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Journal Of Venom Research[JOURNAL]

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Elemental analysis of scorpion venoms.

Al-Asmari AK, Kunnathodi F, Al Saadon K … +1 more , Idris MM

J Venom Res · 2016 · PMID 27826410

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

The relaxant effect of the snake venom on vascular contractility.

Accary C, Hraoui-Bloquet S, Sadek R … +4 more , Alameddine A, Fajloun Z, Desfontis JC, Mallem Y

J Venom Res · 2016 · PMID 27826409

Molecular richness of snake venoms is an important source of proteins and toxins with potent effects on the cardiovascular system. The alteration of the vascular system in the victim after a venomous snake bite is usuall... Molecular richness of snake venoms is an important source of proteins and toxins with potent effects on the cardiovascular system. The alteration of the vascular system in the victim after a venomous snake bite is usually expressed by a significant decrease in blood pressure. Therefore, exploring snake venom to extract and characterize its biomolecules is of considerable medical interest, and formed the basis of this study. We assessed the potential of the venom of , a viper from Lebanon, to induce relaxant effect on isolated Wistar rat aorta via several mechanisms of action. The overall hypotensive effect of venom results from its synergetic action on different channels for the reduction of blood pressure. By actions of its metalloproteinases and phospholipase A2, the venom may induce the production of nitric oxide acting accordingly a vasodilator effect. It could act on the voltage-dependent potassium channels and/or the L-type calcium channels, inhibiting angiotensin converting enzyme and/or inhibiting the α1-adrenoceptors. This work demonstrates vasorelaxant effect of the venom acting on different pathways, reducing blood pressure.

A season of snakebite envenomation: presentation patterns, timing of care, anti-venom use, and case fatality rates from a hospital of southcentral Nepal.

Pandey DP, Vohra R, Stalcup P … +1 more , Shrestha BR

J Venom Res · 2016 · PMID 26998219

Snakebite envenomation affects thousands of people annually in Nepal. Published hospital-based studies of snakebite treatment in Nepal are scarce. Here we present the results of the first prospective, cross-sectional stu... Snakebite envenomation affects thousands of people annually in Nepal. Published hospital-based studies of snakebite treatment in Nepal are scarce. Here we present the results of the first prospective, cross-sectional study of hospitalized envenomed snakebite cases in southcentral Nepal, a region characterized by poor pre-hospital care of snakebites, limited supply and excessive use of antivenom, and a high case/fatality ratio. We seek to identify clinical management problems and suggest potential interventions to improve treatment of snakebites. Out of the 342 patients presented with snakebites to an urban emergency department in the Terai region of Nepal between April and September of 2007, 39 patients were enrolled based on development of ptosis or swelling of bitten body parts. We collected patient demographic information and documented circumstances of snakebite, prehospital care, hospital care, and development of complications. Among 39 envenomated patients admitted to Bharatpur Hospital enrolled in the study 34 (92%) exhibited features of clinically significant neurotoxicity and were treated with antivenom. Antivenom use ranged from 4 to 98 vials of Polyspecific Indian Antivenom per patient. Each of victims (n=34) received antivenom an average of 4.3 (median) ±0.73 (standard error of mean) hours after receiving the snakebite. The overall case fatality rate was 21%. Neurotoxicity developed up to 25.8hr after suspected elapid snakebites. This was not observed for viperid snake bites. No enrolled patients received any of the currently recommended first aid for snake bite. The prevalence of nocturnal elapid snake bites, the practice of inappropriate first aid measures and highly variable administration of antivenom were identified as major challenges to appropriate care in this study. To address these issues we suggest development of a comprehensive checklist for identification of snake species, management of envenomation, and an educational program which teaches proper care at all stages of snakebite treatment.

Enzymatic analysis of venom from Cuban scorpion Rhopalurus junceus.

Díaz-García A, Ruiz-Fuentes JL, Yglesias-Rivera A … +4 more , Rodríguez-Sánchez H, Riquenes Garlobo Y, Fleitas Martinez O, Fraga Castro JA

J Venom Res · 2015 · PMID 26605039

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

Recombinant disintegrin (r-Cam-dis) from Crotalus adamanteus inhibits adhesion of human pancreatic cancer cell lines to laminin-1 and vitronectin.

Suntravat M, Barret HS, Jurica CA … +3 more , Lucena SE, Perez JC, Sánchez EE

J Venom Res · 2015 · PMID 26045944

Pancreatic cancer is a malignant cancer common worldwide having poor prognosis, even when diagnosed at its early stage. Cell adhesion plays a critical role in cancer invasion and metastasis. Integrins are major mediators... Pancreatic cancer is a malignant cancer common worldwide having poor prognosis, even when diagnosed at its early stage. Cell adhesion plays a critical role in cancer invasion and metastasis. Integrins are major mediators of cell adhesion and play an important role in invasion and metastatic growth of human pancreatic cancer cells. Snake disintegrins are the most potent ligands of several integrins and have potential therapeutic applications for cancers. We have previously cloned and expressed a new recombinant RGD-disintegrin from Crotalus adamanteus (r-Cam-dis). This recently published r-Cam-dis has an extra nine amino acids derived from the vector (SPGARGSEF) at the N-terminus end and has strong anti-platelet activity. However, this r-Cam-dis contains the contamination of the cleavage of the N-terminal end of the pET-43.1a cloning vector. In this study, we have cloned r-Cam-dis in a different cloning vector (pGEX-4T-1) showing five different amino acids (GSPEF) at the N-terminal part. This new r-Cam-dis was expressed and tested for inhibition of platelet aggregation, specific binding activity with seven different integrins, and inhibition of adhesion of three different pancreatic cancer cell lines on laminin-1 and vitronectin. The r-Cam-dis showed potent binding to αvβ3 integrin, but was moderate to weak with αvβ5, αvβ6, α2β1, and α6β1. Interestingly, the inhibition of r-Cam-dis on pancreatic cancer cell lines adhesion to laminin-1 was more effective than that to vitronectin. Based on our binding results to integrin receptors and previous adhesion studies using function-blocking monoclonal antibodies, it is suggested that r-Cam-dis could be inhibiting adhesion of pancreatic cancer cell lines through integrins α2β1, α6β1, αvβ5, and αvβ6.

Venom gland components of the ectoparasitoid wasp, Anisopteromalus calandrae.

Perkin LC, Friesen KS, Flinn PW … +1 more , Oppert B

J Venom Res · 2015 · PMID 26998218

The wasp Anisopteromalus calandrae is a small ectoparasitoid that attacks stored product pest beetle larvae that develop inside grain kernels, and is thus a potential insect control tool. The components of A. calandrae v... The wasp Anisopteromalus calandrae is a small ectoparasitoid that attacks stored product pest beetle larvae that develop inside grain kernels, and is thus a potential insect control tool. The components of A. calandrae venom have not been studied, but venom from other organisms contains proteins with potential applications, such as pest management tools and treatments for human diseases. We dissected female A. calandrae and collected venom and associated glands. Using high throughput sequencing, a venom gland transcriptome was assembled that contained 45,432 contigs, 25,726 of which had BLASTx hits. The majority of hits were to Nasonia vitripennis, an ectoparasitoid from the same taxonomic family, as well as other bees, wasps, and ants. Gene ontology grouped sequences into eleven molecular functions, among which binding and catalytic activity had the most representatives. In this study, we highlighted the most abundant sequences, including those that are likely the functional components of the venom. Specifically, we focused on genes encoding proteins potentially involved in host developmental arrest, disrupting the host immune system, host paralysis, and transcripts that support these functions. Our report is the first to characterize components of the A. calandrae venom gland that may be useful as control tools for insect pests and other applications.

Plectreurys tristis venome: A proteomic and transcriptomic analysis.

Zobel-Thropp PA, Thomas EZ, David CL … +2 more , Breci LA, Binford GJ

J Venom Res · 2014 · PMID 25400903

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

Hemolytic venoms from marine cnidarian jellyfish - an overview.

Mariottini GL

J Venom Res · 2014 · PMID 25386336

Cnidarian jellyfish are viewed as an emergent problem in several coastal zones throughout the world. Recurrent outbreaks pose a serious threat to tourists and bathers, as well as to sea-workers, involving health and econ... Cnidarian jellyfish are viewed as an emergent problem in several coastal zones throughout the world. Recurrent outbreaks pose a serious threat to tourists and bathers, as well as to sea-workers, involving health and economical aspects. As a rule, cnidarian stinging as a consequence of nematocyst firing induces merely local symptoms but cardiovascular or neurological complications can also occur. Hemolysis is a frequent effect of cnidarian stinging; this dangerous condition is known to be caused by several venoms and can sometimes be lethal. At present, the bulk of data concerning hemolytic cnidarian venoms comes from the study of benthic species, such as sea anemones and soft corals, but hemolytic factors were found in venoms of several siphonophore, cubozoan and scyphozoan jellyfish, which are mainly involved in the envenomation of bathers and sea-workers. Therefore, the aim of this paper is to review the scientific literature concerning the hemolytic venoms from cnidarian jellyfish taking into consideration their importance in human pathology as well as health implications and possible therapeutic measures.

Peptides with in vitro anti-tumor activity from the venom of the Eastern green mamba, Dendroaspis angusticeps (Elapidae).

Conlon JM, Prajeep M, Mechkarska M … +5 more , Arafat K, Attoub S, Adem A, Pla D, Calvete JJ

J Venom Res · 2014 · PMID 25035794

Two structurally related (48.6% amino acid sequence identity) peptides with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells were purified from the venom of the Eastern green mamba Dendroasp... Two structurally related (48.6% amino acid sequence identity) peptides with cytotoxic activity against human non-small cell lung adenocarcinoma A549 cells were purified from the venom of the Eastern green mamba Dendroaspis angusticeps using reversed phase HPLC. The peptides were identified as members of the three-finger superfamily of snake toxins by mass fingerprinting of tryptic digests. The more potent peptide (LC50 against A549 cells = 56±4µg/ml) was identical to the previously described toxin C13S1C1 and the less active peptide (LC50 against A549 cells = 106±5µg/ml) was identical to toxin F-VIII. Toxin C13S1C1 was also cytotoxic against breast adenocarcinoma MDA-MB-231 cells (LC50 = 62±2µg/ml) and colorectal adenocarcinoma HT-29 cells (LC50 = 110±4µg/ml). Although the peptide was appreciably less hemolytic activity against human erythrocytes (LC50 >600µg/ml), it was cytotoxic to human umbilical vein endothelial HUVEC cells (57±3µg/ml) indicating no differential activity against cell lines derived from neoplastic tissues. Toxin F-VIII was not cytotoxic to MDA-MB-231, HT-29 cells, and HUVEC cells at concentrations up to 300µg/ml and was not hemolytic at concentrations up to 1mg/ml. Neither peptide inhibited growth of reference strains of Escherichia coli or Staphylococcus aureus (MIC values >200μg/ml).

Capillary damage in the area postrema by venom of the northern black-tailed rattlesnake (Crotalus molossus molossus).

Meléndez-Martínez D, Macias-Rodríguez E, Vargas-Caraveo A … +3 more , Martínez-Martínez A, Gatica-Colima A, Plenge-Tellechea LF

J Venom Res · 2014 · PMID 25035793

The Northern black-tailed rattlesnake (Crotalus molossus molossus) venom is mainly hemotoxic, hemorrhagic, and neurotoxic. Its effects in the central nervous system are unknown and only poorly described for all Viperidae... The Northern black-tailed rattlesnake (Crotalus molossus molossus) venom is mainly hemotoxic, hemorrhagic, and neurotoxic. Its effects in the central nervous system are unknown and only poorly described for all Viperidae species in general. This is why we are interested in describe the damage induced by C. m. molossus venom in rat brain, particularly in the area postrema capillaries. Four C. m. molossus venom doses were tested (0.02, 0.05, 0.10 and 0.20mg/kg) injected intramuscularly at the lower limb, incubated by 24 hours and the brains were harvested. Area postrema coronal sections were stained with Haematoxylin and Eosin, and examined to observe the venom effect in quantity of capillaries and porphology. Starting from the 0.10mg/kg treatment we observed lysed extravasated erythrocytes and also capillary breakdown, as a consequence of hemorrhages appearance. The number of capillaries decreased significantly in response to the venom dose increment. Hemorrhages could be caused by the metalloproteinase activity on the basal membrane and the apoptosis generated by L-amino acid oxidases. Hemolysis could be caused by phospholipase A2 hemotoxic effect. We conclude that C. m. molossus crude venom produces hemolysis, capillary breakdown, hemorrhages, and the reduction in number of capillaries in the area postrema.

Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations.

Fernandes CT, Giaretta VM, Prudêncio LS … +7 more , Toledo EO, da Silva IR, Collaço RC, Barbosa AM, Hyslop S, Rodrigues-Simioni L, Cogo JC

J Venom Res · 2014 · PMID 25028603

The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for m... The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78-100% inhibition) and 40mM KCl (45-90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K(+) were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom.

Biochemical and biological characterization of Naja kaouthia venom from North-East India and its neutralization by polyvalent antivenom.

Das D, Urs N, Hiremath V … +2 more , Vishwanath BS, Doley R

J Venom Res · 2013 · PMID 24349704

This study describes biochemical and biological properties of Naja kaouthia (Indian monocled cobra) venom of North-East India. The LD50 of the crude venom was found to be 0.148mg/kg and neurotoxicitic symptoms like paral... This study describes biochemical and biological properties of Naja kaouthia (Indian monocled cobra) venom of North-East India. The LD50 of the crude venom was found to be 0.148mg/kg and neurotoxicitic symptoms like paralysis of lower limbs and heavy difficulty in breathing at sub-lethal dose in mice was observed. The venom exhibited PLA2, indirect hemolytic and myotoxic activities but showed weak proteolytic and low direct hemolytic activities. It did not exhibit any hemorrhage when injected intradermally to mice. Anticoagulant activity was prominent when recalcification, prothrombin and activated partial thrombinplastin time were tested on platelet poor plasma. Rotem analysis of whole citrated blood in presence of venom showed delay in coagulation time and clot formation time. Fibrinogen of whole citrated blood was depleted by venom when analyzed in Sonoclot. Crude venom at 10µg and after 16hr of incubation was found to degrade α chain of fibrinogen. Neutralization study showed that Indian polyvalent antivenom could neutralize some of the biochemical and biological activities as well as its fibrinogenolytic activity.

The effects of selected Australian snake venoms on tumour-associated microvascular endothelial cells (TAMECs) in vitro.

Bateman E, Venning M, Mirtschin P … +1 more , Woods A

J Venom Res · 2013 · PMID 24191190

The effects of various viperid and elapid venoms on the cellular biology of tumour-associated microvascular endothelial cells (TAMECs) were determined in the current study using cells isolated from a rat mammary adenocar... The effects of various viperid and elapid venoms on the cellular biology of tumour-associated microvascular endothelial cells (TAMECs) were determined in the current study using cells isolated from a rat mammary adenocarcinoma. Previous studies to determine the effects of snake venoms on endothelial cells in vitro have in the main been performed on either human umbilical vein endothelial cells (HUVECs), bovine aortic endothelial cells (BAECs) or endothelial cell lines. These cell populations are accessible and easy to maintain in culture, however, it is well established that endothelial cells display vast heterogeneity depending upon the local microenvironment of the tissue from which they are isolated. Vascular targeting agents have been isolated from a variety of snake venoms, particularly from snakes of the Viperidae family, but it is yet to be established to what extent the venoms from Australian elapids possess similar vascular targeting properties. The present study used endothelial cells (ECs) isolated from the microvasculature of a rat mammary adenocarcinoma to determine the effects of a panel of snake venoms, including viperid venoms with known apoptotic activity and elapid venoms (both exotic and indigenous to Australia), on endothelial morphology and viability, paying specific attention to apoptotic responses. Three of the five Australian snake venoms investigated in this study elicited significant apoptotic responses in ECs which were in many ways similar to responses elicited by the selected viperid venoms. This suggests that these Australian elapids may possess vascular targeting components similar to those found within viperid venoms.

Analysis of intraspecific variation in venoms of Acanthophis antarcticus death adders from South Australia.

Herzig V, Kohler M, Grund KF … +3 more , Reeve S, Smith AI, Hodgson WC

J Venom Res · 2013 · PMID 24163732

Intraspecific variation in venom composition and activity has been reported from a wide range of snakes. Geographical origin can be one cause for this variation and has recently been documented from Acanthophis antarctic... Intraspecific variation in venom composition and activity has been reported from a wide range of snakes. Geographical origin can be one cause for this variation and has recently been documented from Acanthophis antarcticus death adders sampled across four different Australian states. The present study examined whether a narrower sampling range of A. antarcticus from four collection sites within one Australian state (i.e., South Australia) would also exhibit variation in venom composition and/or activity. The present LC-MS results reveal marked differences in the venom composition from different collection sites. The most striking difference was the reduced venom complexity found in the only venom originating from a mallee scrub habitat in comparison to the venoms from coastal heath scrub habitats. Interestingly, the pharmacological activity of all venoms was found to be the same, independent of the collection site.

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

Díaz-García A, Morier-Díaz L, Frión-Herrera Y … +5 more , Rodríguez-Sánchez H, Caballero-Lorenzo Y, Mendoza-Llanes D, Riquenes-Garlobo Y, Fraga-Castro JA

J Venom Res · 2013 · PMID 23946884

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

Analysis of nociceptive effects of neurotoxic phospholipase A2 from Vipera nikolskii venom in mice.

Dyachenko IA, Murashev AN, Andreeva TV … +2 more , Tsetlin VI, Utkin YN

J Venom Res · 2013 · PMID 23577231

Phospholipases A2 are represented in snake venoms by several types and possess diverse biological activities including neurotoxicity. Previously, we isolated and characterized two neurotoxic phospholipases A2 (HDP-1 and... Phospholipases A2 are represented in snake venoms by several types and possess diverse biological activities including neurotoxicity. Previously, we isolated and characterized two neurotoxic phospholipases A2 (HDP-1 and HDP-2) from the venom of Nikolski's viper (Vipera nikolskii), which were heterodimers composed of two non-covalently bound subunits. Each heterodimer consisted of an enzymatically active basic subunit and an inactive acidic subunit. In this work, we studied the in vivo biological activity of HDP-2 in mice. The acute toxicity (LD50 = 0.38 μg/gm) and maximal tolerated dose (0.1 μg/gm) were determined. In the hot plate test, HDP-2 at the maximal tolerated dose, reliably prolonged the time of the mouse staying on the plate. However, taking into account the neurotoxicity of HDP-2, we believe that this effect may be explained by a general intoxication rather than specific decrease of pain sensitivity. In this respect HDP-2 differs from other heterodimeric phospholipases A2 like crotoxin, which possess analgesic activity. This difference can be explained by the dissimilarity in the structure of the acidic subunits, suggesting an important role of this subunit in analgesic activity.

The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp.

Alizadehnohi M, Nabiuni M, Nazari Z … +2 more , Safaeinejad Z, Irian S

J Venom Res · 2012 · PMID 23301148

Ovarian cancer is considered to be one of the most important causes of death among women. Cisplatin is one of the oldest chemotherapeutical compounds used for treating ovarian cancer. Previous studies have shown the inhi... Ovarian cancer is considered to be one of the most important causes of death among women. Cisplatin is one of the oldest chemotherapeutical compounds used for treating ovarian cancer. Previous studies have shown the inhibitory effects of bee venom on certain types of cancer. The aim of the present study was to evaluate the cytotoxic effect of bee venom alone and its synergistic cytological effects in combination with cisplatin on ovarian cancerous cisplatin resistant A2780cp cells. To investigate the cytotoxic effect of bee venom on A2780cp cells and its synergetic effect with cisplatin, MTT assay, morphological examination, DNA fragmentation assay, flowcytometric and immunocytochemical analysis were performed. MTT assay revealed that 8µg/ml bee venom, 25mg/ml cisplatin and 4µg/ml bee venom/10mg/ml cisplatin cause an approximately 50% A2780cp cell death after 24hr. Morphological and biochemical analysis indicated an apoptotic type of cell death induced by bee venom and cisplatin, separately and in combination. Immunocytochemistry demonstrated a reduction in the levels of the Bcl2 protein. Overall, our findings suggest that components of bee venom may exert an anti-tumor effect on human ovarian cancer and that has the potential for enhancing the cytotoxic effect of the antitumor agent cisplatin.

Nanoparticle-conjugated animal venom-toxins and their possible therapeutic potential.

Biswas A, Gomes A, Sengupta J … +4 more , Datta P, Singha S, Dasgupta AK, Gomes A

J Venom Res · 2012 · PMID 23236583

Nano-medical approaches to develop drugs have attracted much attention in different arenas to design nanoparticle conjugates for better efficacy of the potential bio-molecules. A group of promising candidates of this cat... Nano-medical approaches to develop drugs have attracted much attention in different arenas to design nanoparticle conjugates for better efficacy of the potential bio-molecules. A group of promising candidates of this category would be venom-toxins of animal origin of potential medicinal value. Traditional systems of medicine as well as folklores mention the use of venom-toxins for the treatment of various diseases. Research has led to scientific validation of medicinal applications of venoms-toxins and many active constituents derived from venoms-toxins are already in clinical use or under clinical trial. Nanomedicine is an emerging field of medicine where nanotechnology is used to develop molecules of nano-scale dimension, so that these molecules can be taken up by the cells more easily and have better efficacy, as compared to large molecules that may tend to get eliminated. This review will focus on some of the potential venoms and toxins along with nanoparticle conjugated venom-toxins of snakes, amphibians, scorpions and bees, etc., for possible therapeutic clues against emerging diseases.

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

Smith JJ, Jones A, Alewood PF

J Venom Res · 2012 · PMID 23236582

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

The pharmacokinetics of Hemiscorpius lepturus scorpion venom and Razi antivenom following intramuscular administration in rat.

Jalali A, Bavarsad-Omidian N, Babaei M … +2 more , Najafzadeh H, Rezaei S

J Venom Res · 2012 · PMID 22826800

Hemiscorpius lepturus (H. lepturus) is one of the most dangerous scorpions in Iran. Intramuscular administration (IM) of available Razi antivenom to H. lepturus venom is used by many of Iranian clinicians. The purpose of... Hemiscorpius lepturus (H. lepturus) is one of the most dangerous scorpions in Iran. Intramuscular administration (IM) of available Razi antivenom to H. lepturus venom is used by many of Iranian clinicians. The purpose of the current study was to investigate the efficiency of IM route for treatment of envenomed patients by H. lepturus. We compared the pharmacokinetics parameters of venom and antivenom via subcutaneous (SC) and IM administration, respectively. The blood samples were taken at various predetermined time intervals, i.e., 10, 40, 60, 180, 210, 360 and 400min following 5μg (131)I-labeled venom and 5, 10, 40, 120 and 360min following 0.2ml of (131)I-labeled antivenom administration. The radio-iodination was carried out using the chloramin-T method. The results showed that pharmacokinetic parameters of the venom were T(elimination half-life) = 103.25min; Vd/F (apparent volume of distribution) = 14.9ml/kg; Cl/F (total blood clearance) = 0.04ml/kg/min; mean resident residual time (MRT) = 244.3min, and for the antivenom T(1/2) = 628.59min, Vd = 666.66ml/kg, Cl = 0.13ml/kg/min and MRT = 1292min. A comparison of pharmacokinetic profiles indicated that the intramuscular administration was helpful in the referral less than 2hr to clinical centers but not those exceeding 3hr. Overall, the data showed that immunotherapy against H. lepturus stings was likely to be more effective through intravenous administration.
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