Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 22, 2024

Snakebite envenoming is an important public health issue responsible for mortality and severe morbidity. Where mainly caused by venom toxins that induce cardiovascular disturbances, neurotoxicity, acute kidney injury, morbidity directly or indirectly destroy cells degrade the extracellular matrix. These are referred to as 'tissue-damaging toxins' have previously been classified in various ways, most of which based on tissues being affected (e.g., cardiotoxins, myotoxins). This categorisation, however, primarily phenomenological not mechanistic. In this review, we propose alternative way classifying cytotoxins their mechanistic effects rather than using a description organ- tissue-based. The mechanisms toxin-induced tissue damage clinical implications discussed. review contributes our understanding fundamental biological processes associated with snakebite envenoming, may pave knowledge-based search novel therapeutic options.

Language: Английский

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Emerging Trends in Snake Venom-Loaded Nanobiosystems for Advanced Medical Applications: A Comprehensive Overview

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 204 - 204

Published: Feb. 6, 2025

Advances in medical nanobiotechnology have notably enhanced the application of snake venom toxins, facilitating development new therapies with animal-derived toxins. The vast diversity species and their complexities underline need for ongoing research. This review is dedicated to exploring integration nanoparticles enable use human aiming develop treatments. complex mixture not only inflicts significant pathological effects but also offers valuable insights creation innovative therapies, particularly realm nanobiotechnology. Nanoscale encapsulation mitigates inherent toxicity amplifies antitumoral, antimicrobial, immunomodulatory properties. synergy between venom-derived macromolecules nanotechnology a novel pathway augmenting efficacy safety conventional antivenom extending applicability beyond treating bites potentially addressing myriad health issues. In conclusion, presents compelling therapeutic frontier that promises improve current treatment modalities ameliorate adverse associated venomous snakebites.

Language: Английский

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MjTX-II, a Lys49-PLA2 from Bothrops moojeni snake venom, restricts Toxoplasma gondii infection via ROS and VEGF regulation

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111417 - 111417

Published: Feb. 1, 2025

Language: Английский

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Cobra Venom: From Envenomation Syndromes to Therapeutic Innovations

International Journal of Peptide Research and Therapeutics, Journal Year: 2024, Volume and Issue: 30(6)

Published: Oct. 4, 2024

Language: Английский

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Oral varespladib for the treatment of snakebite envenoming in India and the USA (BRAVO): a phase II randomised clinical trial

BMJ Global Health, Journal Year: 2024, Volume and Issue: 9(10), P. e015985 - e015985

Published: Oct. 1, 2024

Introduction Snakebite envenoming (SBE) results in over 500 000 deaths or disabling injuries annually. Varespladib methyl, an oral inhibitor of secretory phospholipase A2, is a nearly ubiquitous component snake venoms. We conducted phase II clinical trial to assess efficacy and safety varespladib methyl patients bitten by venomous snakes. Methods This double-blind, randomised, placebo-controlled enrolled emergency departments India the USA. Patients with SBE were randomly assigned (1:1) receive placebo two times per day for 1 week. All received standard care, including antivenom. The primary outcome was change composite Severity Score (SSS) measuring severity envenoming, from baseline average SSS at 6 9 hours. Results Among 95 randomised August 2021 through November 2022, most common snakebites Russell’s vipers (n=29), copperheads (n=18) rattlesnakes (n=14). improved hours 1.1 (95% CI, 0.7 1.6) group versus 1.5 1.0 2.0) (difference −0.4, 95% −0.8 0.1, p=0.13). While key secondary outcomes not statistically different treatment group, benefit seen prespecified subgroup initiating study drug within 5 bite (n=37). For this early clinically important differences observed illness first week, patient-reported function on days 3 7 complete recovery. No death emergent serious adverse event occurred. Conclusion department snakebites, addition antivenom did find evidence difference based SSS. A potentially promising signal snakebite.

Language: Английский

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A multiplexing immunosensing platform for the simultaneous detection of snake and scorpion venoms: Towards a better management of antidote administration

Talanta, Journal Year: 2025, Volume and Issue: 286, P. 127534 - 127534

Published: Jan. 7, 2025

Language: Английский

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Simplifying Traditional Approaches for Accessible Analysis of Snake Venom Enzymes

Toxicon, Journal Year: 2025, Volume and Issue: unknown, P. 108255 - 108255

Published: Jan. 1, 2025

Language: Английский

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Snake venom and cerebrovascular events: insights and public health implications

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 5, 2025

Snakebites are recognized as one of the 20 neglected tropical diseases and represent a major public health concern in subtropical regions Africa, Asia, Latin America. This issue is particularly acute remote, underdeveloped, politically marginalized areas, where access to healthcare preventive measures limited (1,2). According World Health Organization, approximately 4.5 5.4 million snakebites occur globally each year, resulting 2.7 clinical cases an estimated 81,000 138,000 fatalities (3). The most vulnerable populations include individuals engaged agricultural, livestock, fishing, or hunting activities, those living poorly constructed homes, children involved labor, people with education (3).Snakebite envenomation can cause broad spectrum complications, ranging from localized systemic effects. These, bleeding disorders, kidney failure, severe tissue destruction, skin infections, compartment syndrome, serum sickness, among others (4,5). In cases, amputations may be necessary due extensive damage. Venomous also associated significant neurological venom complex mixture toxins enzymes, including phospholipase A2, acetylcholinesterase, hyaluronidase, metalloproteinases. Neurological complications ophthalmoplegia, ptosis, paralysis pharyngeal muscles, intercostal muscles diaphragm (6)(7)(8). Among cerebrovascular accidents, which ischemic type, (9)(10)(11)(12)(13)(14)(15), hemorrhagic type (16)(17)(18)(19)(20)(21). Although stroke rare complication snakebites, it lead death serious sequelae. Little has been said about this complication; reports come there only information its specific characteristics, assessment severity, duration follow-up period (22,23).In occurs, whether hemorrhagic, variety symptoms appear. caused by blockage blood vessels, common reported hemiparesis, altered speech (slurring speech, dysphonia, dysarthria), drowsiness, hypertension, tachycardia (9)(10)(11)(12)(13)(14)(15). within brain, headache, hypotension, hematemesis, hematuria, gums, conjunctival hemorrhage, seizures, respiratory distress. cardiorespiratory arrest, failure coma have both strokes, state consciousness, loss miosis, pupillary reflex, decreased muscle strength present. commonly used diagnostic tests computed tomography magnetic resonance imaging, revealed that strokes affect medium large middle cerebral artery anterior (6,24).The present article aims describe characteristics complication, well implications interventions needed address problem.The composition snake unique species consists heterogeneous proteins peptides (Table 1). four dominant protein families metalloprotease, three-finger toxins, serine protease; these, turn, important human envenomation, responsible for causing coagulopathy, neurotoxicity, myotoxicity, cytotoxicity (25).Other components, such sapharotoxins endothelins, induce vasoconstriction coronary arteries, while certain inhibit angiotensin-converting enzyme (ACE), leading reduction pressure (26). Aminopeptidases, on other hand, contribute hypotension altering vascular tone fluid balance. Meanwhile, interfere coagulation hemorrhages thrombosis, depending biochemical profile venom. Nonenzymatic proteins, C-type lectins identified. These exhibit anticoagulant procoagulant activity, functioning agonists antagonists platelet aggregation, further increasing risk (27)(28)(29)(30)(31).Insert Table 1 3. Pathophysiological mechanism accident development after bite Snake enzymes components neurotoxic, hemotoxic, myotoxic substances, significantly disrupt system alter microvascular dynamics, ultimately through various mechanisms following (26,30,32).The pathophysiology events multifactorial, involving processes thrombus formation, hemorrhage (Figure Each these contributes developing strokes. A comprehensive understanding crucial designing targeted improving outcomes affected individuals.High concentrations disseminated intravascular (DIC), formation thrombi block vessels. Additionally, direct damage endothelium vasculitis, thrombosis. Venom's cardiotoxic effects promote cardiac thromboembolism, hyperviscosity hypovolemia hypoperfusion exacerbates occlusion (33,34). All stroke. For part A2 isoforms vasodilation, sweating, vomiting, reduced intake. result turn watershed infarction, occurring brain susceptible low flow (6,34).Hemorrhagins, another component, endothelial cells increase vessel permeability, potentially spontaneous intracerebral bleeding. heightened venom-induced thrombocytopenia, prolongation prothrombin partial thromboplastin times, impair blood's ability clot favor (4,35,36).Snake coagulopathy critical factor contributing envenomation. Certain metalloproteinases lectins, normal pathways interfering aggregation degrading fibrinogen, key (29). dysregulation characterized widespread depletes clotting factors platelets, paradoxical thrombocytopenia reduces ability, degradation integrity hemorrhagins weakens combined culminate rupture bleeding, posing life-threatening risks individuals. Understanding underlying essential therapeutic strategies mitigate (37). Strokes but often underreported snakebites. true incidence remains largely unknown underreporting limitations existing data. Most available comes case small series, making difficult accurately assess burden complication. 1991 study Ecuador found 5.1% 294 patients who suffered developed intracranial hemorrhages, although was reliance diagnosis without imaging studies (38). more recent Ecuadorian 2003 2.6% 309 bitten Bothrops snakes events, CT scans confirming presence infarcts (35). Sri Lanka, 2007 series 500 Daboia russelii 9 (6). scoping review highlighted snakebite, 77.1% were 20.5% 2.4% infarct-like (24).Data last five years (2019-2024) reveals 23 12 11 occurred male population, majority genus 2). lack topic problem, absence data makes determine magnitude issue, identify develop programs control. reason, emphasize importance conducting large-scale obtain robust all high bites.Insert 2There no conclusive predispose sepsis; conducted 2019, 83 reported, mentions under 50 age did not comorbidities Only 2% had history could potential factors, diabetes mellitus hypertension (24). Another indicates appearance confusion, mild Glasgow scale, hemiparesis should followed additional investigation (6).Regarding snakes, frequent Viperidae family. Despite this, observed prone strokes; however, mention depends snake. atrox up 12.8% report alterations. lanceolatus caribbaeus typically (39). Likewise, poisoning related (6).The extend far beyond immediate medical consequences. While well-known concerning, (such strokes) induced long-term disabilities socioeconomic repercussions. Stroke, particular, leaves debilitating sequelae their dependence system. Snakebite victims located remote areas healthcare, challenges providing timely treatment rehabilitation. geographical isolation leads delayed treatment, poorer prognoses. Patients poor prognosis will likely diminished work, capacity care families, increased treatments pharmaceuticals, inflating costs.Given substantial snakebite impose communities, crucial:-Enhance Surveillance Systems: Improve reporting infrastructure gather detailed data, location incidents, ensuring consistency better preparedness responses (40).-Implement Preventive Campaigns: Launch initiatives high-risk emphasizing like using flashlights at night, avoiding walking barefoot, wearing protective clothing engaging agricultural work. campaigns focus reducing habitats near homes eliminating rodents clutter (30).-Educational Outreach Rural Areas: Educate rural benefits prompt intervention post-snakebite. many regions, traditional medicine cultural beliefs delays care, worsening outcomes. Educational outreach help bridge gap reduce time (41)(42)(43).-Improve Access Antivenom Medicines: Address treatments, antivenoms. Ensuring reliable supply antivenoms vital, shortages, distribution inefficiencies, imports exacerbate prevalent. Efforts promoting local production antivenom suited regional reach (41,44).-Evaluate Healthcare Capabilities: Continuously availability effectiveness services treating includes adequate tools, replacement therapies, mechanical ventilators. Training workers best practices snakebite-related (40,41).-Public Investment: Encourage investment government private entities fund affordable effective widely accessible. alleviate financial systems ensure underserved (42).-Research Development: Promote research aimed pathophysiological impacts snakebiterelated combination effects, productivity costs, concern. Addressing resources, antivenoms, medicines, infrastructure, mitigating By focusing prevention, ongoing research, we communities.Snakebites emergency global challenges, limited.Beyond physical disabilities, economic productivity, systems. consequences underscore need integrated strategies, addressing shortages medicines raising awareness campaigns. issues perspective, mitigated, quality life diseases.The snakebite-induced India, highlights areas. It emphasizes necessity epidemiological understand occurrence development. awareness, education, management, improved prevention management. Finally, primary events. antidotes tailored caseThe authors declare they competing interests.JVG conceived idea, EOP supervised wrote final manuscript. JVG literature review. MLNL assisted revisions. secured funding research. reviewed approved version manuscript.This work supported Universidad de las Américas, Quito, Ecuador, salary resources provided research.Not applicable.Table 1: Specific effect organism. table describes organism venom.Induced biological myotoxic, cytolytic, edematic, inflammation, (45).Fibrinolytic inhibition (45).Induce proteolytic fibrinogen fibrin, induction apoptosis (46).Hypotensive kallikrein-like activity decreases levels, degrades angiotensin I releases bradykinin plasma kininogen potent vasodilator (47).Possible hypotensive effect, VEGF-like action (47).Vasorelaxation, (45).Hypotension (45).Inhibition (45).Hypotension, vasorelaxation, (45).Hypotensive vasodilation (47).

Language: Английский

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Peptide Fraction from Naja mandalayensis Snake Venom Showed Neuroprotection Against Oxidative Stress in Hippocampal mHippoE-18 Cells but Not in Neuronal PC12 Cells

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 277 - 277

Published: Feb. 26, 2025

Functional characterization of peptide fraction (PF) from snake venom has provided novel opportunities to investigate possible neuroprotective compounds relevant pharmaceuticals. This study was performed the PF-mediated neuroprotection obtained Naja mandalayensis venom, a member Elapidae family, using two neuronal cell lines, undifferentiated PC12 and differentiated mHippoE-18, in response H2O2-induced oxidative stress. Cells were pre-treated for 4 h with PF (10, 1, 0.01, 0.001 μg mL-1), thereafter exposed H2O2 (0.5 mmol L-1) 20 h. Then, stress markers label-free differential proteome strategy analyzed understand effects PF. In cells, showed no against mHippoE-18 at 0.01 mL-1 increased viability metabolism cells neurotoxicity, reducing reactive oxygen species (ROS) generation. Interestingly, also exhibited substantial reduction baseline ROS levels compared control, indicating that could have antioxidant features. The comparative proteomic profiling identified 53 proteins expression related action, catalysis, molecular function regulators, structural molecule activity, translation regulatory ATP, binding. + group indicated protein is 6% upregulated, 4% downregulated, 94% unchanged group. Three significant upregulated group, including elongation factor 2 (P58252), proteasome subunit alpha type (E9Q0X0), E2 ubiquitin-conjugating enzyme (A0A338P786), suggested happens through translational regulation degradation defective via complex. Additionally, changed metabolism, synthesis, synaptic intracellular transport, suggesting contains rich mixture bioactive peptides interest pharmacologically. Overall, this offers new evaluating whether PF's features specific are maintained neurodegenerative disease drug development processes.

Language: Английский

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Diagnosis of Indian Big Four and monocled Cobra snakebites in envenomed plasma using smartphone-based digital imaging colourimetry method

PLoS neglected tropical diseases, Journal Year: 2025, Volume and Issue: 19(3), P. e0012913 - e0012913

Published: March 14, 2025

Background Venomous or dry bites can result from snake envenomation. Therefore, developing a detection test for venomous snakebites in envenomed patients prevented unnecessary antivenom therapy bites, thereby, saving them adverse effects and cost of therapy. Methodology This study demonstrates method the diagnosis medically significant ‘Big Four’ Indian venoms ( Naja naja, Bungarus caeruleus, Daboia russelii, Echis carinatus ) plasma experimentally animals (envenomed under laboratory conditions). Rabbit polyclonal antibodies (PAbs) were produced by generating modified bespoke peptides identified computational analysis antigenic sites main toxins found proteome India’s snakes. The antibody formulation (FPAb) prepared mixing five representative PAbs ratio 1:1:1:1:1 demonstrated synergistic immune recognition snakes kaouthia venoms. these vitro vivo conditions FPAb was significantly higher (p<0.05) than commercial polyvalent against native venom toxins. tested to detect subcutaneously rat plasmas until 240 minutes post-injection. Fourier-transform infrared spectroscopy, zeta potential, transmission electron microscopy, atomic force microscopy characterised gold nanoparticles (AuNP) conjugated with FPAb. FPAb-conjugated AuNP aggregation upon interaction toxins, changing colour red through burgundy blue, monitored using smartphone. From digital image colourimetry images, calibration curves obtained, each at different time intervals quantified curves. Conclusion A has been reported. generated India recognise N. both conditions. plasma. potential be useful snakebite management clinical settings.

Language: Английский

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