Journal of Venom Research最新文献

The western diamondback rattlesnake (Crotalus atrox) is a common and widespread North American pit viper species, and its venom possesses medical applications. In this research, we identified 14 of the most common transcripts encoding 11 major venom toxins including transcripts for a three-finger toxin (3FTx) from the crude venom of C. atrox. In silico three-dimensional (3D) structures of 9 venom toxins were predicted by using deduced toxin amino acid sequences and a computer programme-MODELLER. The accuracy of all predicted toxin structures was evaluated by five stereochemical structure parameters including discrete optimised protein energy (DOPE) score, root mean square deviation (RMSD), Z-score, overall quality factor (ERRAT), and φ/ψ dihedral angle distribution of toxin backbone Cα residues, resulting that the overall predicted models are satisfied quality evaluation checks. Our present toxin transcripts and simulated individual toxin structures are important not only for revealing species-specific venom gene expression profiles, but also for predicting the toxin-toxin interactions and designing the structure-based toxin inhibitors for the treatment of snakebites.

The secretions of the Giant Monkey Frog Phyllomedusa bicolor are used by populations in the Amazon regions (mainly the indigenous Katukinas and Kaxinawás). The so-called "toad vaccine" or "kambô" is applied as a medication for infections and to prevent diseases, and also as physical and mental invigorator, and analgesic. Since the 1980s, researchers and companies have been interested in the composition of these secretions. Phyllomedusin, phyllokinin, caerulein and sauvagine are the polypeptides in these secretions that can cause intense effects on smooth muscles, vessels provoking, nausea and vomiting, arterial hypotension, flushing, palpitations, nausea, vomiting, bile secretion and angioedema. These actions are similar to bradykinin. However, the feeling of well-being and improvement of motor skills described by the users seems to be associated with dermorphine, caerulein or deltorphin - peptides with analgesic properties - and their affinity for the opiate receptor systems. Caerulein is a peptide that increases digestive secretions. Phyllomedusin and Phyllokinin lead to blood pressure and digestive effects. Sauvagine release corticotropin and mimics the physiological reactions of exposure to stress. Deltorphins and dermorphins have high affinity for the opiate receptor system and can lead to analgesia. The fame acquired by the therapy motivated the use by individuals from urban areas worldwide, without safety considerations. While in indigenous communities, there is an entire cultural tradition that provides relative safety to the application, however, the extension of use to individuals from urban areas worldwide is a problem, with reports of severe adverse effects and deaths. Undoubtedly, the skin secretions of the Phyllomedusa genus contain substances of intense pharmacological action and that can lead to research for therapeutic uses, but control over their application in rituals outside the forest is needed due the risks presented.

Phylogenetic evidence is provided for horizontal transfer of a natterin-like toxin encoding gene from fungi into the genome of the coral Acropora digitifera. Sequencing analysis of the coral tissues supported that a fungal taxon predicted to be the most likely gene donor was represented in the coral microbiome. Further bioinformatics data suggested widespread recruitment of the natterin-like gene into venomous terrestrial invertebrates, and repositioning of this gene to non-toxic functions in non-venomous teleost fish.

Slow lorises (Nycticebus spp.) are one of six venomous mammals, and the only known venomous primate. In the wild envenomation occurs mainly during conspecific competition for mates and territory, but may also be used as an application against parasites or for predator defense. Envenomation in humans is documented, with the most extreme accounts detailing near-fatal anaphylactic shock. From September 2016 - August 2017, we received questionnaire responses from 80 wild animal practitioners working with Nycticebus spp. in zoos, rescue centres and in the wild. We identified 54 practitioners who had experience of being bitten or were otherwise affected by slow loris venom, and an additional 26 incomplete entries. No fatalities were reported. Fifteen respondents noted that medical intervention was required, 12 respondents indicated no reaction to being bitten (9 of these indicated they were wearing gloves). Symptoms for those affected included: anaphylactic shock, paraesthesia, haematuria, dyspnoea, extreme pain, infection and general malaise. Impact of slow loris bites ranged from instantaneous to long-persisting complications, and healing time ranged from 1 day to >8 months. Extremities, including hands and arms, were mostly affected from the bites. Six of nine species of slow loris were reported to bite, with N. pygmaeus being the most common in our sample. We make suggestions regarding the use of these highly threatened yet dangerous primates as unsuitable tourist photo props and zoo animal ambassadors. We discuss the medical complications experienced in relation to protein sensitisation, and bacterial pathogenesis. We recommend future work to ascertain the protein content of slow loris venom to aid in enabling mitigation of risks posed.

Because snake venoms are complex mixtures of bioactive molecules, snake bites produce a large panel of symptoms which cannot be totally prevented by current antivenoms. Thus investigating plant extracts for antivenomics therapy approaches seemed relevant. Here, we evaluated the potency of the aqueous Buds extract of Eucalyptus (ABEE) to counteract the main enzymatic activities of Montivipera bornmuelleri venom. We showed that ABEE efficiently counteracts the proteolytic, Phospholipases A2 (PLA2), and L-aminoacid oxidase activities (LAAO) of M. bornmuelleri venom. ABEE was found to inhibit Acetylcholine esterase (AChE) and to exhibit a potent antioxidant activity. In addition, M. bornmuelleri venom displays antibacterial properties against Staphylococcus aureus, which were not inhibited by ABEE. We also showed that of M. bornmuelleri venom lacks AChE, either anti-AChE activities. ABEE represents a promising natural source of antivenomics compounds against the deleterious effects of M. bornmuelleri or other Vipera species bites.

Snakebite envenomation is an important global health concern. The current standard treatment approach for snakebite envenomation relies on antibody-based antisera, which are expensive, not universally available, and can lead to adverse physiological effects. Phage display techniques offer a powerful tool for the selection of phage-expressed peptides, which can bind with high specificity and affinity towards venom components. In this research, the amino acid sequences of Phospholipase A₂ (PLA₂) from multiple cottonmouth species were analyzed, and a consensus peptide synthesized. Three phage display libraries were panned against this consensus peptide, crosslinked to capillary tubes, followed by a modified surface panning procedure. This high throughput selection method identified four phage clones with anti-PLA₂ activity against Western cottonmouth venom, and the amino acid sequences of the displayed peptides were identified. This is the first report identifying short peptide sequences capable of inhibiting PLA₂ activity of Western cottonmouth venom in vitro, using a phage display technique. Additionally, this report utilizes synthetic panning targets, designed using venom proteomic data, to mimic epitope regions. M13 phages displaying circular 7-mer or linear 12-mer peptides with antivenom activity may offer a novel alternative to traditional antibody-based therapy.

Bihar is the state with the third largest number of snakebite deaths per year in India. This prospective, one-year study of 608 snakebites provides the first data from Bihar on determinants of unfavourable outcomes in snakebites. Any delay in reaching hospital raised the risk of a snakebite patient for an unfavourable outcome [OR 8.88, CI 2.04-38.8]. Attending a traditional practitioner prior to presenting to the hospital was the only specific, significant delay [OR 3.52, CI 1.26-9.7]. Prevention of unfavourable outcomes occurred by presenting to hospital in less than 1.5 hours [OR 0.23, CI 0.052-1.0]. Motorbike was the best mode of transport [OR 0.37, CI 0.12-1.1]. Other risk factors were patients aged under 15 years [OR 3.79, CI 1.57-9.12] and bites to the upper limb [OR 2.47, CI 1.01-6.04]. Patients who were envenomated had a higher risk of unfavourable outcome, if referred due to antivenom being unavailable [OR 12.2, CI 1.49-100]. To save lives, it is imperative that measures to reduce delays in getting patients to hospital must be included in snakebite management, alongside continued availability of antivenom and assisted ventilation.

Rhopalurus junceus scorpion venom has demonstrated high cytotoxic activity in epithelial cancer cells. In the present study, the effect of scorpion venom on cell viability and apoptosis was evaluated in the MDA-MB-231 human breast carcinoma cell line. Cell viability was analyzed using MTT assay. The cell death event was examined trough end-point RT-PCR to identify the expression of apoptosis-related genes, fluorescent microscopy and mitochondrial membrane potential (ΔΨm) alteration. The results demonstrated that scorpion venom induced apoptosis in MDA-MB-231 cells in a time-dependent manner. Besides, scorpion venom treatment also resulted in p53, bax, noxa, puma, caspase 3 and p21 over-expression, while the expression of bcl-2 and bcl-xl was down-regulated. Apoptosis was associated with depolarization of ΔΨm. The overall effect indicates that the selective cytotoxic effect of the scorpion venom is associated with its apoptosis-inducing effect through the mitochondrial pathway. Therefore, R. junceus scorpion venom may be an interesting natural extract for further investigation in breast cancer treatment strategies.

The Mexican black-tailed rattlesnake Crotalus molossus nigrescens is distributed in the Mexican plateau. Its venom is known to cause hemolysis and presents fibrinogen coagulase, collagenase and fibrinolytic activities. These activities may be associated with hemostatic alterations, such as platelet aggregation, hemolysis and fibrinolysis, often described in ophidic accidents. However, the mechanisms of action of the C. m. nigrescens venom remain unclear. In this study we investigated the in vitro hemotoxic, neurotoxic, and vasculotoxic effects of the venom. We found that this venom produces two types of hemolytic responses, Oxyhemoglobin release and Methemoglobin formation. As a result of the cytotoxicity to endothelial cells produces morphological biphasic toxicity. The first step in this process is characterized by morphological changes, as well as the loss of cellular adhesion and reduction in thickness. The second phase is characterized by massive cellular aggregation and death. It also induced laminin, type IV collagen, perlecan and nidogen degradation. However, the venom did not modulate the muscular fetal and neuronal nicotinic acetylcholine receptors activity. Thus, we concluded that the C. m. nigrescens venom produced hemolysis and hemorrhages via degradation of the basement membrane components and endothelial cell cytotoxicity, but not by neurotoxicity at the receptor level in nicotinic acetylcholine receptors.