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Keywords = animal envenoming

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25 pages, 2112 KB  
Article
Envenomization with Snake Versus Scorpion Venom: Postmortem Repercussions on the Successional Dynamics of Carcass-Attracted Flies in a Forensic Context
by Afnan Saleh Al-Qurashi, Mohammed Saleh Al-Khalifa, Hathal Mohammed Al Dhafer, Mahmoud Saleh Abdel-Dayem, Hossam Ebaid and Ashraf Mohamed Ahmed
Insects 2026, 17(8), 863; https://doi.org/10.3390/insects17080863 - 19 Aug 2026
Abstract
Background: Animal venoms may alter postmortem carcass conditions and thereby influence carrion-associated insects. However, it remains unclear whether lethal envenomization affects adult Diptera as a broad assemblage-level response or as taxon-specific changes during decomposition. Methods: Fifteen rabbits were assigned to control, snake-envenomized, or [...] Read more.
Background: Animal venoms may alter postmortem carcass conditions and thereby influence carrion-associated insects. However, it remains unclear whether lethal envenomization affects adult Diptera as a broad assemblage-level response or as taxon-specific changes during decomposition. Methods: Fifteen rabbits were assigned to control, snake-envenomized, or scorpion-envenomized treatments (with five carcasses each). Carcasses were exposed under semi-natural conditions, until complete dryness, over 11 days postmortem. Adult flies were collected daily for analyzing abundance at total, family, and selected species levels, using negative GLMM, with carcass identity as a random effect and postmortem day as a nonlinear predictor. Results: A total of 5497 adult flies representing 13 species in seven families was recorded. Total fly abundance was similar among treatments and was mainly structured by postmortem day. In contrast, treatment-related temporal patterns were detected at finer taxonomic levels, especially at the family level for Muscidae, Ephydridae, and Sarcophagidae; and at the species level for the sarcophagid Sarcophaga argyrostoma and the ephydrid Actocetor indicus only. Conclusions: both snake and scorpion envenomization did not produce a broad shift in total adult-fly abundance, but in selected Dipteran taxa showing treatment-related responses during particular postmortem periods. These findings should be interpreted cautiously as exploratory observations rather than evidence of a robust venom effect on adult fly communities. Full article
(This article belongs to the Section Role of Insects in Human Society)
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6 pages, 1140 KB  
Case Report
Dangerous Measures: A Case Report and Review of Motoro Ray Envenomation
by Philip Dwek, Omer Jamal, Shaleesa Clarke, Kiran Wadhawan and Andrea K. Boggild
Toxins 2026, 18(6), 270; https://doi.org/10.3390/toxins18060270 - 19 Jun 2026
Viewed by 581
Abstract
Aquatic envenomations may cause severe tissue injury, neurologic morbidity, and even mortality among those whose leisure and/or occupational activities expose them to marine and freshwater animals. The Motoro ray, or Potamotrygon motoro (also known as an ocellate river stingray) is endemic to freshwater [...] Read more.
Aquatic envenomations may cause severe tissue injury, neurologic morbidity, and even mortality among those whose leisure and/or occupational activities expose them to marine and freshwater animals. The Motoro ray, or Potamotrygon motoro (also known as an ocellate river stingray) is endemic to freshwater tributaries throughout Brazil, and is a frequent source of severe envenoming of local fisherman and those residing near waterways. Local wound management including immersion in warm water, wound cleaning and debridement, as well as antibiotics are mainstays of treatment, as are local anesthetics (e.g., nerve blocks) and systemic opioid analgesics; however, high-quality evidence supporting such interventions is lacking. We present a case of a Canadian who was envenomed by his pet Motoro ray, and describe his clinical presentation and evolution of symptoms over the subsequent months. With the ever-increasing trade of exotic wildlife, clinicians, public health authorities, and those within the broader wildlife regulatory ecosystem should be attuned for unanticipated adverse consequences, such as those described herein. We further situate this case within the existing published literature around this particular species of ray, which is not typically considered an ornamental fish. Full article
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2 pages, 147 KB  
Abstract
Venom Biology of the Lesser Weever Fish: Intraspecific Variability, Bioactivity, and Biotechnological Potential
by Ricardo Estevens, Telma Luís, Samuel Ramos Pereira, Vera M. Mendes, Bruno Manadas, Carolina Madeira and Pedro M. Costa
Proceedings 2026, 146(1), 32; https://doi.org/10.3390/proceedings2026146032 - 17 Jun 2026
Viewed by 412
Abstract
Fish venom biology reaches far beyond addressing risks of human envenomation. The critical understanding of venom composition and the drivers that modulate it will enable scientists to deliver a span of novel bioresources with multiple potential biotechnological applications. The lesser weever fish ( [...] Read more.
Fish venom biology reaches far beyond addressing risks of human envenomation. The critical understanding of venom composition and the drivers that modulate it will enable scientists to deliver a span of novel bioresources with multiple potential biotechnological applications. The lesser weever fish (Echiichtys vipera), common in the surf of sandy beaches in Portugal, is a noteworthy case study due to frequent envenomation episodes during summer, albeit the lack of information regarding its venom system and the composition of its venom. We collected about one hundred animals from Costa da Caparica (W Portugal) as beach trawl (arte xávega) by-catch. Histology showed a similar essential microanatomical structure of glands in both venomous spines (dorsal and opercular) and no obvious gender differences. Transversal sections across the spines showed a T-shaped supportive bone structure that harbor masses of large, glandular cells that bear large sacculi. The structure is surrounded by a retractable layer of skin, thicker in the opercular spines comparatively to dorsal. The lack of muscular tissue near the glands and missing venom delivery ducts in the spines suggest that venom secretion in this species is holocrine, i.e., that venom is delivered through rupture of the skin and underlying glandular tissue upon mechanical pressure. Proteomics of the venomous spines (dorsal and opercular) showed a different proteomic signature between males and females, pointing to intersexual variation and suggesting that other biotic and abiotic factors might influence venom composition (maturation stage or geographic distribution). Additionally, protein homology matches performed against known toxins from marine venomous fishes indicated the presence of novel unexplored toxins in this species besides expected cytolysins. Our focus in the future is to identify, isolate and characterize the individual components of this venom. We anticipate new insights on the intraspecific adaptation of fish venom systems to specific ecological needs and advocate for sustainable bioprospecting for novel proteins with high biotechnological potential. Full article
(This article belongs to the Proceedings of The XI Iberian Congress of Ichthyology)
18 pages, 1885 KB  
Article
Interaction of Human Lymphocyte Scavenger Receptors CD5 and CD6 with Toxins from Naja haje, Androctonus australis and Apis mellifera Venoms
by Dalila Khemili, Laura Carrillo-Serradell, Violeta Planells-Romeo, Lucía Aragón-Serrano, Selma Djilani, Djelila Hammoudi-Triki, Khedidja Zerouti, Abdenacer Mouffok, Francisco Lozano and María Velasco-de-Andrés
Biomolecules 2026, 16(5), 681; https://doi.org/10.3390/biom16050681 - 5 May 2026
Viewed by 987
Abstract
Animal venoms induce systemic inflammatory response syndrome through their interaction, inter alia, with pattern recognition receptors (PRRs) of the innate immune system. CD5 and CD6 are lymphoid members of the scavenger receptor cysteine-rich superfamily, endowed with PRR activity against microbial-associated molecular patterns (MAMPs) [...] Read more.
Animal venoms induce systemic inflammatory response syndrome through their interaction, inter alia, with pattern recognition receptors (PRRs) of the innate immune system. CD5 and CD6 are lymphoid members of the scavenger receptor cysteine-rich superfamily, endowed with PRR activity against microbial-associated molecular patterns (MAMPs) derived from bacteria, fungi, viruses and/or parasites. In this study, we aimed to investigate CD5 and CD6 interaction with cobra (Naja haje), scorpion (Androctonus australis) and honeybee (Apis mellifera) venoms. Binding assays revealed direct, dose-dependent and specific interaction of soluble human CD5 and CD6 receptors with protein nature components from the three venoms. Proteomic analysis identified venom nerve growth factor, basic phospholipase A2 (PLA2) and cobra venom factor, in cobra venom, and scorpion venom toxins targeting potassium (α-KTx 8.1) and sodium channels (Neurotoxin-1″ and G-TI) as potentially interacting components with CD5 and CD6. Further studies confirmed direct binding of bee venom main components, phospholipase A2 and melittin, to both soluble CD5 and CD6 receptors. Interestingly, in vitro PLA2 activity from cobra and bee venom was significantly reduced by both soluble CD5 and CD6 receptors. These findings broaden the PRR properties of CD5 and CD6 and support their potential involvement in envenomation pathophysiology. Full article
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13 pages, 1482 KB  
Article
Characterization of Alpha-Bungarotoxin Antibodies Prepared by Different Strategies
by Huijuan Lu, Guowen Zhang, Lin Zhao, Ying Yuan, Bing Gong, Bin Han and Wen-Hui Lee
Toxins 2025, 17(12), 601; https://doi.org/10.3390/toxins17120601 - 16 Dec 2025
Viewed by 973
Abstract
The preparation of an antibody to treat snake envenomation requires a large amount of snake venom. In China, only four types of anti-snake venom sera are clinically available, and the production and immunization strategies for clinically approved anti-snake venom sera still mainly rely [...] Read more.
The preparation of an antibody to treat snake envenomation requires a large amount of snake venom. In China, only four types of anti-snake venom sera are clinically available, and the production and immunization strategies for clinically approved anti-snake venom sera still mainly rely on detoxified antigens, which is a mature technical route commonly adopted by domestic pharmaceutical enterprises. At present, researchers immunize animals with low doses of certain snake venom toxic components or prokaryotically expressed toxic components to reduce the amount of venom needed, and use prepared antisera for their specific investigation purposes. However, it is unclear if low-dose immunized antibody titers and toxin-neutralizing activities are consistent with those of high-dose detoxified crude venom immunized antibodies. In this study, we developed a method for the preparation of highly effective rabbit polyclonal antisera while saving a large amount of toxin. Rabbit polyclonal antisera prepared by low-dose natural α-bungarotoxin (α-BGT) had strong neutralizing effects on the toxin itself and achieved the same antibody titers as antisera prepared with high doses of detoxified α-BGT. Antigen of A maltose binding protein (MBP) fused with α-BGT (MBP-α-BGT) expressed in prokaryotes had low antibody titer and low neutralizing activity. This study provides an effective dosage selection guide and methods for the preparation of polyclonal antibodies and antiserum for investigation purposes. Full article
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20 pages, 1877 KB  
Article
Photobiomodulation with Combined Wavelengths Results in Improved Clinical Recovery in a Murine Model of Bothrops leucurus Venom Envenomation
by Gisele Dias da Silva, Fabiana Lessa Silva, Anaiá da Paixão Sevá, Juneo Freitas Silva, Danilo Machado Deorce, Nerildo de Jesus da Costa Junior, Fernanda Amaral Silva and Fernando Alzamora Filho
Toxins 2025, 17(11), 535; https://doi.org/10.3390/toxins17110535 - 30 Oct 2025
Cited by 1 | Viewed by 1553
Abstract
Snakebite envenomation by Bothrops species is a neglected tropical disease and a major cause of local tissue damage and disability in Latin America. Antivenom therapy is effective against systemic effects but fails to prevent local myonecrosis, inflammation, and pain. This study evaluated photobiomodulation [...] Read more.
Snakebite envenomation by Bothrops species is a neglected tropical disease and a major cause of local tissue damage and disability in Latin America. Antivenom therapy is effective against systemic effects but fails to prevent local myonecrosis, inflammation, and pain. This study evaluated photobiomodulation therapy (PBMT) using infrared (808 nm) alone or in combination with red (660 nm) laser in a murine model of Bothrops leucurus envenomation. A single PBMT session was applied, and animals were evaluated at 24 and 72 h. Combined treatment significantly reduced edema, hyperthermia, plasma CK and LDH, restored nociceptive thresholds, and improved motor recovery compared with infrared alone. Principal component analysis demonstrated clustering of combined-treatment animals with negative controls, supporting a synergistic therapeutic effect. These findings highlight dual-wavelength PBMT as a promising adjunctive approach to antivenom, directly targeting local venom-induced pathology. Full article
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13 pages, 2474 KB  
Article
Renal Effects and Nitric Oxide Response Induced by Bothrops atrox Snake Venom in an Isolated Perfused Kidney Model
by Terentia Batista Sa Norões, Antonio Rafael Coelho Jorge, Helena Serra Azul Monteiro, Ricardo Parente Garcia Vieira and Breno De Sá Barreto Macêdo
Toxins 2025, 17(8), 363; https://doi.org/10.3390/toxins17080363 - 24 Jul 2025
Viewed by 1410
Abstract
The snakes from the genus Bothrops are responsible for most of the ophidic accidents in Brazil, and Bothrops atrox represents one of these species. Envenomation by these snakes results in systemic effects and is often associated with early mortality following snakebite incidents. The [...] Read more.
The snakes from the genus Bothrops are responsible for most of the ophidic accidents in Brazil, and Bothrops atrox represents one of these species. Envenomation by these snakes results in systemic effects and is often associated with early mortality following snakebite incidents. The present study investigates the pharmacological properties of Bothrops atrox venom (VBA), focusing specifically on its impact on renal blood flow. Following the renal perfusion procedure, kidney tissues were processed for histopathological examination. Statistical analysis of all evaluated parameters was conducted using ANOVA and Student’s t-test, with significance set at p < 0.005. Administration of VBA resulted in a marked reduction in both perfusion pressure and renal vascular resistance. In contrast, there was a significant elevation in urinary output and glomerular filtration rate. Histological changes observed in the perfused kidneys were mild. The involvement of nitric oxide in the pressor effects of Bothrops atrox venom was not investigated in renal perfusion systems or in in vivo models. Treatment with VBA led to elevated nitrite levels in the bloodstream of the experimental animals. This effect was completely inhibited following pharmacological blockade with L-NAME. Based on these findings, we conclude that VBA alters renal function and promotes increased nitric oxide production. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
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24 pages, 14728 KB  
Article
Death-Leading Envenomization of Rabbits with Snake Versus Scorpion Venoms: A Comparative Forensic Investigation of Postmortem Decomposition and Beetle Succession
by Afnan Saleh Al-Qurashi, Mohammed Saleh Al-Khalifa, Hathal Mohammed Al Dhafer, Mahmoud Saleh Abdel-Dayem, Hossam Ebaid and Ashraf Mohamed Ahmed
Insects 2025, 16(6), 625; https://doi.org/10.3390/insects16060625 - 13 Jun 2025
Cited by 2 | Viewed by 2135
Abstract
Background:Envenomation by poisonous creatures is a major global cause of mortality. Its concomitant impact on the postmortem corpse decomposition and associated insect succession pattern is still poorly understood. Purpose of the study: This study comparatively investigates the impact of envenomization with [...] Read more.
Background:Envenomation by poisonous creatures is a major global cause of mortality. Its concomitant impact on the postmortem corpse decomposition and associated insect succession pattern is still poorly understood. Purpose of the study: This study comparatively investigates the impact of envenomization with the venoms of the snake Walterinnesia aegyptia L. versus the scorpion, Androctonus crassicauda L., on rabbit corpse decomposition and beetle succession. Methods: Three groups of rabbits (five animals each) were injected with the snake venom, the scorpion venom, or 0.9% saline (control) prior to euthanasia with CO2. The corpse decomposition stages and beetle succession were monitored over 11 days. Results: Four stages of decomposition with venom-dependent duration variation were observed. The scorpion-envenomized corpses showed a longer decay stage and a delayed dry stage. A total of 1094 beetles belonging to 27 species of 14 families were reported. Histeridae, Dermestidae, Scarabaeidae, and Tenebrionidae were the most diversified and prevalent families. Chrysomelidae, Elateridae, Hybosoridae, and Ptinidae were incidentally attracted to control corpses, while Nitidulidae and Zopheridae were only found on control and snake-envenomized ones. Four species belonging to the families Anthicidae, Histeridae, Scarabaeidae, and Tenebrionidae were predominant on all corpses. Four species belonging to the families Chrysomelidae, Curculionidae, Elateridae, and Hybosoridae were distinctively associated with the control corpses. Conclusions: These findings provided evidence that envenomation impacted the decomposition process and beetle succession in a venom-dependent manner, which could be significant for forensic investigations. Full article
(This article belongs to the Section Role of Insects in Human Society)
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12 pages, 2980 KB  
Article
Morphological Insights into Echinometra lucunter Spines Reveal Cellular Sources of Bioactive Molecules
by Juliana Mozer Sciani, Marta Maria Antoniazzi, Carlos Jared, José Roberto Machado Cunha da Silva and Daniel Carvalho Pimenta
Oceans 2025, 6(2), 33; https://doi.org/10.3390/oceans6020033 - 5 Jun 2025
Viewed by 1969
Abstract
Echinometra lucunter, the most abundant sea urchin in Brazil, causes numerous accidents by puncture wounds, primarily on hands and feet. Beyond mechanical trauma, recent research has identified bioactive molecules in spine extracts and coelomic fluid contributing to these inflammatory reactions. This study [...] Read more.
Echinometra lucunter, the most abundant sea urchin in Brazil, causes numerous accidents by puncture wounds, primarily on hands and feet. Beyond mechanical trauma, recent research has identified bioactive molecules in spine extracts and coelomic fluid contributing to these inflammatory reactions. This study investigated spine morphology to better understand the envenomation and defense processes for the animal. Using various microscopy techniques, the spines were revealed to be mineral structures with longitudinal canals and a sponge-like central mesh rich in granular cells. These cells extend from the spine’s center to its edges, terminating in fimbriae-like structures, likely involved in molecular exchange with the environment. The spine tip is more cellular than the base, suggesting a defensive role, while the base provides structural support. Several cell types were identified, including granulocytes, red spherulocytes, and phagocytic amoebocytes, also found in the coelomic fluid. Other cells displayed prominent Golgi apparatuses and secretory granules, indicating specialized secretory functions, likely the source of bioactive molecules involved in chemical defense and spine regeneration. Understanding this cellular structure is crucial for comprehending the urchin’s envenomation and defense mechanisms. Full article
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18 pages, 1858 KB  
Article
A Sting Operation: Risk Assessment and Venom Expenditure by Arizona Bark Scorpions (Centruroides sculpturatus) in a Defensive Context
by Lindsay A. Marston, Gerad A. Fox, Kim Y. Hung, Shannon J. Delo and William K. Hayes
Toxins 2025, 17(4), 198; https://doi.org/10.3390/toxins17040198 - 13 Apr 2025
Cited by 2 | Viewed by 3309
Abstract
Scorpion antipredator behavior incorporates risk assessment that informs decision-making and venom usage. We quantified antipredator behaviors of the clinically significant Arizona bark scorpion (Centruroides sculpturatus) in their natural environment using exposure to two stimuli: a freshly thawed laboratory mouse (Mus [...] Read more.
Scorpion antipredator behavior incorporates risk assessment that informs decision-making and venom usage. We quantified antipredator behaviors of the clinically significant Arizona bark scorpion (Centruroides sculpturatus) in their natural environment using exposure to two stimuli: a freshly thawed laboratory mouse (Mus musculus) and a membrane-covered glass beaker. We videotaped and compared envenomation behaviors between sexes (females, gravid females, and males), across sizes, and between animal orientations (on vertical or horizontal substrates). Results failed to show consistent support for any of our four hypotheses. Females (especially gravid females) were no more likely than males to exhibit higher levels of stinging and venom expenditure. Scorpions on horizontal surfaces compared to those on vertical surfaces, and larger scorpions compared to smaller ones, were likewise no more likely to exhibit higher levels of responsiveness. Mice were more likely to be stung than the membrane-covered beaker, but with fewer and briefer stings, suggesting the scorpions did not attempt to deliver more venom into the mice. Thus, we discerned no clear patterns in risk assessment, stinging, and venom use associated with sex, substrate orientation, body size, or threat stimuli. These findings contrasted with those of several prior laboratory studies. Variation from unaccounted environmental variables may have obfuscated divergent behavioral tactics. Nevertheless, the behaviors we document here provide insights on the range of defensive behaviors exhibited by C. sculpturatus under natural environmental conditions, including the frequency of dry stings (11.8%) to the membrane-covered beakers. Full article
(This article belongs to the Section Animal Venoms)
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17 pages, 1736 KB  
Article
Electrical Cell Impedance Sensing (ECIS): Feasibility of a Novel In Vitro Approach to Studying Venom Toxicity and Potential Therapeutics
by Abhinandan Choudhury, Kaitlin Linne, Tommaso C. Bulfone, Tanvir Hossain, Abu Ali Ibn Sina, Philip L. Bickler, Bryan G. Fry and Matthew R. Lewin
Toxins 2025, 17(4), 193; https://doi.org/10.3390/toxins17040193 - 11 Apr 2025
Cited by 3 | Viewed by 3230
Abstract
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 [...] Read more.
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 sPLA2 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. Full article
(This article belongs to the Special Issue Venoms and Drugs)
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22 pages, 6749 KB  
Article
Neurocellular Stress Response to Mojave Type A Rattlesnake Venom: Study of Molecular Mechanisms Using Human iPSC-Derived Neural Stem Cell Model
by Satish Kumar, Miriam Aceves, Jose Granados, Lorena Guerra, Felicia Juarez, Earl Novilla, Ana C. Leandro, Marcelo Leandro, Juan Peralta, Sarah Williams-Blangero, Elda E. Sanchez, Jacob A. Galan, John Blangero and Joanne E. Curran
Biomolecules 2025, 15(3), 381; https://doi.org/10.3390/biom15030381 - 6 Mar 2025
Cited by 5 | Viewed by 2848
Abstract
The Mojave rattlesnake venom shows significant geographical variability. The venom of Type A animals primarily contains β-neurotoxin referred to as Mojave Toxin (MTX), which makes bites from this snake particularly feared. We performed a genome-wide transcriptomic analysis of the neurocellular response to Mojave [...] Read more.
The Mojave rattlesnake venom shows significant geographical variability. The venom of Type A animals primarily contains β-neurotoxin referred to as Mojave Toxin (MTX), which makes bites from this snake particularly feared. We performed a genome-wide transcriptomic analysis of the neurocellular response to Mojave Type A rattlesnake venom using induced pluripotent stem cell-derived neural stem cells to unveil the molecular mechanisms underlying the damage caused by this snake’s envenomation. Our results suggest that snake venom metalloproteases, although having a limited repertoire in Type A venom, facilitate venom spread by digesting the tissue’s extracellular matrix. The MTX, which is composed of heterodimers of basic and acidic phospholipase-A2, co-opts the host arachidonic acid and Ca2+ second messenger mechanisms and triggers multiple signaling cascades, such as the activation of MAPKs and NF-κB-regulated proinflammatory genes; the neurotransmitter overload in excitatory synapses leading to a presynaptic blockade of nerve signals; and the upregulation of unfolded protein response (UPR) due to the depletion of Ca2+ from the endoplasmic reticulum. The upregulated UPR and the oxidative stress caused by reactive oxygen species generated in cytochromeP4501A1-mediated hydroxylation of arachidonic acid contribute to mitochondrial toxicity. The activation of UPR, mitochondrial toxicity, and oxidative stress synergistically contributed to apoptotic and ferroptotic cell death. Full article
(This article belongs to the Special Issue Pluripotent Stem Cell Models of Human Disease)
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21 pages, 4001 KB  
Article
Pharmacokinetics of Snake Antivenom Following Intravenous and Intramuscular Administration in Envenomed Large Animal Model
by Erika Gamulin, Sanja Mateljak Lukačević, Maja Lang Balija, Ana Smajlović, Dražen Vnuk, Jadranka Gulan Harcet, Maja Tomičić, Ana Hećimović, Beata Halassy and Tihana Kurtović
Pharmaceutics 2025, 17(2), 212; https://doi.org/10.3390/pharmaceutics17020212 - 7 Feb 2025
Cited by 4 | Viewed by 5113
Abstract
Background: The parenteral administration of antivenoms is the mainstay in snakebite envenoming therapy. The standardized protocol does not exist, but it is agreed that the intravenous (i.v.) route is more effective than the others, especially the intramuscular (i.m.) [...] Read more.
Background: The parenteral administration of antivenoms is the mainstay in snakebite envenoming therapy. The standardized protocol does not exist, but it is agreed that the intravenous (i.v.) route is more effective than the others, especially the intramuscular (i.m.) route, based on the monitoring of venom/antivenom pharmacokinetics in the systemic circulation. Recent evidence suggests that the lymphatic system may be crucial in abolishing venom action. Methods: A preclinical study was performed to determine the optimal administration route with emphasis on venom/antivenom interplay in both the blood and lymph of experimentally envenomed sheep. Timed level measurements were used to compare the antivenom effect on the decrement of venom quantities in both relevant body compartments. Hematological and coagulation parameters, as well as proportions of developed anti-antivenom IgGs, were evaluated. Results: The i.m. antivenom resulted in faster and greater lymphatic absorption and complete neutralization of the venom, whereas the i.v. antivenom only slowed its absorption. The total amount of venom reaching the lymph (AUC0-t) was two times lower after i.m. administration. In the systemic circulation, i.m. antivenom had a lower peak concentration (cmax) and a longer time to reach it (tmax). However, the total venom exposure was three times lower than with i.v. antivenom. Irrespective of the treatment approach, both groups showed improvement in blood disorders with no significant difference in humoral response against equine F(ab’)2 fragments. Conclusions: I.m. administration proved to be a viable option for the snakebite management. Full article
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14 pages, 6441 KB  
Article
Cardiotoxic Effects of Lachesis acrochorda Snake Venom in Anesthetized Wistar Rats
by Karen Leonor Ángel-Camilo, Mary Luz Bueno-Ospina, Ivonne Carolina Bolaños Burgos, Santiago Ayerbe-González, José Beltrán-Vidal, Ana Acosta, Jaime Álvarez-Soler and Jimmy Alexander Guerrero-Vargas
Toxins 2024, 16(9), 377; https://doi.org/10.3390/toxins16090377 - 28 Aug 2024
Cited by 5 | Viewed by 3545
Abstract
Ophidism is a public health problem in tropical countries, occurring predominantly in rural areas. In Colombia, among the species responsible for snakebite envenomation, inflicting high mortality, is the Chocoan bushmaster, Lachesis acrochorda, better known locally by the names “verrugosa (warty)” and [...] Read more.
Ophidism is a public health problem in tropical countries, occurring predominantly in rural areas. In Colombia, among the species responsible for snakebite envenomation, inflicting high mortality, is the Chocoan bushmaster, Lachesis acrochorda, better known locally by the names “verrugosa (warty)” and “pudridora (rot-causing)”. In this research, the cardiotoxic effect of the venom of L. acrochorda in male Wistar rats weighing 230 ± 20 g was evaluated. A statistical design of randomized blocks was implemented with three treated groups, injected with lyophilized venom (doses of 3.22 μg/g, 6.43 μg/g, 12.86 μg/g), and a control group injected with 0.9% saline solution. Electrocardiographic (ECG) recordings were taken from the anesthetized animals, revealing an increase in the amplitude of the P and T waves and an increase in the duration of the QT intervals in the electrocardiographic recordings. These increases were not observed in the control biomodels. In the analysis of the CK and CK-MB enzyme levels, increases were also observed in the levels of cardiac isoenzymes in the injected animals, but none in the control animals. The histopathological analyses carried out reveal that the injected animals showed effects such as interfibrillar and perivascular edema, cellular shortening of the cardiomyocytes, foci with tissue destructuring, and necrosis with contraction bands. In conclusion, the venom of the Lachesis acrochorda snake increases the P and T waves and the QT interval and increases the CK and CK-MB enzymes in the blood. Additionally, it causes interfibrillar and perivascular edema in the cardiac tissue, cardiocytolysis, and contraction bands. Full article
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21 pages, 5340 KB  
Article
Importance of the Cysteine-Rich Domain of Snake Venom Prothrombin Activators: Insights Gained from Synthetic Neutralizing Antibodies
by Laetitia E. Misson Mindrebo, Jeffrey T. Mindrebo, Quoc Tran, Mark C. Wilkinson, Jessica M. Smith, Megan Verma, Nicholas R. Casewell, Gabriel C. Lander and Joseph G. Jardine
Toxins 2024, 16(8), 361; https://doi.org/10.3390/toxins16080361 - 15 Aug 2024
Cited by 5 | Viewed by 4520
Abstract
Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and [...] Read more.
Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and can cause severe adverse side effects. Building on recent efforts to develop improved antivenoms, notably through monoclonal antibodies, requires a comprehensive understanding of venom toxins. Among these toxins, snake venom metalloproteinases (SVMPs) play a pivotal role, particularly in viper envenomation, causing tissue damage, hemorrhage and coagulation disruption. One of the current challenges in the development of neutralizing monoclonal antibodies against SVMPs is the large size of the protein and the lack of existing knowledge of neutralizing epitopes. Here, we screened a synthetic human antibody library to isolate monoclonal antibodies against an SVMP from saw-scaled viper (genus Echis) venom. Upon characterization, several antibodies were identified that effectively blocked SVMP-mediated prothrombin activation. Cryo-electron microscopy revealed the structural basis of antibody-mediated neutralization, pinpointing the non-catalytic cysteine-rich domain of SVMPs as a crucial target. These findings emphasize the importance of understanding the molecular mechanisms of SVMPs to counter their toxic effects, thus advancing the development of more effective antivenoms. Full article
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