Search Results (2,142)

Snakebite envenoming remains a major global health challenge. Naja atra (N. atra) envenomation induces severe acute kidney injury (AKI), largely driven by snake venom phospholipase A₂ (SVPLA₂). Increasing evidence suggests that immune dysregulation, in addition to direct cytotoxicity, contributes to delayed renal injury. Here, we investigated whether N. atra SVPLA₂ exposure is associated with macrophage immunometabolic remodeling and functional changes relevant to AKI progression. In vivo, AKI was induced in C57BL/6J mice by intraperitoneal administration of N. atra venom, followed by treatment with the SVPLA₂ inhibitor varespladib. In vitro, bone marrow–derived macrophages were exposed to venom with or without varespladib. N. atra venom exposure was associated with extensive tubular apoptosis, increased renal macrophage abundance, and elevated kidney injury biomarkers. Macrophages exhibited a shift toward a pro-inflammatory polarization signature accompanied by reduced efferocytic capacity. Targeted metabolomics revealed coordinated increases in glycolytic intermediates together with upregulation of key glycolytic enzymes. Pharmacological inhibition of SVPLA₂ partially restored macrophage metabolic features and efferocytic capacity and was accompanied by attenuation of renal injury. Together, these findings support a model in which SVPLA₂ exposure is associated with macrophage immunometabolic remodeling and impaired apoptotic cell clearance during venom-induced AKI. Full article

Tetrodotoxin (TTX), widely known as pufferfish venom, is a low-molecular-weight guanidinium neurotoxin. It can accumulate to extremely high concentrations in certain animals, including pufferfish, blue-ringed octopuses, flatworms, and nemerteans. However, the origin of TTX and the mechanisms that enable such extreme accumulation in these animals remain poorly understood. In this study, using confocal laser scanning microscopy combined with electron immunocytochemistry and ultrastructural analysis, we demonstrate the presence of TTX-positive bacteria associated with specialized cellular structures—type II phagosomes of gut enterocytes—in the highly toxic nemertean Cephalothrix cf. simula. We hypothesize that TTX production in C. cf. simula results from interactions between the nemertean host and its endosymbionts. These findings clarify the origin and accumulation of the toxin in nemerteans and have broader implications for other TTX-bearing species. Full article

Yamakagashi (Rhabdophis tigrinus) is a widely distributed snake species in Japan. Yamakagashi causes venom-induced consumption coagulopathy (VICC) when the amount of infused venom is high, and bites can be fatal if antivenom treatment is delayed. However, yamakagashi antivenom is an unapproved treatment, and its storage capacity is limited, preventing its prompt administration. Therefore, we investigated the application of commercially available drugs, namely tranexamic acid and antithrombin III, in the treatment of VICC caused by yamakagashi venom in a rat model. Furthermore, we investigated the combination of each drug with recombinant thrombomodulin α. Administration of tranexamic acid or antithrombin III alone failed to extend rat survival or correct changes in blood coagulation markers, such as prothrombin time, fibrinogen concentrations, and D-dimer levels, in yamakagashi venom-treated rats. However, combined administration of recombinant thrombomodulin α and tranexamic acid extended rat survival and partially restored blood coagulation markers. Therefore, the combination of recombinant thrombomodulin α and tranexamic acid might represent a useful therapeutic regimen for yamakagashi venom exposure. Full article

The predatory bug Arma custos (Hemiptera: Pentatomidae) is a natural enemy insect capable of preying on over 40 types of agricultural and forestry pests. Here, we describe the characteristics of the morphology and ultrastructure of its venom apparatus visualized using light and electron microscopy. Light microscopy revealed that the venom apparatus of A. custos consists of a pair of main gland and tubular accessory gland. The main gland consist of two lobes, the anterior main gland (AMG) and posterior main gland (PMG). Between the two lobes of the main gland, there is a strong constriction, characterizing a hilum (Hi) where two separate ducts, the venom duct of the main gland (VD) and the duct connecting the accessory gland to the main gland (AMD), are inserted. The VD extends toward the head and connects to the venom pump (VP), while the AMD extends toward the thorax and connects to the accessory gland (AG). Ultrastructural examination of the venom glands reveals that the AMG and PMG consist of a layer of cubic or spherical glandular cells forming a large circular lumen, while the AG exhibits two narrow lumens. The secretory cytoplasm of AMG, PMG, and AG contains a well-developed rough endoplasmic reticulum, along with mitochondria, nuclei, secretory vesicles, autophagosomes, and secretory granules. However, significant differences exist in the ultrastructural characteristics among the three glands. Unlike glandular secretory cells in the venom glands, the ultrastructure of VD, and AMD reveals only well-developed nuclei, mitochondria, and elaborate plasma membrane folds. These results indicate that venom proteins are synthesized and stored by the AMG, PMG, and AG, while the VD and AMD ducts are responsible for transporting the venom. Full article

Encephalitozoon cuniculi is an atypical, opportunistic, obligate intracellular fungal pathogen that infects vertebrates. It survives within the host by modulating the host immune response. Crotoxin (CTX), a bioactive compound isolated from the venom of Crotalus durissus terrificus, has been reported to modulate immune responses. This study evaluated the effects of CTX on the immune response of mice infected with E. cuniculi. Mice were immunosuppressed with cyclophosphamide (Cy), infected with E. cuniculi spores, and treated with a single dose of CTX on the day of experimental. The animals were euthanized on day 14 post-infection. Levels of T helper (Th1, Th2, and Th17) cytokines were measured in plasma, and macrophage and lymphocyte populations were analyzed in peritoneal lavage fluid and spleen. In addition, histopathological alterations, hepatic fungal burden, and mRNA expression levels of NLRP3 inflammasome–related genes were assessed. CTX upregulated NLRP3 inflammasome expression and increased IL-18 production, while reducing fungal burden in E. cuniculi-infected mice. Moreover, CTX increased the proportions of macrophages and B cells and enhanced IFN-γ expression in CD4⁺ and CD8⁺ T lymphocytes. Collectively, these findings indicate that CTX reduces fungal load in Cy-immunosuppressed mice infected with E. cuniculi by priming the NLRP3 inflammasome complex and upregulating IL-18 production. Full article

The easily defanged myth that baby rattlesnakes (genera Crotalus and Sistrurus) are more dangerous than adults has persisted in North America despite all evidence to the contrary. The most often cited reason for the babies-more-dangerous (BMD) myth is the venom-dump (VD) hypothesis: babies, in contrast to adults, cannot control how much venom they expend, and therefore inject all of it when biting. We undertook three approaches to explore the origin, transmission, and prevalence of this myth and its most frequent explanation. First, we examined historical newspaper accounts. From 130 newspaper stories mentioning the relative danger of baby rattlesnakes, we identified a timeline in which (1) most stories prior to 1969 were factually correct; (2) the BMD myth and VD hypothesis likely originated in the mid-to-late 1960s and became entrenched in California, especially, from 1970 to 1999; (3) factually incorrect statements subsequently prevailed throughout North America from 2000 to 2014; and (4) factually correct stories regained prominence with apparent effective messaging success from 2015 onward. We further learned that general information stories about rattlesnakes, more often citing subject experts like university professors, were much more likely to provide accurate information than local snakebite stories, which more often cited health professionals (e.g., physicians, veterinarians, pharmacists) and emergency responders (e.g., police and fire officers) who frequently supplied misinformation. Second, we surveyed familiarity with the BMD myth and VD hypothesis among 53 university classrooms (including one high school) representing 3751 students across 29 states within the United States. Consistent with the California media’s outsized influence on misinformation transmission, familiarity with the myth was greatest in the southwestern states (52.6%) and declined moving north and east, with the least familiarity in the northeastern states (16.4%). Third, a small survey of 75 emergency responders and health professionals from Southern California revealed that a whopping 73.3% actually believed the BMD myth. Numerous organizations generally regarded as authoritative further amplified the misinformation, especially on the internet, where some content persists to this day. Unfortunately, belief in the BMD myth and VD hypothesis can lead to negative consequences, including misinformed risk-taking by those encountering snakes, unwarranted fear among snakebite victims, and inappropriate care delivered by misinformed or patient/family-pressured medical professionals. Our findings target health professionals and emergency responders as priority audiences for education. Full article

The administration of specific immunoglobulin G-based antivenoms is a key strategy for treating snakebite envenoming victims. However, serious adverse reactions, such as anaphylaxis or serum sickness, are frequently observed following such administration. In addition, inflammation associated with delayed wound healing considerably drives the irrational use of antibiotics or anti-inflammatory agents, which may be linked to adverse reactions following antivenom treatment. In this study, we evaluated the factors contributing to adverse effects following the administration of snake antivenom, especially pharmacological treatment and premedication intended to prevent adverse reactions. Our retrospective study was conducted by healthcare professionals in Narathiwat, the southernmost province in Thailand, and it involved 980 patients confirmed to have been snakebitten from 2016 to 2021. Of these cases, 513 were treated with antivenom. Prevalence rates and 95% confidence intervals were calculated, and univariate and multivariate analyses were performed to determine the correlation between adverse reactions and medications. Following antivenom administration, the majority of the patients exhibited no adverse reactions (86.7%). Nevertheless, skin rash, itching, wheezing, angioedema, chest tightness, and fever were observed in 13.3% of those receiving snake antivenom. After the administration of antivenom for Malayan pit viper bite, adverse reactions occurred in 11.7% of the sample, especially among referral patients (p < 0.001). Epinephrine and antihistamines were prescribed as prevention and treatment for hypersensitivity due to antivenom administration. Antibiotics, Non-steroidal Anti-inflammatory drugs (NSAIDs), and acetaminophen were not associated with antivenom-induced adverse reactions. Interestingly, tramadol and antihistamines significantly reduced the occurrence of adverse reactions after antivenom administration (p < 0.05). Well-trained staff, close monitoring alongside resuscitation equipment and medications that can minimise the severity of anaphylactic reactions must be promptly available whenever antivenom is administered. Full article

The French Society for Toxinology (SFET) held its 31st annual meeting (RT31) on 1–2 December 2025 at Hôtel Le Saint Paul in Nice, France, on the famous French Riviera. The meeting, which gathered 75 participants from around the world, was organised there for the second consecutive year, while previous editions were all held in Paris. The RT31 main theme, “Toxins: Playing with and fighting them”, explored recent, cutting-edge research in the field of animal venoms and of toxins from algal, animal, bacterial, fungal, plant and microbial origins, in emphasizing the evolution of the toxins, their modes of action and roles, and ways of counteracting intoxinations. These key topics were largely covered through 26 oral and 18 poster communications, organized into three main thematic areas covering three specific aspects of toxinology, along with a traditional fourth, more general session enabling participants to present recent data outside of these themes but nevertheless providing valuable information to the field. This report presents the abstracts of nine of the invited lectures, 14 of the selected lectures, and 16 of the posters, in accordance with the authors’ agreement to publish them. Also, we announce the winners of the “Best Oral Communication” and “Best Poster Communication” awards, which recognize the outstanding contributions of young researchers and their inventive work in toxinology. Full article

The keeping of non-traditional pets has markedly increased in recent years. These species are frequently maintained under inadequate or illegal conditions, raising substantial concerns regarding animal welfare. Authorities are regularly required to confiscate reptiles, arachnids, and other exotic taxa—often in poor health—and to accommodate them temporarily in transit facilities while long-term placement options are identified. Existing facilities are operating beyond capacity, creating an urgent need for the development of additional infrastructure. Given the potential risks associated with these animals, stringent safety measures are essential. Following an assessment of the hazards linked to housing primarily reptiles and arachnids—including risks related to venomous species, transmission of zoonotic pathogens, and the escape of potentially invasive organisms—the present paper provides a set of recommendations for the design and operation of transit housing facilities. The guidance focuses on infrastructure requirements, routine and emergency procedures, and daily management practices for both animals and facilities. Although these recommendations were developed within the specific regulatory framework of Southern Belgium, they may be applied more broadly, provided that local regulations are appropriately considered. Full article

Background: Lung cancer remains a leading cause of mortality, mainly due to aggressive metastasis and therapeutic resistance. Snake venom metalloproteinases (svMPs), particularly the P-I class, are promising sources for novel antitumor agents. Objectives: This study investigated the impacts of BthMP, a P-I svMPs from Bothrops moojeni venom, on human lung carcinoma (A549) cells in comparison to non-cancerous human bronchial epithelial cells (BEAS-2B). Methods and Results: BthMP demonstrated potent and selective anti-cancer activity. It significantly inhibited key metastatic processes in A549 cells, including adhesion, migration, and invasion, while suppressing long-term proliferation, as shown by reduced colony formation and increased lactate dehydrogenase (LDH) release. Mechanistically, BthMP induced a massive increase in intracellular reactive oxygen species (ROS) by over 2000% and elevated nitric oxide (NO) by 35% in A549 cells, driving a state of lethal oxidative stress. Crucially, these cytotoxic and anti-metastatic effects were minimal in BEAS-2B cells; BthMP even suppressed basal ROS and NO levels in this non-cancerous line. The anti-migratory effects of BthMP were completely dependent on its zinc-based catalytic activity, as they were abolished by pretreatment with ethylenediaminetetraacetic acid. By simultaneously disrupting cell–matrix interactions and inducing selective, catastrophic oxidative stress in cancer cells, BthMP presents a dual-pronged anti-metastatic mechanism. Conclusions: These findings establish BthMP as a promising therapeutic scaffold for developing novel treatments against lung cancer progression. Full article

Background: Snake envenomation represents a significant health concern in some regions of the world, with fatal cases occasionally requiring forensic investigation to estimate the postmortem interval (PMI). However, the influence of venom on carrion decomposition dynamics and arthropod succession patterns remains poorly understood, potentially compromising postmortem interval (PMI) estimations in such cases. Objectives: This study investigated the effects of Naja haje and Cerastes cerastes venoms on decomposition progression and necrophagous arthropod succession. Methods: Fifteen rabbits were allocated into three experimental groups. Two groups received median lethal intravenous doses (LD₅₀) of N. haje or C. cerastes venom, whereas the control group received a saline injection followed by CO₂ euthanasia. The carcasses were subsequently placed under natural field conditions and monitored daily for 15 days. Results: The presence of venom significantly altered decomposition dynamics. C. cerastes venom accelerated early decomposition, shortening both the fresh stage (1 ± 0.22 days vs. 2 ± 0.31 days in controls,) and bloating stage (3 ± 0.35 days vs. 5 ± 0.35 days), while extending both the decay stage (6 ± 0.3 days vs. 6 ± 0.17 days) and the dried stage (5.0 ± 0.44 days vs. 2 ± 0.039 days). N. haje venom showed intermediate effects. Overall arthropod abundance peaked on day 5 and declined thereafter. Control carcasses exhibited significantly higher arthropod abundance than carcasses envenomed with C. cerastes or N. haje. Conclusions: Snake envenomation significantly influenced decomposition kinetics and arthropod colonization patterns. Envenomation with C. cerastes venom produced more pronounced alterations than envenomation with N. haje venom. Full article

Huwentoxin-XI (HWTX-XI) is a 55-amino acid peptide belonging to the family of spider Kuntiz-type toxins (KTTs), isolated from the venom of the Chinese tarantula Cyriopagopus schmidti. Under whole-cell voltage-clamp conditions, HWTX-XI was found to block Kv1.1 potassium channels but had no effect on other potassium channel subunits (Kv1.4, Kv2.1, Kv3.1 and Kv4.2), sodium channels or calcium channels. In the present study, it was found that the substitution of Tyr379 by the valine in the filter region significantly decreased the affinity of toxin HWTX-XI by about 90-fold, indicating that the Kv1.1 filter region is a critical determinant of HWTX-XI potassium channel activity. After intrathecal or intraplantar injections, HWTX-XI decreased the mechanical nociceptive threshold (hyperalgesia) for a long-lasting period. HWTX-XI also significantly increased the firing frequency in mouse DRG neurons. The novel function of HWTX-XI makes it a new tool for studying the relationship between spider toxins and Kv1.1 channels and suggests that Kv1.1 channels might be a novel potential target for preventing and/or treating neuropathic pain. Full article

Peptides from scorpion venom, mainly in species such as Olivierus martensii (formerly Olivierus martensii Karsch, often designated BMK) (BmK) and Tityus serrulatus from the Buthidae family, show real promise as painkillers that skip opioids altogether. They work by hitting specific ion channels and dialing down inflammation. This review gathers information on their molecular setups: disulfide-bridged types and those without, weighing in at 3 to 10 kilodaltons (kDa). Structural features include motifs stabilized by cysteines. In pain signaling, they block voltage-gated sodium channels (NaV) such as NaV1.7 and NaV1.8; take the BmK analgesic–antitumor peptide (BmK-AGAP) for example. Additionally, scorpion venom heat-resistant peptide (SVHRP) reduces microglia activity. Tests on rodents using formalin injections, acetic acid writhing, and chronic constriction injury (CCI) setups reveal pain relief that depends on dose and stacks up to morphine. Pairings like AGAP with lidocaine decrease the effective dose by half. In terms of safety, therapeutic levels have low-toxicity with a median lethal dose (LD50) over 20 mg/kg. Issues crop up with immune responses, unintended targets, and differences in venom batches. Clinical information remains thin, so gaps persist. Engineered versions could change the game for neuropathic pain, inflammatory conditions, and cancer-related discomfort. Standardization plus Phase I studies would help move this forward. Full article

Glioblastoma is a highly invasive primary brain tumor with a poor prognosis, highlighting the need for new therapeutic strategies. Toxins derived from Macrodactyla doreensis have attracted attention for their potential anticancer activity. This study evaluated the anticancer and cytotoxic effects of M. doreensis crude venom on two commonly used glioblastoma cell lines (U251 and LN229), which mirror the phenotype of primary tumors. Cell viability and proliferation were assessed using the CCK-8 assay and colony formation assay, while cell migration and invasion capabilities were detected via wound healing assay and Transwell assay. Annexin V/PI staining and PI-based cell cycle analysis indicated that the crude venom significantly induced cell apoptosis and caused S-phase arrest. Proteomic analysis combined with GO and KEGG enrichment analyses as well as bioinformatics approaches showed that M. doreensis crude venom inhibits glioblastoma cell proliferation by downregulating the expression of CDK2, RRM2, and CHEK1, thereby hindering cell cycle progression and regulating the p53 signaling pathway. Notably, the downregulation of these key glioblastoma-related target genes was validated by qPCR. In addition, network pharmacology analysis indicated that several peptide families present in the sea anemone crude venom, including ShK peptides, inhibitor cystine knot (ICK) peptides, and EGF-like peptides, exhibit notable antitumor potential. Combined with AlphaFold2-based structural modeling and molecular docking, these analyses further elucidated the potential molecular mechanisms underlying their interactions with key targets, such as MD-381 with RRM2, MD-322 with CDK2, and MD-429 with CHEK1. Collectively, these findings highlight the therapeutic potential of M. doreensis crude venom and lay a foundation for the subsequent isolation of novel peptides and their further development in glioblastoma treatment. Full article

Typically, most omics analysis (proteomic and transcriptomic) of snakes are focused on the dominant enzymatic proteins used for evolutionary analysis or those engaged in envenoming symptoms. This study presents a comprehensive multi-assembler transcriptomic analysis focused on the non-dominant and enzymatic or non-enzymatic putative proteins of the venom glands of three medically significant Colombian snake species. Together, these results highlight how continued improvements in modern omics workflows, coupled with extensive manual curation, enable more complete putative protein variants discovery when multiple assemblers are integrated. Here, we reconstructed the toxinomes of the viperids Bothrops asper and Crotalus durissus cumanensis, and the elapid Micrurus mipartitus, by comparing four assemblers (Trinity, SPAdes, SOAPdenovo-Trans k = 31 and k = 97) and integrating them into a non-redundant meta-assembly. Protein-candidate alignments were extensively inspected, and validation of conserved domains and functional motifs are discussed. The curated toxinomes revealed substantial diversity across major and accessory families, and assembler choice strongly affected transcript variant recovery. Together, these results provide a more comprehensive view of venom-gland transcriptome analysis and diversity, expanding the set of candidate venom components for future functional and proteomic validation, with potential implications for venom composition studies and antivenom development. Full article