Animal venoms and toxins Research Papers (original) (raw)

2025

The author would like to take a moment to appreciate a notable few out of the army of supporters who came out during this arduously long scholastic process without whom this work would never have been. First and foremost, a "thank you" is owed to the USDA TSTAR program whose funds kept the snails alive and solvents flowing through the RP-HPLC. Likewise, the infrastructure, teachings and financial support from the University of Hawai'i and more specifically the College of Tropical Agriculture and Human Resources provided a fertile environment conducive to cutting edge science. Through the 3 years over which this study took place, I found myself indebted to two distinct groups of students from Dr. Bingham's lab. Those who worked primarily in the biochemical laboratory saved countless weekend RP-HPLC runs from disaster through due diligence while patiently schooling me on my deficiencies in biochemical processes and techniques. Even more, I would like to thank the students assigned to Dr. Bingham's aquaculture facility who had to work with me directly during this time, not only with regards to this study but also in the foundational design and building of the aquaculture facility. They were often asked to spend a full afternoon from their other responsibilities in my absence to feed my snails, a process that can be excruciating when the snails aren't terribly hungry. This was in addition to their daily upkeep tasks, which often required precious weekend commitments as well. I know the sacrifices you all made and I am sincerely grateful. For their slimy donations, I'd like to thank Hank Lynch and J. J. Jackson because, try as I might, I'm still the world's worst shell collector. Without your contributions, I would have been studying ten empty tanks full of seawater. This brings me to the tireless efforts put forth by the inexhaustible Dr. Jon-Paul Bingham who somehow manages to meet with each of his students every week while teaching the university's flagship biochemistry course and still figures out a way to make himself available for the odd question of protocol. The opportunities this project afforded me along with the guidance and lessons have returned invaluable life experiences that will follow me for the rest of my life. Finally I would like to take a brief moment to show some gratitude to my personal support team. For all the dinners you delivered when I was stuck at school late at night and for providing the at-home logistical support to keep my demeanor and appearance appropriate for the rest of the world, I will always be indebted to Melanie Kosaka. And finally, to my dad who was a single parent wrestling with two maturing sons and now dutifully serves the role of moral supporter in the face of impossible times. Thank you.

2025, Peptides

Cone snail venoms provide a largely untapped source of novel peptide drug leads. To enhance the discovery phase, a detailed comparative proteomic analysis was undertaken on milked venom from the mollusk-hunting cone snail, Conus textile, from three different geographic locations (Hawai'i, American Samoa and Australia's Great Barrier Reef). A novel milked venom conopeptide rich in post-translational modifications was discovered, characterized and named ␣-conotoxin TxIC. We assign this conopeptide to the 4/7 ␣-conotoxin family based on the peptide's sequence homology and cDNA pre-propeptide alignment. Pharmacologically, ␣-conotoxin TxIC demonstrates minimal activity on human acetylcholine receptor models (100 M, <5% inhibition), compared to its high paralytic potency in invertebrates, PD 50 = 34.2 nMol kg -1 . The non-post-translationally modified form, [Pro] 2,8 [Glu] 16 ␣-conotoxin TxIC, demonstrates differential selectivity for the ␣3␤2 isoform of the nicotinic acetylcholine receptor with maximal inhibition of 96% and an observed IC 50 of 5.4 ± 0.5 M. Interestingly its comparative PD 50 (3.6 Mol kg -1 ) in invertebrates was ∼100 fold more than that of the native peptide. Differentiating ␣-conotoxin TxIC from other ␣-conotoxins is the high degree of post-translational modification (44% of residues). This includes the incorporation of ␥-carboxyglutamic acid, two moieties of 4-trans hydroxyproline, two disulfide bond linkages, and C-terminal amidation. These findings expand upon the known chemical diversity of ␣-conotoxins and illustrate a potential driver of toxin phyla-selectivity within Conus.

2025, Toxins

Snakebite represents a significant public health challenge in Central and South America, with Lachesis (Bushmaster) species posing unique clinical challenges due to their severe envenomation effects arising from a combination of potent venom and copious venom yields. Using in vitro coagulation assays, we analyzed the coagulotoxic venom effects from four distinct localities: L. muta from Surinam and French Guiana and L. stenophrys from Costa Rica and Panama. This study examined the venom's impact on human plasma and fibrinogen and evaluated the efficacy of two regionally available antivenoms (PoliVal-ICP and Antivipmyn-Tri) in neutralizing the pathophysiological effects. Our results demonstrated a remarkable consistency in the pseudo-procoagulant venom activity (also known as: thrombin-like) across different species and localities. Antivenom efficacy testing revealed that both the PoliVal-ICP and Antivipmyn-Tri antivenoms effectively neutralized the venom effects across localities for both species, with the ICP antivenom showing the highest neutralization capacity. These toxicology findings highlight the biochemical conservation of venom composition across Lachesis species which underpins effective cross-neutralization in antivenom treatment.

2025, HAL (Le Centre pour la Communication Scientifique Directe)

Climatic signals preserved in the skeletal growth bands of massive corals offer a long-term perspective that allows understanding sea surface temperature changes at different time scales. In the Caribbean Sea and the Gulf of Mexico, coral species such as Orbicella faveolata present massive growth forms in shallow waters that facilitate dating of their skeleton, allowing to perform paleoenvironmental studies in coastal areas where instrumental records are scarce and cover short time periods. This study aimed to characterize coral geochemical records in the skeleton of a hermatypic coral O. faveolata collected in the Cayo Santa María (Cuba) reef and to reconstruct seawater surface annual temperatures for the last two centuries. Records of 230 years for Li/Ca, Sr/Ca, Mg/Ca, U/ Ca, Li/Mg, and Sr-U were obtained. The Li/Ca indicator allowed the reconstruction of SST in the study area from 1778 to 2015, indicating an overall increase of 0.77 °C in the last 50 years. In addition, Li/Ca corroborated with high accuracy the characteristic warming and cooling periods reported for the Caribbean Sea and the Gulf of Mexico since 1778. Orbicella faveolata proved to contain a good multidecadal record of annual temperature and of the Atlantic Multidecadal Variability. These results are the first long-term reconstruction of SST in the Cuban coastal zone and provide relevant information to understand global warming in the Caribbean.

2025, Diving and hyperbaric medicine

We thank Yanagihara and Chen for their comments and for the opportunity to further the discussion. Our statistician has re-examined (and reanalysed) these data, and we have supplied our data to an independent statistician (who supported our subsequent re-analysis) and are more than willing to supply these data to the journal editors should they feel this is necessary. Furthermore, the manuscript was independently reviewed by two reviewers who expressed no concern over our analysis. We are confident of our results. Yanagihara and Chen have incorrectly assumed that the errors displayed in Figure 2 are SEM. These errors represent the 95% confidence limits (CL) and as such their arguments are invalid. Furthermore, they outline that no statistical significance was provided for the specific W4 vs. W3 comparison. Although no specific statistics were displayed in the article, we do outline that LSD post hoc analysis was conducted and the means and 95% CL (as signified in Figure 2) that were...

2025

For VenomVet and VenomVet Plus Infusion Monitoring in Veterinary ER’s and ICU’s

2025, Toxins

Snakebite envenoming is often discussed in terms of lethality and limb loss, but local tissue injury and coagulotoxic effects of venom are significantly more common acute manifestations of snakebite envenoming (SBE). Local tissue injury and the hemorrhagic and coagulotoxic effects of venom are challenging to study in live animals and can be ethically fraught due to animal welfare concerns such that attention to the 3Rs of animal welfare motivates the development of in vitro techniques in this arena. Herein, we tested the use of a wound-healing study technique known as Electric Cell-Substrate Impedance Sensing (ECIS) to assess populations of cultured cells exposed to venom with or without sPLA 2 and/or metalloprotease inhibitors (varespladib and marimastat, respectively). For comparison, the StarMax coagulation analyzer for coagulotoxicity was further used to evaluate the venoms and the neutralizing capabilities of the abovementioned direct toxin inhibitors (DTIs) against the same venoms examined using ECIS. Three viper and three elapid venoms that were examined for their effects on H1975 cells were Agkistrodon contortrix (Eastern Copperhead), Crotalus helleri (Southern Pacific Rattlesnake), and Vipera ammodytes (Horned Viper) and Naja atra (Chinese Cobra), Naja mossambica (Mozambique Spitting Cobra), and Naja nigricollis (Black-necked Spitting Cobra), respectively. The combination of cellular and coagulation techniques appears to usefully discriminate the in vitro capabilities and limitations of specific inhibitors to inhibit specific venom effects. This study suggests that ECIS with or without concomitant coagulation testing is a feasible method to generate reproducible, meaningful preclinical data and could be used with any type of cell line. Importantly, this approach is both quantitative and has the potential of reducing animal use and suffering during the evaluation of potential therapeutics. To further evaluate the potential of this method, rescue studies should be performed.

2025, Toxins

The Philippines has a high diversity of venomous snake species, but there is minimal information on their envenomation effects. This is evidenced by the small number of case reports, the poor reporting of envenomation cases, and the absence of specific antivenoms apart from one against the Philippine cobra (Naja philippinensis). This study sought to profile the action of selected Philippine pit viper venoms on blood coagulation and to investigate whether commercially available non-specific antivenoms can provide adequate protection against these venoms. Venom from the pit vipers Trimeresurus flavomaculatus and Trimeresurus mcgregori were subjected to coagulation assays, antivenom cross-neutralization tests, and thromboelastography. Venoms from both species were able to clot human plasma and isolated human fibrinogen. Consistent with pseudo-procoagulant/thrombin-like activity, the resulting fibrin clots were weak and transient, thereby contributing to net anticoagulation through the depletion of fibrinogen levels. Clotting factors fIXa and fXa were also inhibited by the venoms, further contributing to the net anticoagulant activity. Monovalent and polyvalent antivenoms from the Thai Red Cross Society were effective against both venoms, indicating cross-neutralization of venom toxins; the polyvalent antivenom was able to rescue fibrinogen clotting to a greater degree than the monovalent antivenom. Our findings highlight the coagulopathic effects of these pit viper venoms and suggest the utility of procuring the non-specific antivenoms for areas in the Philippines with a high risk for pit viper envenomation.

2025, Toxins

Echis species (saw-scaled vipers) are WHO Category 1 medically significant venomous snakes with potent procoagulant venoms, which cause lethal venom-induced consumptive coagulopathy in human victims. Despite clinical presentations of bites varying significantly between individuals within the same species, the contribution of age-related changes in the venom biochemistry has not been investigated. This study investigated the ontogenetic changes in Echis pyramidum pyramidum venom and its impact on therapeutic efficacy. The efficacy of various antivenoms (Echitab, Echitab+ ICP, Inosan MENA, Inosan Pan African, and SAVP-Echis) was tested against both venom phenotypes. While both neonate and adult venoms were procoagulant, there were differences in the underlying biochemistry. Neonate venom was found to potently pathophysiologically activate Factor VII and Factor X, and to a lesser degree Factor XII. In contrast, adult venom was a slower clotter, less potent in activating FVII, equipotent with neonate venom on FXII, and inactive on FX. This is the first documentation of FVII and FXII activation for any Echis venom. The significant ontogenetic toxicological variations in Echis species were shown to impact antivenom efficacy. Among the tested antivenoms, SAVP-Echis was the most effective against both venom phenotypes, with adult venom being better neutralized. These findings suggest the need for a reconsideration of venom mixture selection in antivenom production through the inclusion of neonate venom. Additionally, the results indicate differential ontogenetic predatory ecology, providing a foundation for future natural history investigations.

2025, Boletín de Investigaciones Marinas y Costeras

The presence of Ophiothrix synoecina Schoppe in the Guajira area (Cabo de la Vela), and the contribution of new information about its distribution and density, allowed the reevaluation of the category proposed on the Marine Invertebrates Red List, because of its small and fragmentary area of nine localities through the Colombian Caribbean rocky-shore.

2025

Tarantulas (Theraphosidae Thorell, 1869) are typically largebodied spiders that are frequently kept in captivity as pets in private collections, exhibits in public collections (e.g. zoos), and study animals in research collections. Nevertheless, much of the information on captive maintenance of tarantulas is based on trial-and-error approaches, such that folklore husbandry rather than evidence-based husbandry is typical. In addition to the spider's welfare, some species also impose safety considerations for keepers due to aggressive defensive behaviours that include biting, particularly many Old World tarantulas. The orange baboon tarantula (Pterinochilus murinus Pocock, 1897) is a very commonly kept African species of harpactirine tarantula which is successfully maintained in diverse enclosure designs including arboreal, terrestrial, and fossorial setups. Here, we investigated experimentally how different captive enclosure designs influence defensive behaviour in P. murinus, and whether it is possible to improve both tarantula welfare and keeper safety via husbandry methods. We show that spiders were quicker to flee when kept in arboreal enclosures, but more quickly resorted to aggressive defensive behaviours (rearing and biting) when kept in terrestrial enclosures. Keeping this species in fossorial enclosure designs resulted in a relatively low propensity to flee, rear, and bite, suggesting that this design might be optimal for captive P. murinus welfare and keeper safety.

2025, Journal of Proteome Research

Fire ants are well-known by their aggressive stinging behavior, causing many stinging incidents of medical importance. The limited availability of fire ant venom for scientific and clinical uses has restricted, up to now, the knowledge about the biochemistry, immunology, and pharmacology of these venoms. For this study, S. invicta venom was obtained commercially and used for proteomic characterization. For this purpose, the combination of gel-based and gel-free proteomic strategies was used to assign the proteomic profile of the venom from the fire ant S. invicta. This experimental approach permitted the identification of 46 proteins, which were organized into four different groups according to their potential role in fire ant venom: true venom components, housekeeping proteins, body muscle proteins, and proteins involved in chemical communication. The active venom components that may not present toxic roles were classified into three subgroups according to their potential functions: self-venom protection, colony asepsis, and chemical communication. Meanwhile, the proteins classified as true toxins, based on their functions after being injected into the victims' bodies by the fire ants, were classified in five other subgroups: proteins influencing the homeostasis of the victims, neurotoxins, proteins that promote venom diffusion, proteins that cause tissue damage/inflammation, and allergens.

2025, Future Journal of Pharmaceutical Sciences

Background The recent FDA-approved Ycanth (cantharidin) for treating Molluscum contagiosum, a viral skin infection, was first reported from blister beetles. Medicinal insects are reservoirs for exploring bioactive molecules, which have various benefits. Their use in traditional medicinal practices explains why uncovering new chemical substances is worthwhile. Main body of the abstract Insect-derived natural products with diverse and unique structures are significant for drug discovery and development potential. Various natural products are reported from insect sources; in this context, it also emphasizes the importance of active global participation among researchers, as it offers significant potential for developing a sustainable approach to why this should not remain untouched for ever-increasing unmet challenges. Conclusion Hence, practitioners in natural product chemistry and allied disciplines have a role in understating the enormous potential of discovering bioactive metabolites for their medicinal value to human health.

2025, Ela Journal of Forestry and Wildlife

Insects exploit diverse urban habitats; however, the impact of urbanization on their venom potency remains poorly studied. We reviewed literature on insect toxins and their ecological roles, focusing on examples with documented medicinal applications. We analysed studies investigating the abundance and distribution of specific insect species across urban and rural gradients. Finally, we examined research on toxin concentration variations within these species. Our analysis suggests a trend of potentially lower toxin potency in urban insect populations compared to their rural counterparts. These findings suggest a potential evolutionary adaptation in urban insects, with a decrease in toxin production probably as a response to altered ecological pressures. However, further research is necessary to strengthen this link and explore the underlying mechanisms. Investigating the potential decline in insect toxin potency is crucial, particularly considering the documented medicinal properties of some toxins. This knowledge could guide future research on harnessing these toxins for therapeutic applications.

2025, Chromatography - The Most Versatile Method of Chemical Analysis

2025, Journal of Invertebrate Pathology

The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ''self'' from ''non-self" have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different bacterial strains alters the expression of these enzymes and suggesting a correlation between the appearance of the inflammatory reaction and the modification of enzymatic activities. Our study shows for the first time, a specific reaction and enzymatic responses following injection of bacteria in a cnidarian.

2025, Proceedings of the Oklahoma Academy of Science

The true bugs (Hemiptera) are likely one of the most recognized groups of any of the major orders of insects in Oklahoma. Over the last half decade, new geographic distributional records for hemipterans from the state have been provided by our community collaborative effort (Chordas and McAllister 2012, 2016;. Here, we continue to add new state records for two true bugs not previously reported from the state.

2025, Biological Reviews

Despite extensive study of poisonous and venomous organisms and the toxins they produce, a review of the literature reveals inconsistency and ambiguity in the definitions of 'poison' and 'venom'. These two terms are frequently conflated with one another, and with the more general term, 'toxin.' We therefore clarify distinctions among three major classes of toxins (biological, environmental, and anthropogenic or man-made), evaluate prior definitions of venom which differentiate it from poison, and propose more rigorous definitions for poison and venom based on differences in mechanism of delivery. We also introduce a new term, 'toxungen', thereby partitioning toxic biological secretions into three categories: poisons lacking a delivery mechanism, i.e. ingested, inhaled, or absorbed across the body surface; toxungens delivered to the body surface without an accompanying wound; and venoms, delivered to internal tissues via creation of a wound. We further propose a system to classify toxic organisms with respect to delivery mechanism (absent versus present), source (autogenous versus heterogenous), and storage of toxins (aglandular versus glandular). As examples, a frog that acquires toxins from its diet, stores the secretion within cutaneous glands, and transfers the secretion upon contact or ingestion would be heteroglandular-poisonous; an ant that produces its own toxins, stores the secretion in a gland, and sprays it for defence would be autoglandular-toxungenous; and an anemone that produces its own toxins within specialized cells that deliver the secretion via a penetrating wound would be autoaglandular-venomous. Adoption of our scheme should benefit our understanding of both proximate and ultimate causes in the evolution of these toxins.

2024, Enfermedades Infecciosas y Microbiología

introducción. La mortalidad por tuberculosis (tb) es un indicador de los resultados en los programas de control. Aunque en el ámbito mundial los casos han venido disminuyendo durante los últimos 10 años, la carga de la enfermedad sigue siendo alta. La tasa de mortalidad por tb en Colombia para el año 2012 se reportó en 2.07 por cada 100 000 habitantes. objetivo. El objetivo de esta investigación fue identificar casos probables de muerte cuya causa básica haya sido tuberculosis y que no fueron reportados por los sistemas de información durante el año 2012. métodos. Se realizó un estudio retrospectivo, analítico. La población incluida fueron todos los casos de mortalidad directa o asociada a tuberculosis durante el año 2012 en los 30 municipios del departamento del Chocó. La recopilación de la información se realizó a través de entrevistas verbales con los familiares, las autoridades de la comunidad y el personal de salud de cada municipio. resultados. Se identificaron 31 casos de muerte relacionadas con tuberculosis en 12 de los municipios visitados. La distribución por sexo fue ligeramente superior en las mujeres (52%). De la totalidad de los casos encontrados, la población que mayor mortalidad registró fue la indígena (67%), que vive en zonas rurales dispersas (92%) y que presentaba como diagnostico tb de tipo pulmonar (92%). Al verificar la concordancia en el registro de los datos de mortalidad, encontramos que el Departamento Administrativo Nacional de Estadísticas (dane) reportó para el año 2012 seis muertes por tuberculosis en todo el departamento, mientras que el programa departamental de tuberculosis y sivigila tenía en sus registros 21 casos de fallecidos. discusión. En el presente estudio se encontró que en el Departamento del Chocó para el año 2012 existió un subregistro de casos de mortalidad por tuberculosis. Si se consideran los datos del programa departamental, el subregistro fue de 31%; si lo comparamos con los datos del dane, éste fue de 80%.

2024, Biology

Predatory stink bugs capture prey by injecting salivary venom from their venom glands using specialized stylets. Understanding venom function has been impeded by a scarcity of knowledge of their venom composition. We therefore examined the proteinaceous components of the salivary venom of the predatory stink bug Arma custos (Fabricius, 1794) (Hemiptera: Pentatomidae). We used gland extracts and venoms from fifth-instar nymphs or adult females to perform shotgun proteomics combined with venom gland transcriptomics. We found that the venom of A. custos comprised a complex suite of over a hundred individual proteins, including oxidoreductases, transferases, hydrolases, ligases, protease inhibitors, and recognition, transport and binding proteins. Besides the uncharacterized proteins, hydrolases such as venom serine proteases, cathepsins, phospholipase A2, phosphatases, nucleases, alpha-amylases, and chitinases constitute the most abundant protein families. However, salivary proteins sh...

2024, International Immunopharmacology

Stingrays from the Potamotrygon cf. henlei species are widely distributed in high numbers throughout the rivers of central-west Brazil, being the source of numerous envenomations occurring in the dry season, posing a serious public health problem even if not properly reported. The accidents usually involve fishermen and bathers, and to date there is no effective treatment for the injured. Considering these facts and limitations of studies aiming at understanding the effects induced by P. cf. henlei envenoming, this study aimed to describe the principal pharmacological and certain biochemical properties of the mucus and sting venom. We found that mucus and sting venom is toxic to mice having nociceptive, edematogenic and proteolysis activities. Our results also indicate that the inflammatory cellular influx observed could be triggered by the venom and mucus. Furthermore the venom and mucus were partially purified by solid-phase extraction tested for antimicrobial activity in which only the mucus presented activity. It could be inferred from the present study that P. cf. henlei venom possesses a diverse mixture of peptides, enzymes and pharmacologically active components.

2024, Phylum Cnidaria (Corals)

There are 10,000+ species in the phylum Cnidaria, and the vast majority occur in marine systems. Examples include hydroids, true jellyfish, sea anemones and corals. Of the six proposed taxonomic classes in the phylum Cnidaria, only 2 classes Polypodiozoa and Hydrozoa, contain freshwater genera. Class Polypodiozoa is represented by an endoparasite while the class Hydrozoa has more familiar and prevalent members such as Hydra as well as the less familiar but intriguing freshwater jellyfish. Some of the life cycles of freshwater cnidarians have both diagnostic stages of the polyp and medusa while others only exist as the polyp stage. Both stages are often inconspicuous but can be found in various types of freshwater habitats such as ponds, rivers and lakes.

2024, International Journal of Medical Toxicology and Forensic Medicine.

2024

Nosocomial infections caused by antibiotic-resistant bacteria result in significant economic costs and human health issues, including acute lung injury. The purpose of this study was to investigate the scorpion venom in countering lung injury induced by bacterial sepsis. Androctonus crassicauda (Acra) scorpion venom was fractionated using HPLC and tested against bacteria. The anti-bacterial fraction obtained at 36th min (AcraX) was used to generate chitosan-coated particles. Following induction of sepsis in rats, they were administered venom on the sixth hour and sacrificed at 24 h. Lung tissues were used for histopathological analyses and after homogenization, for cytokine (TNF-α, IL-1β, IL-6, and IL-10) measurements by ELISA. Immunohistochemical examinations were performed in terms of extracellular matrix and fibrosis using anti-MMP-2 and MMP-9 antibodies. Among the bacterial strains used in our research for the antibacterial effect of AcraX (S.aureus, K.pneumoniae, A.baumannii, and P.aeruginosa), positive results were obtained only against Klebsiella pneumoniae. The regenerative effect of the venom against lesions developed in tissue and HeLa cell line was also observed. 100% vitality was achieved in the HeLa cell line exposed to the venom. This was also observed histologically via changes in the alveolar septa in lung tissue sections and a decrease in areas of inflammation and the hyaline membrane structure in the sepsis group. In conclusion, Acra venom acts as an efficient anti-inflammatory agent against K. pneumoniae induced pneumoniae.

2024, Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii

Introduction: Measurement of health-related quality of life is mostly used with advanced measurement tools, such as scales. The use of a certain scale in different cultural settings or in age groups other than those it was designed for needs conducting the adaptation process and assessment of psychometric properties of the adapted scale. Aim: This paper presents the results of theoretical validity and reliability analysis of the Polish adaptation of the VQLQ scale for adolescents with Hymenoptera venom allergy. Material and methods: The study sample consisted of 78 adolescents aged 14-19 years, who were treated with venom immunotherapy in Polish allergological centers in 2008 year. Theoretical validity of the scale was analyzed with exploratory factor analysis using the principal components method. Reliability analysis was assessed in terms of internal consistency with Cronbach's α coefficient and by testing Kline's criterion. Results: The results showed satisfactory validity of the scale: factor analysis revealed a 3-factor structure of the scale -extracted factors were described as anxiety, caution and discomfort. All the scale items contributed to unique factors, except for one item concerning limitation in summer due to allergy, which was identified as a separate dimension of health-related quality of life of Polish adolescents with Hymenoptera venom allergy. All the extracted subscales were characterized by values of α coefficient equal or higher than 0.8, what is usually considered as a high-level reliability coefficient. Conclusions: The adapted scale is a valid and reliable tool measuring health-related quality of life in Polish adolescents treated with venom-specific immunotherapy.

2024, bioRxiv (Cold Spring Harbor Laboratory)

Venom systems are ideal models to study genetic regulatory mechanisms that underpin evolutionary novelty. Snake venom glands are thought to share a common origin, but there are major distinctions between venom toxins from the medically significant snake families Elapidae and Viperidae, and toxin gene regulation in elapids is largely unexplored. Here, we used high-throughput RNA-sequencing to profile gene expression and microRNAs between active (milked) and resting (unmilked) venom glands in an elapid (Eastern Brown Snake, Pseudonaja textilis), in addition to comparative genomics, to identify cis-and transacting regulation of venom production in an elapid in comparison to viperids (Crotalus viridis and C. tigris). Although there is conservation in high-level mechanistic pathways regulating venom production, there are histone methylation, transcription factor, and microRNA regulatory differences between these two snake families. Histone methyltransferases (KMT2A, KMT2C and KMT2D) and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland, whereas nuclear factor I (NFI) TFs were upregulated after viperid venom milking. Sp1 and NFI cis-regulatory elements were common to toxin gene promoter regions, but many unique elements were also present between elapid and viperid toxins. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target different toxin transcripts. Our comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin evolution between these two snake families, demonstrating multiple toxin genes and regulatory mechanisms converged to underpin a highly venomous phenotype.

2024, BMC Biology

Background:
The snake genera Atropoides, Cerrophidion, and Metlapilcoaltus form a clade of Neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib.
Results:
All venoms showed myotoxic, and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenoms ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2-inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types.
Conclusions:
This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American Crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.

2024, Toxins

Scorpions use their venom in defensive situations as well as for subduing prey. Since some species of scorpion use their venom more in defensive situations than others, this may have led to selection for differences in effectiveness in defensive situations. Here, we compared the LD50 of the venom of 10 species of scorpions on five different species of target organisms; two insects and three vertebrates. We found little correlation between the target species in the efficacy of the different scorpion venoms. Only the two insects showed a positive correlation, indicating that they responded similarly to the panel of scorpion venoms. We discuss the lack of positive correlation between the vertebrate target species in the light of their evolution and development. When comparing the responses of the target systems to individual scorpion venoms pairwise, we found that closely related scorpion species tend to elicit a similar response pattern across the target species. This was further refl...

2024, Toxins

Australian elapid snake venoms are uniquely procoagulant, utilizing blood clotting enzyme Factor Xa (FXa) as a toxin, which evolved as a basal trait in this clade. The subsequent recruitment of Factor Va (FVa) as a toxin occurred in the last common ancestor of taipans (Oxyuranus species) and brown snakes (Pseudonaja species). Factor II (prothrombin) activation has been stated as the primary mechanism for the lethal coagulopathy, but this hypothesis has never been tested. The additional activation of Factor VII (FVII) by Oxyuranus/Pseudonaja venoms has historically been considered as a minor, unimportant novelty. This study aimed to investigate the significance of toxic FVII activation relative to prothrombin activation by testing a wide taxonomical range of Australian elapid species with procoagulant venoms. The activation of FVII or prothrombin, with and without the Factor Va as a cofactor, was assessed, along with the structural changes involved in these processes. All procoagulant species could activate FVII, establishing this as a basal trait. In contrast, only some lineages could activate prothrombin, indicating that this is a derived trait. For species able to activate both zymogens, Factor VII was consistently more strongly activated than prothrombin. FVa was revealed as an essential cofactor for FVII activation, a mechanism previously undocumented. Species lacking FVa in their venom utilized endogenous plasma FVa to exert this activity. The ability of the human FXa:FVa complex to activate FVII was also revealed as a new feedback loop in the endogenous clotting cascade. Toxin sequence analyses identified structural changes essential for the derived trait of prothrombin activation. This study presents a paradigm shift in understanding how elapid venoms activate coagulation factors, highlighting the critical role of FVII activation in the pathophysiological effects upon the coagulation cascade produced by Australian elapid snake venoms. It also documented the novel use of Factor Va as a cofactor for FVII activation for both venom and endogenous forms of FXa. These findings are crucial for developing better antivenoms and treatments for snakebite victims and have broader implications for drug design and the treatment of coagulation disorders. The research also advances the evolutionary biology knowledge of snake venoms.

2024, Toxins

The nose-horned viper Vipera ammodytes meridionalis is considered one of the most venomous snakes in Europe. However, it is unknown whether ontogenetic variation in venom effects occurs in this subspecies and how this may impact antivenom efficacy. In this study, we compared the procoagulant activities of V. a. meridionalis venom on human plasma between neonate and adult venom phenotypes. We also examined the efficacy of three antivenoms—Viperfav, ViperaTAb, and Inoserp Europe—across our neonate and adult venom samples. While both neonate and adult
V. a. meridionalis venoms produced procoagulant effects, the effects produced by neonate venom were more potent. Consistent with this, neonate venom was a stronger activator of blood-clotting zymogens, converting them into their active forms, with a rank order of Factor X >> Factor VII> Factor XII. Conversely, the less potent adult venom had a rank order of FXII marginally more activated than Factor VII, and both much more so than Factor X. This adds to the growing body of evidence that activation of factors besides FII (prothrombin) and FX are significant variables in reptile venom-induced coagulopathy. Although all three examined antivenoms displayed effective
neutralization of both neonate and adult V. a. meridionalis venoms, they generally showed higher efficacy on adult venom than on neonate venom. The ranking of antivenom efficacy against neonate venom, from the most effective to the least effective, were Viperfav, Inoserp Europe, ViperaTAb; for
adult venom, the ranking was Inoserp Europe, Viperfav, ViperaTAb. Our data reveal ontogenetic variation in V. a meridionalis, but this difference may not be of clinical concern as antivenom was effective at neutralizing both adult and neonate venom phenotypes. Regardless, our results highlight
a previously undocumented ontogenetic shift, likely driven by the documented difference in prey preference observed for this species across age classes.

2024, Toxins

Biofilm formation on exposed surfaces is a serious issue for the food industry and medical health facilities. There are many proposed strategies to delay, reduce, or even eliminate biofilm formation on surfaces. The present study focuses on the applicability of fire ant venom alkaloids (aka ‘solenopsins’, from Solenopsis invicta) tested on polystyrene and stainless steel surfaces relative to the adhesion and biofilm-formation by the bacterium Pseudomonas fluorescens. Conditioning with solenopsins demonstrates significant reduction of bacterial adhesion. Inhibition rates were 62.7% on polystyrene and 59.0% on stainless steel surfaces. In addition, solenopsins drastically reduced cell populations already growing on conditioned surfaces. Contrary to assumptions by previous authors, solenopsins tested negative for amphipathic properties, thus understanding the mechanisms behind the observed effects still relies on further investigation.

2024, Clinical Kidney Journal

2024, Acta Tropica

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2024, Toxins

Animals that specialise in blood feeding have particular challenges in obtaining their meal, whereby they impair blood hemostasis by promoting anticoagulation and vasodilation in order to facilitate feeding. These convergent selection pressures have been studied in a number of lineages, ranging from fleas to leeches. However, the vampire bat (Desmondus rotundus) is unstudied in regards to potential vasodilatory mechanisms of their feeding secretions (which are a type of venom). This is despite the intense investigations of their anticoagulant properties which have demonstrated that D. rotundus venom contains strong anticoagulant and proteolytic activities which delay the formation of blood clots and interfere with the blood coagulation cascade. In this study, we identified and tested a compound from D. rotundus venom that is similar in size and amino acid sequence to human calcitonin gene-related peptide (CGRP) which has potent vasodilatory properties. We found that the vampire bat-...

2024, Toxins

Millions of years of evolution have fine-tuned the ability of venom peptides to rapidly incapacitate both prey and potential predators. Toxicofera reptiles are characterized by serous-secreting mandibular or maxillary glands with heightened levels of protein expression. These glands are the core anatomical components of the toxicoferan venom system, which exists in myriad points along an evolutionary continuum. Neofunctionalisation of toxins is facilitated by positive selection at functional hotspots on the ancestral protein and venom proteins have undergone dynamic diversification in helodermatid and varanid lizards as well as advanced snakes. A spectacular point on the venom system continuum is the long-glanded blue coral snake (Calliophis bivirgatus), a specialist feeder that preys on fast moving, venomous snakes which have both a high likelihood of prey escape but also represent significant danger to the predator itself. The maxillary venom glands of C. bivirgatus extend one quarter of the snake's body length and nestle within the rib cavity. Despite the snake's notoriety its venom has remained largely unstudied. Here we show that the venom uniquely produces spastic paralysis, in contrast to the flaccid paralysis typically produced by neurotoxic snake venoms. The toxin responsible, which we have called calliotoxin (δ-elapitoxin-Cb1a), is a three-finger toxin (3FTx). Calliotoxin shifts the voltage-dependence of Na V 1.4 activation to more hyperpolarised potentials, inhibits inactivation, and produces large ramp currents, consistent with its profound effects on contractile force in an isolated skeletal muscle preparation. Voltage-gated sodium

2024, Egyptian Academic Journal of Biological Sciences

WHO (2018) recorded that every year, about 5.4 million snakebites happen worldwide, which lead to 138,000 deaths, and 400,000 cases of infirmity, Although Snakebite is one of the world’s most dangerous neglected tropical toxic hazards, it receives little care from global health agencies, charities or governments. The aim of the study was to assess the hazardous effects of snakebite through a retrospective study of snakebite toxicity. All snakebite cases who arrived at Benha Fever Hospitals, Egypt, from the first of January 2022 to the end of December 2022 were presented in the study. All socio-demographic and clinical data were collected and analyzed. The present study recorded 74 cases of snake bites with the majority (37.84%) of cases aged between 20 and 29 years, 58.11% were males, and 70.27% came from rural areas. 59.45% occurred during summer, the majority of cases (54.06%) were bitten by nonvenomous snakes, most cases (62.16%) occurred outdoors, and 59.45% of patients were bitten between 12 pm and 12 am. 81.08% of patients presented mainly with pain with local edema, 33.8% and 32.4% were treated with wound care and immobilization of the injured extremity and antivenom therapy respectively, and 81.08% were improved and discharged. Conclusion Snake bite is an emergency topic in Egypt among rural males aged between 20-29 years. commonly observed symptoms were pain and local odema; most of the cases were treated symptomatically and most of them improved and discharged.

2024, Biomédica

Introducción. El ofidismo es un relevante problema de salud pública y, en Colombia, se incluyó como un evento de notificación obligatoria desde el año 2004. Por ser un país tropical con gran diversidad ecosistémica, ocupa el tercer puesto en Latinoamérica, después de México y Brasil, en presentar el mayor número de accidentes ofídicos.Objetivo. Realizar un análisis retrospectivo del accidente ofídico en el departamento de Nariño, con base en los eventos notificados entre los años 2008 y 2017 al Instituto Departamental de Salud de Nariño y al Sistema de Vigilancia en Salud Pública de Colombia.Materiales y métodos. Se hizo un análisis de tipo descriptivo y retrospectivo a partir de la recopilación e interpretación de la información consignada en las fichas de notificación para accidente ofídico del Instituto Departamental de Salud de Nariño, entre los años 2008 y 2017. Se representó la frecuencia del accidente ofídico a nivel municipal mediante la elaboración de un mapa y se identific...

2024, Journal of Proteome Research

The genus Trimeresurus comprises a group of venomous pitvipers endemic to Southeast Asia and the Pacific Islands. Of these, Trimeresurus insularis, the White-lipped Island Pitviper, is a nocturnal, arboreal species that occurs on nearly every major island of the Lesser Sunda archipelago. In the current study, venom phenotypic characteristics of T. insularis sampled from eight Lesser Sunda Islands (Flores,

2024, Journal of Applied Microbiology

Aims: Dinoponera quadriceps venom (DqV) was examined to evaluate the antibacterial activity and its bactericidal action mechanism against Staphylococcus aureus. Methods and Results: DqV was tested against a standard strain of methicillinsensitive Staphylococcus aureus (MSSA), Staph. aureus ATCC 6538P and two standard strains of methicillin-resistant Staphylococcus aureus (MRSA), Staph. aureus ATCC 33591 and Staph. aureus CCBH 5330. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the rate of kill and pH sensitivity of the DqV were determined by microdilution tests. Bactericidal and inhibitory concentrations of DqV were tested to check its action on Staph. aureus membrane permeability and cell morphology. The MIC and MBC of DqV were 6Á25 and 12Á5 lg ml À1 for Staph. aureus ATCC 6538P, 12Á5 and 50 lg ml À1 for Staph. aureus CCBH 5330 and 100 and 100 lg ml À1 for Staph. aureus ATCC 33591, respectively. Complete bacterial growth inhibition was observed after 4 h of incubation with the MBC of DqV. A lowest MIC was observed in alkaline pH. Alteration in membrane permeability was observed through the increase in crystal violet uptake, genetic material release and morphology in atomic force microscopy. Conclusions: The results suggest antibacterial activity of DqV against Staph. aureus and that the venom acts in the cell membrane. Significance and Impact of the Study: Alteration in membrane permeability may be associated with the antimicrobial activity of hymenopteran venoms.

2024

Animais peçonhentos representam um grave problema de saúde pública, dado o elevado número de acidentes que causam. No Brasil, cinco espécies de escorpiões do gênero Tityus, são encontradas: Tityus serrulatus, Tityus bahiensis, Tityus stigmurus, Tityus paraensis e Tityus silvestris, sendo a espécie T. serrulatus, ou escorpião-amarelo, considerada a mais perigosa. O objetivo do estudo é apresentar revisão dos aspectos etiológicos, ecológicos, clínicos, epidemiológicos e profiláticos do escorpionismo e apresentar a Inteligência Artificial como método de estudo deste agravo à saúde. Os autores concluem que o entendimento sobre os sinais e os sintomas são essenciais para o diagnóstico rápido, elemento essencial para estabelecer o tratamento adequado, melhorando, assim, o prognóstico do paciente.

2024, Toxins

Envenomations are complex medical emergencies that can have a range of symptoms and sequelae. The only specific, scientifically-validated treatment for envenomation is antivenom administration, which is designed to alleviate venom effects. A paucity of efficacy testing exists for numerous antivenoms worldwide, and understanding venom effects and venom potency can help identify antivenom improvement options. Some spider venoms can produce debilitating injuries or even death, yet have been largely neglected in venom and antivenom studies because of the low venom yields. Coagulation disturbances have been particularly under studied due to difficulties in working with blood and the coagulation cascade. These circumstances have resulted in suboptimal spider bite treatment for medically significant spider genera such as Loxosceles and Sicarius. This study identifies and quantifies the anticoagulant effects produced by venoms of three Loxoscles species (L. reclusa, L. boneti, and L. laeta)...

2024, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP

Night adders (Causus species within the Viperidae family) are amphibian specialists and a common source of snakebite in Africa. Some species are unique in that they have the longest venom glands of any viper, extending approximately 10% of the body length. Despite their potential medical importance and evolutionary novelty, their venom has received almost no research attention. In this study, venoms from a short-glanded species (C. lichtensteinii) and from a long-glanded species (C. rhombeatus) were compared using a series of proteomic and bioactivity testing techniques to investigate and compare the toxin composition and functioning of the venoms of these two species. Both C. rhombeatus and C. lichtensteinii were similar in overall venom composition and inhibition of blood coagulation through non-clotting proteolytic cleavage of fibrinogen. While the 1D gel profiles were very similar to each other in the toxin types present, 2D gel analyses revealed isoformic differences within eac...

2024

Despite their evolutionary novelty, lizard venoms are much less studied in comparison to the intense research on snake venoms. While the venoms of helodermatid lizards have long been assumed to be for defensive purposes, there is increasing evidence of toxic activities more useful for predation than defence (such as paralytic neurotoxicity). This study aimed to ascertain the effects of Heloderma, Lanthanotus, and Varanus lizard venoms on the coagulation and cardiovascular systems. Anticoagulant toxicity was demonstrated for the Varanus species studied, with the venoms prolonging clotting times in human and bird plasma due to the destructive cleavage of fibrinogen. In contrast, thromboelastographic analyses on human and bird plasmas in this study demonstrated a procoagulant bioactivity for Heloderma venoms. A previous study on Heloderma venom using factor-depleted plasmas as a proxy model suggested a procoagulant factor was present that activated either Factor XI or Factor XII, but could not ascertain the precise target. Our activation studies using purified zymogens confirmed FXII activation. Comparisons of neonate and adult H. exasperatum, revealed the neonates to be more potent in the ability to activate FXII, being more similar to the venom of the smaller species H. suspectum than the adult H. exasperatum. This suggests potent FXII activation a basal trait in the genus, present in the small bodied last common ancestor. This also indicates an ontogenetic difference in prey preferences in the larger Heloderma species paralleing the change in venom biochemistry. In addition, as birds lack Factor XII, the ability to clot avian plasma suggested an additional procoagulant site of action, which was revealed to be the activation of Factor VII, with H. horridum being the most potent. This study also examined the effects upon the cardiovascular system, including the liberation of kinins from kininogen, which contributes to hypotension induction. This form of toxicity was previously described for Heloderma venoms, and was revealed in this study was to also be a pathophysiological effect of Lanthanotus and Varanus venoms. This suggests that this toxic activity was present in the venom of the last common ancestor of the anguimorph lizards, which is consistent with kallikrein enzymes being a shared toxin trait. This study therefore uncovered novel actions of anguimorph lizard venoms, not only contributing to the evolutionary biology body of knowledge but also revealing novel activities to mine for drug design lead compounds.

2024

The study investigated the intraspecific and interspecific variability in venom effects of Agkistro-don viperid snake species and subspecies (eleven venoms total) on plasma clotting times, fibrino-gen levels, and fibrin clot strength. Significant delays in plasma clotting time were observed for A. conanti, A. contortrix mokasen, A. contortrix phaeogaster, A. howardgloydi, A. piscivorus leu-costoma, and A. piscivorus piscivorus. Notably the phylogenetically disjunct lineages A. conanti, A. contortrix mokasen and A. howardgloydi exhibited the most potent anticoagulant effects, indicating independent amplification of a basal trait. Inhibition assays with activated clotting enzymes (Factor XIa, IXa, Xa, and thrombin) revealed that FXa inhibition is another basal trait amplified independently on multiple occasions within the genus but with A. howardgloydi notably more po-tent than all others. Phospholipid degradation and zymogen destruction were identified as mechanisms underlying the variability in venom effects observed experimentally and previous clinical reports. Thromboelastography demonstrated that venoms did not clot fibrinogen directly but affected fibrin clot strength by damaging fibrinogen, that thrombin was subsequently only able to cleave into weak, unstable clots. The ability to activate Protein C, an endogenous anticoag-ulant enzyme, varied across species, with some venoms exceeding that of A. contortrix contortrix venom, which previously yielded the protein diagnostic agent Protac®. Phylogenetic analysis suggested that both fibrinogen degradation and Protein C activation were each amplified multi-ple times within the genus, albeit with negative correlation between these two modes of action. This study highlights the evolutionary, clinical, and biodiscovery implications of venom varia-bility in Agkistrodon species, underscoring their dynamic evolution, emphasizing the need for tailored clinical approaches, and highlighting the potential for novel diagnostic and therapeutic developments inspired by the unique properties of snake venoms.

2024

Snakes in the family Elapidae largely produce venoms rich in three-finger toxins (3FTx) that bind to the α 1 subunit of nicotinic acetylcholine receptors (nAChRs), impeding ion channel activity. These neurotoxins immobilize the prey by disrupting muscle contraction. Coral snakes of the genus Micrurus are specialist predators who produce many 3FTx, making them an interesting system for examining the coevolution of these toxins and their targets in prey animals. We used a bio-layer interferometry technique to measure the binding interaction between 15 Micrurus venoms and 12 taxon-specific mimotopes designed to resemble the orthosteric binding region of the muscular nAChR subunit. We found that Micrurus venoms vary greatly in their potency on this assay and that this variation follows phylogenetic patterns rather than previously reported patterns of venom composition. The long-tailed Micrurus tend to have greater binding to nAChR orthosteric sites than their short-tailed relatives and we conclude this is the likely ancestral state. The repeated loss of this activity may be due to the evolution of 3FTx that bind to other regions of the nAChR. We also observed variations in the potency of the venoms depending on the taxon of the target mimotope. Rather than a pattern of prey-specificity, we found that mimotopes modeled after snake nAChRs are less susceptible to Micrurus venoms and that this resistance is partly due to a characteristic tryptophan→serine mutation within the orthosteric site in all snake mimotopes. This resistance may be part of a Red Queen arms race between coral snakes and their prey.

2024, Toxins

2024, BJSTR

To develop a novel procedure for preparation of equine anti-Daboia siamensis immunoglobulin F (ab’)2 fragments. First, after plasma were diluted by 2 volume pure water, adjusted to pH3.2±0.1, the mixture was digested by 1.5% v/v pepsin... more

2024, Amino Acids

We identified six novel, genetically encoded peptides: four from pit vipers, collectively named vipericidins, and two from the elapid. These new venom-derived cathelicidins exhibited potent killing activity against a number of bacterial strains (S. pyogenes, A. baumannii, E. faecalis, S. aureus, E. coli, K. pneumoniae, and P. aeruginosa), mostly with relatively less potent hemolysis, indicating their possible usefulness as lead structures for the development of new anti-infective agents. It is worth noting that these South American snake venom peptides are comparable in cytotoxicity (e.g., hemolysis) to human cathelicidin LL-37, and much lower than other membrane-active peptides such as mastoparan 7 and melittin from bee venom. Overall, the excellent bactericidal profile of vipericidins suggests they are a promising template for the development of broadspectrum peptide antibiotics.