Search Results (356)

Background/Objectives: Most snakebite incidents in Latin America are caused by species of the Bothrops genus. Their venom induces severe local effects, against which antivenom therapy has limited efficacy. Metabolites derived from Coffea arabica have demonstrated anti-inflammatory and anticoagulant properties, suggesting their potential as therapeutic agents to inhibit the local effects induced by B. asper venom. Methods: Three enzymatic assays were performed: inhibition of the procoagulant and amidolytic activities of snake venom serine proteinases (SVSPs); inhibition of the proteolytic activity of snake venom metalloproteinases (SVMPs); and inhibition of the catalytic activity of snake venom phospholipases A₂ (PLA_2s). Additionally, molecular docking studies were conducted to propose potential inhibitory mechanisms of the metabolites chlorogenic acid, caffeine, and caffeic acid. Results: Green and roasted coffee extracts partially inhibited the enzymatic activity of SVSPs and SVMPs. Notably, the green coffee extract, at a 1:20 ratio, effectively inhibited PLA₂ activity. Among the individual metabolites tested, partial inhibition of SVSP and PLA₂ activities was observed, whereas no significant inhibition of SVMP proteolytic activity was detected. Chlorogenic acid was the most effective metabolite, significantly prolonging plasma coagulation time and achieving up to 82% inhibition at a concentration of 62.5 μM. Molecular docking analysis revealed interactions between chlorogenic acid and key active site residues of SVSP and PLA₂ enzymes from B. asper venom. Conclusions: The roasted coffee extract demonstrated the highest inhibitory effect on venom toxins, potentially due to the formation of bioactive compounds during the Maillard reaction. Molecular modeling suggests that the tested inhibitors may bind to and occupy the substrate-binding clefts of the target enzymes. These findings support further in vivo research to explore the use of plant-derived polyphenols as adjuvant therapies in the treatment of snakebite envenoming. Full article

The venom of Bothrops jararaca (BjV) induces intense and prolonged pain, which is not alleviated by antivenom, along with hemorrhage and inflammation. In this study, we investigated the effects of the specialized pro-resolving lipid mediator (SPM) maresin 2 (MaR2) in a murine model of BjV-evoked pain and inflammation. Mice received a single intraperitoneal (i.p.) injection of MaR2 30 min before the intraplantar BjV injection. MaR2 treatment significantly attenuated mechanical (electronic aesthesiometer) and thermal (hot plate) hyperalgesia in a dose-dependent manner. Additionally, MaR2 restored the balance for the hind-paw static weight distribution. When BjV (0.01, 0.1, and 1 μg) stimulus was administered intraperitoneally, pre-treatment with MaR2 (0.3, 1, or 3 ng) ameliorated mechanical and thermal hyperalgesia in a dose-dependent manner. Moreover, MaR2 (3 ng) effectively reduced the levels of myeloperoxidase activity and cytokines (TNF-α, IL-1β, and IL-6) and superoxide anion (O₂^•−) production induced by intraplantar injection of BjV while enhancing total antioxidant levels (ABTS scavenging). For the peritonitis model induced by BjV, MaR2 pretreatment decreased leukocyte recruitment, hemorrhage, nitric oxide (NO), and O₂^•− generation and gp91phox and inducible nitric oxide synthase (iNOS) mRNA expression. In conclusion, this study presents the first evidence that MaR2 effectively mitigated BjV-induced pain, hemorrhage, and inflammation. Full article

Snakebite remains the most neglected tropical disease globally, with India experiencing the highest rates of mortality and morbidity. While most envenomation cases in India are attributed to the ‘big four’ snakes, research has predominantly focused on Russell’s viper (Daboia russelii), spectacled cobra (Naja naja), and common krait (Bungarus caeruleus), leading to a considerable gap in our understanding of saw-scaled viper (Echis carinatus carinatus) venoms. For instance, the venom gland transcriptome and inter- and intra-population venom variation in E. c. carinatus have largely remained uninvestigated. A single study to date has assessed the effectiveness of commercial antivenoms against this species under in vivo conditions. To address these crucial knowledge gaps, we conducted a detailed investigation of E. c. carinatus venom and reported the first venom gland transcriptome. A proteotranscriptomic evaluation revealed snake venom metalloproteinases, C-type lectins, L-amino acid oxidases, phospholipase A₂s, and snake venom serine proteases as the major toxins. Moreover, we assessed the intra-population venom variation in this species using an array of biochemical analyses. Finally, we determined the venom toxicity and the neutralising efficacy of a commercial antivenom using a murine model of snake envenoming. Our results provide a thorough molecular and functional profile of E. c. carinatus venom. Full article

Background: Ophidism is a globally neglected health problem. In Argentina, Crotalus durissus terrificus (C.d.t., South American rattlesnake) is one of the species of greatest medical importance since its venom contains mainly crotoxin (CTX), a potent enzyme–toxin with PLA₂ activity, which is responsible for its high lethality. Objective: In this work, we aimed to generate nanovenoms (NVs), complexes formed by CTX adsorbed onto 150 nm silica nanoparticles (SiNPs), and to study their physicochemical, biological, and immunomodulatory activities for potential use as adjuvants (ADJs) in antivenom (AV) production. Methods: CTX was isolated and corroborated by SDS-PAGE. Then, CTX was adsorbed on the synthetized Stöber SiNPs’ surfaces, forming a monolayer and retaining its biological activity (as observed by the MTT cell proliferation assay using the THP-1 cell line). Results: Immunomodulatory activity revealed a high pro-inflammatory (IL-1β) response induced by SiNPs followed by NVs. In the case of the anti-inflammatory response, NVs presented significant differences for TGF-β only after cell activation with LPS. No significant differences were observed in IL-10 levels. Conclusions: Thus, these results suggest that NVs together with SiNPs could increase immunogenicity and enhance immune response, turning them into potential tools for the generation of new antivenoms. Full article

Background: Snake envenomation is a major public health issue in Nigeria, primarily due to bites from Echis ocellatus, Naja nigricollis, and Bitis arietans. Understanding their venom composition is essential for effective antivenom development. This study characterizes and compares the venom proteomes of these snakes using iTRAQ-based proteomics, focusing on key toxin families and their relative abundances. Methods: Venom samples were ethically collected from adult snakes, pooled by species, lyophilized, and stored for proteomic analysis. Proteins were extracted, digested with trypsin, and labeled with iTRAQ. Peptides were analyzed via mass spectrometry, and data were processed using Mascot and IQuant for protein identification and quantification. Results: E. ocellatus and B. arietans venoms had similar profiles, rich in C-type lectins, serine proteases, and phospholipase A₂s. These comprised 17%, 11%, and 5% in E. ocellatus and 47%, 10%, and 7% in B. arietans, with metalloproteinases dominating both (53% and 47%). In N. nigricollis, three-finger toxins (9%) were most abundant, followed by metalloproteinases (3%). All species shared four core protein families, with N. nigricollis also containing four uncharacterized proteins. Conclusions: This study highlights venom compositional differences, advancing snake venom biology and informing targeted antivenom development. Full article

Strophanthus sarmentosus is recognised for various ethnomedicinal applications, including treatment after snakebites. However, only limited scientific evidence exists on its antivenomous capabilities. This study investigates the efficacy of methanol and ethylacetate extracts from S. sarmentosus leaves and roots against Echis ocellatus venom. A non-toxic range for the extracts was determined in rats, and assays were performed to test their anti-hemorrhagic and anti-hemolytic activity as well as their influence on venom-induced blood clotting. In all of these experiments, the extracts demonstrated significant positive effects equal to or better than antivenom. Moreover, the extracts strongly inhibited and even abolished the digestion of the vasoactive neuropeptide bradykinin by snake venom metalloproteinases. Strophantus plants are known for their high content of cardiac glycosides, one of which is the commercially available ouabain, that by itself also considerably inhibited venom-induced bradykinin cleavage. Although ouabain is only present in low amounts in S. sarmentosus when compared to other cardenolides of similar structure, it can be hypothesized that members of this substance class may also have inhibitory properties against venom proteases. S. sarmentosus additionally contains bioactive substances such as flavonoids, terpenoids, tannins, saponins, and alkaloids, which contribute to its protective effects. The study provides scientific data to explain the success of the traditional use of S. sarmentosus plant extracts as a first aid against envenomation in rural Africa. Full article

Snakebite is a significant global public health challenge, and the limited application of antivenom has driven the exploration of novel therapies. Combination therapy using small-molecule drugs targeting phospholipases A₂ (PLA2) and metalloproteinases (SVMP) in venom shows great potential. Although Rhamnetin and RXP03 exhibit notable anti-phospholipase and anti-metalloproteinase activities, respectively, their antiophidic potential remains poorly explored. This study aims to evaluate the inhibitory effects of Rhamnetin and RXP03 on snake venom toxicity. Methodologically, we conducted in vitro enzymatic assays to quantify PLA₂/SVMP inhibition, murine models of envenomation (subcutaneous/intramuscular venom injection) to assess local tissue damage and systemic toxicity, and histopathological/biochemical analyses. In vitro experiments demonstrated that Rhamnetin effectively inhibited PLA₂ activity while RXP03 showed potent suppression of SVMP activity, with their combination significantly reducing venom-induced hemorrhagic activity. In murine models, the combined therapy markedly alleviated venom-triggered muscle toxicity and ameliorated oxidative stress. Furthermore, the combination enhanced motor performance and survival rate in mice, improved serum biochemical parameters, corrected coagulation disorders, and attenuated pathological damage in liver, kidney, heart, and lung tissues. This research demonstrates that dual-targeted therapy against metalloproteinases and phospholipases in snake venom can effectively prevent a series of injuries caused by snake venom. Collectively, the combined application of Rhamnetin and RXP03 exhibits significant inhibitory effects on a variety of venom-induced toxicities, providing pharmacological evidence for the development of antivenom therapies. However, the efficacy validation in this study was limited to murine models, and there is a discrepancy with clinical needs for delayed treatment in real-world envenomation scenarios. Despite these limitations, the findings provide robust preclinical evidence supporting the Rhamnetin–RXP03 combination therapy as a cost-effective, broad-spectrum antivenom strategy. Future studies are required to optimize dosing regimens and evaluate clinical translatability. Full article

Jellyfish stings, as one of the most prevalent forms of marine injury, have increasingly become a subject of concern. Despite their simple morphology and structure, jellyfish possess a complex venom composition that can inflict varying degrees of damage on multiple human physiological systems. Consequently, the clinical symptoms associated with jellyfish stings are highly intricate. Although antivenoms have been developed for certain jellyfish species (e.g., C. fleckeri), specific antivenoms targeting the mechanisms of most jellyfish venoms remain understudied. To effectively prevent, treat, and cure jellyfish stings, we adhere to the principle of knowing their nature and their reasons. It is essential to investigate the emission mechanism of jellyfish nematocysts and the composition of their venom. Understanding these factors is crucial for the development of targeted treatment strategies. This review delves into the venom emission mechanism of jellyfish stinging cells, the symptoms resulting from jellyfish stings, and the comprehensive treatment strategies post-sting. It offers a scientific reference for comprehending jellyfish stings and establishes a theoretical foundation for subsequent research endeavors. Full article

Snakebite is a high-priority neglected tropical disease, and a strategic goal based on four pillars has been recommended to reduce mortality and morbidity. One is empowering rural communities through citizen science, education, and engagement. In this study, an integrative approach was used to expand our knowledge of Micrurus nigrocinctus status and characterize its venom. Using citizen science data and field visits to local communities, 99 records of M. nigrocinctus distributed in Antioquia, Chocó, and Córdoba were obtained. Children, young people, and adults recognized M. nigrocinctus as the most common coral snake species in their region, and two specimens were recovered for venomic and Phylogenetic analyses. The M. nigrocinctus venom from Colombia exhibited similar chromatographic and electrophoretic profiles and biological activities and shared nearly identical protein families with Costa Rica. Commercial coral snake antivenoms also recognized and neutralized the whole venom from both countries. However, phylogenetic relationships showed greater divergence with specimens from Costa Rica. Involving communities helps prevent coral snake bites and facilitates access to rare specimens such as M. nigrocinctus, thereby enabling venom analyses, improving antivenom evaluation, and advancing toxinology research for medically significant species. Full article

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. Full article

Plant compounds that inhibit snake venom activities are relevant and can provide active molecules to counteract snake venom effects. Numerous studies on snake viperid venoms found that metalloproteinases play a significant role in the pathophysiology of hemorrhage that occurs on envenomation. Preclinical studies using vitro and in vivo protocols investigated natural compounds and viperid snake venoms, evaluating the enzymatic, procoagulant, hemorrhagic, edematogenic, myotoxic, and lethal activities. Many studies focused on Bothrops venoms and ascribed that angiorrhexis and hemorrhage resulted from the metalloproteinase action on collagen in the basal lamina. This effect resulted in a combined action with phospholipase A2 and hyaluronidase, inducing hemorrhage, edema, and necrosis. Due to the lack of efficient antivenoms in remote areas, traditional native plant treatments remain common, especially in the Amazon. Our group studied plant extracts, isolated compounds, and lapachol synthetic derivative analogs with selective inhibition for Bothrops venom proteolytic and hemorrhagic activity and devoid of phospholipase activity. We highlight those new synthetic naphthoquinones which inhibit snake venom metalloproteinases and that are devoid of other venom enzyme inhibition. This review shows the potential use of snake venom effects, mainly Bothrops venom metalloproteinase activity, as a tool to identify and develop new active molecules against hemorrhagic effects. Full article

The Snakebite Treatment and Research Hospital (SBTRH) is a leading centre for snakebite envenoming care and research in sub-Saharan Africa, treating over 2500 snakebite patients annually. Despite routine data collection, routine analyses are seldom conducted to identify trends or guide clinical practices. This study retrospectively analyzes 1022 snakebite cases at SBTRH from January to June 2024. Most patients were adults (62%) and were predominantly male (72%). Key factors such as age, sex, and time between bite and hospital presentation were associated with outcomes, including recovery, amputation, debridement, and death. Adult males who took more than four hours to arrive to hospital were identified as a high-risk group for poor outcomes. Using patient characteristics, an XGBoost model was developed and was compared to Random Forest and logistic regression models. In general, all models had high positive predictive value and low sensitivity, meaning that if they predicted a patient to experience amputation, debridement, or death, that patient almost always actually experienced amputation, debridement, or death; however, most models rarely made this prediction. The XGBoost model with all features was optimal, given that it had both a high positive predictive value and relatively high sensitivity. This may be of significance to resource-limited settings like SBTRH, where antivenoms can be scarce; however, more research is needed to build better predictive models. These findings underscore the need for targeted interventions for high-risk groups, and further research and integration of machine-learning-driven decision support tools in low-resource-limited clinical settings. Full article

Examination of venom constituent bioactivities from diverse venomous animals shows certain highly conserved classes, including enzymes (e.g., phospholipases and metalloproteinases) and pore-forming proteins. While antivenoms targeting other unique and lethal venom components have proven to be life-saving, venom-enzyme-driven tissue damage and morbidity persists. Broad-acting enzyme inhibitors demonstrate the potential to augment antivenom approaches. In this study, we investigate the potential utility of certain broad-acting inhibitors in cubozoa for the first time. Fluorogenic assays were used to determine the phospholipase A₂ (PLA₂) and matrix metalloproteinase (MMP) activity of the Hawaiian box jellyfish, Alatina alata, and this was compared to representative elapid, viper, and bee venoms. In vitro, evaluation of selected small-molecule inhibitors demonstrated the ability and feasibility of the broad-acting therapeutic doxycycline, which inhibited the PLA₂ and MMP activity of A. alata (approximately 50% reduction at 0.1 mM (95% CI 0.06–0.15) and 2.1 mM (95% CI 1.4–3.0), respectively), in addition to both snake venoms. Additionally, copper gluconate broadly inhibited the PLA₂ activity of bee, snake, and jellyfish venoms. While all venoms are complex mixtures of bioactive molecules, these studies demonstrate that targeting common class components with broad-acting inhibitors shows promise in clinical and preclinical management. Full article

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. Full article

The release of cytokines in the peritoneal fluid after stimulation with Bothrops atrox and Bothrops jararaca venoms is a crucial process in the inflammatory response triggered by these venoms. The toxins present in the venoms of snakes from the Bothrops genus induce a complex inflammatory response, which includes the production and release of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-6, IL-10, IL-1β, chemokines like GM-CSF, MCP-1, and the mast cell degranulation marker MCPT-1. These cytokines play a central role in amplifying inflammation, recruiting leukocytes, and increasing vascular permeability, resulting in edema, pain, and tissue damage at the inoculation site. Peritoneal fluid is commonly used in experimental studies to investigate local inflammatory responses, allowing for the evaluation of the dynamics of inflammatory molecule release. In this study, we used female C57BL/6 mice and observed that Bothrops atrox venom induced a significantly more intense inflammatory response compared to Bothrops jararaca venom. Specifically, Bothrops atrox venom led to a higher release of TNF-α and an increase in MCP-1 levels in peritoneal fluid when compared to Bothrops jararaca venom. These changes resulted in a more pronounced inflammatory condition, with increased leukocyte recruitment in the Bothrops atrox group. Understanding the cytokine profile released in response to these venoms can provide important insights into the pathophysiological mechanisms involved in snakebite accidents and contribute to the development of more effective treatments, such as antivenoms and inflammation modulators. Full article