gov (United States)

    Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

    2016-01-22

    Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX. Published by Elsevier Ireland Ltd.

  12. Gene expression analysis in predicting the effectiveness of insect venom immunotherapy

    NARCIS (Netherlands)

    Niedoszytko, M.; Bruinenberg, M.; de Monchy, J.; Wijmenga, C.; Platteel, M.; Jassem, E.; Oude Elberink, Joanna N.G.

    Background: Venom immunotherapy (VIT) enables longtime prevention of insect venom allergy in the majority of patients. However, in some, the risk of a resystemic reaction increases after completion of treatment. No reliable factors predicting individual lack of efficacy of VIT are currently

  13. Adjuvant effects and antiserum action potentiation by a (herbal) compound 2-hydroxy-4-methoxy benzoic acid isolated from the root extract of the Indian medicinal plant 'sarsaparilla' (Hemidesmus indicus R. Br.).

    Science.gov (United States)

    Alam, M I; Gomes, A

    1998-10-01

    The adjuvant effect and antiserum potentiation of a compound 2-hydroxy-4-methoxy benzoic acid were explored in the present investigation. This compound, isolated and purified from the Indian medicinal plant Hemidesmus indicus R. Br, possessed antisnake venom activity. Rabbits immunized with Vipera russellii venom in the presence and absence of the compound along with Freund's complete adjuvant, produced a precipitating band in immunogel diffusion and immunogel electrophoresis. The venom neutralizing capacity of this antiserum showed positive adjuvant effects as evident by the higher neutralization capacity (lethal and hemorrhage) when compared with the antiserum raised with venom alone. The pure compound potentiated the lethal action neutralization of venom by commercial equine polyvalent snake venom antiserum in experimental models. These observations raised the possibility of the use of chemical antagonists (from herbs) against snake bite, which may provide a better protection in presence of antiserum, especially in the rural parts of India.

  14. Inhibitory effect of a Brazilian marine brown alga Spatoglossum schröederi on biological activities of Lachesis muta snake venom

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    Thaisa Francielle Souza Domingos

    2012-04-01

    Full Text Available The ability of crude extracts of the brown seaweed Spatoglossum schröederi to counteract some of the biological activities of Lachesis muta snake venom was evaluated. In vitro assays showed that only the extract of S. schröederi prepared in ethyl acetate was able to inhibit the clotting of fibrinogen induced by L. muta venom. On the other hand, all extracts were able to inhibit partially the hemolysis caused by venom and those prepared in dichloromethane or ethyl acetate fully neutralized the proteolysis and hemorrhage produced by the venom. Moreover, the dichloromethane or ethyl acetate extracts inhibited the hemolysis induced by an isolated phospholipase A2 from L. muta venom, called LM-PLA2-I. In contrast, the hexane extract failed to protect mice from hemorrhage or to inhibit proteolysis and clotting. These results show that the polarity of the solvent used to prepare the extracts of S. schröederi algae influenced the potency of the inhibitory effect of the biological activities induced by L. muta venom. Thus, the seaweed S. schröederi may be a promising source of natural inhibitors of the enzymes involved in biological activities of L. muta venom.

  15. Sweet Bee Venom Pharmacopuncture May be Effective for Treating Sexual Dysfunction

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    Pavel Lee

    2014-09-01

    Full Text Available Sexual dysfunction (SD is a health problem which occurs during any phase of the sexual response cycle that keeps the individual or couple from experiencing satisfaction from the sexual activity. SD covers a wide variety of symptoms like in men, erectile dysfunction and premature or delayed ejaculation, in women, spasms of the vagina and pain with sexual intercourse, in both sexes, sexual desire and response. And pharmacopuncture, i.e. injection of subclinical doses of drugs, mostly herb medicine, in acupoints, has been adopted with successful results. This case report showed the effect of bee venom on SD. A 51-year-old male patient with SD, who had a past history of taking Western medication to treat his SD and who had previously undergone surgery on his lower back due to a herniated disc, received treatments using pharmacopuncture of sweet bee venom (SBV at Gwanwon (CV4, Hoeeum (CV1, Sinsu (BL23, and Gihaesu (BL24 for 20 days. Objectively, the patient showed improvement on most items on the International Index for Erectile Dysfunction (IIEF like 28 to 29 out of perfect score 30 for erectile function, 10 to 10 out of perfect score 10 for orgasmic function, 6 to 8 out of perfect score 10 for sexual desire, 10 to 13 out of perfect score 15 for satisfaction with intercourse, and 6 to 8 out of perfect score 10 for overall satisfaction; subjectively, his words, the tone of his voice and the look of confidence in his eyes all indicated improvement. Among the variety of effects of SBV pharmacopuncture, urogenital problems such as SD may be health problems that pharmacopuncture can treat effectively.

  16. Comparative in-vivo toxicity of venoms from South Asian hump-nosed pit vipers (Viperidae: Crotalinae: Hypnale

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    Silva Anjana

    2012-08-01

    Full Text Available Abstract Background Envenoming by south Asian hump-nosed pit vipers (Genus: Hypnale is a significant health issue in Sri Lanka and in peninsular India. Bites by these snakes frequently lead to local envenoming, coagulopathy and acute renal failure even resulting in death. Recently the genus was revised and the existence of three species viz H. hypnale, H. nepa and H. zara were recognized. There is, however, a paucity of information on the toxicity of the venoms of these species. Hence, we compared the toxic effects of the three Hypnale venoms using BALB/c mice. Findings Intraperitoneal median lethal doses (LD50 for H. hypnale, H. zara and H. nepa venoms were 1.6, 6.0 and 9.5 μg protein/g respectively. Minimum haemorrhagic doses for venoms of H. hypnale, H. zara and H. nepa were 3.4, 11.0 and 16.6 μg protein/mouse respectively. The minimum necrotic doses for the same venoms were 15.0, 55.1 and 68.2 μg protein/mouse respectively. Severe congestion and petecheal haemorrhages were observed in lungs, kidneys, liver and the alimentary tract. Histopathogical examination of kidneys revealed proximal tubular cell injury and acute tubular necrosis with intact basement membrane indicating possible direct nephrotoxicity. Hypnale venoms caused pulmonary oedema, hepatocellular degeneration and necrosis, focal neuronal degeneration in brain and extramedullary haemopoiesis in spleen. H. hypnale venom caused all above histopathological alterations at lower doses compared to the other two. Conclusion Hypnale venoms cause similar pathological changes with marked differences in the severity of the toxic effects in vivo. Therefore, differences in the severity of the clinical manifestations could possibly be seen among bite victims of the three Hypnale species.

  17. Neuroprotective effects of bee venom acupuncture therapy against rotenone-induced oxidative stress and apoptosis.

    Science.gov (United States)

    Khalil, Wagdy K B; Assaf, Naglaa; ElShebiney, Shaimaa A; Salem, Neveen A

    2015-01-01

    Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic neurodegeneration, mitochondrial impairment, and oxidative stress. Exposure of animals to rotenone induces a range of responses characteristic of PD, including reactive oxygen species production and dopaminergic cell death. Although l-dopa is the drug of choice for improving core symptoms of PD, it is associated with involuntary movements. The current study was directed to evaluate the neuroprotective effect of bee venom acupuncture therapy (BVA) against rotenone-induced oxidative stress, neuroinflammation, and apoptosis in PD mouse model. Forty male Swiss mice were divided into four groups: (1) received saline solution orally and served as normal control, (2) received rotenone (1.5 mg/kg, s.c. every other day for 6 doses), (3) received rotenone concomitantly with l-dopa (25 mg/kg, daily, p.o. for 6 days), and finally (4) received rotenone concomitantly with BVA (0.02 ml once every 3 days for two weeks). Rotenone-treated mice showed impairment in locomotor behavior and a significant reduction in brain dopamine, serotonin, norepinephrine, GSH levels, and paraoxonase activity, whereas a significant increase was observed in brain malondialdehyde, tumor necrosis factor-α, interleukin-β levels besides DNA damage, and over-expression of caspase-3, Bax, and Bcl-2 genes. Significant improvement of the aforementioned parameters was demonstrated after BVA compared to l-dopa therapy. In conclusion, bee venom normalized all the neuroinflammatory and apoptotic markers and restored brain neurochemistry after rotenone injury. Therefore, BVA is a promising neuroprotective therapy for PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Molecular basis of the mutagenic and lethal effects of ultraviolet irradiation

    International Nuclear Information System (INIS)

    Grossman, L.

    1982-01-01

    Using bacteria as a model, the molecular basis of the mutagenic and lethal effects of uv radiation is being studied. Attention is focused on the mechanism of action of uv-1 specific endonucleases in the repair of damaged DNA. The isolation and identification of similar enzymes in human cells are being conducted concurrently

  19. Sub-lethal effects of neonicitinoids on the alfalfa leafcutter bee, Megachile rotundata

    Science.gov (United States)

    Neonicotinoids are commonly used pesticides in U.S. agriculture. For many beneficial insect species, lethal effects of neonicotinoids are well-documented; however, much less is known about sublethal exposure. The alfalfa leaf cutter bee Megachile rotundata is a managed pollinator that constructs com...

  20. Studies on Bee Venom and Its Medical Uses

    Science.gov (United States)

    Ali, Mahmoud Abdu Al-Samie Mohamed

    2012-07-01

    Use of honey and other bee products in human treatments traced back thousands of years and healing properties are included in many religious texts including the Veda, Bible and Quran. Apitherapy is the use of honey bee products for medical purposes, this include bee venom, raw honey, royal jelly, pollen, propolis, and beeswax. Whereas bee venom therapy is the use of live bee stings (or injectable venom) to treat various diseases such as arthritis, rheumatoid arthritis, multiple sclerosis (MS), lupus, sciatica, low back pain, and tennis elbow to name a few. It refers to any use of venom to assist the body in healing itself. Bee venom contains at least 18 pharmacologically active components including various enzymes, peptides and amines. Sulfur is believed to be the main element in inducing the release of cortisol from the adrenal glands and in protecting the body from infections. Contact with bee venom produces a complex cascade of reactions in the human body. The bee venom is safe for human treatments, the median lethal dose (LD50) for an adult human is 2.8 mg of venom per kg of body weight, i.e. a person weighing 60 kg has a 50% chance of surviving injections totaling 168 mg of bee venom. Assuming each bee injects all its venom and no stings are quickly removed at a maximum of 0.3 mg venom per sting, 560 stings could well be lethal for such a person. For a child weighing 10 kg, as little as 93.33 stings could be fatal. However, most human deaths result from one or few bee stings due to allergic reactions, heart failure or suffocation from swelling around the neck or the mouth. As compare with other human diseases, accidents and other unusual cases, the bee venom is very safe for human treatments.

  1. Protective effect of zinc against lethality of the irradiated mice

    International Nuclear Information System (INIS)

    Matsubara, J.; Inada, T.; Machida, K.

    1982-01-01

    The effects of adding 1000 ppm Zn in the drinking water 10 days before gamma irradiation (562 - 1000 rad) of mice were studied. The mice which had received zinc had a lower mortality rate and a longer survival time compared to the controls. The LD 50 of gamma radiation was 690 rad in the control group and 770 rad in the zinc group. Zinc added to the culture medium of human melanoma cells did not shown any change in radiosensitivity; thus the radioprotective effect of zinc appears to work at the whole body level. (U.K.)

  2. The effect of Walterinnesia aegyptia venom proteins on TCA cycle activity and mitochondrial NAD(+)-redox state in cultured human fibroblasts.

    Science.gov (United States)

    Ghneim, Hazem K; Al-Sheikh, Yazeed A; Aboul-Soud, Mourad A M

    2015-01-01

    Fibroblast cultures were used to study the effects of crude Walterinnesia aegyptia venom and its F1-F7 protein fractions on TCA cycle enzyme activities and mitochondrial NAD-redox state. Confluent cells were incubated with 10 μg of venom proteins for 4 hours at 37°C. The activities of all studied TCA enzymes and the non-TCA mitochondrial NADP(+)-dependent isocitrate dehydrogenase underwent significant reductions of similar magnitude (50-60% of control activity) upon incubation of cells with the crude venom and fractions F4, F5, and F7 and 60-70% for fractions F3 and F6. In addition, the crude and fractions F3-F7 venom proteins caused a drop in mitochondrial NAD(+) and NADP(+) levels equivalent to around 25% of control values. Whereas the crude and fractions F4, F5, and F7 venom proteins caused similar magnitude drops in NADH and NADPH (around 55% of control levels), fractions F3 and F6 caused a more drastic drop (60-70% of control levels) of both reduced coenzymes. Results indicate that the effects of venom proteins could be directed at the mitochondrial level and/or the rates of NAD(+) and NADP(+) biosynthesis.

  3. In vivo studies on detoxifying actions of aqueous bark extract of Prosopis cineraria against crude venom from Indian cobra (Naja naja

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    Thirunavukkarasu Sivaraman

    2013-12-01

    Full Text Available Detoxification effect of aqueous, methanol and petroleum ether extracts of medicinal plants such as Aristolochia bracteolata, Mucuna pruriens, Prosopis cineraria and Rauvolfia tetraphylla was systematically screened against lethality of crude venom of Naja naja using Swiss albino mice as animal models. We have herein demonstrated that aqueous bark extract of P. cineraria has substantial anti-venom potential vis-à-vis other extracts used in the present study. The aqueous extract at the dose of 14 mg/kg b.w. was able to almost completely neutralize the lethal activity of 3LD50 (1.12 mg/kg b.w. of the cobra venom and the extract did not cause any types of adverse side-effects to the animal models. The investigation justifies not only the veraciousness of the extract used by traditional healers of Asian subcontinent as antidotes to snake venoms and also suggests that the aqueous extract should contain specific inhibitors to most principle toxic components of the crude venom.

  4. Combined venomics, venom gland transcriptomics, bioactivities, and antivenomics of two Bothrops jararaca populations from geographic isolated regions within the Brazilian Atlantic rainforest.

    Science.gov (United States)

    Gonçalves-Machado, Larissa; Pla, Davinia; Sanz, Libia; Jorge, Roberta Jeane B; Leitão-De-Araújo, Moema; Alves, Maria Lúcia M; Alvares, Diego Janisch; De Miranda, Joari; Nowatzki, Jenifer; de Morais-Zani, Karen; Fernandes, Wilson; Tanaka-Azevedo, Anita Mitico; Fernández, Julián; Zingali, Russolina B; Gutiérrez, José María; Corrêa-Netto, Carlos; Calvete, Juan J

    2016-03-01

    Institute neutralized the lethal effect of both venoms to a similar extent. In addition, immobilized SAB antivenom immunocaptured most of the venom components of the venoms of both B. jararaca populations, but did not show immunoreactivity against vasoactive peptides. The Costa Rican bothropic-crotalic-lachesic (BCL) antivenom showed the same lack of reactivity against vasoactive peptides but, in addition, was less efficient immunocapturing PI- and PIII-SVMPs from the SE venom, and bothropstoxin-I, a CRISP molecule, and a D49-PLA2 from the venom of the southern B. jararaca phylogroup. The remarkable paraspecificity exhibited by the Brazilian and the Costa Rican antivenoms indicates large immunoreactive epitope conservation across the natural history of Bothrops, a genus that has its roots in the middle Miocene. This article is part of a Special Issue entitled: Omics Evolutionary Ecolog. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Snake antivenom for snake venom induced consumption coagulopathy

    OpenAIRE

    Maduwage, Kalana; Buckley, Nick A.; Janaka de Silva, H.; Lalloo, David; Isbister, Geoffrey K.

    2015-01-01

    Background\\ud \\ud Snake venom induced consumption coagulopathy is a major systemic effect of envenoming. Observational studies suggest that antivenom improves outcomes for venom induced consumption coagulopathy in some snakebites and not others. However, the effectiveness of snake antivenom in all cases of venom induced consumption coagulopathy is controversial.\\ud \\ud Objectives\\ud \\ud To assess the effect of snake antivenom as a treatment for venom induced consumption coagulopathy in people...

  6. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

    Directory of Open Access Journals (Sweden)

    Woojin Kim

    2016-01-01

    Full Text Available Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.. BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36 or morphine (0.5, 2, and 5 mg/kg, i.p. alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg or 5-HT3 (MDL-72222, 15 μg receptor antagonist, but not with α2-adrenergic (idazoxan, 10 μg receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.

  7. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice.

    Science.gov (United States)

    Kim, Woojin; Kim, Min Joon; Go, Donghyun; Min, Byung-Il; Na, Heung Sik; Kim, Sun Kwang

    2016-01-22

    Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2 adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.

  8. Snake venom neutralization by Indian medicinal plants (Vitex negundo and Emblica officinalis) root extracts.

    Science.gov (United States)

    Alam, M I; Gomes, A

    2003-05-01

    The methanolic root extracts of Vitex negundo Linn. and Emblica officinalis Gaertn. were explored for the first time for antisnake venom activity. The plant (V. negundo and E. officinalis) extracts significantly antagonized the Vipera russellii and Naja kaouthia venom induced lethal activity both in in vitro and in vivo studies. V. russellii venom-induced haemorrhage, coagulant, defibrinogenating and inflammatory activity was significantly neutralized by both plant extracts. No precipitating bands were observed between the plant extract and snake venom. The above observations confirmed that the plant extracts possess potent snake venom neutralizing capacity and need further investigation.

  9. An overview of Bothrops erythromelas venom

    OpenAIRE

    Nery,Neriane Monteiro; Luna,Karla Patrícia; Fernandes,Carla Freire Celedônio; Zuliani,Juliana Pavan

    2016-01-01

    Abstract This review discusses studies on the venom of Bothrops erythromelas published over the past 36 years. During this period, many contributions have been made to understand the venomous snake, its venom, and its experimental and clinical effects better. The following chronological overview is based on 29 articles that were published between 1979 and 2015, with emphasis on diverse areas. The complexity of this task demands an integration of multidisciplinary research tools to study toxin...

  10. Lethal and Sublethal Effects of Mineral Oil on Potato Pests.

    Science.gov (United States)

    Galimberti, Andrew; Alyokhin, Andrei

    2018-05-28

    Mineral oil is a product used to reduce Potato Virus Y transmission in potato fields. However, there is little information available about other effects that oil may have on insect pests of potato. To better understand how mineral oil affects potato pests, we performed a series of experiments testing the effects of oil on mortality, behavior, and development of potato aphids, Macrosiphum euphorbiae (Thomas) (Hemiptera: Aphididae), green peach aphids, Myzus persicae (Sulzer) (Hemiptera: Aphididae), and Colorado potato beetles, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae). All three species showed negative behavioral responses to oil-treated potato foliage. Oil treatment also increased aphid mortality. Colorado potato beetle mortality was not affected, but developing on oil-treated potato plants resulted in prolonged development and smaller adults. Additionally, oil acted synergistically with the entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Clavicipitaceae); Colorado potato beetle larvae were killed more rapidly when sprayed with both products compared with when sprayed with B. bassiana alone. Based on these results, mineral oil has the potential for expanded use in potato IPM programs.

  11. Inhibitory Effects of Hydroethanolic Leaf Extracts of Kalanchoe brasiliensis and Kalanchoe pinnata (Crassulaceae) against Local Effects Induced by Bothrops jararaca Snake Venom.

    Science.gov (United States)

    Fernandes, Júlia Morais; Félix-Silva, Juliana; da Cunha, Lorena Medeiros; Gomes, Jacyra Antunes Dos Santos; Siqueira, Emerson Michell da Silva; Gimenes, Luisa Possamai; Lopes, Norberto Peporine; Soares, Luiz Alberto Lira; Fernandes-Pedrosa, Matheus de Freitas; Zucolotto, Silvana Maria

    2016-01-01

    The species Kalanchoe brasiliensis and Kalanchoe pinnata, both known popularly as "Saião," are used interchangeably in traditional medicine for their antiophidic properties. Studies evaluating the anti-venom activity of these species are scarce. This study aims to characterize the chemical constituents and evaluate the inhibitory effects of hydroethanolic leaf extracts of K. brasiliensis and K. pinnata against local effects induced by Bothrops jararaca snake venom. Thin Layer Chromatography (TLC) and High Performance Liquid Chromatography coupled with Diode Array Detection and Electrospray Mass Spectrometry (HPLC-DAD-MS/MS) were performed for characterization of chemical markers of the extracts from these species. For antiophidic activity evaluation, B. jararaca venom-induced paw edema and skin hemorrhage in mice were evaluated. In both models, hydroethanolic extracts (125-500 mg/kg) were administered intraperitoneally in different protocols. Inhibition of phospholipase enzymatic activity of B. jararaca was evaluated. The HPLC-DAD-MS/MS chromatographic profile of extracts showed some particularities in the chemical profile of the two species. K. brasileinsis exhibited major peaks that have UV spectra similar to flavonoid glycosides derived from patuletin and eupafolin, while K. pinnata showed UV spectra similar to flavonoids glycosides derived from quercetin and kaempferol. Both extracts significantly reduced the hemorrhagic activity of B. jararaca venom in pre-treatment protocol, reaching about 40% of inhibition, while only K. pinnata was active in post-treatment protocol (about 30% of inhibition). In the antiedematogenic activity, only K. pinnata was active, inhibiting about 66% and 30% in pre and post-treatment protocols, respectively. Both extracts inhibited phospholipase activity; however, K. pinnata was more active. In conclusion, the results indicate the potential antiophidic activity of Kalanchoe species against local effects induced by B. jararaca snake

  12. Inhibitory Effects of Hydroethanolic Leaf Extracts of Kalanchoe brasiliensis and Kalanchoe pinnata (Crassulaceae against Local Effects Induced by Bothrops jararaca Snake Venom.

    Directory of Open Access Journals (Sweden)

    Júlia Morais Fernandes

    Full Text Available The species Kalanchoe brasiliensis and Kalanchoe pinnata, both known popularly as "Saião," are used interchangeably in traditional medicine for their antiophidic properties. Studies evaluating the anti-venom activity of these species are scarce. This study aims to characterize the chemical constituents and evaluate the inhibitory effects of hydroethanolic leaf extracts of K. brasiliensis and K. pinnata against local effects induced by Bothrops jararaca snake venom. Thin Layer Chromatography (TLC and High Performance Liquid Chromatography coupled with Diode Array Detection and Electrospray Mass Spectrometry (HPLC-DAD-MS/MS were performed for characterization of chemical markers of the extracts from these species. For antiophidic activity evaluation, B. jararaca venom-induced paw edema and skin hemorrhage in mice were evaluated. In both models, hydroethanolic extracts (125-500 mg/kg were administered intraperitoneally in different protocols. Inhibition of phospholipase enzymatic activity of B. jararaca was evaluated. The HPLC-DAD-MS/MS chromatographic profile of extracts showed some particularities in the chemical profile of the two species. K. brasileinsis exhibited major peaks that have UV spectra similar to flavonoid glycosides derived from patuletin and eupafolin, while K. pinnata showed UV spectra similar to flavonoids glycosides derived from quercetin and kaempferol. Both extracts significantly reduced the hemorrhagic activity of B. jararaca venom in pre-treatment protocol, reaching about 40% of inhibition, while only K. pinnata was active in post-treatment protocol (about 30% of inhibition. In the antiedematogenic activity, only K. pinnata was active, inhibiting about 66% and 30% in pre and post-treatment protocols, respectively. Both extracts inhibited phospholipase activity; however, K. pinnata was more active. In conclusion, the results indicate the potential antiophidic activity of Kalanchoe species against local effects induced by B

  13. Potentially lethal effects of astrophysical high energy explosive events

    International Nuclear Information System (INIS)

    Zarauza, Dario; Martin, Osmel; Rolando Cardenas

    2007-01-01

    In this work we compare the biological extinction risks posed by different types of high energy explosive events, if they occur at distances close enough to inhabited planets. These events are several kinds of supernovae and gamma ray bursts. We mainly consider the ozone depletion, leaving other effects, as photon retransmission and muon showers, for future work. In order to estimate the damage on ozonosphere, we use a simple analytical model for ozone depletion. We also mention some hints to look for the signatures of these events on Earth biogeochemical record, and evaluate the possibility of applying these results to the astrobiologically interesting sample of stars gathered by Porto de Mello, del Peloso and Ghezzi. (Author)

  14. Mastocytosis and insect venom allergy.

    Science.gov (United States)

    Bonadonna, Patrizia; Zanotti, Roberta; Müller, Ulrich

    2010-08-01

    To analyse the association of systemic allergic hymenoptera sting reactions with mastocytosis and elevated baseline serum tryptase and to discuss diagnosis and treatment in patients with both diseases. In recent large studies on patients with mastocytosis a much higher incidence of severe anaphylaxis following hymenoptera stings than in the normal population was documented. In patients with hymenoptera venom allergy, elevated baseline tryptase is strongly associated with severe anaphylaxis. Fatal sting reactions were reported in patients with mastocytosis, notably after stopping venom immunotherapy. During venom immunotherapy most patients with mastocytosis are protected from further sting reactions. Based on these observations immunotherapy for life is recommended for patients with mastocytosis and venom allergy. The incidence of allergic side-effects is increased in patients with mastocytosis and elevated baseline tryptase, especially in those allergic to Vespula venom. Premedication with antihistamines, or omalizumab in cases with recurrent severe side-effects, can be helpful. In all patients with anaphylaxis following hymenoptera stings, baseline serum tryptase should be determined. A value above 11.4 microg/l is often due to mastocytosis and indicates a high risk of very severe anaphylaxis following re-stings. Venom immunotherapy is safe and effective in this situation.

  15. Evaluating the lethal and pre-lethal effects of a range of fungi against adult Anopheles stephensi mosquitoes

    Directory of Open Access Journals (Sweden)

    Blanford Simon

    2012-11-01

    Full Text Available Abstract Background Insecticide resistance is seriously undermining efforts to eliminate malaria. In response, research on alternatives to the use of chemical insecticides against adult mosquito vectors has been increasing. Fungal entomopathogens formulated as biopesticides have received much attention and have shown considerable potential. This research has necessarily focused on relatively few fungal isolates in order to ‘prove concept’. Further, most attention has been paid to examining fungal virulence (lethality and not the other properties of fungal infection that might also contribute to reducing transmission potential. Here, a range of fungal isolates were screened to examine variation in virulence and how this relates to additional pre-lethal reductions in feeding propensity. Methods The Asian malaria vector, Anopheles stephensi was exposed to 17 different isolates of entomopathogenic fungi belonging to species of Beauveria bassiana, Metarhizium anisopliae, Metarhizium acridum and Isaria farinosus. Each isolate was applied to a test substrate at a standard dose rate of 1×109 spores ml-1 and the mosquitoes exposed for six hours. Subsequently the insects were removed to mesh cages where survival was monitored over the next 14 days. During this incubation period the mosquitoes’ propensity to feed was assayed for each isolate by offering a feeding stimulant at the side of the cage and recording the number probing. Results and conclusions Fungal isolates showed a range of virulence to A. stephensi with some causing >80% mortality within 7 days, while others caused little increase in mortality relative to controls over the study period. Similarly, some isolates had a large impact on feeding propensity, causing >50% pre-lethal reductions in feeding rate, whereas other isolates had very little impact. There was clear correlation between fungal virulence and feeding reduction with virulence explaining nearly 70% of the variation in

  16. Combined Cytogenotoxic Effects of Bee Venom and Bleomycin on Rat Lymphocytes: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Yasmina M. Abd-Elhakim

    2014-01-01

    Full Text Available This study was carried out to determine the cytotoxic and genotoxic effects of bee venom (BV and/or the chemotherapeutic agent bleomycin (BLM on healthy isolated rat lymphocytes utilizing morphometric and molecular techniques. Using the Ficoll-Histopaque density gradient centrifugation technique, lymphocytes were isolated, divided into groups, and subjected to BV and/or BLM at incubation medium concentrations of 10 or 20 μg/mL respectively for 24 and 72 hrs. An MTT assay and fluorescent microscopy examinations were used to assess the cytotoxic effects. To determine the predominant type of BV and/or BLM-induced cell death, LDH release assay was employed beside quantitative expression analyses of the apoptosis-related genes (Caspase-3 and Bcl-2. The genotoxic effects of the tested compounds were evaluated via DNA fragmentation assay. The results of these assays demonstrated that BV potentiates BLM-induced cytotoxicity through increased LDH release and diminished cell viability. Nevertheless, BV significantly inhibited the BLM-induced DNA damage. The results verify that BV significantly attenuates the genotoxic effects of BLM on noncancerous isolated rat lymphocytes but does not diminish BLM cytotoxicity.

  17. Varespladib (LY315920 Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation

    Directory of Open Access Journals (Sweden)

    Matthew Lewin

    2016-08-01

    Full Text Available Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2 activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2 inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite.

  18. Snakebites and ethnobotany in the northwest region of Colombia. Part III: neutralization of the haemorrhagic effect of Bothrops atrox venom.

    Science.gov (United States)

    Otero, R; Núñez, V; Barona, J; Fonnegra, R; Jiménez, S L; Osorio, R G; Saldarriaga, M; Díaz, A

    2000-11-01

    Thirty-one of 75 extracts of plants used by traditional healers for snakebites, had moderate or high neutralizing ability against the haemorrhagic effect of Bothrops atrox venom from Antioquia and Chocó, north-western Colombia. After preincubation of several doses of every extract (7.8-4000 microg/mouse) with six minimum haemorrhagic doses (10 microg) of venom, 12 of them demonstrated 100% neutralizing capacity when the mixture was i.d. injected into mice (18-20 g). These were the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); the whole plants of Pleopeltis percussa (Polypodiaceae), Trichomanes elegans (Hymenophyllaceae) and Senna dariensis (Caesalpiniaceae); rhizomes of Heliconia curtispatha (Heliconiaceae); leaves and branches of Bixa orellana (Bixaceae), Philodendron tripartitum (Araceae), Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae); the ripe fruits of Citrus limon (Rutaceae); leaves, branches and stem of Ficus nymphaeifolia (Moraceae). Extracts of another 19 species showed moderate neutralization (21-72%) at doses up to 4 mg/mouse, e.g. the whole plants of Aristolochia grandiflora (Aristolochiaceae), Columnea kalbreyeriana (Gesneriaceae), Sida acuta (Malvaceae), Selaginella articulata (Selaginellaceae) and Pseudoelephantopus spicatus (Asteraceae); rhizomes of Renealmia alpinia (Zingiberaceae); the stem of Strychnos xinguensis (Loganiaceae); leaves, branches and stems of Hyptis capitata (Lamiaceae), Ipomoea cairica (Convolvulaceae), Neurolaena lobata (Asteraceae), Ocimum micranthum (Lamiaceae), Piper pulchrum (Piperaceae), Siparuna thecaphora (Monimiaceae), Castilla elastica (Moraceae) and Allamanda cathartica (Apocynaceae); the macerated ripe fruits of Capsicum frutescens (Solanaceae); the unripe fruits of Crescentia cujete (Bignoniaceae); leaves and branches of Piper arboreum (Piperaceae) and Passiflora quadrangularis (Passifloraceae). When the extracts were independently administered

  19. In vivo pharmacological study on the effectiveness of available polyclonal antivenom against Hemiscorpius lepturus venom

    Directory of Open Access Journals (Sweden)

    A Jalali

    2011-01-01

    Full Text Available The available Razi Institute antivenom is still, empirically, used by intramuscular (IM administration for the treatment of scorpion stings in humans by six medically dangerous species including Hemiscorpius lepturus (H. lepturus. The aim of this study was to assess the neutralizing ability and effectiveness of the antivenom in inhibiting hemoglobinuria, biochemical changes, increased microalbuminuria and urinary lactate dehydrogenase (LDH following H. lepturus sting. Simultaneous intramuscular administration of 10 μL and 100 μL of antivenom, after 24 hours, had no significant preventive effect on the extent and degree of hemoglobinuria or proteinuria produced in venom-treated rats. After IM administration of antivenom, no significant changes in decreased red blood cell (RBC count and hemoglobin were observed. Immediate intramuscular administration of 10 μL of antivenom had no significant effects on both LDH and microalbuminuria. The present findings did not present correlation with clinical signs. Therefore, to fully assess the efficacy of the available antivenom and make appropriate recommendations, more in vivo or in vitro investigations including antigen-antibody interaction, enzymatic analysis and route-dependent administration are required.

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

    Science.gov (United States)

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

    2017-03-21

    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.

  1. Radioprotection: mechanism and radioprotective agents including honeybee venom

    Energy Technology Data Exchange (ETDEWEB)

    Varanda, E.A.; Tavares, D.C. [UNESP, Araraquara, SP (Brazil). Escola de Ciencias Farmaceuticas. Dept. de Ciencias Biologicas

    1998-07-01

    Since 1949, a great deal of research has been carried on the radioprotective action of chemical substances. These substances have shown to reduce mortality when administered to animals prior to exposure to a lethal dose of radiation. This fact is of considerable importance since it permits reduction of radiation-induced damage and provides prophylactic treatment for the damaging effects produced by radiotherapy. The following radioprotection mechanisms were proposed: free radical scavenger, repair by hydrogen donation to target molecules formation of mixed disulfides, delay of cellular division and induction of hypoxia in the tissues. Radioprotective agents have been divided into four major groups: the thiol compounds, other sulfur compounds, pharmacological agents (anesthetic drugs, analgesics, tranquilizers, etc.) and other radioprotective agents (WR-1065, WR-2721, vitamins C and E, glutathione, etc.). Several studies revealed the radioprotective action of Apis mellifera honeybee venom as well as that of its components mellitin and histamine. Radioprotective activity of bee venom involves mainly the stimulation of the hematopoietic system. In addition, release of histamine and reduction in oxygen tension also contribute to the radioprotective action of bee venom. (author)

  2. Radioprotection: mechanism and radioprotective agents including honeybee venom

    International Nuclear Information System (INIS)

    Varanda, E.A.; Tavares, D.C.

    1998-01-01

    Since 1949, a great deal of research has been carried on the radioprotective action of chemical substances. These substances have shown to reduce mortality when administered to animals prior to exposure to a lethal dose of radiation. This fact is of considerable importance since it permits reduction of radiation-induced damage and provides prophylactic treatment for the damaging effects produced by radiotherapy. The following radioprotection mechanisms were proposed: free radical scavenger, repair by hydrogen donation to target molecules formation of mixed disulfides, delay of cellular division and induction of hypoxia in the tissues. Radioprotective agents have been divided into four major groups: the thiol compounds, other sulfur compounds, pharmacological agents (anesthetic drugs, analgesics, tranquilizers, etc.) and other radioprotective agents (WR-1065, WR-2721, vitamins C and E, glutathione, etc.). Several studies revealed the radioprotective action of Apis mellifera honeybee venom as well as that of its components mellitin and histamine. Radioprotective activity of bee venom involves mainly the stimulation of the hematopoietic system. In addition, release of histamine and reduction in oxygen tension also contribute to the radioprotective action of bee venom. (author)

  3. An insecticidal toxin from Nephila clavata spider venom.

    Science.gov (United States)

    Jin, Lin; Fang, Mingqian; Chen, Mengrou; Zhou, Chunling; Ombati, Rose; Hakim, Md Abdul; Mo, Guoxiang; Lai, Ren; Yan, Xiuwen; Wang, Yumin; Yang, Shilong

    2017-07-01

    Spiders are the most successful insect predators given that they use their venom containing insecticidal peptides as biochemical weapons for preying. Due to the high specificity and potency of peptidic toxins, discoveries of insecticidal toxins from spider venom have provided an opportunity to obtain natural compounds for agricultural applications without affecting human health. In this study, a novel insecticidal toxin (μ-NPTX-Nc1a) was identified and characterized from the venom of Nephila clavata. Its primary sequence is GCNPDCTGIQCGWPRCPGGQNPVMDKCVSCCPFCPPKSAQG which was determined by automated Edman degradation, cDNA cloning, and MS/MS analysis. BLAST search indicated that Nc1a shows no similarity with known peptides or proteins, indicating that Nc1a belongs to a novel family of insecticidal peptide. Nc1a displayed inhibitory effects on Na V and K V channels in cockroach dorsal unpaired median neurons. The median lethal dose (LD50) of Nc1a on cockroach was 573 ng/g. Herein, a study that identifies a novel insecticidal toxin, which can be a potential candidate and/or template for the development of bioinsecticides, is presented.

  4. Effect of fibrin glue derived from snake venom on the viability of autogenous split-thickness skin graft

    Directory of Open Access Journals (Sweden)

    S.C. Rahal

    2004-01-01

    Full Text Available The aim of this study was to analyze the effect of snake venom derived from fibrin glue on the viability of split-thickness skin graft. Nine crossbreed dogs were used. Full-thickness skin segments measuring 4 x 4 cm were bilaterally excised from the proximal radial area on each dog. A split-thickness skin graft was harvestedfrom left lateral thoracic area using a freehand graft knife, and was secured to the left recipient bed using several simple interrupted sutures of 3-0 nylon (sutured graft. A split-thickness skin graft was harvested from the right lateral thoracic area using a graft knife. Fibrin glue derived from snake venom was applied to the recipient bed, and 8 equidistant simple interrupted sutures of 3-0 nylon were used to secure the skin graft (glued graft. Viable and nonviable areas were traced on a transparent sheet and measured using a Nikon Photomicroscope connected to a KS-300 image analysis system. The skin graft and recipient bed were collected from three dogs at day 7, 15, and 30 postoperative. The glued grafts had statistically higher graft viability than sutured grafts. Histological examination showed that the tissue repair process in the glued grafts was more accentuated than sutured grafts. It was possible to conclude that fibrin glue derived from snake venom increased survival of autogenous split-thickness skin graft.

  5. The role of pH in lethal effect of glucose load malignant cells

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Yarmonenko, S.P.; Laser, K.; Fomenkova, T.E.; Kozubek, S.; Korogodin, V.I.

    1985-01-01

    The lethal effect of variuos pH values on Erlich ascites tumour (EAT) calls has been investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect has been investigated by observing cell death in vitro, determining cancerogenity of EAT cells and determining their radiosensitivity. The results of all methods enabled us to conclude that the same values of pH lead to the same effect on EAT cells independently of the way by which the given pH value was reached. The lethal effect markedly increased when the value of pH was lower than 5.6. It is concluded that the basis of the mechanism of glucose load lethal effect is their ''self-acidisation''. The measurement of pH in tumours is proposed as a basic test for determining the suitability of the use of hyperglycemia in clinics and for comparison of the efficiency of various modes of treatment

  6. VenomKB, a new knowledge base for facilitating the validation of putative venom therapies.

    Science.gov (United States)

    Romano, Joseph D; Tatonetti, Nicholas P

    2015-11-24

    Animal venoms have been used for therapeutic purposes since the dawn of recorded history. Only a small fraction, however, have been tested for pharmaceutical utility. Modern computational methods enable the systematic exploration of novel therapeutic uses for venom compounds. Unfortunately, there is currently no comprehensive resource describing the clinical effects of venoms to support this computational analysis. We present VenomKB, a new publicly accessible knowledge base and website that aims to act as a repository for emerging and putative venom therapies. Presently, it consists of three database tables: (1) Manually curated records of putative venom therapies supported by scientific literature, (2) automatically parsed MEDLINE articles describing compounds that may be venom derived, and their effects on the human body, and (3) automatically retrieved records from the new Semantic Medline resource that describe the effects of venom compounds on mammalian anatomy. Data from VenomKB may be selectively retrieved in a variety of popular data formats, are open-source, and will be continually updated as venom therapies become better understood.

  7. The effects of oil sands wastewater on fish resulting from exposure to sub-lethal concentrations

    International Nuclear Information System (INIS)

    Birkholz, D.A.; Goudey, J.S.; Balch, G.C.; Nelson, L.R.; MacKinnon, M.

    1995-01-01

    Rainbow trout, Oncorhynchus mykiss, were exposed to sub-lethal concentrations of oil sands wastewater in flow through laboratory experiments as well as to artificial ponds containing sub-lethal concentrations of tailings pond water and fine tails in order to study the viability of the wet landscape remediation option. Large (200--300 g) fish were used for all the exposures in this preliminary study and the following data were collected: blood cell counts, sex hormone concentrations, sexual maturation, stress protein concentrations, PAH-metabolites in bile, condition factors, liver somatic indices, mixed function oxygenase induction, PAHs in muscle, external condition and the condition of internal organs. The data obtained from this study revealed no adverse effects upon fish during extended field exposures. Given similar exposure conditions in the release waters of a wet landscape reclamation, the data suggest that there may be no adverse effects upon fish, however, longer term studies, other indicator organisms and additional chronic tests should be conducted

  8. Estimation of the contribution of ionization and excitation to the lethal effect of ionizing radiation

    International Nuclear Information System (INIS)

    Petin, V.G.; Komarov, V.P.

    1982-01-01

    A simple theoretical model is proposed for estimating the differential contribution of ionization and excitation to the lethal effect of ionizing radiation. Numerical results were obtained on the basis of published experimental data on the ability of bacterial cells Escherichia coli to undergo photoreactivation of radiation-induced damage. It was shown that inactivation by excitation may be highly significant for UV-hypersensitive cells capable of photoreactivation; inactivation by excitation increased with the energy of ionizing radiation and the volume of irradiated suspensions. The data are in qualitative agreement with the assumption of a possible contribution of the UV-component of Cerenkov radiation to the formation of excitations responsible for the lethal effect and the phenomenon of photoreactivation after ionizing radiation. Some predictions from the model are discussed. (orig.)

  9. Preventive Effects of Bee Venom Derived Phospholipase A₂ on Oxaliplatin-Induced Neuropathic Pain in Mice.

    Science.gov (United States)

    Li, Dongxing; Kim, Woojin; Shin, Dasom; Jung, Yongjae; Bae, Hyunsu; Kim, Sun Kwang

    2016-01-19

    Oxaliplatin, a chemotherapy drug used to treat colorectal cancer, induces specific sensory neurotoxicity signs that are aggravated by cold and mechanical stimuli. Here we examined the preventive effects of Bee Venom (BV) derived phospholipase A₂ (bvPLA₂) on oxaliplatin-induced neuropathic pain in mice and its immunological mechanism. The cold and mechanical allodynia signs were evaluated by acetone and von Frey hair test on the hind paw, respectively. The most significant allodynia signs were observed at three days after an injection of oxaliplatin (6 mg/kg, i.p.) and then decreased gradually to a normal level on days 7-9. The oxaliplatin injection also induced infiltration of macrophages and upregulated levels of the pro-inflammatory cytokine interleukin (IL)-1β in the lumbar dorsal root ganglia (DRG). Daily treatment with bvPLA₂ (0.2 mg/kg, i.p.) for five consecutive days prior to the oxaliplatin injection markedly inhibited the development of cold and mechanical allodynia, and suppressed infiltration of macrophages and the increase of IL-1β level in the DRG. Such preventive effects of bvPLA₂ were completely blocked by depleting regulatory T cells (Tregs) with CD25 antibody pre-treatments. These results suggest that bvPLA₂ may prevent oxaliplatin-induced neuropathic pain by suppressing immune responses in the DRG by Tregs.

  10. Effects of Bee Venom Acupuncture on Surgically Induced Endometriosis in Rats

    Directory of Open Access Journals (Sweden)

    Yong-Hyun Lee

    2006-02-01

    Full Text Available Purpose : Bee Venom Acupuncture(BVA is known to affect inflammation and immune system. This study examined the macroscopic, hormonal and immunological effects of BVA on rats with surgically induced endometriosis. Method : Endometrial tissue was implanted in the serosal wall of the small intestine in rats. The rats were divided randomly into an experimental and control group. The experimental group was treated with BVA injection on kwanwon(CV4 three times per week, and the control group was given an oral dose of normal saline every day. 6 weeks later, the size of the ectopic uterine tissue was estimated, and the serum progesterone, estradiol and cytokine(TNF-α, IL-2, IL-4, IL-6, IL-10 concentrations were analyzed. Result : The size of the ectopic uterine implants in the experimental group was much smaller than that in the control group. The estradiol, IL-2 concentrations were significantly lower and the IL-6, IL-10 concentrations were significantly higher in the serum of the experimental group than in the control group. there was no significant difference in the concentration of the other cytokine. Conclusion : These results suggest that BVA is an effective treatment for endometriosis.

  11. Female Rats are Less Susceptible during Puberty to Lethal Effects of Percutaneous Exposure to VX

    Science.gov (United States)

    2015-12-17

    lethal dose determination for percutaneous exposure to soman and VX in guinea pigs and the effectiveness of decontamination with M291 SDK or SANDIA...di-isopropylamino) ethyl] methyl phosphonthioate) through pig , human and guinea pig skin in vitro, Toxicol. In Vitro 20 (2006) 1532–1536. [6] R... production and transepidermal water loss [TEWL]) change with age [3,14,15]. As reviewed in Ref. [28], the barrier function of the stratum corneum is

  12. Cardiopulmonary complications induced by Iranian Mesobuthus eupeus scorpion venom in anesthetized rabbits

    Directory of Open Access Journals (Sweden)

    E Zayerzadeh

    2010-01-01

    Full Text Available Scorpion envenomation is a life-threatening condition, especially in children and elderly individuals affected by respiratory and cardiovascular diseases. In this study, the toxic effects of median lethal dose (LD50 injections of Mesobuthus eupeus (Me venom on the heart and lungs of anesthetized rabbits were investigated. Six rabbits were selected and alterations in their electrocardiogram, heart rate, respiration and blood pressure before and after venom injection were recorded. Cardiac troponin T (cTnT, creatinine kinase muscle-brain fraction (CK-MB and lactate dehydrogenase (LDH were measured at 0, 1 and 3 hours after envenomation and pathology studies were carried out postmortem. All the animals showed signs and symptoms of envenomation within 40 minutes and died 3 to 3.5 hours after venom injection. Pathology studies revealed alveolar edema in 100% of the rabbits and myocardial infarction in 16%. The main histopathological changes were myocytolysis, coagulation necrosis, focal hemorrhage, thrombus formation both in myocardium and on endocardial surfaces as well as inflammatory infiltrates in the heart and hemorrhage, vascular thrombus and interstitial inflammation in the lungs. ECG monitoring of rabbits showed ST elevation, ST depression and inverted T and Q waves. In addition, although cTnT levels increased in 16% of the animals and serum LDH was also augmented, none of these changes was statistically significant. The enzyme CK-MB also did not show any change after Me venom injection. In conclusion, the results of this study showed that Me venom killed animals in less than 3.5 hours through severe pulmonary damage and it appears that the deaths could not be attributed to cardiovascular lesions. Therefore, Me venom effects on the lungs are so important that they appear to be independent of heart damage.

  13. Allergen-specific immunotherapy of Hymenoptera venom allergy

    DEFF Research Database (Denmark)

    Schiener, Maximilian; Graessel, Anke; Ollert, Markus

    2017-01-01

    Stings of hymenoptera can induce IgE-mediated hypersensitivity reactions in venom-allergic patients, ranging from local up to severe systemic reactions and even fatal anaphylaxis. Allergic patients' quality of life can be mainly improved by altering their immune response to tolerate the venoms...... by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy......, but was additionally used to create tools which enable the analysis of therapeutic venom extracts on a molecular level. Therefore, during the last decade the detailed knowledge of the allergen composition of hymenoptera venoms has substantially improved diagnosis and therapy of venom allergy. This review focuses...

  14. Allergen-specific immunotherapy of Hymenoptera venom allergy

    DEFF Research Database (Denmark)

    Schiener, Maximilian; Graessel, Anke; Ollert, Markus

    2017-01-01

    by injecting increasing venom doses over years. This venom-specific immunotherapy is highly effective and well tolerated. However, component-resolved information about the venoms has increased in the last years. This knowledge is not only able to improve diagnostics as basis for an accurate therapy...

  15. Effects of Bee Venom on Glutamate-Induced Toxicity in Neuronal and Glial Cells

    Directory of Open Access Journals (Sweden)

    Sang Min Lee

    2012-01-01

    Full Text Available Bee venom (BV, which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS. Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell viability and signal transduction in glutamate-treated neuronal and microglial cells in the presence and absence of BV. We induced glutamatergic toxicity in neuronal cells and microglial cells and found that BV protected against cell death. Furthermore, BV significantly inhibited the cellular toxicity of glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK, ERK, and p38 following exposure to glutamate. These findings suggest that treatment with BV may be helpful in reducing glutamatergic cell toxicity in neurodegenerative diseases.

  16. Effects of Bee Venom Acupuncture on the Rehabilitation and Quality of Life in Rheumatoid Arthritis Patients

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    Lee Sang-Hoon

    2002-12-01

    Full Text Available Objective: To evaluate the effects of bee venom acupuncture(BVA on the rehabilitation and quality of life in rheumatoid arthritis(RA patients Methods: Patients with RA were treated with the BVA therapy twice a week for 3 months. Tender joint counts, swollen joint counts, morning stiffness, Erythrocyte Sedimentation Rate(ESR, C-reactive protein(CRP, patient global assessment, physician global assessment, Korean health assessment questionnaire(KHAQ were estimated and analyzed before and after BVA therapy. Results: Tender joint counts, swollen joint counts, morning stiffness showed significant decrease after BVA therapy. But, as acute inflammatory reactants, ESR showed no significant difference and CRP showed significant increase after BVA therapy. Patient global assessment, physician global assessment, and KHAQ index showed significant improvement after BVA therapy. Conclusions: BVA therapy can improve rehabilitation and health-related quality of life in RA patients as well as clinical symptoms and signs. Further study is required in more population with large scale including acute inflammatory reaction of BVA therapy.

  17. Anti-fibrotic effect of natural toxin bee venom on animal model of unilateral ureteral obstruction.

    Science.gov (United States)

    An, Hyun Jin; Kim, Kyung Hyun; Lee, Woo Ram; Kim, Jung Yeon; Lee, Sun Jae; Pak, Sok Cheon; Han, Sang Mi; Park, Kwan Kyu

    2015-05-29

    Progressive renal fibrosis is the final common pathway for all kidney diseases leading to chronic renal failure. Bee venom (BV) has been widely used as a traditional medicine for various diseases. However, the precise mechanism of BV in ameliorating the renal fibrosis is not fully understood. To investigate the therapeutic effects of BV against unilateral ureteral obstruction (UUO)-induced renal fibrosis, BV was given intraperitoneally after ureteral ligation. At seven days after UUO surgery, the kidney tissues were collected for protein analysis and histologic examination. Histological observation revealed that UUO induced a considerable increase in the number of infiltrated inflammatory cells. However, BV treatment markedly reduced these reactions compared with untreated UUO mice. The expression levels of TNF-α and IL-1β were significantly reduced in BV treated mice compared with UUO mice. In addition, treatment with BV significantly inhibited TGF-β1 and fibronectin expression in UUO mice. Moreover, the expression of α-SMA was markedly withdrawn after treatment with BV. These findings suggest that BV attenuates renal fibrosis and reduces inflammatory responses by suppression of multiple growth factor-mediated pro-fibrotic genes. In conclusion, BV may be a useful therapeutic agent for the prevention of fibrosis that characterizes progression of chronic kidney disease.

  18. Anti-Fibrotic Effect of Natural Toxin Bee Venom on Animal Model of Unilateral Ureteral Obstruction

    Directory of Open Access Journals (Sweden)

    Hyun Jin An

    2015-05-01

    Full Text Available Progressive renal fibrosis is the final common pathway for all kidney diseases leading to chronic renal failure. Bee venom (BV has been widely used as a traditional medicine for various diseases. However, the precise mechanism of BV in ameliorating the renal fibrosis is not fully understood. To investigate the therapeutic effects of BV against unilateral ureteral obstruction (UUO-induced renal fibrosis, BV was given intraperitoneally after ureteral ligation. At seven days after UUO surgery, the kidney tissues were collected for protein analysis and histologic examination. Histological observation revealed that UUO induced a considerable increase in the number of infiltrated inflammatory cells. However, BV treatment markedly reduced these reactions compared with untreated UUO mice. The expression levels of TNF-α and IL-1β were significantly reduced in BV treated mice compared with UUO mice. In addition, treatment with BV significantly inhibited TGF-β1 and fibronectin expression in UUO mice. Moreover, the expression of α-SMA was markedly withdrawn after treatment with BV. These findings suggest that BV attenuates renal fibrosis and reduces inflammatory responses by suppression of multiple growth factor-mediated pro-fibrotic genes. In conclusion, BV may be a useful therapeutic agent for the prevention of fibrosis that characterizes progression of chronic kidney disease.

  19. Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae

    International Nuclear Information System (INIS)

    Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

    2012-01-01

    Highlights: ► We investigated the effects of different LET radiation in A. oryzae. ► Both γ-rays and ion beams induced base substitutions, frameshifts, deletions. ► Both γ-rays and ion beams induced genome-wide large-scale mutations in A. oryzae. ► Some differences in the types and frequencies of mutations were found. ► Our results provide new basic insights into the mutation breeding of A. oryzae. - Abstract: Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was 12 C 5+ ion beams with an LET of 121 keV/μm. The 12 C 5+ ion beams had a 3.6-times higher lethal effect than low-LET (0.2 keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. 12 C 6+ ion beams with an LET of 86 keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to 12 C 6+ ion beams increased with an increase in dose and reached 3.47 × 10 −3 at 700 Gy. In the dose range from 0 to 700 Gy, 12 C 5+ ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67 × 10 −3 ) at 400 Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between 12 C 5+ ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2 bp was generally low

  20. [Effect of bee venom injection on TrkA and TRPV1 expression in the dorsal root ganglion of rats with collagen-induced arthritis].

    Science.gov (United States)

    Xian, Pei-Feng; Chen, Ying; Yang, Lu; Liu, Guo-Tao; Peng, Peng; Wang, Sheng-Xu

    2016-06-01

    To investigate the therapeutic effect of acupoint injection of bee venom on collagen-induced arthritis (CIA) in rats and explore the mechanism of bee venom therapy in the treatment of rheumatoid arthritis. Fifteen male Wistar rats were randomly divided into bee venom treatment group (BV group), CIA model group, and control group. In the former two groups, CIA was induced by injections of collagen II+IFA (0.2 mL) via the tail vein, and in the control group, normal saline was injected instead. The rats in BV group received daily injection of 0.1 mL (3 mg/mL) bee venom for 7 consecutive days. All the rats were assessed for paw thickness and arthritis index from days 14 to 21, and the pain threshold was determined on day 21. The expressions of TRPV1 and TrkA in the dorsal root ganglion at the level of L4-6 were detected using immunohistochemistry and Western blotting, respectively. The rats in CIA model group started to show paw swelling on day 10, and by day 14, all the rats in this group showed typical signs of CIA. In BV group, the rats receiving been venom therapy for 7 days showed a significantly smaller paw thickness and a low arthritis index than those in the model group. The pain threshold was the highest in the control group and the lowest in the model group. TRPV1-positive cells and TrkA expression in the dorsal root ganglion was significantly reduced in BV group as compared with that in the model group. s Injection of bee venom can decrease expression of TRPV1 and TrkA in the dorsal root ganglion to produce anti-inflammatory and analgesic effects, suggesting the potential value of bee venom in the treatment of rheumatoid arthritis.

  1. Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-κB.

    Science.gov (United States)

    Kollipara, Pushpa Saranya; Kim, Jung Hyun; Won, Dohee; Lee, Sang Min; Sung, Ha Chang; Chang, Hyun Sok; Lee, Kang Tae; Lee, Kang Sik; Park, Mi Hee; Song, Min Jong; Song, Ho Sueb; Hong, Jin Tae

    2014-03-01

    In the present study we experimented on a multimodal therapeutic approach, such as combining chemotherapy agent (Bee venom) with cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom showed an IC(50) value of 3 μg/ml in both cell lines. The co-culture of NK-92MI cell lines with lung cancer cells also show a decrease in viability upto 50 % at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture with NSCLC cells and found that there is a further decrease in cell viability upto 70 and 75 % in A549 and NCI-H460 cell lines respectively. We further investigated the expression of various apoptotic and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various death receptor proteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNA binding activity and luciferase activity of NF-κB was also inhibited after co-culture with bee venom treated NK-92MI cell lines. The knock down of death receptors with si-RNA has reversed the decrease in cell viability and NF-κB activity after co-culture with bee venom treated NK-92MI cells. Thus this new approach can enhance the anti-cancer effect of bee venom at a much lower concentration.

  2. Venom evolution widespread in fishes: a phylogenetic road map for the bioprospecting of piscine venoms.

    Science.gov (United States)

    Smith, William Leo; Wheeler, Ward C

    2006-01-01

    Knowledge of evolutionary relationships or phylogeny allows for effective predictions about the unstudied characteristics of species. These include the presence and biological activity of an organism's venoms. To date, most venom bioprospecting has focused on snakes, resulting in six stroke and cancer treatment drugs that are nearing U.S. Food and Drug Administration review. Fishes, however, with thousands of venoms, represent an untapped resource of natural products. The first step involved in the efficient bioprospecting of these compounds is a phylogeny of venomous fishes. Here, we show the results of such an analysis and provide the first explicit suborder-level phylogeny for spiny-rayed fishes. The results, based on approximately 1.1 million aligned base pairs, suggest that, in contrast to previous estimates of 200 venomous fishes, >1,200 fishes in 12 clades should be presumed venomous. This assertion was corroborated by a detailed anatomical study examining potentially venomous structures in >100 species. The results of these studies not only alter our view of the diversity of venomous fishes, now representing >50% of venomous vertebrates, but also provide the predictive phylogeny or "road map" for the efficient search for potential pharmacological agents or physiological tools from the unexplored fish venoms.

  3. Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae.

    Science.gov (United States)

    Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

    2012-12-01

    Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was (12)C(5+) ion beams with an LET of 121keV/μm. The (12)C(5+) ion beams had a 3.6-times higher lethal effect than low-LET (0.2keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. (12)C(6+) ion beams with an LET of 86keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to (12)C(6+) ion beams increased with an increase in dose and reached 3.47×10(-3) at 700Gy. In the dose range from 0 to 700Gy, (12)C(5+) ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67×10(-3)) at 400Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between (12)C(5+) ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2bp was generally low, deletions >20bp were characteristic for (12)C(5+) ion beams. γ-rays had a tendency to generate mutants carrying a multitude of mutations in the same locus. Both forms of radiation also induced genome-wide large-scale mutations including chromosome rearrangements and large deletions. These results provide new basic insights into the mutation breeding of A. oryzae using ionizing radiation. Crown Copyright © 2012. Published

  4. Cognitive effects of electro-acupuncture and pregabalin in a trigeminal neuralgia rat model induced by cobra venom

    Directory of Open Access Journals (Sweden)

    Chen RW

    2017-08-01

    Full Text Available Ruo-Wen Chen,1,2 Hui Liu,2 Jian-Xiong An,1,2 Xiao-Yan Qian,2 Yi-De Jiang,2 Doris K Cope,3 John P Williams,3 Rui Zhang,1 Li-Na Sun1 1Department of Anesthesiology, Weifang Medical University, Weifang City, Shandong, 2Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China; 3Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The objective of this study was to investigate the effects of electro-acupuncture (EA and pregabalin on cognition impairment induced by chronic trigeminal neuralgia (TN in rats. Design: Controlled animal study. Setting: Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University. Subjects: Forty adult male Sprague Dawley rats. Methods: Rats were randomly divided into four groups. The TN model was induced by administration of cobra venom to the left infraorbital nerve. On postoperative day 14, either EA or pregabalin was administered, free behavioral activities were observed. Spatial learning and memory abilities were determined in the Morris water maze. The ultrastructural alterations of the Gasserian ganglion, medulla oblongata and hippocampus were examined by electron microscopy. The changes on long-term potentiation were investigated. Results: After treatment, the exploratory behavior increased and the grooming behavior decreased (P<0.05 for the EA group and pregabalin group compared with the cobra venom group; moreover, demyelination of neurons in Gasserian ganglion and medulla oblongata was reversed. The number of platform site crossings, the average percentages of time in the target quadrant and the field excitatory postsynaptic potential slopes increased (P<0.05 in the EA group compared to the cobra venom group. However, the pregabalin group

  5. Effect of Echinacea purpurea (Asteraceae aqueous extract on antibody response to Bothrops asper venom and immune cell response

    Directory of Open Access Journals (Sweden)

    Fernando Chaves

    2007-03-01

    Full Text Available The effect of aqueous extract of Echinacea purpurea roots on the murine antibody response to Bothrops asper snake venom in vivo was studied. Three groups were used. Group #1, baseline control, was treated with snake venom plus PBS. Group #2 was treated with snake venom plus sodium alginate as adjuvant (routine method used at Instituto Clodomiro Picado, and group #3 or experimental group, was treated with snake venom plus aqueous extract of E. purpurea root as adjuvant. In all groups, the first inoculation was done with Freund’s complete adjuvant (FCA. By the time of the second bleeding, mice in group #3 showed a remarkable increment in the level of anti-venom antibodies compared with those in groups #1 or #2. In vitro immune cell proliferation as a response to aqueous extract of E. purpurea root was studied using human lymphocytes activated with different lectins (Con A, PHA and PWM. In all cases, increase in percentage of lymphoproliferation was greater when E. purpurea root extract was used in addition to individual lectins. Rev. Biol. Trop. 55 (1: 113-119. Epub 2007 March. 31.Se estudió in vivo, el efecto del extracto acuoso de las raíces de Echinacea purpurea en la respuesta de los anticuerpos murinos al veneno de la serpiente Bothrops asper. El grupo 1 control, fue tratado con el veneno y PBS. El grupo 2 con veneno y alginato de sodio (método utilizado en el Instituto Clodomiro Picado, y el grupo 3 o experimental, con veneno y extracto acuoso de las raíces de E. purpurea. En todos los grupos, la primera inmunización fue hecha con FCA (Freund’s Complete Adjuvant. En las muestras correspondientes a la segunda sangría, los ratones del grupo 3 mostraron un marcado incremento en el nivel de anticuerpos, en comparación con los ratones de los otros grupos. También se determinó la proliferación de células inmunes in vitro, como respuesta al extracto acuoso de la raíz de E. purpurea, utilizando linfocitos humanos activados con

  6. Proteomic characterization of venom of the medically important Southeast Asian Naja sumatrana (Equatorial spitting cobra).

    Science.gov (United States)

    Yap, Michelle Khai Khun; Fung, Shin Yee; Tan, Kae Yi; Tan, Nget Hong

    2014-05-01

    The proteome of Naja sumatrana (Equatorial spitting cobra) venom was investigated by shotgun analysis and a combination of ion-exchange chromatography and reverse phase HPLC. Shotgun analysis revealed the presence of 39 proteins in the venom while the chromatographic approach identified 37 venom proteins. The results indicated that, like other Asiatic cobra venoms, N. sumatrana contains large number of three finger toxins and phospholipases A2, which together constitute 92.1% by weight of venom protein. However, only eight of the toxins can be considered as major venom toxins. These include two phospholipases A2, three neurotoxins (two long neurotoxins and a short neurotoxin) and three cardiotoxins. The eight major toxins have relative abundance of 1.6-27.2% venom proteins and together account for 89.8% (by weight) of total venom protein. Other venom proteins identified include Zn-metalloproteinase-disintegrin, Thaicobrin, CRISP, natriuretic peptide, complement depleting factors, cobra venom factors, venom nerve growth factor and cobra serum albumin. The proteome of N. sumatrana venom is similar to proteome of other Asiatic cobra venoms but differs from that of African spitting cobra venom. Our results confirm that the main toxic action of N. sumatrana venom is neurotoxic but the large amount of cardiotoxins and phospholipases A2 are likely to contribute significantly to the overall pathophysiological action of the venom. The differences in toxin distribution between N. sumatrana venom and African spitting cobra venoms suggest possible differences in the pathophysiological actions of N. sumatrana venom and the African spitting cobra venoms, and explain why antivenom raised against Asiatic cobra venom is not effective against African spitting cobra venoms. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Dominant lethal effect of gamma radiation of 60Co in Biomphalaria glabrata (SAY, 1818)

    International Nuclear Information System (INIS)

    Tallarico, Lenita de Freitas

    2003-01-01

    Germ cell mutations are used in ecotoxicological studies as biomarkers of population effects and indicators of ecological changes. Biomphalaria glabrata, a freshwater mollusk, is a good experimental model for biomonitoring studies due to its biological characteristics and the ecological importance of this invertebrate group. The dominant lethal test was established in B. glabrata for the detection of germ cell mutations. Results with chemical mutagens showed that this system is efficient, specific and sensitive in the evaluation of germ cell mutations induced by reference mutagens. In this work, the dominant lethal effects of gamma radiation of 60 Co were studied. A preliminary experiment was done to establish the dose range and to estimate the chronology of spermatogenesis in B. glabrata. This estimate is possible because of the uniformity in response to ionizing radiation between germ cells at homologous stages of spermatogenesis in widely different species. In general, pre-meiotic germ cells are less sensitive to the induction of lethal dominant mutations than post-meiotic cells. This effect can be attributed to: young gametogenic cells - mitotically active - have greater repair ability from sub-lethal DNA damage and there is a selective elimination of the damaged cells. In our system: induction of lethal dominant mutations causes an increase in the frequency of malformations and, cytotoxic effect is displayed as a reduction in the crossing rates. Total duration of spermatogenesis was estimated in approximately 36 days, with the following distribution of stages: 1 to 13 days - spermatogonia, 14 to 20 days - spermatocytes, 21 to 36 days - spermatids and spermatozoa. Based on this chronology, irradiated wild-type snails with 2,5; 10 and 20Gy and crossed with non-irradiated albino snails after 7, 17, 23, 30 and 36 days. The frequencies of malformations in the heterozygous wild-type offspring of the nonirradiated albino snails were used as indicator of germ cell

  8. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway.

    Science.gov (United States)

    Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya; An, Byeong Jun; Song, Ho Sueb; Han, Sang Bae; Kim, Jang Heub; Song, Min Jong; Hong, Jin Tae

    2012-01-01

    We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1-5 μg/ml) and melittin (0.5-2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Effect of salinity on the upper lethal temperature tolerance of early-juvenile red drum.

    Science.gov (United States)

    McDonald, Dusty; Bumguardner, Britt; Cason, Paul

    2015-10-01

    Previous work investigating the temperature tolerance of juvenile red drum ranging 18-50mm TL found evidence for positive size dependence (smaller fish less tolerant to higher temperatures) suggesting smaller size classes (temperatures. Here, we explored the upper lethal temperature tolerance (ULT) in smaller-sized red drum which ranged from 10 to 20mm TL across multiple salinities to further understand the thermal limitations of this propagated game fish. In order to investigate the combined effect of temperature and salinity on ULT, temperature trials were conducted under three levels of salinity which commonly occur along the coast of Texas (25, 35, and 45ppt). The rate of temperature increase (+0.25°C/h) was designed to mimic a natural temperature increase of a summer day in Texas. We determined that the lethal temperature at 50% (LT50) did not differ between the three salinities examined statistically; median lethal temperature for individuals exposed to 25ppt ranged from 36.4 to 37.7°C, 35ppt ranged from 36.4 to 37.7°C, and 45ppt ranged from 36.1 to 37.4°C. Further, LT50 data obtained here for early-juvenile red drum did not differ from data of a similar experiment examining 25mm TL sized fish. Published by Elsevier Ltd.

  10. Direct organogenesis of Mandevilla illustris (Vell) Woodson and effects of its aqueous extract on the enzymatic and toxic activities of Crotalus durissus terrificus snake venom.

    Science.gov (United States)

    Biondo, R; Soares, A M; Bertoni, B W; França, S C; Pereira, A M S

    2004-03-01

    In order to produce explants of Mandevilla illustris (Vell) Woodson for the "Cerrado in vitro", the Germplasm Bank of UNAERP, we carried out a micropropagation protocol using MS or MS/3 medium supplemented with different concentrations of 6-benzyladeninepurine (BA), Zeatin or 2-isopentenyladenine for nodal segment growth, and alpha-naphthaleneacetic acid, indole-3-butyric acid (IBA) or 1,4 dithiothreitol for rooting. For nodal segments, all the cytokinins tested yielded similar results. However, 2.22 micro M BA is more economical to use. MS/3 medium supplemented with 0.49 micro M IBA was the most appropriate medium for rooting, resulting in 29% rooted explants. The crude aqueous extract from the subterranean system (SS) of M. illustris was assayed for its inhibitory action on the enzymatic activity of Crotalus durissus terrificus snake venom, isolated basic phospholipase A2 (CB) and crotoxin. It totally inhibited the phospholipase activity of crude Cdt venom and CB toxin and inhibited the phospholipase activity of crotoxin by 49%. The toxic action of both the crude venom and crotoxin was partially inhibited-there was a prolonged survival time and a 40.0% decrease in lethality.

  11. Inhibitory effects of bee venom on mast cell-mediated allergic inflammatory responses.

    Science.gov (United States)

    Kang, Yun-Mi; Chung, Kyung-Sook; Kook, In-Hoon; Kook, Yoon-Bum; Bae, Hyunsu; Lee, Minho; An, Hyo-Jin

    2018-06-01

    Although bee venom (BV) is a toxin that causes bee stings to be painful, it has been widely used clinically for the treatment of certain immune‑associated diseases. BV has been used traditionally for the treatment of chronic inflammatory diseases. In this regard, the present study analyzed the effect of BV on the regulation of inflammatory mediator production by mast cells and their allergic inflammatory responses in an animal model. HMC‑1 cells were treated with BV prior to stimulation with phorbol‑12‑myristate 13‑acetate plus calcium ionophore A23187 (PMACI). The production of allergy‑associated pro‑inflammatory mediators was examined, and the underlying mechanisms were investigated. Furthermore, to investigate whether BV exhibits anti‑inflammatory effects associated with anti‑allergic effects in vivo, a compound 48/80‑induced anaphylaxis model was used. BV inhibited histamine release, mRNA expression and production of cytokines in the PMACI‑stimulated HMC‑1 cells. Furthermore, the inhibitory effects of BV on mitogen‑activated protein kinase (MAPK), MAPK kinase, signal transducer and activator of transcription 3 (STAT3) and Akt were demonstrated. The present study also investigated the ability of BV to inhibit compound 48/80‑induced systemic anaphylaxis in vivo. BV protected the mice against compound 48/80‑induced anaphylactic‑associated mortality. Furthermore, BV suppressed the mRNA expression levels of pro‑inflammatory cytokines, and suppressed the activation of MAPK and STAT3 in this model. These results provide novel insights into the possible role of BV as a modulator for mast cell‑mediated allergic inflammatory disorders.

  12. Daboia russellii and Naja kaouthia venom neutralization by lupeol acetate isolated from the root extract of Indian sarsaparilla Hemidesmus indicus R.Br.

    Science.gov (United States)

    Chatterjee, Ipshita; Chakravarty, A K; Gomes, A

    2006-06-15

    The present study reports the isolation and purification of lupeol acetate from the methanolic root extract of Indian medicinal plant Hemidesmus indicus (L.) R.Br. (family: Asclepiadaceae) which could neutralize venom induced action of Daboia russellii and Naja kaouthia on experimental animals. Lupeol acetate could significantly neutralize lethality, haemorrhage, defibrinogenation, edema, PLA(2) activity induced by Daboia russellii venom. It also neutralized Naja kaouthia venom induced lethality, cardiotoxicity, neurotoxicity and respiratory changes in experimental animals. Lupeol acetate potentiated the protection by snake venom antiserum action against Daboia russellii venom induced lethality in male albino mice. Venom induced changes in lipid peroxidation and super oxide dismutase activity was antagonized by lupeol acetate. Snake venom neutralization by lupeol acetate and its possible mechanism of action has been discussed.

  13. Antibacterial Activity and Antibiotic-Enhancing Effects of Honeybee Venom against Methicillin-Resistant Staphylococcus aureus

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    Sang Mi Han

    2016-01-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA, along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV, alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC, minimum bactericidal concentrations (MBC and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity.

  14. Effect of Tityus serrulatus venom on cytokine production and the activity of murine macrophages

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    Vera L. Petricevich

    2002-01-01

    Full Text Available The purpose of this study was to investigate the effects of Tityus serrulatus venom (TSV on murine peritoneal macrophages evaluated in terms of activation. The effects of crude TSV were analysed by detection of cytokines, oxygen intermediate metabolites (H2O2 and nitric oxide (NO in supernatants of peritoneal macrophages. Several functional bioassays were employed including an in vitro model for envenomating: cytotoxicity of TSV was assessed using the lyses percentage. Tumor necrosis factor (TNF activity was assayed by measuring its cytotoxic activity on L-929 cells, and interleukin-6 (IL-6 and interferon-γ (IFN-γ were assayed by enzyme-linked immunosorbent assay, whereas NO levels were detected by Griess colorimetric reactions in culture supernatant of macrophages incubated with TSV and subsequently exposed to either lipopolysaccharide or IFN-γ. Incubation of macrophages with TSV increased production of IL-6 and IFN-γ in a dose-dependent manner. TNF production was not detected in supernatants treated with TSV at any concentration. The increase in IL-6 secretion was not associated with concentration-dependent cytoxicity of TSV on these cells. These data suggest that the cytotoxicity does not appear to be the main cause of an increased cytokine production by these cells. Although NO is an important effector molecule in macrophage microbicidal activity, the inducing potential of the test compounds for its release was found to be very moderate, ranging from 125 to 800 mM. Interestingly, NO levels of peritoneal macrophages were increased after IFN-γ. Moreover, NO production had an apparent effect on macrophage activity. The results obtained here also shown that the TSV induces an important elevation in H2O2 release. These results combined with NO production suggest that TSV possesses significant immunomodulatory activities capable of stimulating immune functions in vitro.

  15. Pharmacological evaluation of bee venom and melittin

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    Camila G. Dantas

    Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

  16. Lethal and mutagenic effects of fast neutrons of different energy on Streptomyces griseus spores

    International Nuclear Information System (INIS)

    Podgorskaya, M.E.; Tulina, G.G.; Serdechnaya, A.I.; Matselyukh, B.P.

    1986-01-01

    A study was made of lethal and mutagenic effects of fast neutrons of different energy on spores of prototrophic and auxotrophic strains of Streptomyces griseus. Relative biological effectiveness of fast neutrons is higher than that of γ-rays and depends on beam energy. Neutrons of 22-50 MeV induce Streptomyces griseus mutations more frequently (by one order of magnitude) than neutrons of 1.4-1.6 MeV do. The obtained mutants can be used in studying Streptomyces griseus genetics

  17. Effects of sweet bee venom pharmacopuncture treatment for chemotherapy-induced peripheral neuropathy: a case series.

    Science.gov (United States)

    Park, Jae-Woo; Jeon, Ju-Hyun; Yoon, Jeungwon; Jung, Tae-Young; Kwon, Ki-Rok; Cho, Chong-Kwan; Lee, Yeon-Weol; Sagar, Stephen; Wong, Raimond; Yoo, Hwa-Seung

    2012-06-01

    This is a case series reporting safety and degree of response to 1 dose level of sweet bee venom pharmacopuncture (SBVP) or melittin as a symptom-control therapy for chemotherapy-induced peripheral neuropathy (CIPN). All treatments were conducted at the East West Cancer Center (EWCC), Dunsan Oriental Hospital, Daejeon University, Republic of Korea, an institution that uses complementary therapies for cancer patients. Five consecutive patients with CIPN were referred to the EWCC from March 20, 2010, to April 10, 2010. Patients with World Health Organization Chemotherapy-Induced Peripheral Neuropathy (WHO CIPN) grade 2 or more were treated with SBVP for 3 treatment sessions over a 1-week period. Measures of efficacy and safety. Validated Visual Analog System (VAS) pain scale, WHO CIPN grade, and Functional Assessment of Cancer Therapy-General (FACT-G) were compared before and after the 1-week course of treatment. To ensure the safety of SBVP, pretreatment skin response tests were given to patients to avoid any potential anaphylactic adverse effects. All patients were closely examined for any allergenic responses following each treatment session. One patient discontinued treatment after the first session, and 4 patients completed all treatment sessions. Using each patient as their own comparator, marked improvements of VAS, WHO CIPN grade, and physical section scores of FACT-G were seen in 3 patients. Most important, there were no related adverse side effects found. This safety results of the SBVP therapy merits further investigations in a larger size trial for it to develop into a potential intervention for managing CIPN symptoms. This study will be extended to a dose-response evaluation to further establish safety and response, prior to a randomized trial.

  18. Effect of low level Doses of fast neutrons on the toxicity of snake venom through measuring some biophysical properties of blood serum of rats

    International Nuclear Information System (INIS)

    Hanafy, M.S.; Metwali, R.

    2001-01-01

    This study was conducted to investigate the effect of low level doses of fission neutrons from Cf 252 source on sublethal doses (low medium) of snake venom cerastes cerastes by injecting albino eats with unirradiated or irradiated venom and measuring the biophysical alterations in the blood serum of the rats. The biophysical properties of the total serum proteins were studied through measuring their dielectric relaxation and the electric conductivity in the frequency range 0.1→5 MHz at 4 degree C. The absorption spectra of the extracted total serum protein were also measured. The results indicated that there are pronounced changes in the molecular constructions of the total serum protein such as the molecular radii, shape, the relaxation time and dielectric increment for the rats injected with unirradiated venom but for the rats injected with irradiated venom (3x10 8 n/cm 2 ) corresponding values approach the control value. These changes in the molecular constructions of the total serum protein indicate changes in its biochemical properties. This fact was revealed in a previous work, where the irradiation with the fast neutrons were found to decrease the toxicity of the venom

  19. Experimental Study on Anti-body effects of Anti-BV on the Bee Venom Herbal Acupuncture

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    Ki Rok Kwon

    2005-02-01

    Full Text Available Objectives : To observe physiological anti-body effects of anti-BV, acute toxic response, measurement of LD50, and the effects of anti-body were evaluated. Methods : LD50 of Anti-Bee Venom were measured, and to analyze acute toxic responses, weight, and the anti-body effects various concentrations of Anti-BV were diluted and the survival rate was measured. Cell blood count (CBC, liver, spleen, and kidney pathologies were observed from the histological aspects. Results : Experiment was conducted to observe Anti-BV as the anti-body to the bee venom and the following results were obtained: 1. Anti-BV was injected intraperitoneally and no toxic responses were witnessed. All of the experiment subjects stayed alive during the experiment, making LD50 analysis impossible. 2. Anti-BV was injected intraperitoneally in mice and no significant weight changes were measured between the control group and the experiment groups. 3. Measuring the concentration dependent survival rate, the highest survival rate was at the concentration of 1.25×102mg/kg(1/2.000 for Anti-BV. 4. No particular results were shown in the CBC test. 5. Observation of changes in the organ tissues, Anti-BV was found to suppress blood stasis in the liver and inhibit necrosis of the cells. Conclusion : Above results suggest that Anti-BV doesn't cause any toxic responses in the body and works as an anti-body to the bee venom. Further studies must be followed to secure the findings.

  20. Lethal and sublethal effects of imidacloprid on Osmia lignaria and clothianidin on Megachile rotundata (Hymenoptera: Megachilidae).

    Science.gov (United States)

    Abbott, V A; Nadeau, J L; Higo, H A; Winston, M L

    2008-06-01

    We examined lethal and sublethal effects of imidacloprid on Osmia lignaria (Cresson) and clothianidin on Megachile rotundata (F.) (Hymenoptera: Megachilidae). We also made progress toward developing reliable methodology for testing pesticides on wild bees for use in pesticide registration by using field and laboratory experiments. Bee larvae were exposed to control, low (3 or 6 ppb), intermediate (30 ppb), or high (300 ppb) doses of either imidacloprid or clothianidin in pollen. Field experiments on both bee species involved injecting the pollen provisions with the corresponding pesticide. Only O. lignaria was used for the laboratory experiments, which entailed both injecting the bee's own pollen provisions and replacing the pollen provision with a preblended pollen mixture containing imidacloprid. Larval development, emergence, weight, and mortality were monitored and analyzed. There were no lethal effects found for either imidacloprid or clothianidin on O. lignaria and M. rotundata. Minor sublethal effects were detected on larval development for O. lignaria, with greater developmental time at the intermediate (30 ppb) and high doses (300 ppb) of imidacloprid. No similar sublethal effects were found with clothianidin on M. rotundata. We were successful in creating methodology for pesticide testing on O. lignaria and M. rotundata; however, these methods can be improved upon to create a more robust test. We also identified several parameters and developmental stages for observing sublethal effects. The detection of sublethal effects demonstrates the importance of testing new pesticides on wild pollinators before registration.

  1. Comparison of the Effects between Sweet Bee Venom Pharmacopuncture and Scolopendrid Pharmacopuncture on Carpal Tunnel Syndrome (Randomized, Controlled Clinical Trial

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    Ji-young Ku

    2010-12-01

    Full Text Available Objectives : The purpose of this study is to compare the effects of Sweet Bee Venom Pharmacopuncture and Scolopendrid Pharmacopuncture on Carpal Tunnel Syndrome. Methods : From February to September 2010, the number of patients with Carpal Tunnel Syndrome who volunteered for this clinical study was 16 and 7 out of 16 patients complained both hands. Total 23 cases of hands were randomly divided by 2 groups. We injected Sweet Bee Venom Pharmacopuncture on PC7(Daereung twice a week for 4weeks for experimental group(n=11, and Scolopendrid Pharmacopuncture with the same methods for control group(n=12. One case was dropped out due to itchiness of allergic response in the experimental group. Improvement of the symptoms was evaluated by Visual Analogue Scale, Pain Rating Scale, Tinel’s sign, Phalen’s sign and Nerve Conduction Velocity. Nerve Conduction Velocity was checked at baseline and the end of the trial and others were checked at baseline, after 2 and 4 weeks. Results : Both groups showed significant improvement in Visual Analogue Scale, Pain Rating Scale, but no significant difference between two groups. Only the control group showed significant reduction of the‘ poitive response’in the Tinel’s sign and Phalen’s sign. However, no groups improved in Nerve Conduction Velocity. Conclusions : These results showed that Sweet Bee Venom Pharmacopuncture and Scolopendrid Pharmacopuncture could decrease the symptoms of Carpal Tunnel Syndrome. Further studies will be required to examine more cases for the long period and use more various concentration and amount pharmacopuncture for the effect on Carpal Tunnel Syndrome.

  2. Lethal and sublethal effects of glyphosate (roundup active) to embryos of colombian anurans

    International Nuclear Information System (INIS)

    Triana Velasquez, Teofila Maria; Montes Rojas, Claudia; Bernal Bautista, Manuel Hernando

    2013-01-01

    Glyphosate is an herbicide widely used in agriculture, which may affect non-target species. the aim of this study was to determine the lethal (median lethal concentration - LC 5 0) and sublethal effects (changes on body size and development) of glyphosate (roundup active) to embryos of four anuran species, exposed during 96 hours under laboratory and microcosm tests. under laboratory conditions, engystomops pustulosus was the most tolerant species (LC 5 0 = 3033,18 ?g a.e./L) and rhinella marina was the most sensitive (lc50 = 1421,46 ?g a.e./L), which also showed a delayed development and significantly reduced body size. The other species had an intermediate LC50 (Rhinella humboldti = 2899.54 ?g a.e./L; hypsiboas crepitans = 2151,88 ?g a.e./L). In all cases, the laboratory LC 5 0 was lower than the concentration used in field (5392.92 ?g a.e./L), indicating a high toxic effect. In the microcosm tests, embryos of e. pustulosus were the most tolerant (LC 5 0 = 19,41 kg a.e./ha), while R. humboldti were the most sensitive (LC 5 0 = 10,61 kg a.e./ha). In this case, all four study species had a higher LC 5 0 than the concentration sprayed in field (3,69 kg a.e./ ha), so a lower lethal effect, and there were no significant differences in body size and development. This result shows that the glyphosate, as the commercial presentation roundup active, produce a moderate mortality on anuran embryos.

  3. Mast Cells Can Enhance Resistance to Snake and Honeybee Venoms

    Science.gov (United States)

    Metz, Martin; Piliponsky, Adrian M.; Chen, Ching-Cheng; Lammel, Verena; Åbrink, Magnus; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

    2006-07-01

    Snake or honeybee envenomation can cause substantial morbidity and mortality, and it has been proposed that the activation of mast cells by snake or insect venoms can contribute to these effects. We show, in contrast, that mast cells can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which can degrade venom components. Mast cells also significantly reduced the morbidity and mortality induced by honeybee venom. These findings identify a new biological function for mast cells in enhancing resistance to the morbidity and mortality induced by animal venoms.

  4. Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

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    Liling Yang

    2017-10-01

    Full Text Available Background/Aims: Forsythia suspensa Vahl. (Oleaceae fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN, the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF

  5. Harvesting Venom Toxins from Assassin Bugs and Other Heteropteran Insects.

    Science.gov (United States)

    Walker, Andrew Allan; Rosenthal, Max; Undheim, Eivind E A; King, Glenn F

    2018-04-21

    Heteropteran insects such as assassin bugs (Reduviidae) and giant water bugs (Belostomatidae) descended from a common predaceous and venomous ancestor, and the majority of extant heteropterans retain this trophic strategy. Some heteropterans have transitioned to feeding on vertebrate blood (such as the kissing bugs, Triatominae; and bed bugs, Cimicidae) while others have reverted to feeding on plants (most Pentatomomorpha). However, with the exception of saliva used by kissing bugs to facilitate blood-feeding, little is known about heteropteran venoms compared to the venoms of spiders, scorpions and snakes. One obstacle to the characterization of heteropteran venom toxins is the structure and function of the venom/labial glands, which are both morphologically complex and perform multiple biological roles (defense, prey capture, and extra-oral digestion). In this article, we describe three methods we have successfully used to collect heteropteran venoms. First, we present electrostimulation as a convenient way to collect venom that is often lethal when injected into prey animals, and which obviates contamination by glandular tissue. Second, we show that gentle harassment of animals is sufficient to produce venom extrusion from the proboscis and/or venom spitting in some groups of heteropterans. Third, we describe methods to harvest venom toxins by dissection of anaesthetized animals to obtain the venom glands. This method is complementary to other methods, as it may allow harvesting of toxins from taxa in which electrostimulation and harassment are ineffective. These protocols will enable researchers to harvest toxins from heteropteran insects for structure-function characterization and possible applications in medicine and agriculture.

  6. Clinical investigation compared with the effects of the bee-venom Acupuncture on knee joint with osteoarthritis

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    Wang Wu-Hao

    2001-12-01

    Full Text Available Objective: This study is designed to find out the effects of the Bee-Venom Acupuncture on knee joint with osteoarthritis. Methods: We are investigated that outpatients suffer from knee joint pain deciphered at the division of Acupuncture in Jaseng oriental medicine hospital from the 13, July 1999 to unti111, November 2000. We make an estimated of the score from both before or after its treatment about 70 cases of diagnostic patient with the osteoarthritis of knee joints by biochemical method and X-RAY analysis, we observed in the progress of symptoms. Results: These results found that sex distinction with a disease caused much more female than male at the ratio of I to 5.36 in the proportion of males to females, jobs is mainly ranked with a housewife and approximately 82.9% of cases before our hospital have ever treated at the other clinics or hospitals. On the hand, the distribution interval of a case history is mainly followed by disease in below 6 month, interval of the period-treatment is mainly gone within 3 month and frequency of treatment is examined into II to 15 times, more than 16 times and below 10 times, respectively. We are estimated with the score of functional barrier from both before or after its treatment against osteoarthritis' patients and produced in the usefulness from the totally point of fields except the aid-device after its treatment In summary, these results demonstrated that Bee Venom, Acupuncture enhanced more than 82.9% to the improvement of treatment and p<0.05 considered to be statistically significant. Conclusion: These results suggest that Bee-venom Acupuncture may be playa role in the significant usefulness and have need of actively application for the clinical trials against osteoarthritis' patients.

  7. Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects

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    Gihyun Lee

    2016-05-01

    Full Text Available Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Bee venom is a toxin that bees use for their protection from enemies. However, for centuries it has been used in the Orient as an anti-inflammatory medicine for the treatment of chronic inflammatory diseases. Bee venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new alternatives for the control of inflammatory diseases. Recent experimental studies show that the biological functions of melittin could be applied for therapeutic use in vitro and in vivo. Reports verifying the therapeutic effects of melittin are accumulating in the literature, but the cellular mechanism(s of the anti-inflammatory effects of melittin are not fully elucidated. In the present study, we review the current knowledge on the therapeutic effects of melittin and its detailed mechanisms of action against several inflammatory diseases including skin inflammation, neuroinflammation, atherosclerosis, arthritis and liver inflammation, its adverse effects as well as future prospects regarding the use of melittin.

  8. Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects.

    Science.gov (United States)

    Lee, Gihyun; Bae, Hyunsu

    2016-05-11

    Inflammation is a pervasive phenomenon triggered by the innate and adaptive immune systems to maintain homeostasis. The phenomenon normally leads to recovery from infection and healing, but when not properly phased, inflammation may cause immune disorders. Bee venom is a toxin that bees use for their protection from enemies. However, for centuries it has been used in the Orient as an anti-inflammatory medicine for the treatment of chronic inflammatory diseases. Bee venom and its major component, melittin, are potential means of reducing excessive immune responses and provide new alternatives for the control of inflammatory diseases. Recent experimental studies show that the biological functions of melittin could be applied for therapeutic use in vitro and in vivo. Reports verifying the therapeutic effects of melittin are accumulating in the literature, but the cellular mechanism(s) of the anti-inflammatory effects of melittin are not fully elucidated. In the present study, we review the current knowledge on the therapeutic effects of melittin and its detailed mechanisms of action against several inflammatory diseases including skin inflammation, neuroinflammation, atherosclerosis, arthritis and liver inflammation, its adverse effects as well as future prospects regarding the use of melittin.

  9. Effects of bee venom acupuncture on heart rate variability, pulse wave, and cerebral blood flow for types of Sasang Constitution

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    Lee Sang-min

    2009-03-01

    Full Text Available 1. Objectives: To evaluate effects of bee venom acupuncture on cardiovascular system and differences according to each constitution. 2. Methods: Heart rate variability, pulse wave and the velocity of cerebral blood flow were measured before bee venom acupuncture(BVA, right after and after 30 minuets, had been applied to 20 subjects. 3. Results: 1. BVA did not have effects on measurement variables of heart rate variability. 2. BVA had effects on pulse wave, showing total time, radial augmentation index up and height of percussion wave, time to percussion wave, sum of pulse pressure down. 3. BVA did not have effects on the cerebral blood flow velocity when considering not Sasang Constitution 4. Considering Sasang Constitution, BVA demonstrates different responses in time to preincisura wave, mean blood flow velocity, peak systolic velocity and end diastolic velocity. 4.Conclusion: From those results, the following conclusions are obtained. Cause BVA alters pulse wave and makes differences in the cerebral blood flow velocity according to Sasang Constitution. Various methods of BVA treatment are needed considering Sasang Constitution.

  10. Biochemical characterization of the venom of the coral snake Micrurus tener and comparative biological activities in the mouse and a reptile model.

    Science.gov (United States)

    Bénard-Valle, Melisa; Carbajal-Saucedo, Alejandro; de Roodt, Adolfo; López-Vera, Estuardo; Alagón, Alejandro

    2014-01-01

    The objective of this study was to identify the venom components that could play a relevant role during envenomation caused by the coral snake Micrurus tener, through its biochemical characterization as well as the analysis of its effects on a murine model. Furthermore, it aimed to evaluate crude venom, in addition to its components, for possible specificity of action on a natural prey model (Conopsis lineata). The toxicity of the crude venom (delivered subcutaneously) showed a significant difference between the Median Lethal Dose (LD₅₀) in mice (4.4 μg/g) and in Conopsis lineata (12.1 μg/g) that was not observed when comparing the Median Paralyzing Dose (PD₅₀) values (mice = 4.7 μg/g; snakes = 4.1 μg/g). These results are evidence that the choice of study model strongly influences the apparent effects of crude venom. Moreover, based on the observed physical signs in the animal models, it was concluded that the most important physical effect caused by the venom is flaccid paralysis, which facilitates capture and subduing of prey regardless of whether it is alive; death is a logical consequence of the lack of oxygenation. Venom fractionation using a C18 reverse phase column yielded 35 fractions from which 16.6% caused paralysis and/or death to both animal models, 21.9% caused paralysis and/or death only to C. lineata and 1.6% were murine specific. Surprisingly, the diversity of snake-specific fractions did not reflect a difference between the PD₅₀s of the crude venom in mice and snakes, making it impossible to assume some type of specificity for either of the study models. Finally, the great diversity and abundance of fractions with no observable effect in snakes or mice (42.7%) suggested that the observed lethal fractions are not the only relevant toxic fractions within the venom and emphasized the possible relevance of interaction between components to generate the syndrome caused by the venom as a whole. Copyright © 2013 Elsevier Ltd. All rights

  11. Low cost venom extractor based on Arduino(®) board for electrical venom extraction from arthropods and other small animals.

    Science.gov (United States)

    Besson, Thomas; Debayle, Delphine; Diochot, Sylvie; Salinas, Miguel; Lingueglia, Eric

    2016-08-01

    Extracting venom from small species is usually challenging. We describe here an affordable and versatile electrical venom extractor based on the Arduino(®) Mega 2560 Board, which is designed to extract venom from arthropods and other small animals. The device includes fine tuning of stimulation time and voltage. It was used to collect venom without apparent deleterious effects, and characterized for the first time the venom of Zoropsis spinimana, a common spider in French Mediterranean regions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time.

    Science.gov (United States)

    Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

    2015-12-01

    Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro.

  13. Honey Bee Venom (Apis mellifera Contains Anticoagulation Factors and Increases the Blood-clotting Time

    Directory of Open Access Journals (Sweden)

    Hossein Zolfagharian

    2015-12-01

    Full Text Available Objectives: Bee venom (BV is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50, and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Blood samples were obtained from 10 rabbits, and the prothrombin time (PT and the partial thromboplastin time (PTT tests were conducted. The approximate lethal dose (LD values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa, respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2 and melittin, and that can increase the blood clotting times in vitro.

  14. Ultrastructural analysis of early toxic effects produced by bee venom phospholipase A2 and melittin in Sertoli cells in rats.

    Science.gov (United States)

    Tilinca, Mariana; Florea, Adrian

    2018-01-01

    In this study, we aimed to investigate the testicular toxicity of two molecules derived from bee venom (BV): phospholipase A2 (PlA2) and melittin (Mlt). Ultrastructural effects of purified BV PlA2 and Mlt were assessed consecutive to repeated dose (30 days) and acute toxicity studies. For the subchronic treatment, PlA2 and Mlt were injected in daily doses equivalent to those released by a bee sting (105 μg PlA2/kg/day and 350 μg Mlt/kg/day), while in the acute treatment their doses corresponded to those released by 100 bee stings (9.3 mg PlA2/kg and 31 mg Mlt/kg). Both PlA2 and Mlt affected the Leydig cells and the cells in seminiferous tubules, the Sertoli cells first of all. PlA2 injection resulted in detachment of the Sertoli cells from the surrounding cells, and extracellular vacuolations, cytoplasmic vacuolations in their basal region and in branches as well, detachment of spermatids, residual bodies and sometimes even spermatocytes into the lumen, changes that had a higher magnitude after the acute treatment. Mlt injection induced similar ultrastructural alterations, but more severe, including degeneration of cellular organelles and cellular necrosis, resulting into rarefaction of the seminiferous epithelium; the ultrastructural changes had a higher magnitude after the 30 repeated dose treatment. We concluded that either of the two molecules tested here, PlA2 and Mlt, were Sertoli cells toxicants at the used doses, and they participated both in the BV testicular toxicity. We consider the observed changes as part of a preceding mechanism of the more severe alterations produced by the BV. It also remains possible that these early unspecific changes reported here could represent the response of the SCs not only to the components of bee venom, but to molecules of other venoms as well. The Sertoli cells were the primary target of PlA2 and Mlt in the spermatogenic epithelium, and their alteration led to further degenerative changes of the germ cells. Since

  15. Hemostatic properties of Venezuelan Bothrops snake venoms with special reference to Bothrops isabelae venom.

    Science.gov (United States)

    Rodríguez-Acosta, Alexis; Sánchez, Elda E; Márquez, Adriana; Carvajal, Zoila; Salazar, Ana M; Girón, María E; Estrella, Amalid; Gil, Amparo; Guerrero, Belsy

    2010-11-01

    In Venezuela, Bothrops snakes are responsible for more than 80% of all recorded snakebites. This study focuses on the biological and hemostatic characteristics of Bothrops isabelae venom along with its comparative characteristics with two other closely related Bothrops venoms, Bothrops atrox and Bothrops colombiensis. Electrophoretic profiles of crude B. isabelae venom showed protein bands between 14 and 100 kDa with the majority in the range of 14-31 kDa. The molecular exclusion chromatographic profile of this venom contains five fractions (F1-F5). Amidolytic activity evaluation evidenced strong thrombin-like followed by kallikrein-like activities in crude venom and in fractions F1 and F2. The fibrinogenolytic activity of B. isabelae venom at a ratio of 100:1 (fibrinogen/venom) induced a degradation of A alpha and B beta chains at 15 min and 2 h, respectively. At a ratio of 100:10, a total degradation of A alpha and B beta chains at 5 min and of gamma chains at 24 h was apparent. This current study evidences one of rarely reported for Bothrops venoms, which resembles the physiologic effect of plasmin. B. isabelae venom as well as F2 and F3 fractions, contain fibrinolytic activity on fibrin plate of 36, 23.5 and 9.45 mm(2)/microg, respectively using 25 microg of protein. Crude venom and F1 fraction showed gelatinolytic activity. Comparative analysis amongst Venezuelan bothropoid venoms, evidenced that the LD(50) of B. isabelae (5.9 mg/kg) was similar to B. atrox-Puerto Ayacucho 1 (6.1 mg/kg) and B. colombiensis-Caucagua (5.8 mg/kg). B. isabelae venom showed minor hemorrhagic activity, whereas B. atrox-Parguasa (Bolivar state) was the most hemorrhagic. In this study, a relative high thrombin-like activity was observed in B. colombiensis venoms (502-568 mUA/min/mg), and a relative high factor Xa-like activity was found in B. atrox venoms (126-294 mUA/min/mg). Fibrinolytic activity evaluated with 10 microg protein, showed that B. isabelae venom contained higher

  16. [Underlying Mechanisms of Methamphetamine-Induced Self-Injurious Behavior and Lethal Effects in Mice].

    Science.gov (United States)

    Mori, Tomohisa; Sawaguchi, Toshiko

    2018-01-01

    Relatively high doses of psychostimulants induce neurotoxicity on the dopaminergic system and self-injurious behavior (SIB) in rodents. However the underlying neuronal mechanisms of SIB remains unclear. Dopamine receptor antagonists, N-methyl-D-aspartic acid (NMDA) receptor antagonists, Nitric Oxide Synthase (NOS) inhibitors and free radical scavengers significantly attenuate methamphetamine-induced SIB. These findings indicate that activation of dopamine as well as NMDA receptors followed by radical formation and oxidative stress, especially when mediated by NOS activation, is associated with methamphetamine-induced SIB. On the other hand, an increase in the incidence of polydrug abuse is a major problem worldwide. Coadministered methamphetamine and morphine induced lethality in more than 80% in mice, accompanied by an increase in the number of poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine were significantly attenuated by pretreatment with a phospholipase A2 inhibitor or a radical scavenger, or by cooling of body from 30 to 90 min after drug administration. These results suggest that free radicals play an important role in the increased lethality induced by the coadministration of methamphetamine and morphine. Therefore, free radical scavengers and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine. These findings may help us better understand for masochistic behavior, which is a clinical phenomenon on SIB, as well as polydrug-abuse-induced acute toxicity.

  17. Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae

    Energy Technology Data Exchange (ETDEWEB)

    Toyoshima, Yoshiyuki, E-mail: toyoshima@yamasa.com [Soy Sauce Laboratory, Yamasa Corporation, 2-10-1 Araoicho, Choshi, Chiba 288-0056 (Japan); Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo [Soy Sauce Laboratory, Yamasa Corporation, 2-10-1 Araoicho, Choshi, Chiba 288-0056 (Japan); Hamada, Ryoko; Iwashita, Kazuhiro [Fundamental Research Division, National Research Institute of Brewing, 3-7-1 Kagamiyama, Higashihiroshima, Hiroshima 739-0046 (Japan); Satoh, Katsuya; Narumi, Issay [Ion Beam Mutagenesis Research Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

    2012-12-15

    Highlights: ► We investigated the effects of different LET radiation in A. oryzae. ► Both γ-rays and ion beams induced base substitutions, frameshifts, deletions. ► Both γ-rays and ion beams induced genome-wide large-scale mutations in A. oryzae. ► Some differences in the types and frequencies of mutations were found. ► Our results provide new basic insights into the mutation breeding of A. oryzae. - Abstract: Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was {sup 12}C{sup 5+} ion beams with an LET of 121 keV/μm. The {sup 12}C{sup 5+} ion beams had a 3.6-times higher lethal effect than low-LET (0.2 keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. {sup 12}C{sup 6+} ion beams with an LET of 86 keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to {sup 12}C{sup 6+} ion beams increased with an increase in dose and reached 3.47 × 10{sup −3} at 700 Gy. In the dose range from 0 to 700 Gy, {sup 12}C{sup 5+} ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67 × 10{sup −3}) at 400 Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between {sup 12}C{sup 5+} ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all

  18. Protective properties of plasma of burnt and irradiated rats against lethal effect of endotoxins in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Budagov, R S; Chureyeva, L N

    1984-10-01

    The purpose of this work was to estimate protective properties of plasma in disease with increased endotoxemia. Burns and acute radiation sickness were used as models of suppression of physiological mechanisms of detoxication. Experiments were performed on male Wistar rats and mice, which received 3rd degree burns over 15% of the body surface, whole body gamma irradiation at 7.5 Gr or both. At 3 hours, 3, 7 and 12 days after the exposure the animals were decapitated and blood collected. The irradiated mice received 0.2 ml endotoxin intraperitoneally, 1.0 ml freshly prepared rat plasma, then the lethality of the mice in 24 hours was observed. It was found that the plasma of intact rats was capable of decreasing the lethal effects of S. typhimurium and E. coli endotoxins in vivo in mice. Deep skin burns, acute radiation sickness and the combined effects of radiation and thermal injury did not change this phenomenon. The plasma of the experimental rats retained the protective properties at various periods of time after the thermal, radiation and combined exposures. The functioning of the humoral detoxication mechanism is radioresistant, indirectly indicating the nonimmunoglobulin nature of endotoxin inactivators. 19 references.

  19. Using photopigment biomarkers to quantify sub-lethal effects of petroleum pollution on natural phytoplankton assemblages

    International Nuclear Information System (INIS)

    Swistak, J.; Pinckney, J.; Piehler, M.; Paerl, H.

    1995-01-01

    Although much work has been undertaken to determine the toxicity of petroleum pollutants to phytoplankton, most studies have used pure cultures to monitor growth of selected phytoplankton species. Fewer have considered the net effect on entire microalgal communities. Using high performance liquid chromatography (HPLC) to characterize diagnostic microalgal pigments, the authors were able to simultaneously assess sub-lethal pollutant effects on entire communities as well as on individual phytoplankton functional groups. Incubations of natural water samples with diesel fuel, an important contributor to coastal petroleum pollution, revealed significant changes in photopigments and relative abundance of taxonomic groups at sub-lethal concentrations. Differential rates of change of indicator pigment concentrations suggest a range of sensitivity among phytoplankton groups. In preliminary experiments, cyanobacteria exhibited the greatest overall tolerance to the diesel fuel concentrations tested, while cryptomonads displayed the most sensitivity. The authors are currently evaluating the responses of seasonal phytoplankton populations from 3 sites exposed to varied levels of petroleum pollution. HPLC will be used to characterize phytoplankton populations and to determine if the most abundant groups are also the most tolerant of diesel fuel. Preliminary experiments indicate that diesel fuel pollution may modify the structure and function of phytoplankton communities and subsequently alter the trophodynamics of impacted systems

  20. Comparative venom toxicity between Pteromalus puparum and Nasonia vitripennis (Hymenoptera: Pteromalidae) toward the hemocytes of their natural hosts, non-target insects and cultured insect cells.

    Science.gov (United States)

    Zhang, Zhong; Ye, Gong-Yin; Cai, Jun; Hu, Cui

    2005-09-01

    Crude venoms from two parasitoid species, Pteromalus puparum and Nasonia vitripennis (Hymenoptera: Pteromalidae) were assayed for biological activities toward hemocytes from two species of their natural hosts and eight species of their non-natural hosts as well as two lines of cultured Lepidoptera cells, respectively. By inhibiting the spreading and viability of insect hemocytes, the venom from P. puparum displayed significantly higher activities toward plasmatocytes and granular cells from both larvae and pupae of two natural hosts, Pieris rapae and Papilio xuthus, and lower activity toward those from Spodoptera litura, Musca domestica and Sarcophaga peregrina. However, no effect was found towards any type of hemocytes from other five insects tested, namely, Ectropis oblique, Galleria mellonella, Sesamia inferens, Bombyx mori and Parnara guttata. In contrast, the venom from N. vitripennis showed a narrower range of targeted insects. It appeared to have highly adverse effects on the spreading and viability of plasmatocytes and granular cells only from the natural hosts, M. domestica and S. peregrina, little toxicity to cells from P. rapae and P. xuthus, and no effect on any of the other insects tested. Pteromalus puparum venom also apparently presented a high ability to block the spreading of Tn-5B1-4 cells derived from Trichoplusia ni, and high cytotoxicity to the cells and Ha cells derived from Helicoverpa armigera. Nasonia vitripennis venom, however, only had a marked lethal effect to Ha cells. In addition, the possibility that the host range of a defined parasitoid could be assessed using our method of treating hemocytes from candidate insects with venom in vitro, and the potential of our venoms tested in the development of bio-insecticides, insect-resistant transgenic plants, are discussed.

  1. Antiparasitic effects induced by polyclonal IgY antibodies anti-phospholipase A2 from Bothrops pauloensis venom.

    Science.gov (United States)

    Borges, Isabela Pacheco; Silva, Mariana Ferreira; Santiago, Fernanda Maria; de Faria, Lucas Silva; Júnior, Álvaro Ferreira; da Silva, Rafaela José; Costa, Mônica Soares; de Freitas, Vitor; Yoneyama, Kelly Aparecida Geraldo; Ferro, Eloísa Amália Vieira; Lopes, Daiana Silva; Rodrigues, Renata Santos; de Melo Rodrigues, Veridiana

    2018-06-01

    Activities of phospholipases (PLAs) have been linked to pathogenesis in various microorganisms, and implicated in cell invasion and so the interest in these enzymes as potential targets that could contribute to the control of parasite survival and proliferation. Chicken eggs immunized with BnSP-7, a Lys49 phospholipase A 2 (PLA 2 ) homologue from Bothrops pauloensis snake venom, represent an excellent source of polyclonal antibodies with potential inhibitory activity on parasite PLA s. Herein, we report the production, characterization and anti-parasitic effect of IgY antibodies from egg yolks of hens immunized with BnSP-7. Produced antibodies presented increasing avidity and affinity for antigenic toxin epitopes throughout immunization, attaining a plateau after 4weeks. Pooled egg yolks-purified anti-BnSP-7 IgY antibodies were able to specifically recognize different PLA 2 s from Bothrops pauloensis and Bothrops jararacussu venom. Antibodies also neutralized BnSP-7 cytotoxic activity in C2C12 cells. Also, the antibodies recognized targets in Leishmania (Leishmania) amazonensis and Toxoplasma gondii extracts by ELISA and immunofluorescence assays. Anti-BnSP-7 IgY antibodies were cytotoxic to T. gondii tachyzoite and L. (L.) amazonensis promastigotes, and were able to decrease proliferation of both parasites treated before infection. These data suggest that the anti-BnSP-7 IgY is an important tool for discovering new parasite targets and blocking parasitic effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Venom toxicity and composition in three Pseudomyrmex ant species having different nesting modes.

    Science.gov (United States)

    Touchard, Axel; Labrière, Nicolas; Roux, Olivier; Petitclerc, Frédéric; Orivel, Jérôme; Escoubas, Pierre; Koh, Jennifer M S; Nicholson, Graham M; Dejean, Alain

    2014-09-01

    We aimed to determine whether the nesting habits of ants have influenced their venom toxicity and composition. We focused on the genus Pseudomyrmex (Pseudomyrmecinae) comprising terrestrial and arboreal species, and, among the latter, plant-ants that are obligate inhabitants of myrmecophytes (i.e., plants sheltering ants in hollow structures). Contrary to our hypothesis, the venom of the ground-dwelling species, Pseudomyrmex termitarius, was as efficacious in paralyzing prey as the venoms of the arboreal and the plant-ant species, Pseudomyrmex penetrator and Pseudomyrmex gracilis. The lethal potency of P. termitarius venom was equipotent with that of P. gracilis whereas the venom of P. penetrator was less potent. The MALDI-TOF MS analysis of each HPLC fraction of the venoms showed that P. termitarius venom is composed of 87 linear peptides, while both P. gracilis and P. penetrator venoms (23 and 26 peptides, respectively) possess peptides with disulfide bonds. Furthermore, P. penetrator venom contains three hetero- and homodimeric peptides consisting of two short peptidic chains linked together by two interchain disulfide bonds. The large number of peptides in P. termitarius venom is likely related to the large diversity of potential prey plus the antibacterial peptides required for nesting in the ground. Whereas predation involves only the prey and predator, P. penetrator venom has evolved in an environment where trees, defoliating insects, browsing mammals and ants live in equilibrium, likely explaining the diversity of the peptide structures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. HYMENOPTERA ALLERGENS: FROM VENOM TO VENOME

    Directory of Open Access Journals (Sweden)

    Edzard eSpillner

    2014-02-01

    Full Text Available In Western Europe hymenoptera venom allergy primarily relates to venoms of the honeybee and the common yellow jacket. In contrast to other allergen sources, only a few major components of hymenoptera venoms had been characterized until recently. Improved expression systems and proteomic detection strategies have allowed the identification and characterization of a wide range of additional allergens. The field of hymenoptera venom allergy research has moved rapidly from focusing on venom extract and single major allergens to a molecular understanding of the entire venome as a system of unique and characteristic components. An increasing number of such components has been identified, characterized regarding function and assessed for allergenic potential. Moreover, advanced expression strategies for recombinant production of venom allergens allow selective modification of molecules and provide insight into different types of IgE reactivities and sensitization patterns. The obtained information contributes to an increased diagnostic precision in hymenoptera venom allergy and may serve for monitoring, reevaluation and improvement of current therapeutic strategies.

  4. Effect of two viscosity models on lethality estimation in sterilization of liquid canned foods.

    Science.gov (United States)

    Calderón-Alvarado, M P; Alvarado-Orozco, J M; Herrera-Hernández, E C; Martínez-González, G M; Miranda-López, R; Jiménez-Islas, H

    2016-09-01

    A numerical study on 2D natural convection in cylindrical cavities during the sterilization of liquid foods was performed. The mathematical model was established on momentum and energy balances and predicts both the heating dynamics of the slowest heating zone (SHZ) and the lethal rate achieved in homogeneous liquid canned foods. Two sophistication levels were proposed in viscosity modelling: 1) considering average viscosity and 2) using an Arrhenius-type model to include the effect of temperature on viscosity. The remaining thermodynamic properties were kept constant. The governing equations were spatially discretized via orthogonal collocation (OC) with mesh size of 25 × 25. Computational simulations were performed using proximate and thermodynamic data for carrot-orange soup, broccoli-cheddar soup, tomato puree, and cream-style corn. Flow patterns, isothermals, heating dynamics of the SHZ, and the sterilization rate achieved for the cases studied were compared for both viscosity models. The dynamics of coldest point and the lethal rate F0 in all food fluids studied were approximately equal in both cases, although the second sophistication level is closer to physical behavior. The model accuracy was compared favorably with reported sterilization time for cream-style corn packed at 303 × 406 can size, predicting 66 min versus an experimental time of 68 min at retort temperature of 121.1 ℃. © The Author(s) 2016.

  5. Lethal effects of selected novel pesticides on immature stages of Trichogramma pretiosum (Hymenoptera: Trichogrammatidae).

    Science.gov (United States)

    Khan, Muhammad Ashraf; Ruberson, John R

    2017-12-01

    Trichogramma pretiosum Riley is an important egg parasitoid and biological control agent of caterpillar pests. We studied the acute toxicity of 20 pesticides (14 insecticides/miticides, three fungicides and three herbicides) exposed to recommended field rates. Egg, larval, and pupal stages of the parasitoid in their hosts were dipped in formulated solutions of the pesticides and evaluated 10 days later for percentage of host eggs with holes, number of parasitoids emerged per egg with holes, and stage-specific mortality of immature as well as adult wasps within the host eggs. Seven insecticides (buprofezin, chlorantraniliprole, spirotetramat, flonicamid, flubendiamide) and miticides (spiromesifen, cyflumetofen), one herbicide (nicosulfuron), and three fungicides (myclobutanil, pyraclostrobin, trifloxystrobin + tebuconazole) caused no significant mortality to immature stages or pre-emergent adult parasitoids relative to controls. By contrast, seven insecticides/miticides (abamectin, acetamiprid, dinotefuran, fipronil, novaluron, spinetoram, tolfenpyrad) adversely affected immature and pre-emergent adult T. pretiosum, with tolfenpyrad being particularly lethal. Two herbicides had moderate (glufosinate ammonium) to severe (s-metolachlor) acute lethal effects on the immature parasitoids. This study corroborates earlier findings with adult T. pretiosum. Over half of the pesticides - and all the fungicides - tested in the current study would appear to be compatible with the use of T. pretiosum in integrated pest management programs, with respect to acute parasitoid mortality. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  6. Effect of sulfhydryls on potentiation of radiation-induced cell lethality by substituted anthraquinones

    International Nuclear Information System (INIS)

    Kimler, B.F.

    1984-01-01

    The effects of various substituted anthraquinones (SAQ's) and Adriamycin (ADR) were investigated in cultured Chinese hamster V79 cells. These drugs cause a potentiation of radiation-induced cell lethality, albeit by different mechanisms. One possibility is that these components operate through the production of free radicals which then produce DNA strand breaks and crosslinks. If so, then one should be able to change the degree of cell kill by modifying sulfhydryl (SH) levels such that free radical processes are altered. Diamide, buthionine-S, R-sulfoximine, and N-ethylmaleimide (NEM) were used to reduce intracellular SH levels. Cysteamine and dithiotheitol were used to increase SH levels. In general, altered SH levels did not affect SAQ-induced cytotoxicity at low drug concentrations. When drug-tested cells were also irradiated, survival levels were generally those predicted from assuming purely additive interactions. On the other hand, survival after treatment with high concentrations of ADR and one other SAQ were decreased by concomitant treatment with NEM. Since altered SH levels do not produce changes in the potentiation of radiation-induced cell lethality by SAQs, it is concluded that free radicals are not involved in this potentiation. A free radical-mediated process may be involved in the cytotoxicity induced by ADR and other SAQs; however, it is not a simple process

  7. Lethal and pre-lethal effects of a fungal biopesticide contribute to substantial and rapid control of malaria vectors.

    Directory of Open Access Journals (Sweden)

    Simon Blanford

    Full Text Available Rapidly emerging insecticide resistance is creating an urgent need for new active ingredients to control the adult mosquitoes that vector malaria. Biopesticides based on the spores of entomopathogenic fungi have shown considerable promise by causing very substantial mortality within 7-14 days of exposure. This mortality will generate excellent malaria control if there is a high likelihood that mosquitoes contact fungi early in their adult lives. However, where contact rates are lower, as might result from poor pesticide coverage, some mosquitoes will contact fungi one or more feeding cycles after they acquire malaria, and so risk transmitting malaria before the fungus kills them. Critics have argued that 'slow acting' fungal biopesticides are, therefore, incapable of delivering malaria control in real-world contexts. Here, utilizing standard WHO laboratory protocols, we demonstrate effective action of a biopesticide much faster than previously reported. Specifically, we show that transient exposure to clay tiles sprayed with a candidate biopesticide comprising spores of a natural isolate of Beauveria bassiana, could reduce malaria transmission potential to zero within a feeding cycle. The effect resulted from a combination of high mortality and rapid fungal-induced reduction in feeding and flight capacity. Additionally, multiple insecticide-resistant lines from three key African malaria vector species were completely susceptible to fungus. Thus, fungal biopesticides can block transmission on a par with chemical insecticides, and can achieve this where chemical insecticides have little impact. These results support broadening the current vector control paradigm beyond fast-acting chemical toxins.

  8. Effects of Sweet Bee Venom on cardiovascular system in the conscious telemetered Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Lim Chung-San

    2010-09-01

    Full Text Available Objectives:This study was performed to analyse the effects of Sweet Bee Venom(Sweet BV on cardiovascular system in the conscious telemetered Beagle Dogs. Methods:All experiments were conducted at Biotoxtech Company, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP. Male Beagle dogs of 13-19 months old were chosen for the pilot study and surgical implantation was performed for conscious telemetered Beagle dogs. And after confirming condition of Beagle dogs was stable, Sweet BV was administered 4 times(first: 0.0 ㎎/㎏, 2nd: 0.01 ㎎/㎏, 3rd: 0.1 ㎎/㎏, and forth: 0.5 ㎎/㎏, one time/week in thigh muscle of Beagle dogs. And blood pressure, heart rate, electrocardiography and clinical responses were measured. Equal amount of normal saline to the Sweet BV experiment groups was administered to the control group. 1. In the analysis of body weight and taking amount, Beagle dogs did not show significant changes. 2. In the clinical observation, responses of pain and edema were showed depend on dosage of Sweet BV. 3. In the analysis of blood pressure, treatment with Sweet BV did not show significant changes in the dosage of 0.01 ㎎/㎏, but in the dosage of 0.1 ㎎/㎏ and 0.5 ㎎/㎏, treatment with Sweet BV increased blood pressure significantly. 4. In the analysis of heart rate, treatment of Sweet BV did not show significant changes in all dosage and period. 5. In the analysis of electrocardiography, treatment of Sweet BV was not showed significant changes in all dosage and period. Conclusion:Above findings suggest that Sweet BV is relatively safe treatment in the cardiovascular system. But in the using of over dosage, Sweet BV may the cause of increasing blood pressure. Further studies on the subject should be conducted to yield more concrete evidences.

  9. Lethal Effect on Bacterium of Decay of Incorporated Radioactive Atoms (3H, 14C, 32P)

    International Nuclear Information System (INIS)

    Apelgot, Sonia

    1968-01-01

    The biological effect of decay of 3 H, 14 C and 32 P incorporated into a bacterium depends on the nature of the organic molecule labelled, on the position of the isotope within it and on the isotope itself. In sum, results obtained to date show that: The decay of 3 H atoms incorporated into certain macromolecules of a bacterium causes sterilization through ionization by the ß - particle emitted; transmutation is of negligible importance. This self-irradiation is comparable in effect with X-rays and is affected in a similar manner by the same factors: temperature, presence of a radioprotector, radiosensitivity of the strain. Decay of 14 C or 32 P atoms incorporated into bacterial DNA is lethal because of the transmutation effect; ionizations produced by emitted ß - particles may be disregarded. Survival curves for 32 P transmutations depend on the experimental conditions. Some of the results obtained with 32 P are similar to those obtained with X-rays, e.g. effects of temperature, radical capture and oxygen, while others are similar to those of u.v. light, e.g., effect of growth conditions. Comparative tests made with 32 P indicate that the recoil energy of transmutation is not the phenomenon responsible for the lethal effect observed. Comparison of the results obtained after X-irradiation or decay of 3 H or 32 P incorporated into the DNA of bacteria of the same strain of E. coli shows that the efficiency of a 32 P transmutation is about four times greater than that of an ionization produced at random within the same DNA. (author) [fr

  10. Bee Venom Phospholipase A2: Yesterday's Enemy Becomes Today's Friend.

    Science.gov (United States)

    Lee, Gihyun; Bae, Hyunsu

    2016-02-22

    Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson's disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes.

  11. Bothrops fonsecai snake venom activities and cross-reactivity with commercial bothropic venom.

    Science.gov (United States)

    Collaço, Rita de Cássia O; Randazzo-Moura, Priscila; Tamascia, Mariana L; da Silva, Igor Rapp F; Rocha, Thalita; Cogo, José C; Hyslop, Stephen; Sanny, Charles G; Rodrigues-Simioni, Léa

    2017-01-01

    In this work, we examined some biochemical and biological activities of Bothrops fonsecai venom, a pitviper endemic to southeastern Brazil, and assessed their neutralization by commercial bothropic antivenom (CAv). Cross-reactivity of venom with CAv was also assessed by immunoblotting and size-exclusion high performance chromatography (SE-HPLC). Bothrops fonsecai venom had PLA 2 , proteolytic and esterase activities that were neutralized to varying extents by venom:antivenom ratios of 5:1 and 5:2 (PLA 2 and esterase activities) or not significantly by either venom:antivenom ratio (proteolytic activity). The minimum hemorrhagic dose (69.2μg) was totally neutralized by both ratios. Clotting time in rat citrated plasma was 33±10.5s (mean±SD; n=5) and was completely neutralized by a 5:2 ratio. Edema formation was dose-dependent (1-30μg/site) and significantly inhibited by both ratios. Venom (10-300μg/mL) caused neuromuscular blockade in extensor digitorum longus preparations; this blockade was inhibited best by a 5:2 ratio. Venom caused myonecrosis and creatine kinase release in vivo (gastrocnemius muscle) and in vitro (extensor digitorum longus) that was effectively neutralized by both venom:antivenom ratios. Immunoblotting showed that venom components of ~25-100kDa interacted with CAv. SE-HPLC profiles for venom incubated with CAv or specific anti-B. fonsecai antivenom raised in rabbits (SAv) indicated that CAv had a higher binding capacity than SAv, whereas SAv had higher affinity than CAv. These findings indicate that B. fonsecai venom contains various activities that are neutralized to different extents by CAv and suggest that CAv could be used to treat envenoming by B. fonsecai. Copyright © 2016. Published by Elsevier Inc.

  12. Inhibition of local effects induced by Bothrops erythromelas snake venom: Assessment of the effectiveness of Brazilian polyvalent bothropic antivenom and aqueous leaf extract of Jatropha gossypiifolia.

    Science.gov (United States)

    Félix-Silva, Juliana; Gomes, Jacyra A S; Xavier-Santos, Jacinthia B; Passos, Júlia G R; Silva-Junior, Arnóbio A; Tambourgi, Denise V; Fernandes-Pedrosa, Matheus F

    2017-01-01

    Bothrops erythromelas is a snake of medical importance responsible for most of the venomous incidents in Northeastern Brazil. However, this species is not included in the pool of venoms that are used in the Brazilian polyvalent bothropic antivenom (BAv) production. Furthermore, it is well known that antivenom therapy has limited efficacy against venom-induced local effects, making the search for complementary alternatives to treat snakebites an important task. Jatropha gossypiifolia is a medicinal plant widely indicated in folk medicine as an antidote for snakebites, whose effectiveness against Bothrops jararaca venom (BjV) has been previously demonstrated in mice. In this context, this study assessed the effectiveness of the aqueous extract (AE) of this plant and of the BAv against local effects induced by B. erythromelas venom (BeV). Inhibition of BeV-induced edematogenic and hemorrhagic local effects was assayed in mice in pre-treatment (treatment prior to BeV injection) and post-treatment (treatment post-envenomation) protocols. Inhibition of proteolytic, phospholipase A 2 (PLA 2 ) and hyaluronidase enzymatic activities of BeV were evaluated in vitro. BAv cross-reactivity and estimation of antibody titers against BeV and BjV were assessed by Ouchterlony double diffusion test. The results show that in pre-treatment protocol AE and BAv presented very similar effects (about 70% of inhibition for edematogenic and 40% for hemorrhagic activities). However, BAv poorly inhibited edema and hemorrhage in post-envenomation protocol, whilst, in contrast, AE was significantly active even when used after BeV injection. AE was able to inhibit all the tested enzymatic activities of BeV, while BAv was active only against hyaluronidase activity, which could justify the low effectiveness of BAv against BeV-induced local effects in vivo. Ouchterlony's test showed positive cross-reactivity against BeV, but the antibody titers were slightly higher against BjV. Together, these

  13. Heterochromatin position effects on circularized sex chromosomes cause filicidal embryonic lethality in Drosophila melanogaster.

    Science.gov (United States)

    Ferree, Patrick M; Gomez, Karina; Rominger, Peter; Howard, Dagnie; Kornfeld, Hannah; Barbash, Daniel A

    2014-04-01

    Some circularized X-Y chromosomes in Drosophila melanogaster are mitotically unstable and induce early embryonic lethality, but the genetic basis is unknown. Our experiments suggest that a large region of X-linked satellite DNA causes anaphase bridges and lethality when placed into a new heterochromatic environment within certain circularized X-Y chromosomes. These results reveal that repetitive sequences can be incompatible with one another in cis. The lethal phenotype also bears a remarkable resemblance to a case of interspecific hybrid lethality.

  14. Sub-lethal effects of Vip3A toxin on survival, development and fecundity of Heliothis virescens and Plutella xylostella.

    Science.gov (United States)

    Gulzar, Asim; Wright, Denis J

    2015-11-01

    The assessment of sub-lethal effects is important to interpret the overall insecticide efficacy in controlling insect pest populations. In addition to the lethal effect, sub-lethal effects may also occur in exposed insects. Vegetative insecticidal proteins (Vips) have shown a broad spectrum of insecticidal activity against many insect pest species. In this study the sub-lethal effects of the Bacillus thuringiensis vegetative insecticidal toxin Vip3A on the development and reproduction of Heliothis virescens F. and Plutella xylostella L. were evaluated in the laboratory. The results indicated that the sub-lethal concentration of Vip3A increased the duration of the larval and pupal stages as compared with the control treatment for both species. The percent pupation and percent adult emergence were significantly lower for Vip3A-treated insects. The proportion of pairs that produced eggs and the longevity of adults were not significantly different between treatments. H. virescens and P. xylostella treated with Vip3A showed an 11 and 17 % decrease in their intrinsic rate of increase (rm) respectively compared with untreated insects. The results from this study will be helpful to develop the strategy to incorporate Vip 3A containing crops in an integrated pest management programme.

  15. Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca.

    Science.gov (United States)

    Lauridsen, Line P; Laustsen, Andreas H; Lomonte, Bruno; Gutiérrez, José María

    2017-01-06

    toxicity screening of the fractions, using the mouse lethality assay, identified four peaks as those having toxicity higher than that of the crude venom. These fractions predominantly contain α-neurotoxins of the 3FTx family. This toxicovenomic characterization agrees with the clinical and experimental manifestations of envenomings by this species, in which a strong neurotoxic effect predominates. Therefore, our findings suggest that immunotherapy against envenomings by N. melanoleuca should be directed towards the neutralization of 3FTxs; this has implications for the improvement of current antivenoms and for the development of novel antivenoms based on biotechnological approaches. A screening of the immunoreactivity of three antivenoms being distributed in sub-Saharan Africa revealed that they immunoreact with the fractions containing α-neurotoxins, although with different antibody titers. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The lethal effect of longwave ultraviolet light and PUVA. An analysis based upon human mesenchymal cells in vitro

    International Nuclear Information System (INIS)

    Jongh, G. de; Bergers, M.; Boezeman, J.B.M.; Verhagen, A.R.; Mier, P.D.

    1984-01-01

    The lethal effect of UVA and PUVA radiation was studied in cultures of fresh and mature monocytes. UVA radiation alone was shown to possess a lethal effect at doses which are attained in the dermis in vivo. The synergistic action of 8-methoxypsoralen and UVA radiation predominated in PUVA radiation, but again a residual effect of UVA alone was demonstrated mathematically. Mature cells were less sensitive than fresh monocytes. The results indicate that a monolayer culture of non-dividing, mesenchymal cells offers considerable advantages over in vivo systems as a model for the study of phototoxicity. (author)

  17. Study of the immune response by antibodies against the Bothrops asper venom for the elaboration of a antiophidic vaccine for bovines

    International Nuclear Information System (INIS)

    Gonzalez Rojas, Katherine

    2014-01-01

    Active immunization has determined against Bothrops asper snake venom (tested in murine and bovine models) a induced response by antibody able to prevent in immunized animals. A coagulopathy or death is developed after of be administered with adequate doses of poison. The amount of B. asper venom has defined the poisoning induced in bovine and murine models. The plasmatic concentration of equine antibodies against B. asper venom is specified to prevent coagulopathy and lethality induced by this venom in murine and bovine models. Murine and bovine models have verified the active immunization reached in a concentration of antibodies against B. asper venom equal or greater to the maximum concentration achieved by intravenous administration of antivenoms from equine origin. The concentration of antibodies induced by the active immunization is evaluated against B. asper venom to prevent the development of coagulopathy and lethality induced by the venom in murine and bovine models [es

  18. Computational Studies of Snake Venom Toxins.

    Science.gov (United States)

    Ojeda, Paola G; Ramírez, David; Alzate-Morales, Jans; Caballero, Julio; Kaas, Quentin; González, Wendy

    2017-12-22

    Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin.

  19. Computational Studies of Snake Venom Toxins

    Directory of Open Access Journals (Sweden)

    Paola G. Ojeda

    2017-12-01

    Full Text Available Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most potentially interesting toxins. Some computational techniques predict toxin molecular targets, and the binding mode to these targets. This review gives an overview of current knowledge on the ~2200 sequences, and more than 400 three-dimensional structures of snake toxins deposited in public repositories, as well as of molecular modeling studies of the interaction between these toxins and their molecular targets. We also describe how modern bioinformatics have been used to study the snake venom protein phospholipase A2, the small basic myotoxin Crotamine, and the three-finger peptide Mambalgin.

  20. Indirect effects are involved in the production of potentially lethal damage in X irradiated escherichia coli

    International Nuclear Information System (INIS)

    Billen, D.

    1985-01-01

    When living cells are exposed to low LET radiation, 60 to 70% of the resulting lethality is said to be due to indirect effects. Using the OH radical scavengers: glycerol n-butanol, t-butanol, and NO/sub 2//sup -/. The authors observed that a radiosensitive E. coli K-12 mutant (W 3110 thy/sup -/ polAl/sup -/) lacking DNA polymerase 1 displays a markedly enhanced radioresistance when exposed to X rays in the presence of these chemicals. The extent of protection afforded by these chemicals correlated with their OH radical scavenging ability over the limited range of concentrations of the chemicals studied. (Only non-toxic concentrations of the chemicals were used). The presence of 2M glycerol during irradiation of the PolAl/sup -/ cells results in a survival level higher than that seen for the unprotected parent strain (W 3110 thy polA/sup +/)

  1. The membrane stress response buffers lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network.

    Science.gov (United States)

    Thibault, Guillaume; Shui, Guanghou; Kim, Woong; McAlister, Graeme C; Ismail, Nurzian; Gygi, Steven P; Wenk, Markus R; Ng, Davis T W

    2012-10-12

    Lipid composition can differ widely among organelles and even between leaflets of a membrane. Lipid homeostasis is critical because disequilibrium can have disease outcomes. Despite their importance, mechanisms maintaining lipid homeostasis remain poorly understood. Here, we establish a model system to study the global effects of lipid imbalance. Quantitative lipid profiling was integral to monitor changes to lipid composition and for system validation. Applying global transcriptional and proteomic analyses, a dramatically altered biochemical landscape was revealed from adaptive cells. The resulting composite regulation we term the "membrane stress response" (MSR) confers compensation, not through restoration of lipid composition, but by remodeling the protein homeostasis network. To validate its physiological significance, we analyzed the unfolded protein response (UPR), one facet of the MSR and a key regulator of protein homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality control, and membrane integrity-functions otherwise lethally compromised in lipid dysregulated cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Vascular effects and electrolyte homeostasis of the natriuretic peptide isolated from Crotalus oreganus abyssus (North American Grand Canyon rattlesnake) venom

    NARCIS (Netherlands)

    Da Silva, S.L.; Dias-Junior, C.A.; Baldasso, P.A.; Damico, D.C.; Carvalho, B.M.; Garanto, A.; Acosta, G.; Oliveira, E.; Albericio, F.; Soares, A.M.; Marangoni, S.; Resende, R.R.

    2012-01-01

    Crotalus oreganus abyssus is a rattlesnake that is usually found in the Grand Canyon, United States of America. Knowledge regarding the composition of C. o. abyssus venom is scarce. New natriuretic peptides (NPs) have been isolated and characterized from the venoms of members of the Crotalinae

  3. Lethal and sublethal effects of azadirachtin and cypermethrin on Habrobracon hebetor (Hymenoptera: Braconidae).

    Science.gov (United States)

    Abedi, Zahra; Saber, Moosa; Gharekhani, Gholamhossein; Mehrvar, Ali; Kamita, Shizuo George

    2014-04-01

    Habrobracon hebetor Say is an ectoparasitoid of larval stage of various lepidopteran pests. Lethal and sublethal effects of azadirachtin and cypermethrin were evaluated on adult and preimaginal stages of H. hebetor under laboratory conditions. Contact exposure bioassays with adults indicated that the lethal concentration (LC50) of two commercial azadirachtin-containing formulations, NeemGuard and BioNeem, were 43.5 and 10.2 microg a.i./ml, respectively. The LC50 of cypermethrin was 5.4 microg a.i./ml. When larval stage of H. hebetor was exposed to these insecticides with a field recommended concentration of NeemGuard, BioNeem, or cypermethrin by a dip protocol, the emergence rate was reduced by 39.0, 36.6, and 97.6%, respectively. To assay the sublethal effects of these insecticides, adult wasps were exposed to an LC30 concentration of the insecticides, and then demographic parameters of the surviving wasps were determined. Fecundity, fertility, and parameters including the intrinsic rate of increase (r(m)) were affected negatively. The r(m) values following exposure to NeemGuard, BioNeem, cypermethrin, or mock treatment were 0.143, 0.149, 0.160, and 0.179, respectively, female offspring per female per day, respectively. The current study showed that cypermethrin had more acute toxicity on larval and adult stages of H. hebetor compared with azadirachin. The commercial formulations of azadirachtin and cypermethrin negatively affected most of the life table parameters of the parasitoid. Semifield and field studies are needed for obtaining more applicable results on combining H. hebetor and the tested insecticides for an integrated pest management-based strategy for crop protection.

  4. A systematic review of the clinical effectiveness and cost-effectiveness of Pharmalgen® for the treatment of bee and wasp venom allergy.

    Science.gov (United States)

    Hockenhull, J; Elremeli, M; Cherry, M G; Mahon, J; Lai, M; Darroch, J; Oyee, J; Boland, A; Dickson, R; Dundar, Y; Boyle, R

    2012-01-01

    Each year in the UK, there are between two and nine deaths from anaphylaxis caused by bee and wasp venom. Anaphylactic reactions can occur rapidly following a sting and can progress to a life-threatening condition within minutes. To avoid further reactions in people with a history of anaphylaxis to bee and wasp venom, the use of desensitisation, through a process known as venom immunotherapy (VIT), has been investigated and is in use in the UK. VIT consists of subcutaneous injections of increasing amounts of purified bee and/or wasp venom extract. Pharmalgen® products (ALK Abelló) have had UK marketing authorisation for VIT (as well as diagnosis) of allergy to bee venom (using Pharmalgen Bee Venom) and wasp venom (using Pharmalgen Wasp Venom) since March 1995. This review assessed the clinical effectiveness and cost-effectiveness of Pharmalgen in providing immunotherapy to individuals with a history of type 1 [immunoglobulin E (IgE)-mediated] systemic allergic reaction to bee and wasp venom. A comprehensive search strategy using a combination of index terms (e.g. Pharmalgen) and free-text words (e.g. allerg$) was developed and used to interrogate the following electronic databases: EMBASE, MEDLINE, The Cochrane Library. Papers were included if they studied venom immunotherapy using Pharmalgen (PhVIT) in patients who had previously experienced a systemic reaction to a bee and/or a wasp sting. Comparators were any alternative treatment options available in the NHS without VIT. Included outcomes were systemic reactions, local reactions, mortality, anxiety related to the possibility of future allergic reactions, health-related quality of life (QoL) and adverse reactions (ARs) to treatment. Cost-effectiveness outcomes included cost per quality-adjusted life-years (QALYs) gained. Because of the small number of published randomised controlled trials (RCTs), no meta-analyses were conducted. A de novo economic model was developed to assess the cost-effectiveness of Ph

  5. Further Identification of the Effect of Bradykinin Potentiating Factor Isolated From Scorpion Venom on Irradiated White Rat

    International Nuclear Information System (INIS)

    Hasan, H.F.

    2011-01-01

    Scorpion venom of Androctonus amoreuxi contains a strong bradykinin potentiating factor (BPF) that augments bradykinin effect through enhancing its release and acts as an angiotensin converting enzyme inhibitor (ACEI). Both irradiation and stimulation of renin-angiotensin system (RAS) induce oxidative stress. Possible interruption of the RAS with an ACEI induced by BPF isolated from the scorpion, Androctonus amoreuxi venom or the presence of angiotensin II receptor blocker (ARB) losartan and/or γ- radiation were evaluated. The examined parameters included blood erythrocytes count (RBC), total leucocytic count (WBC), haemoglobin content (Hb) and hematocrit value (Hct) as well as, glutathione content (GSH), malondialdehyde (MDA) and advanced oxidative protein product (AOPP) of kidney homogenate besides aldosterone, sodium, potassium, chloride, calcium, urea, creatinine and uric acid levels of serum. A group of rats (70 - 80 gm each) were received i.p. injection of BPIF (1μg / g body wt) twice per week for three weeks, while the other group received i.p. injection of losartan (5μg / g body wt) twice per week for three weeks. γ-Irradiation was performed at a dose level of 4Gy. All animals were examined after an investigation period of 21 days from γ- irradiation. Either BPF or losartan was performed together with irradiation. The results pointed out that irradiation discerned a significant elevation in the level of MDA, AOPP, aldosterone, sodium, urea and creatinine, and a significant drop in the haematological values (RBCs, WBCs, Hb and Hct), GSH, calcium and uric acid. Repeated injections of BPF or losartan had a beneficial result against the deleterious effect of γ- irradiation. The present investigation clarifies comparable effects for treatment of radiation damage to the kidney through RAS by BPF as (ACEI) and losartan as (ARB). The present work adds further identification to the properties of BPF in controlling of radiation damage. Therapeutic agents from

  6. Cytotoxic and Pro-Apoptotic Effects of Honey Bee Venom and Chrysin on Human Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elaheh Amini

    2015-06-01

    Full Text Available Background: The anti-cancer effects of honey bee venom (BV and chrysin might open a new window for treatment of chemo-resistant cancers. This study was designed to evaluate cytotoxic and pro-apoptotic effects of BV and chrysin on A2780cp cistplatin- resistant human ovarian cancer cells. Methods: As per the study objectives, A2780cp cells were categorized to 4 groups: 3 experiment groups (treated either with BV or chrysin or BV + chrysin and 1 control group (untreated cells.  Experiment group cells were cultured and treated by different concentrations of BV and chrysin for 24 hours. Then, experiment and control cells were studied with MTT assay, Annexin V-FITC, DAPI and Acridine Orange / Propidium Iodide statining, flow cytometry, caspase-3 and -9 assay, measurement of intracellular level of reactive oxygen species (ROS and RT-PCR. Results: MTT assay showed that 8 μg/mL BV, 40 µg/ml chrysin and 6 + 15 μg/mL BV + chrysin co-treatment induced 50% cell death on A2780cp cells compared with controls (P < 0.001. Morphological observations by inverted and fluorescent microscopy revealed ROS generation and apoptotic cell death under exposure to BV or chrysin or BV + chrysin co-treatment. Caspase-3 and -9 assay demonstrated that BV and chrysin triggered apoptosis through intrinsic pathway and RT-PCR demonstrated down-regulation of Bcl-2. Conclusion: Honey bee venom and chrysin are effective for destroying chemoresistant ovarian cancer cells through activation of intrinsic apoptosis, which propose them as potential candidates to be used in development of improved chemotherapeutic agents in the future.

  7. Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation.

    Directory of Open Access Journals (Sweden)

    Nikele Nadur-Andrade

    2016-10-01

    Full Text Available Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv, as well as the mechanisms involved was investigated.Bmv (1 μg was injected through the intraplantar route in the right hind paw of mice. Mechanical hyperalgesia and allodynia were evaluated by von Frey filaments at different time points after venom injection. Low level laser therapy (LLLT was applied at the site of Bmv injection at wavelength of red 685 nm with energy density of 2.2 J/cm2 at 30 min and 3 h after venom inoculation. Neuronal activation in the dorsal horn spinal cord was determined by immunohistochemistry of Fos protein and the mRNA expression of IL-6, TNF-α, IL-10, B1 and B2 kinin receptors were evaluated by Real time-PCR 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia and decreased Fos expression, induced by Bmv as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors. Finally, an increase on IL-10, was observed following LLLT.These data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites.

  8. Lethal and sublethal effects of pesticides in the management of Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae) on Capsicum annuum L.

    Science.gov (United States)

    Breda, Mariana O; Oliveira, José V; Esteves Filho, Alberto B; Barbosa, Douglas Rs; Santos, Andrezo A

    2017-10-01

    The evaluation of lethal and sublethal effects is of great importance for a complete assessment of the total impact of chemical compounds upon pest populations and the development of management strategies. In this study, we evaluated the lethal and sublethal effects of different synthetic and botanical products on the broad mite Polyphagotarsonemus latus (Banks), a major pest of Capsicum annuum L. and other crops. Abamectin had the highest lethal effect on P. latus, followed by spiromesifen, azadirachtin, neem oil and nitrogen fertiliser + citric acid. The sublethal effects of the products were indicated by the influence on mite population growth, affecting the numbers of females, males, larvae, pupae and eggs. Furthermore, a negative instantaneous rate of increase in P. latus and repellent effects were observed. The lethal and sublethal effects of abamectin, spiromesifen, azadirachtin and neem oil significantly affect P. latus population growth, as well as causing repellence to this mite on C. annuum, and they should be considered in the integrated pest management of this mite. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  9. Single Chain Antibody Fragment against Venom from the Snake Daboia russelii formosensis

    Directory of Open Access Journals (Sweden)

    Chi-Hsin Lee

    2017-10-01

    Full Text Available Russell’s vipers containing hemotoxic and neurotoxic venom commonly cause snake envenomation. Horse-derived antivenom is a specific antidote, but its production is expensive and has side effects. Developing a cost-effective and more tolerable therapeutic strategy is favorable. In this study, using glutaraldehyde-attenuated Daboia russelii formosensis (DRF venom proteins to immunize chickens, polyclonal yolk-immunoglobulin (IgY antibodies were generated and showed a specific binding affinity. Phage display technology was used to generate two antibody libraries of single-chain variable fragments (scFvs containing 3.4 × 107 and 5.5 × 107 transformants, respectively. Phage-based ELISA indicated that specific clones were enriched after bio-panning. The nucleotide sequences of scFv-expressing clones were analyzed and classified into six groups in the short linker and four groups in the long linker. These scFv antibodies specifically bound to DRF proteins, but not other venom proteins. Mass spectrometric data suggested that these scFv antibodies may recognize phospholipase A2 RV-4 or RV-7. In vivo studies showed that anti-DRF IgY exhibited complete protective effects and mixed scFv antibodies increased the survival rate and time of mice challenged with a lethal dose of DRF proteins. These antibodies can be potentially applied in a rapid diagnostic method or for treatment in the future.

  10. Single Chain Antibody Fragment against Venom from the Snake Daboia russelii formosensis.

    Science.gov (United States)

    Lee, Chi-Hsin; Lee, Yu-Ching; Lee, Yueh-Lun; Leu, Sy-Jye; Lin, Liang-Tzung; Chen, Chi-Ching; Chiang, Jen-Ron; Mwale, Pharaoh Fellow; Tsai, Bor-Yu; Hung, Ching-Sheng; Yang, Yi-Yuan

    2017-10-27

    Russell's vipers containing hemotoxic and neurotoxic venom commonly cause snake envenomation. Horse-derived antivenom is a specific antidote, but its production is expensive and has side effects. Developing a cost-effective and more tolerable therapeutic strategy is favorable. In this study, using glutaraldehyde-attenuated Daboia russelii formosensis (DRF) venom proteins to immunize chickens, polyclonal yolk-immunoglobulin (IgY) antibodies were generated and showed a specific binding affinity. Phage display technology was used to generate two antibody libraries of single-chain variable fragments (scFvs) containing 3.4 × 10⁷ and 5.5 × 10⁷ transformants, respectively. Phage-based ELISA indicated that specific clones were enriched after bio-panning. The nucleotide sequences of scFv-expressing clones were analyzed and classified into six groups in the short linker and four groups in the long linker. These scFv antibodies specifically bound to DRF proteins, but not other venom proteins. Mass spectrometric data suggested that these scFv antibodies may recognize phospholipase A2 RV-4 or RV-7. In vivo studies showed that anti-DRF IgY exhibited complete protective effects and mixed scFv antibodies increased the survival rate and time of mice challenged with a lethal dose of DRF proteins. These antibodies can be potentially applied in a rapid diagnostic method or for treatment in the future.

  11. Lethal and sublethal effects of azadirachtin on the bumblebee Bombus terrestris (Hymenoptera: Apidae).

    Science.gov (United States)

    Barbosa, Wagner Faria; De Meyer, Laurens; Guedes, Raul Narciso C; Smagghe, Guy

    2015-01-01

    Azadirachtin is a biorational insecticide commonly reported as selective to a range of beneficial insects. Nonetheless, only few studies have been carried out with pollinators, usually emphasizing the honeybee Apis mellifera and neglecting other important pollinator species such as the bumblebee Bombus terrestris. Here, lethal and sublethal effects of azadirachtin were studied on B. terrestris via oral exposure in the laboratory to bring out the potential risks of the compound to this important pollinator. The compound was tested at different concentrations above and below the maximum concentration that is used in the field (32 mg L(-1)). As most important results, azadirachtin repelled bumblebee workers in a concentration-dependent manner. The median repellence concentration (RC50) was estimated as 504 mg L(-1). Microcolonies chronically exposed to azadirachtin via treated sugar water during 11 weeks in the laboratory exhibited a high mortality ranging from 32 to 100 % with a range of concentrations between 3.2 and 320 mg L(-1). Moreover, no reproduction was scored when concentrations were higher than 3.2 mg L(-1). At 3.2 mg L(-1), azadirachtin significantly inhibited the egg-laying and, consequently, the production of drones during 6 weeks. Ovarian length decreased with the increase of the azadirachtin concentration. When azadirachtin was tested under an experimental setup in the laboratory where bumblebees need to forage for food, the sublethal effects were stronger as the numbers of drones were reduced already with a concentration of 0.64 mg L(-1). Besides, a negative correlation was found between the body mass of male offspring and azadirachtin concentration. In conclusion, our results as performed in the laboratory demonstrated that azadirachtin can affect B. terrestris with a range of sublethal effects. Taking into account that sublethal effects are as important as lethal effects for the development and survival of the colonies of B. terrestris

  12. Pharmacokinetics of Snake Venom

    OpenAIRE

    Suchaya Sanhajariya; Stephen B. Duffull; Geoffrey K. Isbister

    2018-01-01

    Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present) and Medline (1946–present). For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, ...

  13. Effects of Sweet Bee Venom on the Central Nervous System in Rats -using the Functional Observational Battery-

    Directory of Open Access Journals (Sweden)

    Joong Chul An

    2011-09-01

    Full Text Available Objectives: This study was performed to analyse the effects of Sweet Bee Venom(Sweet BV-pure melittin, the major component of honey bee venom on the central nervous system in rats. Methods: All experiments were conducted at Biotoxtech Company, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP. Male rats of 5 weeks old were chosen for this study and after confirming condition of rats was stable, Sweet BV was administered in thigh muscle of rats. And checked the effects of Sweet BV on the central nervous system using the functional observational battery (FOB, which is a neuro-toxicity screening assay composed of 30 descriptive, scalar, binary, and continuous endpoints. And home cage observations, home cage removal and handling, open field activity, sensorimotor reflex test/physiological measurements were conducted. Results: 1. In the home cage observation, there was not observed any abnormal signs in rats. 2. In the observation of open field activity, the reduction of number of unit areas crossed and rearing count was observed caused by Sweet BV treatment. 3. In the observation of handling reactivity, there was not observed any abnormal signs in rats. 4. In the observation of sensorimotor reflex tests/physiological measurements, there was not observed any neurotoxic signs in rats. 5. In the measurement of rectal temperature, treatment of Sweet BV did not showed great influences in the body temperature of rats. Conclusions: Above findings suggest that Sweet BV is relatively safe treatment in the central nervous system. But in the using of over dose, Sweet BV may the cause of local pain and disturbance of movement. Further studies on the subject should be conducted to yield more concrete evidences.

  14. Bee venom therapy: Potential mechanisms and therapeutic applications.

    Science.gov (United States)

    Zhang, Shuai; Liu, Yi; Ye, Yang; Wang, Xue-Rui; Lin, Li-Ting; Xiao, Ling-Yong; Zhou, Ping; Shi, Guang-Xia; Liu, Cun-Zhi

    2018-04-11

    Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Immunology of Bee Venom.

    Science.gov (United States)

    Elieh Ali Komi, Daniel; Shafaghat, Farzaneh; Zwiener, Ricardo D

    2017-01-20

    Bee venom is a blend of biochemicals ranging from small peptides and enzymes to biogenic amines. It is capable of triggering severe immunologic reactions owing to its allergenic fraction. Venom components are presented to the T cells by antigen-presenting cells within the skin. These Th2 type T cells then release IL-4 and IL-13 which subsequently direct B cells to class switch to production of IgE. Generating venom-specific IgE and crosslinking FcεR1(s) on the surface of mast cells complete the sensitizing stage in allergic individuals who are most likely to experience severe and even fatal allergic reactions after being stung. Specific IgE for bee venom is a double-edged sword as it is a powerful mediator in triggering allergic events but is also applied successfully in diagnosis of the venom allergic patient. The healing capacity of bee venom has been rediscovered under laboratory-controlled conditions using animal models and cell cultures. The potential role of enzymatic fraction of bee venom including phospholipase A2 in the initiation and development of immune responses also has been studied in numerous research settings. Undoubtedly, having insights into immunologic interactions between bee venom components and innate/specific immune cells both locally and systematically will contribute to the development of immunologic strategies in specific and epitope-based immunotherapy especially in individuals with Hymenoptera venom allergy.

  16. Lethal Epistaxis.

    Science.gov (United States)

    Byard, Roger W

    2016-09-01

    Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year-old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77-year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified. © 2016 American Academy of Forensic Sciences.

  17. The venom optimization hypothesis revisited.

    Science.gov (United States)

    Morgenstern, David; King, Glenn F

    2013-03-01

    Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non-proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence. However, because venoms are protein-rich, they come with a high metabolic price tag. The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non-essential to survival of the animal. The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure. Indeed, various behaviors have been identified that appear consistent with frugality of venom use. This has led to formulation of the "venom optimization hypothesis" (Wigger et al. (2002) Toxicon 40, 749-752), also known as "venom metering", which postulates that venom is metabolically expensive and therefore used frugally through behavioral control. Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems. We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom. However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy. We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Evaluation of lethal effect of microwave exposure on protoscolices of hydatid cyst in vitro

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    Zahra Eslamirad

    2015-10-01

    Full Text Available Objective: To investigate the lethal effect of microwave radiation on protoscolices of hydatid cyst. Methods: The protoscolices were divided in two separate groups. The first group received continuous irradiation while the second group received repetitive irradiation. According to the exposure time, the first and the second groups were divided into 8 subgroups. Non-treated protoscolices were considered as the control in each experiment. The protoscolex mortality rate was calculated, and changes in temperature difference in protoscolex suspension before and after the irradiation and the mortality rate with the increase of exposure time were recorded. Results: The results showed that microwave was able to increase the mortality rate of protoscolices in hydatid cyst. The mortality rate from 20% in 20 s of continuous exposure was increased to 100% in 50 s. Also, the differences between the mortality rates in subgroups of the first and the second groups and the control were significant (P < 0.001. Although the effect of temperature change in repetitive irradiation was not significant, non-thermal repetitive irradiation effects were obviously stronger than the thermal continuous irradiation effects. Conclusions: It seems that, microwaves especially in the repetitive mode, may be used as a supplementary measure for both treatment and prevention of hydatidosis.

  19. Effect of Bothrops alternatus snake venom on macrophage phagocytosis and superoxide production: participation of protein kinase C

    Directory of Open Access Journals (Sweden)

    SS Setubal

    2011-01-01

    Full Text Available Envenomations caused by different species of Bothrops snakes result in severe local tissue damage, hemorrhage, pain, myonecrosis, and inflammation with a significant leukocyte accumulation at the bite site. However, the activation state of leukocytes is still unclear. According to clinical cases and experimental work, the local effects observed in envenenomation by Bothrops alternatus are mainly the appearance of edema, hemorrhage, and necrosis. In this study we investigated the ability of Bothrops alternatus crude venom to induce macrophage activation. At 6 to 100 ¼g/mL, BaV is not toxic to thioglycollate-elicited macrophages; at 3 and 6 ¼g/mL, it did not interfere in macrophage adhesion or detachment. Moreover, at concentrations of 1.5, 3, and 6 ¼g/mL the venom induced an increase in phagocytosis via complement receptor one hour after incubation. Pharmacological treatment of thioglycollate-elicited macrophages with staurosporine, a protein kinase (PKC inhibitor, abolished phagocytosis, suggesting that PKC may be involved in the increase of serum-opsonized zymosan phagocytosis induced by BaV. Moreover, BaV also induced the production of anion superoxide (O2_ by thioglycollate-elicited macrophages. This BaV stimulated superoxide production was abolished after treating the cells with staurosporine, indicating that PKC is an important signaling pathway for the production of this radical. Based on these results, we suggest that phagocytosis and reactive oxygen species are involved in the pathogenesis of local tissue damage characteristic of Bothrops spp. envenomations.

  20. [Insect venom allergies : Update 2016 for otorhinolaryngologists].

    Science.gov (United States)

    Klimek, L; Dippold, N; Sperl, A

    2016-12-01

    Due to the increasing incidence of hymenoptera venom allergies and the potentially life-threatening reactions, it is important for otolaryngologists working in allergology to have an understanding of modern diagnostic and treatment standards for this allergic disease. Molecular diagnosis with recombinant single allergens from bee and wasp venom components improves the diagnostics of insect venom allergies, particularly in patients with double-positive extract-based test results. Detection of specific sensitizations to bee or wasp venom enables double sensitizations to be better distinguished from cross-reactivity. Based on patient history and test results, the patient is initially advised on avoidance strategies and prescribed an emergency medication kit. Then, the indication for allergen-specific immunotherapy (AIT) is evaluated. The dose-increase phase can be performed using conventional, cluster, rush, or ultra-rush schedules, whereby rapid desensitization (rush AIT) performed in the clinic seems to be particularly effective as initial treatment.

  1. Lethal and behavioral effects of pesticides on the insect predator Macrolophus pygmaeus.

    Science.gov (United States)

    Martinou, A F; Seraphides, N; Stavrinides, M C

    2014-02-01

    Macrolophus pygmaeus (Hemiptera: Miridae) is a common generalist predator in Mediterranean agro-ecosystems. We evaluated the lethal effects of six insecticides and a fungicide on M. pygmaeus nymphs exposed to the pesticides through three routes of exposure: direct, residual and oral. Chlorantraniliprole and emamectin-benzoate caused less than 25% mortality to M. pygmaeus and were classified as harmless according to the International Organization for Biological Control rating scheme. In contrast, thiacloprid and metaflumizone caused 100% and 80% mortality, respectively, and were classified as harmful. Indoxacarb and spinosad resulted in close to 30% mortality to the predator, and were classified as slightly harmful, while the fungicide copper hydroxide caused 58% mortality and was rated as moderately harmful. Chlorantraniliprole and thiacloprid were selected for further sublethal testing by exposing M. pygmaeus to two routes of pesticide intake: pesticide residues and feeding on sprayed food. Thiacloprid led to an increase in resting and preening time of the predator, and a decrease in plant feeding. Chlorantraniliprole resulted in a decrease in plant feeding, but no other behaviors were affected. In addition, thiacloprid significantly reduced the predation rate of M. pygmaeus, whereas chlorantraniliprole had no significant effect on predation rate. The results of the study suggest that thiacloprid is not compatible with M. pygmaeus, while further research needs to be carried out for metaflumizone and copper hydroxide. All other products seem to be relatively compatible with M. pygmaeus, though studies on their sublethal effects will shed more light into their safety. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Gamma radiation effects on crotoxin (toxin of crotalus durissus terrificus venom)

    International Nuclear Information System (INIS)

    Souza Filho, J.N.; Rogero, J.R.

    1988-01-01

    The crotoxin is a great neurotoxin found on Crotalus durissus terrificus venom. This protein was isolated using molecular exclusion cromatography with Sephadex G-75 and irradiated in a source of 60 Co GAMMA-CELL in the concentration of 2 mg/ml 0.85% NaCl with dose rate of 1.19 x 10 3 Gy/hr. The doses used were 250, 500, 1000 and 2000 Gy. It was determinated for this samples, the proteic concentration, the diffusion immunoassay using crotalic antiserum and eletrophoresis (SDS-PAGE). The results showed some changes on the irradiated toxin. Preliminary results with doses of radiation of 100, 250, 500 and 1000 Gy showed that the letal dose 50% (LD50) in mice increase greatly with the increase of radiation's dose. (author) [pt

  3. Effects of gamma radiation on crotoxin (toxin of Crotalus durissus terrificus venom)

    International Nuclear Information System (INIS)

    Souza Filho, J.N.; Rogero, J.R.

    1988-07-01

    The crotoxin in a great neurotoxin found on Crotalus durissus terrificus venom. This protein was isolated using molecular exclusion cromatrography with Sephadex G-75 and irradiated in a source of 60 Co GAMMACELL in the concentration of 2 mg/ml 0.85% NaCl with dose rate of 1.19 x 10 3 Gy/hr. The doses used were 250, 500, 1000 and 2000 Gy. It was determinated for this samples, the proteic concentration, the diffusion immunoassay using crotalic antiserum and eletrophoresis (SDS-PAGE). The results showed some changes on the irradiated toxin. Preliminary results with doses of radiation of 100, 250, 500 and 1000 Gy showed that the letal dose 50% (LD50) in mice increase greatly with the increase of radiation's dose. (author) [pt

  4. Effects of radiolysis products on crotamine (toxin from Crotalus durissus terrificus venom)

    International Nuclear Information System (INIS)

    Costa, T.A. da; Rogero, J.R.

    1988-07-01

    Ionizing Radiations changes the molecular structure due to chemical bond destruction. These chemical alterations are able to change the biological properties of the biomolecules. Crotamine was obtained from Crotalus durissus terrificus venom by molecular exclusion cromatography and irradiated in a concentration of 1 mg/ml in aqueous solution with gamma radiation produced by a 60 Co source. We used doses of 100 Gy, 2000 Gy and 5000 Gy (dose rate = 1,14 x 10 3 Gy/h). We performed the following experiments: proteic concentration, SDS-PAGE and immunodiffusion. Preliminary results showed a reduction of 55% in proteic concentration; with dose of 5000 Gy; an increase of the number of bands in SDS-PAGE suggesting the appearance of protein aggregates that was proportional as the dose increases. The immunodifusion data showed a reduction of the immunochemical activity against the Butantan antisera. (author) [pt

  5. Functional diversity of non-lethal effects, chemical camouflage, and variation in fish avoidance in colonizing beetles.

    Science.gov (United States)

    Resetarits, William J; Pintar, Matthew R

    2016-12-01

    Predators play an extremely important role in natural communities. In freshwater systems, fish can dominate sorting both at the colonization and post-colonization stage. Specifically, for many colonizing species, fish can have non-lethal, direct effects that exceed the lethal direct effects of predation. Functionally diverse fish species with a range of predatory capabilities have previously been observed to elicit functionally equivalent responses on oviposition in tree frogs. We tested this hypothesis of functional equivalence of non-lethal effects for four predatory fish species, using naturally colonizing populations of aquatic beetles. Among taxa other than mosquitoes, and with the exception of the chemically camouflaged pirate perch, Aphredoderus sayanus, we provide the first evidence of variation in colonization or oviposition responses to different fish species. Focusing on total abundance, Fundulus chrysotus, a gape-limited, surface-feeding fish, elicited unique responses among colonizing Hydrophilidae, with the exception of the smallest and most abundant taxa, Paracymus, while Dytiscidae responded similarly to all avoided fish. Neither family responded to A. sayanus. Analysis of species richness and multivariate characterization of the beetle assemblages for the four fish species and controls revealed additional variation among the three avoided species and confirmed that chemical camouflage in A. sayanus results in assemblages essentially identical to fishless controls. The origin of this variation in beetle responses to different fish is unknown, but may involve variation in cue sensitivity, different behavioral algorithms, or differential responses to species-specific fish cues. The identity of fish species occupying aquatic habitats is crucial to understanding community structure, as varying strengths of lethal and non-lethal effects, as well as their interaction, create complex landscapes of predator effects and challenge the notion of functional

  6. Inhibition of secretary PLA₂--VRV-PL-VIIIa of Russell's viper venom by standard aqueous stem bark extract of Mangifera indica L.

    Science.gov (United States)

    Dhananjaya, B L; Sudarshan, S

    2015-03-01

    The aqueous extract of Mangifera indica is known to possess anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic phospholipases A2s, which are the most toxic and lethal component of snake venom is still unknown. Therefore, this study was carried out to evaluate the modulatory effect of standard aqueous bark extract of M. indica on VRV-PL-VIIIa of Indian Russells viper venom. Mangifera indica extract dose dependently inhibited the GIIB sPLA2 (VRV-PL-VIIIa) activity with an IC50 value of 6.8±0.3 μg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 96% at ~40 μg/ml concentration. Further, M. indica extract at different concentrations (0-50 μg/ml) inhibited the edema formed in a dose dependent manner. It was found that there was no relieve of inhibitory effect of the extract when examined as a function of increased substrate and calcium concentration. The inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inducing activities. As the inhibition is independent of substrate, calcium concentration and was irreversible, it can be concluded that M. indica extracts mode of inhibition could be due to direct interaction of components present in the extract with PLA2 enzyme. In conclusion, the aqueous extract of M. indica effectively inhibits svPLA2 (Snake venom phospholipase A2) enzymatic and its associated toxic activities, which substantiate its anti-snake venom properties. Further in-depth studies are interesting to known on the role and mechanism of the principal inhibitory constituents present in the extract, so as to develop them into potent anti-snake venom and as an anti-inflammatory agent.

  7. The effects of gut commensal bacteria depletion on mice exposed to acute lethal irradiation

    International Nuclear Information System (INIS)

    Hou Bing; Xu Zhiwei; Zhang Chenggang

    2007-01-01

    The prevention and management of bacterial infection are the mainstays of therapies for irradiation victims. However, worries about adverse effects arise from gut commensal flora depletion owing to the broad-spectrum antibiotics treatment. In the present study, we investigated the effects of gut bacteria depletion on the mice receiving total-body irradiation (TBI) at a single dose of 12 Gy. One group of mice was merely exposed to TBI but was free of antibiotic treatment throughout the experiment, while the other two groups of mice were additionally given broad-spectrum antibiotics, either from 2 weeks before or immediately after irradiation. The survival time of each animal in each group was recorded for analysis. Results showed that the mean survival time of mice was longest in the group without antibiotic treatment and shortest in the group treated with broad-spectrum antibiotics from 2 weeks before TBI. In conclusion, our data suggested that depletion of gut commensal bacteria with broad-spectrum antibiotics seemed deleterious for mammals receiving lethal TBI. (author)

  8. Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

    International Nuclear Information System (INIS)

    Won, Young-Suk; Song, Ji-Won; Lim, Jong-Hwan; Lee, Mee-Young; Moon, Og-Sung; Kim, Hyoung-Chin; Son, Hwa-Young; Kwon, Hyo-Jung

    2016-01-01

    Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [ 14 C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.

  9. Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Won, Young-Suk [Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk (Korea, Republic of); Song, Ji-Won [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of); Lim, Jong-Hwan [Huons Research Center, Gyonggido (Korea, Republic of); Lee, Mee-Young [Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of); Moon, Og-Sung; Kim, Hyoung-Chin [Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk (Korea, Republic of); Son, Hwa-Young [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of); Kwon, Hyo-Jung, E-mail: hyojung@cnu.ac.kr [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of)

    2016-01-15

    Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [{sup 14}C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.

  10. Investigation of the lethal and behavioral effects of commercial insecticides on the parasitoid wasp Copidosoma truncatellum.

    Science.gov (United States)

    Ramos, Rodrigo S; de Araújo, Vitor C R; Pereira, Renata R; Martins, Júlio C; Queiroz, Obiratanea S; Silva, Ricardo S; Picanço, Marcelo C

    2018-01-01

    Copidosoma truncatellum (Hymenoptera: Encyrtidae) is an important parasitoid wasp of the soybean looper, Chrysodeixis includens, but its effectiveness can be severely curtailed by the application of certain insecticides. Therefore, to identify insecticides that are potentially compatible with C. truncatellum, the lethal and behavioral effects of nine chemicals used to control the soybean looper were evaluated for their toxicity to the wasp. Chlorantraniliprole, chlorfenapyr, flubendiamide, and indoxacarb were the least toxic insecticides to the parasitoid, resulting in mortalities of less than 25%. In contrast, cartap, deltamethrin, and methomyl caused 100% mortality, and acephate and spinosad caused 76% and 78% mortality, respectively. At least one of the detoxifying enzymes (monooxygenase, glutathione S-transferase, and/or esterases) may be involved in the mechanisms underlying the selectivity of chlorantraniliprole, chlorfenapyr, flubendiamide, and indoxacarb for the parasitoid based on the results for the insecticide plus synergist treatment. Changes in the behavioral patterns (walking time and resting time) of the parasitoid were found with exposure to acephate, flubendiamide, indoxacarb and methomyl, but behavioral avoidance was not observed. Our results indicate that the insecticides chlorantraniliprole and chlorfenapyr are the most suitable for inclusion in integrated pest management strategies for the control of C. includens. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Lethal and sublethal effects of neem on Aphis gossypii and Cycloneda sanguinea in watermelon

    Directory of Open Access Journals (Sweden)

    Cíntia Ribeiro Souza

    2015-05-01

    Full Text Available The objective of this study was to evaluate the impact of oil extract of neem, Azadirachta indica, on the watermelon aphid Aphis gossypii and its natural enemy Cycloneda sanguinea. Toxicity bioassays were conducted with the commercial product DalNeem (1,475 g L-1 azadirachtin at 0.0037 µg a.i. mL-1, 0.0074 µg a.i. mL-1 and 0.0148 µg a.i. mL-1, Malathion at 1 µg a.i. mL-1 and distilled water as a control treatment. The products were sprayed to watermelon leaf discs, and the insects were exposed to the product residues. The instantaneous population growth rate of A. gossypii and the survival of C. sanguinea larvae exposed to the different treatments were calculated. A decrease in the instantaneous population growth rate of A. gossypii with increasing concentrations of neem was observed, and the aphids did not reproduce on the leaf discs treated with malathion during the first 24 hours of exposure due to its rapid lethal effect on adult insects. The larvae of the predator C. sanguinea exposed to malathion survived only for 24 hours. The survival of the predator exposed to different concentrations of neem was also significantly reduced compared to the predators exposed only to water. However, laboratory experiments may overestimate the effect of neem on predators because the individuals cannot employ escape behavior caused by neem repellency.

  12. Viper and cobra venom neutralization by beta-sitosterol and stigmasterol isolated from the root extract of Pluchea indica Less. (Asteraceae).

    Science.gov (United States)

    Gomes, A; Saha, Archita; Chatterjee, Ipshita; Chakravarty, A K

    2007-09-01

    We reported previously that the methanolic root extract of the Indian medicinal plant Pluchea indica Less. (Asteraceae) could neutralize viper venom-induced action [Alam, M.I., Auddy, B., Gomes, A., 1996. Viper venom neutralization by Indian medicinal plant (Hemidesmus indicus and P. indica) root extracts. Phytother. Res. 10, 58-61]. The present study reports the neutralization of viper and cobra venom by beta-sitosterol and stigmasterol isolated from the root extract of P. indica Less. (Asteraceae). The active fraction (containing the major compound beta-sitosterol and the minor compound stigmasterol) was isolated and purified by silica gel column chromatography and the structure was determined using spectroscopic analysis (EIMS, (1)H NMR, (13)C NMR). Anti-snake venom activity was studied in experimental animals. The active fraction was found to significantly neutralize viper venom-induced lethal, hemorrhagic, defibrinogenation, edema and PLA(2) activity. Cobra venom-induced lethality, cardiotoxicity, neurotoxicity, respiratory changes and PLA(2) activity were also antagonized by the active component. It potentiated commercial snake venom antiserum action against venom-induced lethality in male albino mice. The active fraction could antagonize venom-induced changes in lipid peroxidation and superoxide dismutase activity. This study suggests that beta-sitosterol and stigmasterol may play an important role, along with antiserum, in neutralizing snake venom-induced actions.

  13. Lethal and sublethal effects of marine sediment extracts on fish cells and chromosomes

    Science.gov (United States)

    Landolt, Marsha L.; Kocan, Richard M.

    1984-03-01

    The cost of conducting conventional chronic bioassays with every potentially toxic compound found in marine ecosystems is prohibitive; therefore short-term toxicity tests which can be used for rapid screening were developed. The tests employ cultured fish cells to measure lethal, sublethal or genotoxic effects of pure compounds and complex mixtures. The sensitivity of these tests has been proven under laboratory conditions; the following study used two of these tests, the anaphase aberration test and a cytotoxicity assay, under field conditions. Sediment was collected from 97 stations within Puget Sound, Washington. Serial washings of the sediment in methanol and dichloromethane yielded an organic extract which was dried, dissolved in DMSO and incubated as a series of dilutions with rainbow trout gonad (RTG-2) cells. The toxic effects of the extract were measured by examining the rate of cell proliferation and the percentage of damaged anaphase figures. Anaphase figures were considered to be abnormal if they exhibited non-disjunctions, chromosome fragments, or chromosome bridges. A second cell line (bluegill fry, BF-2) was also tested for cell proliferation and was included because, unlike the RTG-2 cell line, it contains little or no mixed function oxygenase activity. Of 97 stations tested, 35 showed no genotoxic activity, 42 showed high genotoxic activity (P≤.01) and the remainder were intermediate. Among the toxic sites were several deep water stations adjacent to municipal sewage outfalls and four urban waterways contaminated by industrial and municipal effluents. Extracts from areas that showed genotoxic effects also inhibited cell proliferation and were cytotoxic to RTG-2 cells. Few effects were noted in the MFO deficient BF-2 cells. Short term in vitro tests provide aquatic toxicologists with a versatile and cost effective tool for screening complex environments. Through these tests one can identify compounds or geographic regions that exhibit high

  14. Microbubble-Mediated Ultrasound Enhances the Lethal Effect of Gentamicin on Planktonic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Han-Xiao Zhu

    2014-01-01

    Full Text Available Previous research has found that low-intensity ultrasound enhanced the lethal effect of gentamicin on planktonic E. coli. We aimed to further investigate whether microbubble-mediated low-intensity ultrasound could further enhance the antimicrobial efficacy of gentamicin. The planktonic E. coli (ATCC 25922 was distributed to four different interventions: control (GCON, microbubble only (GMB, ultrasound only (GUS, and microbubble-mediated ultrasound (GMUS. Ultrasound was applied with 100 mW/cm2 (average intensity and 46.5 KHz, which presented no bactericidal activity. After 12 h, plate counting was used to estimate the number of bacteria, and bacterial micromorphology was observed with transmission electron microscope. The results showed that the viable counts of E. coli in GMUS were decreased by 1.01 to 1.42 log10 CFU/mL compared with GUS (P<0.01. The minimal inhibitory concentration (MIC of gentamicin against E. coli was 1 μg/mL in the GMUS and GUS groups, lower than that in the GCON and GMB groups (2 μg/mL. Transmission electron microscopy (TEM images exhibited more destruction and higher thickness of bacterial cell membranes in the GMUS than those in other groups. The reason might be the increased permeability of cell membranes for gentamicin caused by acoustic cavitation.

  15. Radioprotective effect of chitosan in sub-lethally X-ray irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Yoshikazu; Ikota, Nobuo; Arima, Hiromi; Watanabe, Yoshito; Yukawa, Masae; Ozawa, Toshihiko [National Inst. of Radiological Sciences, Chiba (Japan); Kim, Hee-Sun [Korea Hydro and Nuclear Power Corp., Seoul (Korea, Republic of). Radiation Health Research Inst.; Bom, Hee-Seung; Kim, Young-Ho [Chonnam Univ., Kwangju (Korea, Republic of). Hospital

    2003-03-01

    The radioprotective effect of chitosan was studied in mice following whole-body X-ray irradiation. C3H/He mice were exposed to 7 Gy, and their survival rates were examined. The survival rates of chitosan-diet mice were about 20% higher than those of mice on a standard diet, and the rates dropped sharply to a plateau at day 10 after X-ray irradiation. The chitosan-diet mice had an increased weight ratio of spleen to body within the experimental period. The leukocyte, thrombocyte, and erythrocyte counts as well as the hematocrit and hemoglobin levels were recovered significantly and more rapidly in the chitosan-diet mice than the standard-diet mice at day 14 after irradiation. The scavenging abilities of chitosan were evaluated by the electron spin resonance (ESR) spin-trapping method. These observations suggested that chitosan led to hematopoetic activation and leuko-cytogenesis in mice after sub-lethal dose irradiation, and that the biological response might be caused by radical trapping or scavenging. (author)

  16. Analgesic Effects of Diluted Bee Venom Acupuncture Mediated by δ-Opioid and α2-Adrenergic Receptors in Osteoarthritic Rats.

    Science.gov (United States)

    Huh, Jeong-Eun; Seo, Byung-Kwan; Lee, Jung-Woo; Kim, Chanyoung; Park, Yeon-Cheol; Lee, Jae-Dong; Baek, Yong-Hyeon

    2017-06-23

    Context • Pain from osteoarthritis is associated with peripheral nociception and central pain processing. Given the unmet need for innovative, effective, and well-tolerated therapies, many patients, after looking for more satisfactory alternatives, decide to use complementary and alternative modalities. The analgesic mechanism of subcutaneous injections of diluted bee venom into an acupoint is thought to be part of an anti-inflammatory effect and the central modulation of pain processing. Objectives • Using the rat model of collagenase-induced osteoarthritis (CIOA), the study intended to investigate the analgesic effects of bee venom acupuncture (BVA) as they are related to the acupuncture points and dosage used and to determine whether the analgesic mechanisms of BVA for pain were mediated by opioid or adrenergic receptors. Design • Male Sprague-Dawley rats were randomly assigned to one of 19 groups, with n = 10 for each group. Setting • The study was conducted at the East-West Bone and Joint Research Institute at Kyung Hee University (Seoul, South Korea). Intervention • All rats were intra-articularly injected with collagenase solution in the left knee, followed by a booster injection performed 4 d after the first injection. For the groups receiving BVA treatments, the treatment was administered into the ST-36 acupoint, except for 1 group that received the treatment into a nonacupoint. Three BVA intervention groups received no pretreatment with agonists or antagonists; 1 of them received a dose of 1 mg/kg of bee venom into acupoint ST-36, 1 received a dose of 2 mg/kg into acupoint ST-36, and 1 received a dose of 1 mg/kg into a nonacupoint location. For the intervention groups receiving pretreatments, the opioid-receptor or adrenergic-receptor agonists or antagonists were injected 20 min before the 1-mg/kg BVA treatments. Outcome Measures • Changes in the rats' pain thresholds were assessed by evaluation of pain-related behavior, using a tail flick

  17. Analysis of the intersexual variation in Thalassophryne maculosa fish venoms.

    Science.gov (United States)

    Lopes-Ferreira, Mônica; Sosa-Rosales, Ines; Bruni, Fernanda M; Ramos, Anderson D; Vieira Portaro, Fernanda Calheta; Conceição, Katia; Lima, Carla

    2016-06-01

    Gender related variation in the molecular composition of venoms and secretions have been described for some animal species, and there are some evidences that the difference in the toxin (s) profile among males and females may be related to different physiopathological effects caused by the envenomation by either gender. In order to investigate whether this same phenomenon occurs to the toadfish Thalassophryne maculosa, we have compared some biological and biochemical properties of female and male venoms. Twenty females and males were collected in deep waters of the La Restinga lagoon (Venezuela) and, after protein concentration assessed, the induction of toxic activities in mice and the biochemical properties were analyzed. Protein content is higher in males than in females, which may be associated to a higher size and weight of the male body. In vivo studies showed that mice injected with male venoms presented higher nociception when compared to those injected with female venoms, and both venoms induced migration of macrophages into the paw of mice. On the other hand, mice injected with female venoms had more paw edema and extravasation of Evans blue in peritoneal cavity than mice injected with male venoms. We observed that the female venoms had more capacity for necrosis induction when compared with male venoms. The female samples present a higher proteolytic activity then the male venom when gelatin, casein and FRETs were used as substrates. Evaluation of the venoms of females and males by SDS-PAGE and chromatographic profile showed that, at least three components (present in two peaks) are only present in males. Although the severity of the lesion, characterized by necrosis development, is related with the poisoning by female specimens, the presence of exclusive toxins in the male venoms could be associated with the largest capacity of nociception induction by this sample. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. [Lethal effect after transmutation of 33P incorporated into bacteriophage S 13 and mechanisms of DNA double helix rupture].

    Science.gov (United States)

    Apelgot, S

    1980-04-01

    The experiments show the lethal effect of the beta decay of 33P incorporated in DNA of bacteriophage S 13. The lethal efficiency is high, 0.72 at 0 degrees C and 0.55 at--197 degrees C. The presence of a radical scavenger like AET has no influence. It was found previously that for such phages with single-stranded DNA, the lethal efficiency of 32P decay is unity, and that the lethal event is a DNA single-strand break, owing to the high energy of the nucleogenic 32S atom. As the recoil energy of the 33S atom is too low to account for such a break, it is suggested that the reorganization of the phosphate molecule into sulphate is able to bring about a DNA single-strand break with an efficiency as high as 0.7, at 0 degrees C. A model for the DNA double-strand-break produced by a transmutation processes is suggested.

  19. Phospholipases A2: enzymatic assay for snake venom (Naja naja karachiensis) with their neutralization by medicinal plants of Pakistan.

    Science.gov (United States)

    Asad, Muhammad H H B; Durr-E-Sabih; Yaqab, Tahir; Murtaza, Ghulam; Hussain, Muhammad S; Hussain, Muhammad S; Nasir, Muhammad T; Azhar, Saira; Khan, Shujaat A; Hussain, Izhar

    2014-01-01

    Phospholipases A2 (PLA2) are the most lethal and noxious component of Naja naja karachiensis venom. They are engaged to induce severe toxicities after their penetration in victims. Present study was designed to highlight hydrolytic actions of PLA. in an egg yolk mixture and to encounter their deleterious effects via medicinal plants of Pakistan. PLA2 were found to produce free fatty acids in a dose dependent manner. Venom at concentration of 0.1 mg was found to liberate 26.6 pmoles of fatty acids with a decline in pH1 of 0.2 owing to the presence of PLA2 (133 Unit/mg). When quantity of venom was increased up to 8 mg, it caused to release 133 pmoles of free fatty acids with a decrease in 1.0 pH due to abundance in PLA, (665 Unit/mg). The rest of other doses of venom (0.3-4.0 mg) was found to liberate fatty acids between these two upper and lower limits. Twenty eight medicinal plants (0.1-0.6 mg) were tried to abort PLA, hydrolytic action, however, all were found useful (50-100%) against PLA,. Bauhinia variegate L., Citrus limon (L.). Burm.f. Enicostemnma hyssopifolium (Willd.) Verdoorn, Ocimum sanctum. Psoralea corylifolia L. and Stenolobium stans (L.) D. Don were found excellent in switching off 100% phospholipases A, at their lowest concentration (0.1 mg). Three plants extract were found useful only at lower concentration (0.1 mg), however, their higher doses were seemed to aggravate venom response. Eight medicinal plants failed to neutralize PLA, rather their higher doses were found effective. Standard antidote and rest of other plants extract were able to show maximum of 50% efficiencies. Therefore, it is necessary to identify and isolate bioactive constituent(s) from above cited six medicinal plants to eradicate the problem of snake bite in the future.

  20. In vitro neutralization of the scorpion, Buthus tamulus venom toxicity.

    Science.gov (United States)

    Venkateswarlu, Y; Janakiram, B; Reddy, G R

    1988-01-01

    Scorpion (Buthus tamulus) venom was subjected to neutralization by treating the venom with various chemicals such as hydrochloric acid, sodium hydroxide, thiourea, formaldehyde, zinc sulphate, acetic acid and trichloroacetic acid. The venom was also subjected to heat treatment. The levels of total protein, free amino acids and protease activity in neutralized venom decreased significantly. The decrease in venom protein and free amino acids was in proportion to the duration of the heat treatment and the concentration of chemicals used except zinc sulphate, sodium hydroxide and thiourea. Protease activity of neutralized venom samples also showed a decrease except with zinc sulphate which enhanced the enzyme activity. Intramuscular injection of formaldehyde, trichlcroacetic acid and heat treated venoms into albino rats produced low mortality while thiourea and zinc sulphate were not effective in reducing the mortality. Hydrochloric acid and acetic acid treated venoms reduced the mortality by 50% with a decrease in the symptoms of envenomation. The changes were attributed to the denaturing of venom protein by chemical and heat treatments.

  1. Treating autoimmune disorders with venom-derived peptides.

    Science.gov (United States)

    Shen, Bingzheng; Cao, Zhijian; Li, Wenxin; Sabatier, Jean-Marc; Wu, Yingliang

    2017-09-01

    The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.

  2. Isolation of biologically active peptides from the venom of Japanese carpenter bee, Xylocopa appendiculata

    OpenAIRE

    Kawakami, Hiroko; Goto, Shin G.; Murata, Kazuya; Matsuda, Hideaki; Shigeri, Yasushi; Imura, Tomohiro; Inagaki, Hidetoshi; Shinada, Tetsuro

    2017-01-01

    Background Mass spectrometry-guided venom peptide profiling is a powerful tool to explore novel substances from venomous animals in a highly sensitive manner. In this study, this peptide profiling approach is successfully applied to explore the venom peptides of a Japanese solitary carpenter bee, Xylocopa appendiculata (Hymenoptera: Apoidea: Apidae: Anthophila: Xylocopinae: Xylocopini). Although interesting biological effects of the crude venom of carpenter bees have been reported, the struct...

  3. Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly.

    Science.gov (United States)

    Aird, Steven D; Aggarwal, Shikha; Villar-Briones, Alejandro; Tin, Mandy Man-Ying; Terada, Kouki; Mikheyev, Alexander S

    2015-08-28

    While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown. Using next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation. Given log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness. Natural selection then acts on the additive genetic variance of these components, in proportion to their contributions to overall fitness. Adaptive

  4. Lethal and Sublethal Effects of Insecticides Used on Citrus, on the Ectoparasitoid Tamarixia radiata.

    Science.gov (United States)

    Beloti, Vitor Hugo; Alves, Gustavo Rodrigues; Araújo, Diogo Feliciano Dias; Picoli, Mateus Manara; Moral, Rafael de Andrade; Demétrio, Clarice Garcia Borges; Yamamoto, Pedro Takao

    2015-01-01

    Huanglongbing (HLB) is a disease associated with the bacteria "Candidatus Liberibacter spp." and has been devastating citrus orchards around the world. Its management involves control of the insect vector, the Asian citrus psyllid Diaphorina citri Kuwayama. However, the indiscriminate use of chemicals has caused pest outbreaks and eliminated the natural enemies of the vector, such as the parasitoid Tamarixia radiata (Waterston), the main agent for biological control of D. citri. This study assessed the lethal and sublethal effects of insecticides recommended for integrated production of citrus on the parasitoid T. radiata. When adult parasitoids were exposed to residues of 25 insecticides, 20% of them, i.e., gamma-cyhalothrin, etofenprox, azadirachtin, tebufenozide and pyriproxyfen, were considered as harmless (Class 1), 12% as slightly harmful (Class 2), 12% as moderately harmful (Class 3) and 56% as harmful (Class 4), according to the classification proposed by the IOBC/WPRS. Afterward, 14 insecticides (5 harmless and 9 harmful) were sprayed on the parasitoid pupae. Of the 14 insecticides tested, only the organophosphates dimethoate and chlorpyrifos affected the parasitoid emergence. The effects of insecticides on the parasitism capacity of adults exposed to residues of azadirachtin, etofenprox, gamma-cyhalothrin, pyriproxyfen and tebufenozide (harmless) were also evaluated. Tebufenozide and gamma-cyhalothrin affected the parasitism of the F0 generation, but did not affect the emergence of the F1 and F2 generations. Therefore, for an effective IPM program, selective insecticides or harmful pesticides to adult parasitoids could be used in the field, provided that the adults do not occur naturally and the chemical applications do not coincide with parasitoid releases.

  5. Lethal and Sublethal Effects of Insecticides Used on Citrus, on the Ectoparasitoid Tamarixia radiata.

    Directory of Open Access Journals (Sweden)

    Vitor Hugo Beloti

    Full Text Available Huanglongbing (HLB is a disease associated with the bacteria "Candidatus Liberibacter spp." and has been devastating citrus orchards around the world. Its management involves control of the insect vector, the Asian citrus psyllid Diaphorina citri Kuwayama. However, the indiscriminate use of chemicals has caused pest outbreaks and eliminated the natural enemies of the vector, such as the parasitoid Tamarixia radiata (Waterston, the main agent for biological control of D. citri. This study assessed the lethal and sublethal effects of insecticides recommended for integrated production of citrus on the parasitoid T. radiata. When adult parasitoids were exposed to residues of 25 insecticides, 20% of them, i.e., gamma-cyhalothrin, etofenprox, azadirachtin, tebufenozide and pyriproxyfen, were considered as harmless (Class 1, 12% as slightly harmful (Class 2, 12% as moderately harmful (Class 3 and 56% as harmful (Class 4, according to the classification proposed by the IOBC/WPRS. Afterward, 14 insecticides (5 harmless and 9 harmful were sprayed on the parasitoid pupae. Of the 14 insecticides tested, only the organophosphates dimethoate and chlorpyrifos affected the parasitoid emergence. The effects of insecticides on the parasitism capacity of adults exposed to residues of azadirachtin, etofenprox, gamma-cyhalothrin, pyriproxyfen and tebufenozide (harmless were also evaluated. Tebufenozide and gamma-cyhalothrin affected the parasitism of the F0 generation, but did not affect the emergence of the F1 and F2 generations. Therefore, for an effective IPM program, selective insecticides or harmful pesticides to adult parasitoids could be used in the field, provided that the adults do not occur naturally and the chemical applications do not coincide with parasitoid releases.

  6. Proteomic identification of gender molecular markers in Bothrops jararaca venom.

    Science.gov (United States)

    Zelanis, André; Menezes, Milene C; Kitano, Eduardo S; Liberato, Tarcísio; Tashima, Alexandre K; Pinto, Antonio F M; Sherman, Nicholas E; Ho, Paulo L; Fox, Jay W; Serrano, Solange M T

    2016-04-29

    larger than males. This sexual size dimorphism suggests the tendency for female specimens to feed on larger prey, and for male specimens to go on a diet similar to that of juveniles. Variation in the snake venom proteome is a ubiquitous phenomenon occurring at all taxonomic levels. At the intraspecific variation level, the individual contribution to the venom proteome is important but effects contributed by age and feeding habits may also affect the proteome phenotype. Whether sex-based factors play a role in venom variation of a species that shows sexual size dimorphism is poorly known. The use of proteomic strategies supported by transcriptomic data allows a more comprehensive assessment of venom proteomes uncovering components that are gender-specific. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. The effects of radiation dose-rate and quality on the induction of dominant lethals in mouse spermatids

    International Nuclear Information System (INIS)

    Searle, A.G.; Beechey, G.V.

    1981-01-01

    Hybrid male mice were given 3 Gy (300 rad) doses of X- or γ-irradiation at dose-rates of either 0.6 or 0.002 Gy/min for each radiation. Germ-cells treated as spermatids were tested for dominant lethality. Effects on spermatogonia were evaluated by studying testis-weight, sperm-count and sperm abnormalities. The rate of induction of dominant lethal mutations was 2.1 times as high after acute X-irradiation as after protracted γ-irradiation. Most of this difference resulted from the change in radiation quality, since the relative effectiveness of X- versus γ-irradiation was 1.9 at low and 1.6 at high dose rates. For each radiation, however, fewer dominant lethals were induced at low dose-rates than at high (low/high ratios of 0.8 and 0.9 respectively) although differences did not reach a significant level. There were no statistically significant effects of dose rate on testis-weight of sperm-count in the X-ray series, but there were significantly less severe effects on both with protraction of the γ-irradiation. Evidence for effects of radiation quality on these characters was conflicting. Frequencies of abnormal spermatozoa were markedly increased 7 weeks after irradiation but there were no consistent effects of radiation intensity or quality. (orig.)

  8. Enhanced sensitivity to the lethal and mutagenic effects of photosensitizing action of chlorpromazine in ethylenediaminetetraacetate-treated Escherichia coli

    International Nuclear Information System (INIS)

    Yonei, S.; Todo, T.

    1982-01-01

    Ethylenediaminetetraacetate (EDTA) treatment of Escherichia coli H/r30 (Arg - ) enhanced cell sensitivity to the lethal and mutagenic effects of the photosensitizing action of chlorpromazine (CPZ). The most obvious effect of EDTA on the fluence-survival curve was an elimination of the shoulder. In the absence of EDTA, CPZ plus near-UV radiation did not induce the reversion from arginine-auxotroph to autotroph of E. coli H/r30. However, when EDTA (5 mM)-treated cells were subjected to CPZ plus near-UV radiation, the induced reversion frequency increased with time of irradiation. It is concluded that the enhanced penetration of CPZ into E. coli cells by EDTA facilitates the drug binding to DNA within the cells upon near-UV irradiation and that this is the cause for the enhanced photosensitized lethal and mutagenic effects of CPZ. (author)

  9. Effects of metallothionein on zinc metabolism in lethal-milk mutant mice

    International Nuclear Information System (INIS)

    Grider, A. Jr.

    1986-01-01

    The lethal-milk mice (C57BL/6J-Im) exhibit various pleiotropic effects, including a congenital otolith defect, production of zinc-deficient milk, and clinical signs of a systemic Zn deficiency by one year of age. The clinical signs include alopecia, dermatitis, and skin lesions. The systemic zinc deficiency may be due to increased levels of metallothionein (MT) in the intestine and/or liver of Im mice. The untreated Im mice contain twice as much intestinal MT as do C57BL/6J-(+/sup im//+ /sup Im/) (B6) controls. This was determined by a sulfhydryl assay, by the 109 Cd-saturation/hemolysate method, and by the 65 Zn-binding assay. Various concentrations of Cd or Zn were added to the drinking water three days before assaying for MT. Compared to B6 mice, the Im mice exhibited more MT in their liver by the 65 Zn-MT binding assay (3-fold) and by the 109 Cd-saturation/hemolysate method (18-fold). The effects of the two zinc treatments did not differ significantly between Im and B6 mice. The retention and excretion of 65 Zn (administered intraperitoneally) were determined over a 14-day period, but the results did not different between the Im and B6 mice. The increased concentrations of MT within the Im mice was not significantly different for the intestine and liver. Based on these data and other studies, the Im mice may exhibit alterations in zinc homeostasis due to some deregulation of MT metabolism, including the inner ear of the fetus, the lactating mammary gland, and the intestine and liver of adults by one year of age

  10. Effects of metallothionein on zinc metabolism in lethal-milk mutant mice

    Energy Technology Data Exchange (ETDEWEB)

    Grider, A. Jr.

    1986-01-01

    The lethal-milk mice (C57BL/6J-Im) exhibit various pleiotropic effects, including a congenital otolith defect, production of zinc-deficient milk, and clinical signs of a systemic Zn deficiency by one year of age. The clinical signs include alopecia, dermatitis, and skin lesions. The systemic zinc deficiency may be due to increased levels of metallothionein (MT) in the intestine and/or liver of Im mice. The untreated Im mice contain twice as much intestinal MT as do C57BL/6J-(+/sup im//+ /sup Im/) (B6) controls. This was determined by a sulfhydryl assay, by the /sup 109/Cd-saturation/hemolysate method, and by the /sup 65/Zn-binding assay. Various concentrations of Cd or Zn were added to the drinking water three days before assaying for MT. Compared to B6 mice, the Im mice exhibited more MT in their liver by the /sup 65/Zn-MT binding assay (3-fold) and by the /sup 109/Cd-saturation/hemolysate method (18-fold). The effects of the two zinc treatments did not differ significantly between Im and B6 mice. The retention and excretion of /sup 65/Zn (administered intraperitoneally) were determined over a 14-day period, but the results did not different between the Im and B6 mice. The increased concentrations of MT within the Im mice was not significantly different for the intestine and liver. Based on these data and other studies, the Im mice may exhibit alterations in zinc homeostasis due to some deregulation of MT metabolism, including the inner ear of the fetus, the lactating mammary gland, and the intestine and liver of adults by one year of age.

  11. Toxicity Effects of Toad (Rhinella jimi Stevaux, 2002 Venom in Chicken (Gallus gallus domesticus

    Directory of Open Access Journals (Sweden)

    Ivana Cristina Nunes Gadelha

    2014-01-01

    Full Text Available This study aimed to evaluate the pathological changes that occur after administering different doses of R. jimi (Stevaux, 2002 parotoid glands secretion to Gallus gallus domesticus chicks. Twenty-three animals were used in this study and were divided into 5 groups that received a toad venom dose of 0, 3.0 mg/kg, 6.0 mg/kg, 10.0 mg/kg, and 25.0 mg/kg. After 48 h, the necropsy and pathological examinations were performed. No clinical signs of toxicity were observed in any group. Macroscopically, hepatomegaly, areas of liver necrosis, splenomegaly, necrotic and hemorrhagic cardiac regions, hydropericardium, dark necrotic lesions of Meckel’s diverticulum, and hemorrhages in the lungs and kidneys were detected. Histopathological changes included diffuse vacuolar degeneration of hepatocytes, severe sinusoidal congestion, focal areas of hemorrhage in the parenchyma, swollen cardiac fibers, necrotic myocardial fibers, moderate to acute diffuse alveolar hemorrhage, vacuolar degeneration of the renal tubular epithelium, necrosis of renal tubules, and extensive hemorrhagic areas below the brain and cerebellar meninges. In conclusion, pathological changes of the R. jimi toxins in chicks were noted in the heart, spleen, liver, Meckel’s diverticulum, lungs, and kidneys. Most of the changes were similar to those observed in humans and animals exposed to toxins from other toad species.

  12. Identification and characterization of B-cell epitopes of 3FTx and PLA(2) toxins from Micrurus corallinus snake venom.

    Science.gov (United States)

    Castro, K L; Duarte, C G; Ramos, H R; Machado de Avila, R A; Schneider, F S; Oliveira, D; Freitas, C F; Kalapothakis, E; Ho, P L; Chávez-Olortegui, C

    2015-01-01

    The main goal of this work was to develop a strategy to identify B-cell epitopes on four different three finger toxins (3FTX) and one phospholipase A2 (PLA2) from Micrurus corallinus snake venom. 3FTx and PLA2 are highly abundant components in Elapidic venoms and are the major responsibles for the toxicity observed in envenomation by coral snakes. Overlapping peptides from the sequence of each toxin were prepared by SPOT method and three different anti-elapidic sera were used to map the epitopes. After immunogenicity analysis of the spot-reactive peptides by EPITOPIA, a computational method, nine sequences from the five toxins were chemically synthesized and antigenically and immunogenically characterized. All the peptides were used together as immunogens in rabbits, delivered with Freund's adjuvant for a first cycle of immunization and Montanide in the second. A good antibody response against individual synthetic peptides and M. corallinus venom was achieved. Anti-peptide IgGs were also cross-reactive against Micrurus frontalis and Micrurus lemniscatus crude venoms. In addition, anti-peptide IgGs inhibits the lethal and phospholipasic activities of M. corallinus crude venom. Our results provide a rational basis to the identification of neutralizing epitopes on coral snake toxins and show that their corresponding synthetic peptides could improve the generation of immuno-therapeutics. The use of synthetic peptide for immunization is a reasonable approach, since it enables poly-specificity, low risk of toxic effects and large scale production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Melt With This Kiss: Paralyzing and Liquefying Venom of The Assassin Bug Pristhesancus plagipennis (Hemiptera: Reduviidae).

    Science.gov (United States)

    Walker, Andrew A; Madio, Bruno; Jin, Jiayi; Undheim, Eivind A B; Fry, Bryan G; King, Glenn F

    2017-04-01

    Assassin bugs (Hemiptera: Heteroptera: Reduviidae) are venomous insects, most of which prey on invertebrates. Assassin bug venom has features in common with venoms from other animals, such as paralyzing and lethal activity when injected, and a molecular composition that includes disulfide-rich peptide neurotoxins. Uniquely, this venom also has strong liquefying activity that has been hypothesized to facilitate feeding through the narrow channel of the proboscis-a structure inherited from sap- and phloem-feeding phytophagous hemipterans and adapted during the evolution of Heteroptera into a fang and feeding structure. However, further understanding of the function of assassin bug venom is impeded by the lack of proteomic studies detailing its molecular composition.By using a combined transcriptomic/proteomic approach, we show that the venom proteome of the harpactorine assassin bug Pristhesancus plagipennis includes a complex suite of >100 proteins comprising disulfide-rich peptides, CUB domain proteins, cystatins, putative cytolytic toxins, triabin-like protein, odorant-binding protein, S1 proteases, catabolic enzymes, putative nutrient-binding proteins, plus eight families of proteins without homology to characterized proteins. S1 proteases, CUB domain proteins, putative cytolytic toxins, and other novel proteins in the 10-16-kDa mass range, were the most abundant venom components. Thus, in addition to putative neurotoxins, assassin bug venom includes a high proportion of enzymatic and cytolytic venom components likely to be well suited to tissue liquefaction. Our results also provide insight into the trophic switch to blood-feeding by the kissing bugs (Reduviidae: Triatominae). Although some protein families such as triabins occur in the venoms of both predaceous and blood-feeding reduviids, the composition of venoms produced by these two groups is revealed to differ markedly. These results provide insights into the venom evolution in the insect suborder

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

    Directory of Open Access Journals (Sweden)

    Mehdi Khoobdel

    2013-12-01

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

  15. Antiallodynic Effects of Bee Venom in an Animal Model of Complex Regional Pain Syndrome Type 1 (CRPS-I).

    Science.gov (United States)

    Lee, Sung Hyun; Lee, Jae Min; Kim, Yun Hong; Choi, Jung Hyun; Jeon, Seung Hwan; Kim, Dong Kyu; Jeong, Hyeon Do; Lee, You Jung; Park, Hue Jung

    2017-09-15

    Neuropathic pain in a chronic post-ischaemic pain (CPIP) model mimics the symptoms of complex regional pain syndrome type I (CRPS I). The administration of bee venom (BV) has been utilized in Eastern medicine to treat chronic inflammatory diseases accompanying pain. However, the analgesic effect of BV in a CPIP model remains unknown. The application of a tight-fitting O-ring around the left ankle for a period of 3 h generated CPIP in C57/Bl6 male adult mice. BV (1 mg/kg ; 1, 2, and 3 times) was administered into the SC layer of the hind paw, and the antiallodynic effects were investigated using the von Frey test and by measuring the expression of neurokinin type 1 (NK-1) receptors in dorsal root ganglia (DRG). The administration of BV dose-dependently reduced the pain withdrawal threshold to mechanical stimuli compared with the pre-administration value and with that of the control group. After the development of the CPIP model, the expression of NK-1 receptors in DRG increased and then decreased following the administration of BV. SC administration of BV results in the attenuation of allodynia in a mouse model of CPIP. The antiallodynic effect was objectively proven through a reduction in the increased expression of NK-1 receptors in DRG.

  16. Dominant lethal and ovarian effects of plutonium-239 in female mice

    International Nuclear Information System (INIS)

    Searle, A.G.; Beechey, C.V.; Green, D.; Howells, G.R.

    1982-01-01

    (C3H x 101)F 1 female mice were injected intravenously with 239 Pu in trisodium citrate, then mated in pairs to strain CBA males, to test for dominant lethality. In the first experiment 10μCi kg -1 and in the second 20μCi kg -1 body mass was injected. Matings were after 6 days in the first experiment (estimated ovarian absorbed dose of 0.1 Gy) and after 3,6 or 12 weeks in the second (estimated ovarian doses of 1.11, 2.45 and 5.91 Gy respectively). No evidence of dominant lethal induction was found in the first experiment, but in the second there was a significant increase over controls in pre-implantation loss in all three series. Post-implantation lethality increased significantly (by 12%) only after 12 weeks' exposure. With the 6- and 12-week exposures (especially the latter) luteal counts fell, fewer females becoming pregnant than in controls. This is attributed to oocyte killing by the α-particles. Histological and autoradiographic investigations showed a marked reduction in ovarian size and follicular numbers with fission-tracks clustered mainly over the medullary stroma. The preimplantation loss may stem from lowered fertilization of oocytes because of their damage, so that the best measure of dominant lethality is that based on post-implantation death. (author)

  17. Activity evaluation from different native or irradiated with {sup 60} Co gamma rays snake venoms and their inhibitory effect on Leishmania (Leishmania) amazonensis; Avaliacao da atividade de diferentes venenos de serpentes, nativos ou irradiados, com radiacao gama de {sup 60} Co, quanto ao poder inibitorio do crescimento de Leishmania (Leishmania) amazonensis

    Energy Technology Data Exchange (ETDEWEB)

    Lourenco, Cecilia de Oliveira

    2000-07-01

    Cutaneous leishmaniasis is a disease, caused by Leishmania parasites, that occurs frequently in tropical and sub-tropical regions of the world. Skin lesions that could results in disfiguring aspect characterize it. The treatment is based on few drugs as antimony salts or pentamidine that are toxic with increasing resistance by the parasite. Alternative forms of disease treatment are in constant search, including natural components as snake venoms. Previous studies demonstrate that some components of snake venoms have an inhibitory effect against those parasites, including Leishmania species. Although snake venoms presented high toxicity, several methods have been described to detoxify most or some of their toxic components, with favorable results by the use of gamma irradiation. In this report we tested several native and irradiated snake venoms for inhibitory effect against Leishmania (Leishmania) amazonensis parasite and LLCMK{sub 2} mammalian cells, with enzymatic tests and electrophoresis. There are significant activity in Acanthophis antarcticus, Agkistrodon bilineatus, Bothrops moojeni, Bothrops jararaca, Hoplocephalus stephensi, Naja melanoleuca, Naja mossambica, Pseudechis australis, Pseudechis colletti, Pseudechis guttatus and Pseudechis porphyriacus, venom being inactive Pseudonaja textilis, Notechis ater niger, Notechis scutatus. Oxyuranus microlepidotus and Oxyuranus scutellatus venoms. After 2 KGy of {sup 60}Co irradiation most venom loses significantly their activity. Venoms with antileishmanial activity presented L-amino acid oxidase (L-AO) activity and showed common protein with a molecular weight about 60kDa in SDS-PAGE. These results indicate that L-AO activity in those venoms are probably related with antileishmanial effect. (author)

  18. Effects of lethal dose of γ-irradiation on intestinal enzymes of the pigeons Columba livia intermedia Strickland

    International Nuclear Information System (INIS)

    Gadhia, P.K.

    1979-01-01

    Effect of γ-irradiation with lethal dose (1000 rads) on alkaline phosphatase and glucose-6-phosphatase have been studied in two different regions (duodenum and ileum) of small intestine of pigeons. The enzymes were studied at different intervals like 2, 4, 6 and 8 days after irradiation. The sp. activities of enzyme increased significantly both in duodenum and ileum. However, significant increase in alkaline phosphatase and glucose-6-phosphatase were observed at the 2nd and the 4th days post-irradiation respectively. The increase in enzyme activities may present de novo synthesis of these enzymes after lethal dose of irradiation. The histologic picture revealed that after the 4th day of irradiation, the number of goblet cells increased and after the 6th day crypt-villus system was destroyed completely as compared to sham-irradiated pigeons. (author)

  19. Effects of lethal dose of. gamma. -irradiation on intestinal enzymes of the pigeons Columba livia intermedia Strickland

    Energy Technology Data Exchange (ETDEWEB)

    Gadhia, P.K. (South Gujarat Univ., Surat (India). Dept. of Biosciences); Shah, V.C. (Gujarat Univ. School of Sciences, Ahmedabad (India))

    1979-09-01

    Effect of ..gamma..-irradiation with lethal dose (1000 rads) on alkaline phosphatase and glucose-6-phosphatase have been studied in two different regions (duodenum and ileum) of small intestine of pigeons. The enzymes were studied at different intervals like 2, 4, 6 and 8 days after irradiation. The sp. activities of enzyme increased significantly both in duodenum and ileum. However, significant increase in alkaline phosphatase and glucose-6-phosphatase were observed at the 2nd and the 4th days post-irradiation respectively. The increase in enzyme activities may present de novo synthesis of these enzymes after lethal dose of irradiation. The histologic picture revealed that after the 4th day of irradiation, the number of goblet cells increased and after the 6th day crypt-villus system was destroyed completely as compared to sham-irradiated pigeons.

  20. The status of taxonomy and venom in sea snakes

    DEFF Research Database (Denmark)

    Redsted Rasmussen, Arne; Sanders, Kate L.

    2017-01-01

    The status of taxonomy and venom in sea snakesArne R Rasmussen1, Kate L Sanders21 The Royal Danish Academy of Fine Arts, School of Architecture, Design & Conservation, Copenhagen, Denmark2 School of Earth and Environmental Sciences, University of Adelaide, Adelaide, South Australia 5000, Australia......, the Aipysurus group was separated from the other viviparous sea snakes at around 5.8 million years before present and in the Hydrophis lineage the Hydrophis group was separated from the three semi-marine lineages at around 4.4 million years before present. The venoms of sea snakes are rather simple, typically...... containing a-neurotoxins and phospholipases A2 (PLA2s), and in terms of lethality are known to be more potent than the venoms from terrestrial snakes....

  1. Bee Venom Phospholipase A2: Yesterday’s Enemy Becomes Today’s Friend

    OpenAIRE

    Gihyun Lee; Hyunsu Bae

    2016-01-01

    Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases inc...

  2. Protective Effects of Intratracheally-Administered Bee Venom Phospholipase A2 on Ovalbumin-Induced Allergic Asthma in Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Hwa Jung

    2016-09-01

    Full Text Available Asthma is a common chronic disease characterized by bronchial inflammation, reversible airway obstruction, and airway hyperresponsiveness (AHR. Current therapeutic options for the management of asthma include inhaled corticosteroids and β2 agonists, which elicit harmful side effects. In the present study, we examined the capacity of phospholipase A2 (PLA2, one of the major components of bee venom (BV, to reduce airway inflammation and improve lung function in an experimental model of asthma. Allergic asthma was induced in female BALB/c mice by intraperitoneal administration of ovalbumin (OVA on days 0 and 14, followed by intratracheal challenge with 1% OVA six times between days 22 and 30. The infiltration of immune cells, such as Th2 cytokines in the lungs, and the lung histology, were assessed in the OVA-challenged mice in the presence and absence of an intratracheal administration of bvPLA2. We showed that the intratracheal administration of bvPLA2 markedly suppressed the OVA-induced allergic airway inflammation by reducing AHR, overall area of inflammation, and goblet cell hyperplasia. Furthermore, the suppression was associated with a significant decrease in the production of Th2 cytokines, such as IL-4, IL-5, and IL-13, and a reduction in the number of total cells, including eosinophils, macrophages, and neutrophils in the airway.

  3. Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom.

    Science.gov (United States)

    Olmedo, Hidekel; Herrera, María; Rojas, Leonardo; Villalta, Mauren; Vargas, Mariángela; Leiguez, Elbio; Teixeira, Catarina; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo; Montero, Mavis L

    2014-01-01

    The adjuvanticity of aluminum hydroxide and calcium phosphate on the antibody response in mice towards the venom of the snake Bothrops asper was studied. It was found that, in vitro, most of the venom proteins are similarly adsorbed by both mineral salts, with the exception of some basic phospholipases A2, which are better adsorbed by calcium phosphate. After injection, the adjuvants promoted a slow release of the venom, as judged by the lack of acute toxicity when lethal doses of venom were administered to mice. Leukocyte recruitment induced by the venom was enhanced when it was adsorbed on both mineral salts; however, venom adsorbed on calcium phosphate induced a higher antibody response towards all tested HPLC fractions of the venom. On the other hand, co-precipitation of venom with calcium phosphate was the best strategy for increasing: (1) the capacity of the salt to couple venom proteins in vitro; (2) the venom ability to induce leukocyte recruitment; (3) phagocytosis by macrophages; and (4) a host antibody response. These findings suggest that the chemical nature is not the only one determining factor of the adjuvant activity of mineral salts.

  4. Lethal and Mutagenic Effects of Tritium Decay Produced by Tritiated Compounds Incorporated into Bacteria and Bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Person, S. [Pennsylvania State University, University Park, PA (United States)

    1968-06-15

    The work discussed below is predominantly from the author's laboratory. Some effects of tritium decay on bacteria and bacteriophages, using labelled compounds that are incorporated preferentially into DNA, RNA or protein, have been studied. A relatively high killing efficiency, the probability that a single decay produces loss of colony-forming ability in bacteria or loss of plaque-forming ability in bacteriophages, is observed for thymidine- methyl-{sup 3}H decay, but this is thought to be due to S-particle ionization damage. The most definitive experiments involved a comparison of killing efficiencies for decays originating as thymidine-methyl-{sup 3}H in phage DNA and as amino acid-{sup 3}H in phage protein with the calculated {beta}-particle path length through, the DNA in the two cases. Experimental and calculated values are essentially the same. Radiation-dose calculations to many different bacterial sub-volumes were determined for several different distributions of radioactivity. The high killing efficiency for thymidine-methyl- {sup 3}H decay can be explained by {beta}-particle ionizations, providing DNA is the sensitive target molecule and it is organized in a central volume of the cell (see also Ref.[24]). Although both the lethal and mutagenic effect of thymidine-methyl-{sup 3}H and amino acid-{sup 3}H decays can readily be explained on the basis of {beta}-particle ionizations, the observed large mutation frequency produced by uracil-5{sup 3}H decay cannot. The majority of mutations produced by uracil-5{sup 3}H decays are due to a specific chemical rearrangement of the parent molecule, since decays from uracil-6{sup 3}H are 6 to 7-fold less mutagenic. It is clear that the decays leading to mutations for cells labelled with uracil-5{sup 3}H originate as cytosine-5{sup 3}H in bacterial DNA. Recent work shows that the specific chemical rearrangement causes a C --> T(u) genetic coding change. (author)

  5. Allergies to Insect Venom

    Science.gov (United States)

    ... insects (as might be the case when a nest is disturbed, or when Africanized honeybees are involved); ... test with the five commercially available venoms; honey bee, paper wasp, yellow jacket, yellow hornet and white- ...

  6. Guillain-Barré syndrome following bee venom acupuncture.

    Science.gov (United States)

    Lee, Hyun Jo; Park, In Seok; Lee, Jon-In; Kim, Joong-Seok

    2015-01-01

    Bee venom acupuncture has been widely used in Oriental medicine with limited evidence of effectiveness. Most of the complications due to bee venom acupuncture are local or systemic allergic reactions. However, serious medical and neurological complications have also been reported. We herein describe the treatment of a 68-year-old woman who developed progressive quadriplegia 10 days after receiving multiple honeybee venom sting acupuncture treatments. The electrophysiological findings were consistent with Guillain-Barré syndrome (GBS). The temporal relationship between the development of GBS and honeybee venom sting acupuncture is suggestive of a cause-and-effect relationship, although the precise pathophysiology and causative components in honeybee venom need to be verified.

  7. Interactive lethal and mutagenic effects of ultraviolet light and bleomycin in yeast: synergism or antagonism?

    Science.gov (United States)

    Lillo, O L; Severgnini, A A; Nunes, E M

    1997-11-01

    The mutagenic interactions of ultraviolet light and bleomycin in haploid populations of Saccharomyces cerevisiae were analyzed. Survival and mutation frequency as a function of different bleomycin concentrations after one conditioning dose of UV radiation were determined. Furthermore, corresponding interaction functions and sensitization factors were calculated. A synergistic interaction between UV light and bleomycin was shown for both lethal and mutagenic events when the cells were in nutrient broth during the treatments. Conversely, the interaction between UV light and bleomycin was antagonistic when the cells were in deionized water during the treatment. The magnitude of lethal and mutagenic interactions depends on dose, and thus presumably on the number of lesions. The observed interactions between UV light and bleomycin suggest that the mechanism that is most likely involved is the induction of repair systems with different error probabilities during the delay of cell division.

  8. Pharmacokinetics of Snake Venom

    Directory of Open Access Journals (Sweden)

    Suchaya Sanhajariya

    2018-02-01

    Full Text Available Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present and Medline (1946–present. For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, the disposition of snake venom was described by a two-compartment model consisting of a rapid distribution phase and a slow elimination phase, with half-lives of 5 to 48 min and 0.8 to 28 h, respectively, following rapid intravenous injection of the venoms or toxins. When the venoms or toxins were administered intramuscularly or subcutaneously, an initial absorption phase and slow elimination phase were observed. The bioavailability of venoms or toxins ranged from 4 to 81.5% following intramuscular administration and 60% following subcutaneous administration. The volume of distribution and the clearance varied between snake species. For humans, 24 out of 666 initially identified publications contained sufficient information and timed venom concentrations in the absence of antivenom therapy for data extraction. The data were extracted and modelled in NONMEM. A one-compartment model provided the best fit, with an elimination half-life of 9.71 ± 1.29 h. It is intended that the quantitative information provided in this review will provide a useful basis for future studies that address the pharmacokinetics of snakebite in humans.

  9. Snake Venom Metalloproteinases

    OpenAIRE

    Gâz Florea Şerban Andrei; Gâz Florea Adriana; Kelemen Hajnal; Muntean Daniela-Lucia

    2016-01-01

    As more data are generated from proteome and transcriptome analysis revealing that metalloproteinases represent most of the Viperid and Colubrid venom components authors decided to describe in a short review a classification and some of the multiple activities of snake venom metalloproteinases. SVMPs are classified in three major classes (P-I, P-II and P-III classes) based on the presence of various domain structures and according to their domain organization. Furthermore, P-II and P-III clas...

  10. Effects of irradiated Bothropstoxin-1 and Bothrops jararacussu crude venom on the immune system; Acao da Bothropstoxina-1 e do veneno total de Bothrops jararacussu irradiados sobre o sistema imune

    Energy Technology Data Exchange (ETDEWEB)

    Caproni, Priscila

    2009-07-01

    Ionizing radiation has been successfully employed to modify the immunological properties of biomolecules and has been proven to be a powerful tool to attenuate snake venoms toxicity without affecting and even increasing their immunogenic properties. Very promising results were obtained when crude animal venoms, as well as isolated toxins, were treated with {sup 60}Co gamma rays, yielding toxoids with good immunogenicity, however, little is known about the modifications that irradiated molecules undergo and even less about the immunological response that such antigens elicit. At the present work, we have evaluated the effects on immune system of B10.PL and BALB/c mice of Bothrops jararacussu crude venom and isolated bothropstoxin-1 (Bthx-1), before and after gamma radiation exposition. According to our data, irradiation process promoted structural modifications on both isolated toxin and crude venom, characterized by higher molecular weight protein (aggregates and oligomers) formation. Irradiated samples were immunogenic and the antibodies elicited by them were able to recognize the native toxin in ELISA. These results indicate that irradiation of toxic proteins can promote significant modifications in their structures, but still retain many of the original antigenic and immunological properties. Also, our data indicate that the irradiated protein induced higher titers of IgG2b, suggesting that Th1 cells were predominantly involved. Results from Western blot assay showed that antibodies raised against irradiated bothropstoxin-1 recognize both native isolated toxin or crude venom. Cytotoxicity assay showed that irradiated toxin and crude venom were less toxic than their native counterpart. Thus, the viability of the macrophages cultured in the presence of irradiated Bthx-1 or crude venom was higher if compared with their native forms. LDH Assay showed that irradiated Bthx-1 promotes less muscular damage than the native form. Our data confirm a potential use of

  11. A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome.

    Science.gov (United States)

    Cuykendall, Tawny N; Satyaki, P; Ji, Shuqing; Clay, Derek M; Edelman, Nathaniel B; Kimchy, Alexandra; Li, Ling-Hei; Nuzzo, Erin A; Parekh, Neil; Park, Suna; Barbash, Daniel A

    2014-10-27

    Hybrid sons between Drosophila melanogaster females and D. simulans males die as 3rd instar larvae. Two genes, D. melanogaster Hybrid male rescue (Hmr) on the X chromosome, and D. simulans Lethal hybrid rescue (Lhr) on chromosome II, interact to cause this lethality. Loss-of-function mutations in either gene suppress lethality, but several pieces of evidence suggest that additional factors are required for hybrid lethality. Here we screen the D. melanogaster autosomal genome by using the Bloomington Stock Center Deficiency kit to search for additional regions that can rescue hybrid male lethality. Our screen is designed to identify putative hybrid incompatibility (HI) genes similar to Hmr and Lhr which, when removed, are dominant suppressors of lethality. After screening 89% of the autosomal genome, we found no regions that rescue males to the adult stage. We did, however, identify several regions that rescue up to 13% of males to the pharate adult stage. This weak rescue suggests the presence of multiple minor-effect HI loci, but we were unable to map these loci to high resolution, presumably because weak rescue can be masked by genetic background effects. We attempted to test one candidate, the dosage compensation gene male specific lethal-3 (msl-3), by using RNA interference with short hairpin microRNA constructs targeted specifically against D. simulans msl-3 but failed to achieve knockdown, in part due to off-target effects. We conclude that the D. melanogaster autosomal genome likely does not contain additional major-effect HI loci. We also show that Hmr is insufficient to fully account for the lethality associated with the D. melanogaster X chromosome, suggesting that additional X-linked genes contribute to hybrid lethality. Copyright © 2014 Cuykendall et al.

  12. Snake venoms components with antitumor activity in murine melanoma cells

    International Nuclear Information System (INIS)

    Queiroz, Rodrigo Guimaraes

    2012-01-01

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  13. Enzymatic analysis of Hemiscorpius lepturus scorpion venom using zymography and venom-specific antivenin.

    Science.gov (United States)

    Seyedian, Ramin; Pipelzadeh, Mohammad Hassan; Jalali, Amir; Kim, Euikyung; Lee, Hyunkyoung; Kang, Changkeun; Cha, Mijin; Sohn, Eun-Tae; Jung, Eun-Sun; Rahmani, Ali Hassan; Mirakabady, Abbas Zare

    2010-09-15

    Hemiscorpius lepturus envenomation exhibits various pathological changes in the affected tissues, including skin, blood cells, cardiovascular and central nervous systems. The enzymatic activity and protein component of the venom have not been described previously. In the present study, the electrophoretic profile of H. lepturus venom was determined by SDS-PAGE (12 and 15%), resulting in major protein bands at 3.5-5, 30-35 and 50-60 kDa. The enzymatic activities of the venom was, for the first time, investigated using various zymography techniques, which showed the gelatinolytic, caseinolytic, and hyaluronidase activities mainly at around 50-60 kDa, 30-40 kDa, and 40-50 kDa, respectively. Among these, the proteolytic activities was almost completely disappeared in the presence of a matrix metalloproteinase inhibitor, 1, 10-phenanthroline. Antigen-antibody interactions between the venom and its Iranian antivenin was observed by Western blotting, and it showed several antigenic proteins in the range of 30-160 kDa. This strong antigen-antibody reaction was also demonstrated through an enzyme-linked immunosorbent assay (ELISA). The gelatinase activity of the venom was suppressed by Razi institute polyvalent antivenin, suggesting the inhibitory effect of the antivenin against H. lepturus venom protease activities. Prudently, more extensive clinical studies are necessary for validation of its use in envenomed patients. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Anti-scorpion venom activity of Andrographis paniculata: A combined and comparative study with anti-scorpion serum in mice

    Directory of Open Access Journals (Sweden)

    Ranjana S Kale

    2013-01-01

    Conclusions: Present study demonstrates that, both plant extract and ASV have their own scorpion venom neutralising ability in vivo and in vitro, but their combination is most effective in venom neutralizing ability.

  15. A 13-year real-life study on efficacy, safety and biological effects of Vespula venom immunotherapy.

    Science.gov (United States)

    Albanesi, Marcello; Nico, Andrea; Sinisi, Alessandro; Giliberti, Lucia; Rossi, Maria Pia; Rossini, Margherita; Kourtis, Georgios; Rucco, Anna Simona; Loconte, Filomena; Muolo, Loredana; Zurlo, Marco; Di Bona, Danilo; Caiaffa, Maria Filomena; Macchia, Luigi

    2018-01-01

    Hymenoptera venom immunotherapy (VIT) is a clinically effective treatment. However, little is known about its long-term clinical efficacy and biological effects. Several mechanisms have been proposed to account for VIT efficacy, including reduction of specific IgE and induction of allergen-specific IgG 4 , but the overall picture remains elusive. We investigated Vespula VIT clinical efficacy up to 8 years after discontinuation and the kinetics of Vespula -specific IgE and IgG 4 . Out of 686 consecutive patients we retrospectively selected and analysed a series of 23 patients with Vespula allergy that underwent a 5-year IT course, followed by a prolonged follow-up. Clinical efficacy of VIT was assessed as number and severity of reactions to Vespula re-stinging events. The presence of Vespula -specific IgE and IgG 4 was also monitored over time. During the VIT treatment, patients were protected, reporting no reactions or mild reactions in occasion of re-stinging events. This protection was entirely maintained during the follow-up, up to 8 years. Skin reactivity (reflecting mast cell-bound Vespula -specific IgE) and circulating Vespula -specific IgE levels declined substantially during VIT. Notably, this reduction was maintained over time during the follow-up. Moreover, all the patients were analysed for IgG 4 . A robust induction of Vespula -specific IgG 4 was observed during the VIT course, with a substantial decline during the follow-up. We conclude that Vespula VIT is a clinically effective treatment, which induces long-term protection after discontinuation. The reduction of specific IgE, assessed by skin tests and RAST, closely matches the VIT- induced protection, while the IgG 4 induction seems not to be associated with VIT clinical efficacy in the long term.

  16. Allergen immunotherapy for insect venom allergy

    DEFF Research Database (Denmark)

    Dhami, S; Zaman, H; Varga, E-M

    2016-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety...... of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were...

  17. Anaphylaxis to Insect Venom Allergens

    DEFF Research Database (Denmark)

    Ollert, Markus; Blank, Simon

    2015-01-01

    available for diagnostic measurement of specific IgE in venom-allergic patients. These recombinant venom allergens offer several promising possibilities for an improved diagnostic algorithm. Reviewed here are the current status, recent developments, and future perspectives of molecular diagnostics of venom...

  18. Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom.

    Science.gov (United States)

    Castanheira, Letícia Eulalio; Lopes, Daiana Silva; Gimenes, Sarah Natalie Cirilo; Deconte, Simone Ramos; Ferreira, Bruno Antônio; Alves, Patricia Terra; Filho, Luiz Ricardo Goulart; Tomiosso, Tatiana Carla; Rodrigues, Renata Santos; Yoneyama, Kelly Aparecida Geraldo; Araújo, Fernanda de Assis; Rodrigues, Veridiana de Melo

    2017-09-01

    The present work reports the effects of a C-type lectin (BpLec) isolated from Bothrops pauloensis snake venom upon in vitro and in vivo angiogenesis models. Initially, we noted that BpLec was not cytotoxic to endothelial cells (tEnd) in doses up to 40μg/mL, but lower doses (2.5μg/mL, 5μg/mL, 10μg/mL and 20μg/mL) reduced tEnd cells adhesion to some extracellular matrix proteins and inhibited the in vitro vessel formation in Matrigel assay stimulated by bFGF. β-galactosides (d-lactose, N-acetyl-d-galactosamine and d-galactose) at 400mM reversed the effect of BpLec on tEnd cells adhesion, whereas d-galactose (400mM) partially reversed BpLec property of inhibiting vessel formation by tEnd cells in Matrigel. In vivo assays showed that BpLec increased hemoglobin content and capillary vessels number in polyether-polyurethane sponge discs subcutaneously implanted into dorsal skin mice. Additionally, BpLec also reduced collagen deposition and did not induce a pro-inflammatory response, as demonstrated by the decreased the secretion of some inflammatory cytokines, whereas myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities were not altered by BpLec. Taken together, our results indicate that BpLec might represent an interesting angiogenesis and inflammatory modulator that could also be used for searching possible therapeutic targets involved in these processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Analgesic Effects of Bee Venom Derived Phospholipase A(2) in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain.

    Science.gov (United States)

    Li, Dongxing; Lee, Younju; Kim, Woojin; Lee, Kyungjin; Bae, Hyunsu; Kim, Sun Kwang

    2015-06-29

    A single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms. Our recent study demonstrated that BV alleviates oxaliplatin-induced cold allodynia in rats, via noradrenergic and serotonergic analgesic pathways. In this study, we have further investigated whether BV derived phospholipase A2 (bvPLA2) attenuates oxaliplatin-induced cold and mechanical allodynia in mice and its mechanism. The behavioral signs of cold and mechanical allodynia were evaluated by acetone and a von Frey hair test on the hind paw, respectively. The significant allodynia signs were observed from one day after an oxaliplatin injection (6 mg/kg, i.p.). Daily administration of bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days markedly attenuated cold and mechanical allodynia, which was more potent than the effect of BV (1 mg/kg, i.p.). The depletion of noradrenaline by an injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 50 mg/kg, i.p.) blocked the analgesic effect of bvPLA2, whereas the depletion of serotonin by injecting DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for three successive days did not. Furthermore, idazoxan (α2-adrenegic receptor antagonist, 1 mg/kg, i.p.) completely blocked bvPLA2-induced anti-allodynic action, whereas prazosin (α1-adrenegic antagonist, 10 mg/kg, i.p.) did not. These results suggest that bvPLA2 treatment strongly alleviates oxaliplatin-induced acute cold and mechanical allodynia in mice through the activation of the noradrenergic system, via α2-adrenegic receptors, but not via the serotonergic system.

  20. Mutagenesis-mediated virus extinction: virus-dependent effect of viral load on sensitivity to lethal defection.

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    Héctor Moreno

    Full Text Available BACKGROUND: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI on progeny production of several RNA viruses under enhanced mutagenesis. RESULTS: The effect of the mutagenic base analogue 5-fluorouracil (FU on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity of infection (MOI, or in a moderate titer decrease without extinction at high MOI. The effect of the MOI is similar for LCMV and vesicular stomatitis virus (VSV, but minimal or absent for the picornaviruses foot-and-mouth disease virus (FMDV and encephalomyocarditis virus (EMCV. The increase in mutation frequency and Shannon entropy (mutant spectrum complexity as a result of virus passage in the presence of FU was more accentuated at low MOI for LCMV and VSV, and at high MOI for FMDV and EMCV. We present an extension of the lethal defection model that agrees with the experimental results. CONCLUSIONS: (i Low infecting load favoured the extinction of negative strand viruses, LCMV or VSV, with an increase of mutant spectrum complexity. (ii This behaviour is not observed in RNA positive strand viruses, FMDV or EMCV. (iii The accumulation of defector genomes may underlie the MOI-dependent behaviour. (iv LCMV coinfections are allowed but superinfection is strongly restricted in BHK-21 cells. (v The dissimilar effects of the MOI on the efficiency of mutagenic-based extinction of different RNA viruses can have implications for the design of antiviral protocols based on lethal mutagenesis, presently under development.

  1. [Influence of electromagnetic radiation on toxicity of Vipera lebetina obtusa venom].

    Science.gov (United States)

    Abiev, G A; Babaev, E I; Topchieva, Sh A; Chumburidze, T B; Nemsitsveridze, N G

    2009-11-01

    The aim of the article was to study the effect of electromagnetic radiation on toxicity of Vipera lebetina obtusa venom. It was found that mice intoxicated with snake venom, with moderate to high exposure to electromagnetic radiation and mice intoxicated with venom, which had not been exposed to the radiation showed the same symptoms of intoxication and death. At the same time, the longevity of mice intoxicated with venom exposed to electromagnetic radiation was higher. The longevity of mice in control group was 25+/-5 min. The longevity of mice intoxicated with exposed to electromagnetic radiation snake venom was from 29 to 60 min. The research showed that the longevity of mice intoxicated with snake venom rose with the level of electromagnetic radiation intensity the snake was exposed to. Accordingly, snake venom, with exposure to high intensity electromagnetic radiation is less toxic.

  2. Lethal effects of solar radiation in proficient and deficient bacteria in repair systems

    International Nuclear Information System (INIS)

    Sousa Neto, A. de.

    1980-01-01

    A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author)

  3. Physiological effects of low doses of Cerastes cerastes crude venom and its influence on doxorubicin treated rats

    International Nuclear Information System (INIS)

    AL-Sadoon, M. K.; Salama, S. F.

    2012-01-01

    The purpose of this study was to investigate the effects of C. cerastes crude venom (CCV) and its influence on doxorubicin (DOX) treated male rats. Thirty two male rats were arranged into four equal groups, control, CCV-group, DOX-group and CCV + DOX-groups. Control group was injected intraperitoneally (i.p.) with saline for 10 days, while CCV-group was injected i.p. with crude CCV at a dose of . Ld50 for 10 days. DOX-group was injected i.p. with DOX at a dose of 2.5 mg/kg body weight for 10 days. CCV + DOX-group was injected i.p. with 2.5 mg/kg daily of DOX and CCV . Ld50 for 10 days. In the CCV group, significant decrease in contents of serum advanced oxidation protein products (AOPP) and malondialdehyde (MDA) as well as significant increase in blood reduced glutathione (GSH), red blood cells (RBCs), platelet counts, hemoglobin content (Hb), hematocrit value (Hct), total leukocyte, neutrophil, lymphocyte counts and relative spleen weight (RSW) were recorded. In DOX- group, a significant increase in contents of serum AOPP and MDA besides a significant decrease in GSH, Hb, Hct, RBCs, platelet counts, , total leukocytes, neutrophils, lymphocytes counts and RSW were recorded. In DOX+ CCV- group, a significant decrease of the serum AOPP and MDA in addition to a significant increase of GSH, RBCs, platelets counts, Hb and Hct were shown as compared with DOX- group, while the suppression of RSW, total leukocytes, neutrophils, lymphocytes counts and histological changes of spleen were non significantly alleviated

  4. Enhanced lethal effect of combined ACNU with x-ray on cultured HeLaS3 cells

    International Nuclear Information System (INIS)

    Kanazawa, Haruyuki; Miyamoto, Tadaaki

    1983-01-01

    The combined effects of ACNU and X-irradiation on cultured HeLaS 3 cells were investigated. Pretreatment with either ACNU or X-ray induced a substantial reduction in shoulder width the D 0 value of the dose-response curve for the other agent, given later was unchanged. ACNU did not inhibit the recovery of sublethal damage (SLD) induced by X-ray when this treatment preceded the spilit-dose experiment. Our results indicate that some cell damage induced by each agent is transmissible to the progeny of the surviving cells and that the interaction of ACNU and X-irradiation was lethal to the cells. (author)

  5. Bee venom treatment for refractory postherpetic neuralgia: a case report.

    Science.gov (United States)

    Lee, Seung Min; Lim, Jinwoong; Lee, Jae-Dong; Choi, Do-Young; Lee, Sanghoon

    2014-03-01

    Bee venom has been reported to have antinociceptive and anti-inflammatory effects in experimental studies. However, questions still remain regarding the clinical use of bee venom. This report describes the successful outcome of bee venom treatment for refractory postherpetic neuralgia. A 72-year-old Korean man had severe pain and hypersensitivity in the region where he had developed a herpes zoster rash 2 years earlier. He was treated with antivirals, painkillers, steroids, and analgesic patches, all to no effect. The patient visited the East-West Pain Clinic, Kyung Hee University Medical Center, to receive collaborative treatment. After being evaluated for bee venom compatibility, he was treated with bee venom injections. A 1:30,000 diluted solution of bee venom was injected subcutaneously along the margins of the rash once per week for 4 weeks. Pain levels were evaluated before every treatment, and by his fifth visit, his pain had decreased from 8 to 2 on a 10-point numerical rating scale. He experienced no adverse effects, and this improvement was maintained at the 3-month, 6-month, and 1-year phone follow-up evaluations. Bee venom treatment demonstrates the potential to become an effective treatment for postherpetic neuralgia. Further large-sample clinical trials should be conducted to evaluate the overall safety and efficacy of this treatment.

  6. Rosmarinic acid, a new snake venom phospholipase A2 inhibitor from Cordia verbenacea (Boraginaceae): antiserum action potentiation and molecular interaction.

    Science.gov (United States)

    Ticli, Fábio K; Hage, Lorane I S; Cambraia, Rafael S; Pereira, Paulo S; Magro, Angelo J; Fontes, Marcos R M; Stábeli, Rodrigo G; Giglio, José R; França, Suzelei C; Soares, Andreimar M; Sampaio, Suely V

    2005-09-01

    Many plants are used in traditional medicine as active agents against various effects induced by snakebite. The methanolic extract from Cordia verbenacea (Cv) significantly inhibited paw edema induced by Bothrops jararacussu snake venom and by its main basic phospholipase A2 homologs, namely bothropstoxins I and II (BthTXs). The active component was isolated by chromatography on Sephadex LH-20 and by RP-HPLC on a C18 column and identified as rosmarinic acid (Cv-RA). Rosmarinic acid is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid [2-O-cafeoil-3-(3,4-di-hydroxy-phenyl)-R-lactic acid]. This is the first report of RA in the species C. verbenacea ('baleeira', 'whaler') and of its anti-inflammatory and antimyotoxic properties against snake venoms and isolated toxins. RA inhibited the edema and myotoxic activity induced by the basic PLA2s BthTX-I and BthTX-II. It was, however, less efficient to inhibit the PLA2 activity of BthTX-II and, still less, the PLA2 and edema-inducing activities of the acidic isoform BthA-I-PLA2 from the same venom, showing therefore a higher inhibitory activity upon basic PLA2s. RA also inhibited most of the myotoxic and partially the edema-inducing effects of both basic PLA2s, thus reinforcing the idea of dissociation between the catalytic and pharmacological domains. The pure compound potentiated the ability of the commercial equine polyvalent antivenom in neutralizing lethal and myotoxic effects of the crude venom and of isolated PLA2s in experimental models. CD data presented here suggest that, after binding, no significant conformation changes occur either in the Cv-RA or in the target PLA2. A possible model for the interaction of rosmarinic acid with Lys49-PLA2 BthTX-I is proposed.

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

    Science.gov (United States)

    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. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and

  8. Lethal and mutagenic effects of radiation and alkylating agents on two strains of mouse L5178Y cells

    International Nuclear Information System (INIS)

    Evans, H.H.; Horng, M.; Beer, J.Z.

    1986-01-01

    The two closely related strains of L5178Y (LY) mouse lymphoma cells, LY-R and LY-S, have been shown to differ in their sensitivity to UV and ionizing radiation. In the present work, the lethal and mutagenic effects of ethyl methanesulfonate (EMS), methyl nitrosourea (MNU) and UV radiation (254 nm) were compared in the two strains. Mutability at the Na + /K + -ATPase locus as well as the HGPRT locus was determined. The authors found strain LY-S to be more resistant than strain LY-R to the lethal effects of UV radiation. In contrast, strain LY-S was more sensitive to the cytotoxic effects of the two alkylating agents. In spite of these differences in sensitivity, the authors found strain LY-S to be less mutable than strain LY-R by all 3 agents at the HGPRT locus. At the Na + /K + -ATPase locus, strain LY-S was also less mutable than strain LY-R by equal concentrations of EMS and UV radiation and by equitoxic concentrations of MNU. However, the difference between the strains was much more pronounced at the HGPRT locus than at the Na + /K + -ATPase locus. The authors have suggested that the interaction of unrepaired lesions in strain LY-S tends to cause an excess of deletions and multilocus effects, which in turn result in a locus-dependent decrease in the recovery of viable LY-S mutant cells. (Auth.)

  9. Identification of anti-tumoral effect of a polypeptide isolated from Scorpionfish Scorpaena plumieri venom and assessment of its potential use for tumor diagnosis

    International Nuclear Information System (INIS)

    Soprani, Juliana

    2008-01-01

    Cancer has killed millions of people worldwide. Despite the increasing knowledge about the molecular basis of tumor development, few advances have been reached in clinical therapy and diagnoses, which shows the importance of new drugs development for therapeutic and diagnosis purpose. Venomous creatures have been studied as potential sources of pharmacological agents and physiological tools. A lot of work has been done about biological activity of terrestrial animals, but comparatively less research has been undertaken on venomous marine creature, particularly fish, which means that marine toxins represent a vast and unexplored source of novel molecules with therapeutical potential. In this work, the scorpion fish Scorpaena plumieri crude venom (SPB) and a gelatinolytic protease purified from this venom (SPGP) were evaluated for their applicability for in vivo tumor detection. In vitro results showed that both. SPB and SPGP, possess a powerful antitumor effects on p53-wild-type glioblastoma cells (LD 50 = 3,9 ± 0,98μg/mL and 8,00 x 10 -12 ± 2,94 x 10 -12 M, respectively) and Ehrlich ascites carcinoma cells (LD 50 =14,05 ± 2,95 μg/mL and 1,22 x 10 -11 ± 6,56 x 10 -12 M, respectively). P53 mutant glioblastoma cells were more resistant to both, SPB and SPGP treatment (LD 50 > 125 μg/mL and LD 50 > 1,39 x 10 -9 M, respectively). The morphological changes observed in the cell lines treated with SPB and SPGP, and the data of DAPI staining, indicate that the antitumor effect of these substances occurs via apoptosis. Radioactive probes of SPB ([ 99m Tc] SPB) and SPGP ([ 125 I] SPGP) with high specific activity and high radiochemical purity were synthesized. Data of biodistribution studies, performed by intravenous injections in Swiss mice bearing Ehrlich carcinoma cells, showed that SPB has poor uptake in tumor region. On the other hand, SPGP had a substantial uptake in tumor at ali analyzed times. Intratumoral administration of [ 125 I]SPGP increased its uptake by

  10. Coral snake venoms: mode of action and pathophysiology of experimental envenomation

    Directory of Open Access Journals (Sweden)

    Oswald Vital Brazil

    1987-06-01

    Full Text Available Coral snakes, the New World Elapidae, are included in the genera Micniroides and Micrurus. The genus Mlcrurus comprises nearly all coral snake species and those which are responsible for human snake-bite accidents. The following generalizations concerning the effects induced by their venoms, and their venom-properties can be made. Coral snake venoms are neurotoxic, producing loss of muscle strenght and death by respiratory paralysis. Local edema and necrosis are not induced nor blood coagulation or hemorrhages. Proteolysis activity is absent or of very low grade. They display phospholipase A2 activity. Nephrotoxic effects are not evoked. The main toxins from elapid venoms are postsynaptic and presynaptic neurotoxins and cardiotoxins. Phospholipases A2 endowed with myonecrotic or cardiotoxin-like properties are important toxic components from some elapid venoms. The mode of action of Micrurus frontalis, M. lemniscatus, M. corallinus and M. fulvius venoms has been investigated in isolated muscle preparations and is here discussed. It is shown that while M. frontalis and M. lemniscatus venoms must contain only neurotoxins that act at the cholinergic end-plate receptor (postsynaptic neurotoxins, M. corallinus venom also inhibits evoked acetylcholine release by the motor nerve endings (presynaptic neurotoxin-like effect and M. fulvius induces muscle fiber membrane depolarization (cardiotoxin-like effect. The effects produced by M. corallinus and M. fulvius venoms in vivo in dogs and M. frontalis venom in dogs and monkeys are also reported.

  11. Bee Venom Phospholipase A2: Yesterday’s Enemy Becomes Today’s Friend

    Science.gov (United States)

    Lee, Gihyun; Bae, Hyunsu

    2016-01-01

    Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson’s disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes. PMID:26907347

  12. Snake Venom Metalloproteinases

    Directory of Open Access Journals (Sweden)

    Gâz Florea Şerban Andrei

    2016-03-01

    Full Text Available As more data are generated from proteome and transcriptome analysis revealing that metalloproteinases represent most of the Viperid and Colubrid venom components authors decided to describe in a short review a classification and some of the multiple activities of snake venom metalloproteinases. SVMPs are classified in three major classes (P-I, P-II and P-III classes based on the presence of various domain structures and according to their domain organization. Furthermore, P-II and P-III classes were separated in subclasses based on distinctive post-translational modifications. SVMPs are synthesized in a latent form, being activated through a Cys-switch mechanism similar to matrix metalloproteinases. Most of the metalloproteinases of the snake venom are responsible for the hemorrhagic events but also have fibrinogenolytic activity, poses apoptotic activity, activate blood coagulation factor II and X, inhibit platelet aggregation, demonstrating that SVMPs have multiple functions in addition to well-known hemorrhagic function.

  13. Which immunotherapy product is better for patients allergic to Polistes venom? A laboratory and clinical study.

    Science.gov (United States)

    Savi, Eleonora; Incorvaia, Cristoforo; Boni, Elisa; Mauro, Marina; Peveri, Silvia; Pravettoni, Valerio; Quercia, Oliviero; Reccardini, Federico; Montagni, Marcello; Pessina, Laura; Ridolo, Erminia

    2017-01-01

    Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal. We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP). The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom. The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom.

  14. Comparison of Phylogeny, Venom Composition and Neutralization by Antivenom in Diverse Species of Bothrops Complex

    Science.gov (United States)

    Peixoto, Pedro S.; Bernardoni, Juliana L.; Oliveira, Sâmella S.; Portes-Junior, José Antonio; Mourão, Rosa Helena V.; Lima-dos-Santos, Isa; Sano-Martins, Ida S.; Chalkidis, Hipócrates M.; Valente, Richard H.; Moura-da-Silva, Ana M.

    2013-01-01

    In Latin America, Bothrops snakes account for most snake bites in humans, and the recommended treatment is administration of multispecific Bothrops antivenom (SAB – soro antibotrópico). However, Bothrops snakes are very diverse with regard to their venom composition, which raises the issue of which venoms should be used as immunizing antigens for the production of pan-specific Bothrops antivenoms. In this study, we simultaneously compared the composition and reactivity with SAB of venoms collected from six species of snakes, distributed in pairs from three distinct phylogenetic clades: Bothrops, Bothropoides and Rhinocerophis. We also evaluated the neutralization of Bothrops atrox venom, which is the species responsible for most snake bites in the Amazon region, but not included in the immunization antigen mixture used to produce SAB. Using mass spectrometric and chromatographic approaches, we observed a lack of similarity in protein composition between the venoms from closely related snakes and a high similarity between the venoms of phylogenetically more distant snakes, suggesting little connection between taxonomic position and venom composition. P-III snake venom metalloproteinases (SVMPs) are the most antigenic toxins in the venoms of snakes from the Bothrops complex, whereas class P-I SVMPs, snake venom serine proteinases and phospholipases A2 reacted with antibodies in lower levels. Low molecular size toxins, such as disintegrins and bradykinin-potentiating peptides, were poorly antigenic. Toxins from the same protein family showed antigenic cross-reactivity among venoms from different species; SAB was efficient in neutralizing the B. atrox venom major toxins. Thus, we suggest that it is possible to obtain pan-specific effective antivenoms for Bothrops envenomations through immunization with venoms from only a few species of snakes, if these venoms contain protein classes that are representative of all species to which the antivenom is targeted. PMID

  15. Which immunotherapy product is better for patients allergic to Polistes venom? A laboratory and clinical study.

    Directory of Open Access Journals (Sweden)

    Eleonora Savi

    Full Text Available Venom immunotherapy (VIT is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal.We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP.The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8% compared with inhibition by mAP venom (64.2% and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1% and by mAP venom (73.6%. Instead, the clinical protection from stings was not statistically different between the two kinds of venom.The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom.

  16. Caenorhabditis elegans as a Model for Toxic Effects of Nanoparticles: Lethality, Growth, and Reproduction.

    Science.gov (United States)

    Maurer, Laura L; Ryde, Ian T; Yang, Xinyu; Meyer, Joel N

    2015-11-02

    The nematode Caenorhabditis elegans is extensively utilized in toxicity studies. C. elegans offers a high degree of homology with higher organisms, and its ease of use and relatively inexpensive maintenance have made it an attractive complement to mammalian and ecotoxicological models. C. elegans provides multiple benefits, including the opportunity to perform relatively high-throughput assays on whole organisms, a wide range of genetic tools permitting investigation of mechanisms and genetic sensitivity, and transparent bodies that facilitate toxicokinetic studies. This unit describes protocols for three nanotoxicity assays in C. elegans: lethality, growth, and reproduction. This unit focuses on how to use these well-established assays with nanoparticles, which are being produced in ever-increasing volume and exhibit physicochemical properties that require alteration of standard toxicity assays. These assays permit a broad phenotypic assessment of nanotoxicity in C. elegans, and, when used in combination with genetic tools and other assays, also permit mechanistic insight. Copyright © 2015 John Wiley & Sons, Inc.

  17. Evaluation of effects of long term exposure on lethal toxicity with mammals.

    Science.gov (United States)

    Verma, Vibha; Yu, Qiming J; Connell, Des W

    2014-02-01

    The relationship between exposure time (LT50) and lethal exposure concentration (LC50) has been evaluated over relatively long exposure times using a novel parameter, Normal Life Expectancy (NLT), as a long term toxicity point. The model equation, ln(LT50) = aLC50(ν) + b, where a, b and ν are constants, was evaluated by plotting lnLT50 against LC50 using available toxicity data based on inhalation exposure from 7 species of mammals. With each specific toxicant a single consistent relationship was observed for all mammals with ν always mammals and then be extended to estimate toxicity at any exposure time with other mammals. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  18. Serotonergic mechanism of the relieving effect of bee venom acupuncture on oxaliplatin-induced neuropathic cold allodynia in rats.

    Science.gov (United States)

    Lee, Ji-Hye; Li, Dong Xing; Yoon, Heera; Go, Donghyun; Quan, Fu Shi; Min, Byung-Il; Kim, Sun Kwang

    2014-12-06

    Oxaliplatin, an important chemotherapy drug for advanced colorectal cancer, often induces peripheral neuropathy, especially cold allodynia. Our previous study showed that bee venom acupuncture (BVA), which has been traditionally used in Korea to treat various pain symptoms, potently relieves oxaliplatin-induced cold allodynia in rats. However, the mechanism for this anti-allodynic effect of BVA remains poorly understood. We investigated whether and how the central serotonergic system, a well-known pathway for acupuncture analgesia, mediates the relieving effect of BVA on cold allodynia in oxaliplatin-injected rats. The behavioral signs of cold allodynia in Sprague-Dawley (SD) rats were induced by a single injection of oxaliplatin (6 mg/kg, i.p.). Before and after BVA treatment, the cold allodynia signs were evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. For BVA treatment, a diluted BV (0.25 mg/kg) was subcutaneously administered into Yaoyangguan (GV3) acupoint, which is located between the spinous processes of the fourth and the fifth lumbar vertebra. Serotonin was depleted by a daily injection of DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for 3 days. The amount of serotonin in the spinal cord was measured by ELISA. Serotonergic receptor antagonists were administered intraperitoneally or intrathecally before BVA treatment. The serotonin levels in the spinal cord were significantly increased by BVA treatment and such increase was significantly reduced by PCPA. This PCPA pretreatment abolished the relieving effect of BVA on oxaliplatin-induced cold allodynia. Either of methysergide (mixed 5-HT1/5-HT2 receptor antagonist, 1 mg/kg, i.p.) or MDL-72222 (5-HT3 receptor antagonist, 1 mg/kg, i.p) blocked the anti-allodynic effect of BVA. Further, an intrathecal injection of MDL-72222 (12 μg) completely blocked the BVA-induced anti-allodynic action, whereas NAN-190 (5-HT1A receptor antagonist, 15 μg, i.t.) or

  19. Role of the inflammasome in defense against venoms

    Science.gov (United States)

    Palm, Noah W.; Medzhitov, Ruslan

    2013-01-01

    Venoms consist of a complex mixture of toxic components that are used by a variety of animal species for defense and predation. Envenomation of mammalian species leads to an acute inflammatory response and can lead to the development of IgE-dependent venom allergy. However, the mechanisms by which the innate immune system detects envenomation and initiates inflammatory and allergic responses to venoms remain largely unknown. Here we show that bee venom is detected by the NOD-like receptor family, pyrin domain-containing 3 inflammasome and can trigger activation of caspase-1 and the subsequent processing and unconventional secretion of the leaderless proinflammatory cytokine IL-1β in macrophages. Whereas activation of the inflammasome by bee venom induces a caspase-1–dependent inflammatory response, characterized by recruitment of neutrophils to the site or envenomation, the inflammasome is dispensable for the allergic response to bee venom. Finally, we find that caspase-1–deficient mice are more susceptible to the noxious effects of bee and snake venoms, suggesting that a caspase-1–dependent immune response can protect against the damaging effects of envenomation. PMID:23297192

  20. Human antibody fragments specific for Bothrops jararacussu venom reduce the toxicity of other Bothrops sp. venoms.

    Science.gov (United States)

    Roncolato, Eduardo Crosara; Pucca, Manuela Berto; Funayama, Jaqueline Carlos; Bertolini, Thaís Barboza; Campos, Lucas Benício; Barbosa, José Elpidio

    2013-01-01

    Approximately 20,000 snakebites are registered each year in Brazil. The classical treatment for venomous snakebite involves the administration of sera obtained from immunized horses. Moreover, the production and care of horses is costly, and the use of heterologous sera can cause hypersensitivity reactions. The production of human antibody fragments by phage display technology is seen as a means of overcoming some of these disadvantages. The studies here attempted to test human monoclonal antibodies specific to Bothrops jararacussu against other Bothrops sp. venoms, using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Using the Griffin.1 phage antibody library, this laboratory previously produced scFvs capable of inhibiting the phospholipase and myotoxic activities of Bothrops jararacussu venom. The structural and functional similarities of the various forms of phospholipase A2 (PLA₂) in Bothrops venom served as the basis for the present study wherein the effectiveness of those same scFvs were evaluated against B. jararaca, B. neuwiedi, and B. moojeni venoms. Each clone was found to recognize all three Bothrops venoms, and purified scFvs partially inhibited their in vitro phospholipase activity. In vivo assays demonstrated that the scFv clone P2B7 reduced myotoxicity and increased the survival of animals that received the test venoms. The results here indicate that the scFv P2B7 is a candidate for inclusion in a mixture of specific antibodies to produce a human anti-bothropic sera. This data demonstrates that the human scFv P2B7 represents an alternative therapeutic approach to heterologous anti-bothropic sera available today.

  1. Addiction to Snake Venom.

    Science.gov (United States)

    Das, Saibal; Barnwal, Preeti; Maiti, Tanay; Ramasamy, Anand; Mondal, Somnath; Babu, Dinesh

    2017-07-03

    The nature of addiction depends on various factors. The tendency to have already used several addictive substances and to seek high sensation experiences as a result of specific personality traits may lead to extreme and peculiar forms of addictions. Even belonging to specific social and cultural background may lead to such forms of addiction such as intentional snake bite and willful envenomation. In this article, we have discussed the peculiarities and practical insight of such addiction to snake venom. The possible molecular mechanism behind such venom-mediated reinforcement has also been highlighted. Finally, we have stressed upon the treatment and de-addiction measures.

  2. Predation risk affects growth and reproduction of an invasive snail and its lethal effect depends on prey size

    Science.gov (United States)

    Guo, Jing; Martín, Pablo R.; Zhang, Chunxia

    2017-01-01

    The behavior of invasive species under predation risk has been studied extensively, but their growth and reproductive responses have rarely been investigated. We conducted experiments with juveniles and adults of the invasive freshwater snail Pomacea canaliculata, and we observed changes in growth and reproduction in response to predation risk from a caged predator (Trachemys scripta elegans). P. canaliculata produced eggs earlier in the presence of predators and injured conspecifics compared with the control group (no risk), although the total number of egg masses laid by per female was exceeded by that of the controls after 15 days. Egg hatching success noticeably decreased under predation risk, and the incubation period was significantly prolonged; however, the oviposition height of the snails was not affected. A lethal effect of predation risk was detected in juvenile snails but not in adults. The growth of juvenile P. canaliculata was inhibited under predation risk, probably due to a reduction in food intake. Adult females exhibited a greater reduction in growth under predation risk than males, which likely resulted in part from the high reproductive investment of females in egg laying. These results indicate that P. canaliculata snails under predation risk face a trade-off between predator avoidance and growth and reproduction, where the lethal effect of predation risk is linked to the size of the prey. PMID:29136660

  3. Predation risk affects growth and reproduction of an invasive snail and its lethal effect depends on prey size.

    Directory of Open Access Journals (Sweden)

    Jing Guo

    Full Text Available The behavior of invasive species under predation risk has been studied extensively, but their growth and reproductive responses have rarely been investigated. We conducted experiments with juveniles and adults of the invasive freshwater snail Pomacea canaliculata, and we observed changes in growth and reproduction in response to predation risk from a caged predator (Trachemys scripta elegans. P. canaliculata produced eggs earlier in the presence of predators and injured conspecifics compared with the control group (no risk, although the total number of egg masses laid by per female was exceeded by that of the controls after 15 days. Egg hatching success noticeably decreased under predation risk, and the incubation period was significantly prolonged; however, the oviposition height of the snails was not affected. A lethal effect of predation risk was detected in juvenile snails but not in adults. The growth of juvenile P. canaliculata was inhibited under predation risk, probably due to a reduction in food intake. Adult females exhibited a greater reduction in growth under predation risk than males, which likely resulted in part from the high reproductive investment of females in egg laying. These results indicate that P. canaliculata snails under predation risk face a trade-off between predator avoidance and growth and reproduction, where the lethal effect of predation risk is linked to the size of the prey.

  4. Snake Venom Metalloproteinases and Their Peptide Inhibitors from Myanmar Russell’s Viper Venom

    Directory of Open Access Journals (Sweden)

    Khin Than Yee

    2016-12-01

    Full Text Available Russell’s viper bites are potentially fatal from severe bleeding, renal failure and capillary leakage. Snake venom metalloproteinases (SVMPs are attributed to these effects. In addition to specific antivenom therapy, endogenous inhibitors from snakes are of interest in studies of new treatment modalities for neutralization of the effect of toxins. Two major snake venom metalloproteinases (SVMPs: RVV-X and Daborhagin were purified from Myanmar Russell’s viper venom using a new purification strategy. Using the Next Generation Sequencing (NGS approach to explore the Myanmar RV venom gland transcriptome, mRNAs of novel tripeptide SVMP inhibitors (SVMPIs were discovered. Two novel endogenous tripeptides, pERW and pEKW were identified and isolated from the crude venom. Both purified SVMPs showed caseinolytic activity. Additionally, RVV-X displayed specific proteolytic activity towards gelatin and Daborhagin showed potent fibrinogenolytic activity. These activities were inhibited by metal chelators. Notably, the synthetic peptide inhibitors, pERW and pEKW, completely inhibit the gelatinolytic and fibrinogenolytic activities of respective SVMPs at 5 mM concentration. These complete inhibitory effects suggest that these tripeptides deserve further study for development of a therapeutic candidate for Russell’s viper envenomation.

  5. Production of high titre antibody response against Russell's viper venom in mice immunized with ethanolic extract of fruits of Piper longum L. (Piperaceae) and piperine.

    Science.gov (United States)

    Shenoy, P A; Nipate, S S; Sonpetkar, J M; Salvi, N C; Waghmare, A B; Chaudhari, P D

    2014-01-15

    Piper longum L. fruits have been traditionally used against snakebites in north-eastern and southern region of India. The aim of the study was to assess the production of antibody response against Russell's viper venom in mice after prophylactic immunization with ethanolic extract of fruits of Piper longum L. and piperine. The mice sera were tested for the presence of antibodies against Russell's viper venom by in vitro lethality neutralization assay and in vivo lethality neutralization assay. Polyvalent anti-snake venom serum (antivenom) manufactured by Haffkine Bio-Pharmaceutical Corporation Ltd. was used as standard. Further confirmation of presence of antibodies against the venom in sera of mice immunized with PLE and piperine was done using indirect enzyme-linked immunosorbent assay (ELISA) and double immunodiffusion test. Treatment with PLE-treated mice serum and piperine-treated mice serum was found to inhibit the lethal action of venom both in the in vitro lethality neutralization assay and in vivo lethality neutralization assay. ELISA testing indicated that there were significantly high (pPiper longum and piperine produced a high titre antibody response against Russell's viper venom in mice. The antibodies against PLE and piperine could be useful in antivenom therapy of Russell's viper bites. PLE and piperine may also have a potential interest in view of the development of antivenom formulations used as antidote against snake bites. Copyright © 2013 Elsevier GmbH. All rights reserved.

  6. Micrurus snake venoms activate human complement system and generate anaphylatoxins

    Directory of Open Access Journals (Sweden)

    Tanaka Gabriela D

    2012-01-01

    Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

  7. [New drug developments of snake venom polypeptides and progress].

    Science.gov (United States)

    Fu, Sihai; Feng, Mei; Xiong, Yan

    2017-11-28

    The value of snake venom polypeptides in clinical application has drawn extensive attention, and the development of snake polypeptides into new drugs with anti-tumor, anti-inflammatory, antithrombotic, analgesic or antihypertensive properties has become the recent research hotspot. With the rapid development of molecular biology and biotechnology, the mechanisms of snake venom polypeptides are also gradually clarified. Numerous studies have demonstrated that snake venom polypeptides exert their pharmacological effects by regulating ion channels, cell proliferation, apoptosis, intracellular signaling pathway, and expression of cytokine as well as binding to relevant active sites or receptors.

  8. Population-level effects of fitness costs associated with repressible female-lethal transgene insertions in two pest insects.

    Science.gov (United States)

    Harvey-Samuel, Tim; Ant, Thomas; Gong, Hongfei; Morrison, Neil I; Alphey, Luke

    2014-05-01

    Genetic control strategies offer great potential for the sustainable and effective control of insect pests. These strategies involve the field release of transgenic insects with the aim of introducing engineered alleles into wild populations, either permanently or transiently. Their efficacy can therefore be reduced if transgene-associated fitness costs reduce the relative performance of released insects. We describe a method of measuring the fitness costs associated with transgenes by analyzing their evolutionary trajectories when placed in competition with wild-type alleles in replicated cage populations. Using this method, we estimated lifetime fitness costs associated with two repressible female-lethal transgenes in the diamondback moth and olive fly as being acceptable for field suppression programs. Furthermore, using these estimates of genotype-level fitness costs, we were able to project longer-term evolutionary trajectories for the transgenes investigated. Results from these projections demonstrate that although transgene-associated fitness costs will ultimately cause these transgenes to become extinct, even when engineered lethality is repressed, they may persist for varying periods of time before doing so. This implies that tetracycline-mediated transgene field persistence in these strains is unlikely and suggests that realistic estimates of transgene-associated fitness costs may be useful in trialing 'uncoupled' gene drive system components in the field.

  9. Effects of Helicobacter pylori infection on common lethal factors for hepatitis B virus-related cirrhosis

    Directory of Open Access Journals (Sweden)

    LI Yuling

    2015-09-01

    Full Text Available ObjectiveTo study the relationship between Helicobacter pylori (H. pylori infection and common lethal factors for hepatitis B virus-related cirrhosis (HBC. MethodsA total of 235 patients with HBC who were admitted to our hospitals from October 2008 to October 2014 were retrospectively analyzed. The infection rate of H. pylori in those patients was calculated. In the 155 patients with esophagogastric varices and 97 patients with portal hypertensive gastropathy (PHG, the infection rate of H. pylori was compared between those with different degrees of esophagogastric varices or PHG. In the 32 patients whose blood ammonia was determined, the level of blood ammonia was compared between H. pylori-positive and -negative groups. Between-group comparison of continuous data was performed by t test and analysis of variance, and between-group comparison of categorical data was performed by χ2 test. ResultsThe infection rate of H. pylori in the 235 patients with HBC was 80.85% (190/235. In the 155 patients with esophagogastric varices, who had tortuous serpentine uplift or bead-like changes of esophageal varices and tumor-like changes (with or without gastric erosion of gastric varices visible under endoscopy, there was significant difference in infection rate of H. pylori between patients with mild, moderate, and severe varices (50.55% (46/91 vs 43.59% (17/39 vs 76% (19/25, χ2=6.913, P<0.05. In the 97 patients with PHG, who had snake skin-like changes, cherry red spots, scarlet rash, and erosion bleeding of gastric mucosa visible under endoscopy, there was significant difference in infection rate of H. pylori between patients with mild and severe PHG (43.33% (26/60 vs 67.57% (25/37, χ2=5.391, P<005.In patients whose blood ammonia was determined, patients in H. pylori-positive group had a significantly higher average concentration of blood ammonia than those in H. pylori-negative group (62.76±13.43 vs 47.20±12.51 μmol/L, t= 3.39, P<0

  10. Sensitivity of Vibrio cholerae cells to lethal and mutagenic effect of UV-irradiation mediated by plasmids

    International Nuclear Information System (INIS)

    Tiganova, I.G.; Evdokimova, N.M.; Aleshkin, G.I.

    1988-01-01

    The effect of UV-irradiation on Vibrio cholerae cells and its changes mediated by the plasmid R245 have been studied. Vibrio cholerae strains 569B and RV31 have been shown to be considerably more sensitive to lethal effect of UV-irradiation as compared with Escherichia coli and Salmonella typhimurium cells. Highly toxigenic strain 569B and practically atoxigenic strain RV31 have the same UV-sensitivity. Lethla effect of UV-irradiation on Vibrio cholerae cells is incresed when the irradiated cells are plated on enriched media. UV-induction of mutations was not registered in plasmidless strains of Vibrio cholerae. Plasmid R245 increase UV-resistance of vibrio cells and makes them UV-mutable

  11. Molecular components and toxicity of the venom of the solitary wasp, Anoplius samariensis

    International Nuclear Information System (INIS)

    Hisada, Miki; Satake, Honoo; Masuda, Katsuyoshi; Aoyama, Masato; Murata, Kazuya; Shinada, Testuro; Iwashita, Takashi; Ohfune, Yasufumi; Nakajima, Terumi

    2005-01-01

    The solitary spider wasp, Anoplius samariensis, is known to exhibit a unique long-term, non-lethal paralysis in spiders that it uses as a food source for its larvae. However, neither detailed venom components nor paralytic compounds have ever been characterized. In this study, we examined the components in the low molecular weight fraction of the venom and the paralytic activity of the high molecular weight fraction. The major low molecular weight components of the venom were identified as γ-aminobutyric acid and glutamic acid by micro-liquid chromatography/electrospray ionization mass spectrometry and nuclear magnetic resonance spectrometry analysis. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass analysis revealed that the A. samariensis venom contained the various proteins with weights of 4-100 kDa. A biological assay using Joro spiders (Nephila clavata) clearly showed that the high molecular weight fraction of the venom prepared by ultrafiltration exerted as potent non-lethal long-term paralysis as the whole venom, whereas the low molecular weight fraction was devoid of any paralytic activity. These results indicated that several venomous proteins in the high molecular weight fraction are responsible for the paralytic activity. Furthermore, we determined the primary structure of one component designated As-fr-19, which was a novel multiple-cysteine peptide with high sequence similarity to several sea anemone and snake toxins including dendrotoxins, rather than any insect toxic peptides identified so far. Taken together, our data showed the unprecedented molecular and toxicological profiles of wasp venoms

  12. Bioinformatics-Aided Venomics

    Directory of Open Access Journals (Sweden)

    Quentin Kaas

    2015-06-01

    Full Text Available Venomics is a modern approach that combines transcriptomics and proteomics to explore the toxin content of venoms. This review will give an overview of computational approaches that have been created to classify and consolidate venomics data, as well as algorithms that have helped discovery and analysis of toxin nucleic acid and protein sequences, toxin three-dimensional structures and toxin functions. Bioinformatics is used to tackle specific challenges associated with the identification and annotations of toxins. Recognizing toxin transcript sequences among second generation sequencing data cannot rely only on basic sequence similarity because toxins are highly divergent. Mass spectrometry sequencing of mature toxins is challenging because toxins can display a large number of post-translational modifications. Identifying the mature toxin region in toxin precursor sequences requires the prediction of the cleavage sites of proprotein convertases, most of which are unknown or not well characterized. Tracing the evolutionary relationships between toxins should consider specific mechanisms of rapid evolution as well as interactions between predatory animals and prey. Rapidly determining the activity of toxins is the main bottleneck in venomics discovery, but some recent bioinformatics and molecular modeling approaches give hope that accurate predictions of toxin specificity could be made in the near future.

  13. Are ticks venomous animals?

    Czech Academy of Sciences Publication Activity Database

    Cabezas-Cruz, A.; Valdés, James J.

    2014-01-01

    Roč. 11, JUL 2014 (2014), s. 47 ISSN 1742-9994 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : ticks * venom * secreted proteins * toxicoses * pathogens * convergence Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.051, year: 2014

  14. Effects of DDE on experimentally poisoned free-tailed bats (Tadarida brasiliensis): Lethal brain concentrations

    Science.gov (United States)

    Clark, D.R.; Kroll, J.C.

    1977-01-01

    Adult female free-tailed bats (Tadarida brasiliensis) were collected at Bracken Cave, Texas, and shipped to the Patuxent Wildlife Research Center. Treated mealworms (Tenebrio molitor) containing 107 ppm DDE were fed to 17 bats; five other bats were fed untreated mealworms. After 40 days on dosage, during which one dosed bat was killed accidentally, four dosed bats were frozen and the remaining 17 were starved to death. The objective was to elevate brain levels of DDE to lethality and measure these concentrations. After the feeding period, dosed bats weighed less than controls. After starvation, the body condition of dosed bats was poorer than that of controls even though there was no difference in the amounts of carcass fat. During starvation, dosed bats lost weight faster than controls. Also, four dosed bats exhibited the prolonged tremoring that characterizes DDE poisoning. DDE increased in brains of starving bats as fat was metabolized. The estimated mean brain concentration of DDE diagnostic of death was 519 ppm with a range of 458-564 ppm. These values resemble diagnostic levels known for two species of passerine birds, but they exceed published levels for two free-tailed bats from Carlsbad Caverns, New Mexico.

  15. Effect of restricted access to food on metabolic changes in lethally X-irradiated rats. I

    International Nuclear Information System (INIS)

    Toropila, M.; Ahlers, I.; Ahlersova, E.; Praslicka, M.

    1982-01-01

    Differences in the reaction of glucose in blood and in that of glycogen in liver in animals with free access to food and in those with restricted food intake to lethal irradiation by X-rays were studied. SPF bred male rats of the Wistar strain were fed by common laboratory diet and by tap water ad libitum (AL group) or food was accessible to them (in unlimited amounts) only in the period between 09.00 a. m. and 11.00 a. m. (meal-fed group, MF), all under standard laboratory conditions. After more than three weeks of adaptation to the nutrition patterns and 22 h after the last food intake, animals of both groups were irradiated with a single whole-body 14.35 Gy dose of X-rays and/or sham irradiated, respectively. Glucose concentration in blood was increased in both groups during the experiment; terminal hyperglycaemia was more expressed in the MF group. Due to the high initial glycogen concentration in the liver of MF irradiated animals the accumulation of glycogen was substantially lower and started later than in irradiated AL animals. (author)

  16. RBE of Cf-252 neutrons as determined by its lethal, mutagenic, and cytogenetic effects on human cells

    International Nuclear Information System (INIS)

    Ban, Sadayuki

    1989-01-01

    To assess the biological effects of neutrons, a man-made spontaneously fissioning isotope, Cf-252, is useful as an experimental model to obtain basic biological data on mixed radiation of gamma-rays and neutrons. The paper describes the lethal effect of Cf-252 radiation on human skin fibroblasts, its lethal and mutagenic effect on HeLa MR cells, and the micronuclei inducing effect on human peripheral lymphocytes. Dose-survival responses of three fibroblast cell strains exposed to Cf-252 radiation are measured. Individual difference is larger than the experimental fluctuation. D 10 values of each strain are obtained from the linear model and linear-quadratic model. Though the dose rate of X-ray is higher than that of Cf-252 radiations, the mean value of RBE(n+γ) is simply obtained as 1.86+0.31 (RBE:relative biological effectiveness). RBE(n) of Cf-252 neutrons to high-dose-rate X-rays is 2.29. After X-ray irradiation, the survival curve of HeLa MR cells gives an extrapolation number of 3.6. It is 1.3 after Cf-252 irradiation. At 50% survival, RBE(n+γ) and RBE(n) are 2.05 and 2.6, respectively. At 10% survival they are 2.05 and 2.6. The mutation frequencies after X-ray irradiation showed a significant non-linear increase with dose. Those after Cf-252 irradiation increase linearly with dose. (N.K.)

  17. Context-dependent interactive effects of non-lethal predation on larvae impact adult longevity and body composition.

    Science.gov (United States)

    Chandrasegaran, Karthikeyan; Kandregula, Samyuktha Rao; Quader, Suhel; Juliano, Steven A

    2018-01-01

    Predation impacts development, behavior and morphology of prey species thereby shaping their abundances, distribution and community structure. Non-lethal threat of predation, specifically, can have a strong influence on prey lifehistory characteristics. While investigations often focus on the impact of predation threat on prey in isolation, tests of its interactive effects with food availability and resource competition on prey survival and fitness can improve understanding of costs, benefits and trade-offs of anti-predator strategies. This study, involving Aedes aegypti mosquitoes as a model organism, investigates both simple and interactive effects of predation threat during the larval stage on survival, size at and time to maturity, stored teneral reserves of glycogen, protein and lipid in adults, and adult longevity. Our results show that development times of mosquito larvae were increased (by 14.84% in males and by 97.63% in females), and size of eclosing adults decreased (by 62.30% in males and by 58.33% in females) when exposed to lowered nutrition and elevated intraspecific competition, but that predation had no detectable effect on these simple traits. Teneral reserves of glycogen, protein and lipid and adult longevity were positively correlated with adult body size. Non-lethal predation threat had significant interactive effects with nutrition and larval competition on teneral reserves in males and adult longevity in males and females. The sexes responded differently to conditions encountered as larvae, with the larval environment affecting development and adult characteristics more acutely for females than for males. The outcome of this study shows how threat of predation on juveniles can have long-lasting effects on adults that are likely to impact mosquito population dynamics and that may impact disease transmission.

  18. The effect of embryonal thymic calf extracts on neonatally thymectomized mice and on mice lethally irradiated with gamma rays

    International Nuclear Information System (INIS)

    Czaplicki, J.; Blonska, B.; Stec, L.

    1981-01-01

    The effect of embryonal thymic calf extracts (ETCE) on mice thymectomized at birth was investigated. ETCE was found to induce an increase in leukopenia and decrease in the level of serum gamma globulins; it also reduced survival time in mice. The effect of ETCE on lethally irradiated mice was also examined. Only long-term administration of ETCE prior to gamma irradiation at 750 rad prolonged the survival time of mice (40% permanent survival) as compared with irradiated controls; the leukocytes from mice retained mitotic capability. Neither long-term treatment with ETCE prior to irradiation at 1000 rad, nor short-term administration prior to 750 rad affected survival time. ETCE administered after irradiation of mice with 750 rad caused a rapid decrease in blood leukocytes and a significantly lowered survival time. (Auth.)

  19. Lethal and mutagenic effects of radiation and chemicals on cultured fish cells derived the erythrophoroma of goldfish (Carassius auratus)

    Energy Technology Data Exchange (ETDEWEB)

    Mitani, H. (Tokyo Univ. (Japan). Inst. of Zoology)

    1983-01-01

    GEM 199 cells derived from an eryhtrophoroma of goldfish (Carassius auratus), which had a high plating efficiency, were used to investigate the lethal and mutational effects of radiations (UV and ..gamma..-rays) and chemicals (4NQO and MNNG). The cells were more resistant to rays than mammalian cells and CAF-MM1 cells derived from the normal fin tissue of goldfish. They were also more resistant to UV-irradiation than CAF-MM1 cells. Photoreactivation after UV-irradiation was present in GEM 199 cells for both survival and mutation. The initial shoulder of the survival curve of UV-irradiated cells was reduced greatly by caffeine, suggesting a high activity of the post-replication repair. The spontaneous mutation frequency to ouabain resistance was 1-5x10/sup -6/ clones per viable cell. MNNG was effective in inducing ouabain-resistant mutation, while 4NQO and ..gamma..-rays did not induce mutation.

  20. Sub-lethal effects of pesticide residues in brood comb on worker honey bee (Apis mellifera development and longevity.

    Directory of Open Access Journals (Sweden)

    Judy Y Wu

    Full Text Available BACKGROUND: Numerous surveys reveal high levels of pesticide residue contamination in honey bee comb. We conducted studies to examine possible direct and indirect effects of pesticide exposure from contaminated brood comb on developing worker bees and adult worker lifespan. METHODOLOGY/PRINCIPAL FINDINGS: Worker bees were reared in brood comb containing high levels of known pesticide residues (treatment or in relatively uncontaminated brood comb (control. Delayed development was observed in bees reared in treatment combs containing high levels of pesticides particularly in the early stages (day 4 and 8 of worker bee development. Adult longevity was reduced by 4 days in bees exposed to pesticide residues in contaminated brood comb during development. Pesticide residue migration from comb containing high pesticide residues caused contamination of control comb after multiple brood cycles and provided insight on how quickly residues move through wax. Higher brood mortality and delayed adult emergence occurred after multiple brood cycles in contaminated control combs. In contrast, survivability increased in bees reared in treatment comb after multiple brood cycles when pesticide residues had been reduced in treatment combs due to residue migration into uncontaminated control combs, supporting comb replacement efforts. Chemical analysis after the experiment confirmed the migration of pesticide residues from treatment combs into previously uncontaminated control comb. CONCLUSIONS/SIGNIFICANCE: This study is the first to demonstrate sub-lethal effects on worker honey bees from pesticide residue exposure from contaminated brood comb. Sub-lethal effects, including delayed larval development and adult emergence or shortened adult longevity, can have indirect effects on the colony such as premature shifts in hive roles and foraging activity. In addition, longer development time for bees may provide a reproductive advantage for parasitic Varroa destructor

  1. Ingested boric acid effect on the venom chemistry of Solenopsis invicta Buren (Hymenoptera: Formicidae)

    Science.gov (United States)

    During a field evaluation of a boric acid bait against the red imported fire ant, Solenopsis invicta Buren, it was observed that workers of intoxicated colonies produced stings with less toxic effects compared to workers from healthy colonies. In this study, the effect of boric acid on the levels o...

  2. Antioxidant activity and irritation property of venoms from Apis species.

    Science.gov (United States)

    Somwongin, Suvimol; Chantawannakul, Panuwan; Chaiyana, Wantida

    2018-04-01

    Pharmacological effects of bee venom has been reported, however, it has been restricted to the bee venom collected from European honey bee (Apis mellifera). The aim of the present study was to compare the antioxidant activities and irritation properties of venoms collected from four different Apis species in Thailand, which includes Apis cerena (Asian cavity nesting honeybee), Apis florea (dwarf honeybee), Apis dorsata (giant honeybee), and A. mellifera. Melittin content of each bee venom extracts was investigated by using high-performance liquid chromatography. Ferric reducing antioxidant power, 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid), and 1, 1-diphenyl-2-picrylhydrazyl assay were used to determine the antioxidant activity, whereas, hen's egg test chorioallantoic membrane assay was used to determine the irritation property of each bee venom extracts. Melittin was the major constituent in all bee venom extracts. The melittin content in A. dorsata, A. mellifera, A. florea, and A. cerena were 95.8 ± 3.2%, 76.5 ± 1.9%, 66.3 ± 8.6%, and 56.8 ± 1.8%, respectively. Bee venom extract from A. dorsata possessed the highest antioxidant activity with the inhibition of 41.1 ± 2.2% against DPPH, Trolox equivalent antioxidant capacity of 10.21 ± 0.74 mM Trolox/mg and equivalent concentration (EC 1 ) of 0.35 ± 0.02 mM FeSO 4 /mg. Bee venom extract from A. mellifera exhibited the highest irritation, followed by A. cerena, A. dorsata, and A. florea, respectively. Melittin was the compound responsible for the irritation property of bee venom extracts since it could induce severe irritation (irritation score was 13.7 ± 0.5, at the concentration of 2 mg/ml). The extract from A. dorsata which possessed the highest antioxidant activity showed no irritation up to the concentration of 0.1 mg/ml. Therefore, bee venom extract from A. dorsata at the concentration not more than 0.1 mg/ml would be suggested for using

  3. Priming dose of phenylhydrazine protects against hemolytic and lethal effects of 2-butoxyethanol

    International Nuclear Information System (INIS)

    Palkar, Prajakta S.; Philip, Binu K.; Reddy, Ramesh N.; Mehendale, Harihara M.

    2007-01-01

    Protection against a high dose of a toxicant by prior exposure to another toxicant is called heteroprotection. Our objective was to establish a heteroprotection model in RBCs. Female Sprague Dawley rats treated with an LD90 dose of 2-butoxyethanol (BE, 1500 mg/kg in water, 5 ml/kg po) 14 days after priming with 0.9% NaCl suffered 90% mortality by 15 days, whereas all rats receiving the LD90 dose of BE 14 days after priming with phenylhydrazine (PHZ, 125 mg/kg in 0.9% NaCl, 3 ml/kg po) survived. Hematocrit decreased from normal 45% to 24% by day 3 after PHZ priming and improved thereafter. Increasing the time interval between the priming and LD90 dose to 21 days abolished the heteroprotection. RBCs obtained on days 7 and 14 after PHZ priming unlike those on day 21 were resilient to the hemotoxic metabolite of BE, butoxyacetic acid (BAA). Unaltered hepatic alcohol and aldehyde dehydrogenase activities upon PHZ priming suggested that bioactivation of BE to BAA was unaffected. Lower renal (6 and 12 h) and hepatic (12 h) BAA levels and 3 fold higher excretion of BAA in PHZ-primed rat urine suggested a protective role of toxicokinetics. Higher erythropoietin, reticulocytes, and resiliency of PHZ-primed rat RBCs indicated that newly formed RBCs are resilient to hemolytic BAA. The antioxidant levels in the PHZ-primed rat RBCs did not indicate a protective role in heteroprotection. In conclusion, the resistance of PHZ-primed rats against BE-induced hemotoxicity and lethality is mediated by a combination of altered toxicokinetics, robust erythropoiesis, and resiliency of new RBCs

  4. Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells.

    Science.gov (United States)

    Shikata, Yuki; Kiga, Masaki; Futamura, Yushi; Aono, Harumi; Inoue, Hiroyuki; Kawada, Manabu; Osada, Hiroyuki; Imoto, Masaya

    2017-04-01

    The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. Evaluation of effects of long term exposure on lethal toxicity with mammals

    International Nuclear Information System (INIS)

    Verma, Vibha; Yu, Qiming J.; Connell, Des W.

    2014-01-01

    The relationship between exposure time (LT 50 ) and lethal exposure concentration (LC 50 ) has been evaluated over relatively long exposure times using a novel parameter, Normal Life Expectancy (NLT), as a long term toxicity point. The model equation, ln(LT 50 ) = aLC 50 ν + b, where a, b and ν are constants, was evaluated by plotting lnLT 50 against LC 50 using available toxicity data based on inhalation exposure from 7 species of mammals. With each specific toxicant a single consistent relationship was observed for all mammals with ν always <1. Use of NLT as a long term toxicity point provided a valuable limiting point for long exposure times. With organic compounds, the Kow can be used to calculate the model constants a and v where these are unknown. The model can be used to characterise toxicity to specific mammals and then be extended to estimate toxicity at any exposure time with other mammals. -- Highlights: • Model introduces a new parameter, normal life expectancy, to explain changes in toxicity with time. • Model is innovatory as it can be used to calculate toxicity at any, particularly long exposure times. • Toxicity is influenced by normal life expectancy of the organism particularly longer exposure times. • The model was applicable to all the mammals (7 species) evaluated. • The model can be used to predict toxicity at different exposure times with untested mammals species. -- The RLE model provides a mathematical description of the change in toxicity over time for a particular chemical. This represents a major advance on the use of Haber's Rule in toxicology

  6. Study on Bee venom and Pain

    Directory of Open Access Journals (Sweden)

    Hyoung-Seok Yun

    2000-07-01

    Full Text Available In order to study Bee venom and Pain, We searched Journals and Internet. The results were as follows: 1. The domestic papers were total 13. 4 papers were published at The journal of korean acupuncture & moxibustion society, 3 papers were published at The journal of korean oriental medical society, Each The journal of KyoungHee University Oriental Medicine and The journal of korean sports oriental medical society published 1 papers and Unpublished desertations were 3. The clinical studies were 4 and the experimental studies were 9. 2. The domestic clinical studies reported that Bee venom Herbal Acupuncture therapy was effective on HIVD, Subacut