Agonists of melatonin receptors strongly promote the functional recovery from the neuroparalysis induced by neurotoxic snakes DOI Creative Commons
Giorgia D’Este, F Fabris, Marco Stazi

et al.

PLoS neglected tropical diseases, Journal Year: 2024, Volume and Issue: 18(1), P. e0011825 - e0011825

Published: Jan. 8, 2024

Snake envenoming is a major, but neglected, tropical disease. Among venomous snakes, those inducing neurotoxicity such as kraits (Bungarus genus) cause potentially lethal peripheral neuroparalysis with respiratory deficit in large number of people each year. In order to prevent the development deadly paralysis, hospitalization pulmonary ventilation and use antivenoms are primary therapies currently employed. However, hospitals frequently out reach for envenomated patients there general consensus that additional, non-expensive treatments, deliverable even long after snake bite, needed. Traumatic or toxic degenerations motor neurons activates pro-regenerative intercellular signaling program taking place at neuromuscular junction (NMJ). We recently reported axis melatonin-melatonin receptor 1 (MT1) plays major role recovery function NMJs degeneration axon terminals caused by massive Ca2+ influx. Here we show small chemical MT1 agonists: Ramelteon Agomelatine, already licensed treatment insomnia depression, respectively, strong promoters neuroregeneration paralysis induced krait venoms mice, which also mediated. The venom from Bungarus species representative class neurotoxic snakes (including taipans, coral some Alpine vipers addition other kraits) was chosen. functional NMJ demonstrated using electrophysiological, imaging lung detection methods. According present results, propose Agomelatine should be tested human bitten acting presynaptically promote their health. Noticeably, these drugs commercially available, safe, non-expensive, have bench life can administered snakebite places far away health facilities.

Language: Английский

Bioinformatics-Guided Identification and Quantification of Biomarkers of Crotalus atrox Envenoming and its Neutralization by Antivenom DOI Creative Commons
Auwal A. Bala, Anas Bedraoui,

Salim El Mejjad

et al.

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100956 - 100956

Published: March 1, 2025

Language: Английский

Citations

0
Plant-derived secondary metabolites against Bothrops envenomation: A review DOI
Mayara A. Romanelli,

Taissa Nunes Guerrero,

Elvis Lopes Brito

et al.

Toxicon, Journal Year: 2025, Volume and Issue: unknown, P. 108340 - 108340

Published: April 1, 2025

Language: Английский

Citations

0
Exploring the Utility of Recombinant Snake Venom Serine Protease Toxins as Immunogens for Generating Experimental Snakebite Antivenoms DOI Creative Commons
Nessrin Alomran, Patricia A. Blundell, Jaffer Alsolaiss

et al.

Toxins, Journal Year: 2022, Volume and Issue: 14(7), P. 443 - 443

Published: June 29, 2022

Snakebite is a neglected tropical disease that causes high rates of global mortality and morbidity. Although snakebite can cause variety pathologies in victims, haemotoxic effects are particularly common typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Despite polyclonal antibody-based antivenoms being the mainstay life-saving therapy for snakebite, they associated with limited cross-snake species efficacy, as there often extensive toxin variation between snake venoms, including those used immunogens antivenom production. This restricts therapeutic utility any to certain geographical regions. In this study, we explored feasibility using recombinantly expressed toxins stimulate focused, pathology-specific, antibodies order broadly counteract specific envenoming. Three venom serine proteases (SVSP) toxins, sourced from geographically diverse medically important viper were successfully HEK293F mammalian cells murine immunisation. Analyses resulting antibody responses revealed ancrod RVV-V stimulated strongest immune responses, experimental directed against these recombinant SVSP mixture three different immunogens, extensively recognised exhibited immunological binding towards native venoms. While showed some reduction abnormal clotting parameters crude venom, specifically reducing depletion fibrinogen levels prolongation prothrombin times, degradation experiments protected venom- toxin-induced fibrinogenolytic functional activities. Overall, our findings further strengthen case use supplemental focused desirable capable neutralising pathological effects, therefore potentially circumventing limitations current therapies.

Language: Английский

Citations

14
Action of Varespladib (LY-315920), a Phospholipase A2 Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of Lachesis muta rhombeata (South-American Bushmaster) Venom DOI Creative Commons

Pamella G. Gutierres,

Diego Roberto Pereira,

Nataly L. Vieira

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 12, 2022

Varespladib (VPL) was primarily developed to treat inflammatory disturbances associated with high levels of serum phospholipase A2 (PLA2). VPL has also demonstrated be a potential antivenom support agent prevent PLA2-dependent effects produced by snake venoms. In this study, we examined the action on coagulant, haemorrhagic and enzymatic activities Lachesis muta rhombeata (South-American bushmaster) venom. Conventional colorimetric assays were performed for PLA2, caseinolytic esterasic activities; in vitro coagulant prothrombin time (PT) activated partial thromboplastin (aPTT) rat citrated plasma through quick timer coagulometer, whereas dimensions haloes obtained after i.d. injections venom Wistar rats determined using ImageJ software. Venom (1 mg/ml) exhibited accentuated proteases PLA2in vitro, abolishing PLA2 activity from 0.01 mM; did not affect at any tested concentrations (0.001-1 mM). mM) alone efficiently prevented mg/ml)-induced procoagulant disorder extrinsic pathway, its association commercial successfully changes both intrinsic pathways; itself failed avoid disorders (0.5 mg/kg)-induced hemorrhagic slightly reduced or combined (antivenom:venom ratio 1:3 'v/w') rats, producing no protective parameter. conclusion, does inhibit other major groups L. m. venom, antagonize efficaciously preventing venom-induced coagulation disturbances.

Language: Английский

Citations

13
Agonists of melatonin receptors strongly promote the functional recovery from the neuroparalysis induced by neurotoxic snakes DOI Creative Commons
Giorgia D’Este, F Fabris, Marco Stazi

et al.

PLoS neglected tropical diseases, Journal Year: 2024, Volume and Issue: 18(1), P. e0011825 - e0011825

Published: Jan. 8, 2024

Snake envenoming is a major, but neglected, tropical disease. Among venomous snakes, those inducing neurotoxicity such as kraits (Bungarus genus) cause potentially lethal peripheral neuroparalysis with respiratory deficit in large number of people each year. In order to prevent the development deadly paralysis, hospitalization pulmonary ventilation and use antivenoms are primary therapies currently employed. However, hospitals frequently out reach for envenomated patients there general consensus that additional, non-expensive treatments, deliverable even long after snake bite, needed. Traumatic or toxic degenerations motor neurons activates pro-regenerative intercellular signaling program taking place at neuromuscular junction (NMJ). We recently reported axis melatonin-melatonin receptor 1 (MT1) plays major role recovery function NMJs degeneration axon terminals caused by massive Ca2+ influx. Here we show small chemical MT1 agonists: Ramelteon Agomelatine, already licensed treatment insomnia depression, respectively, strong promoters neuroregeneration paralysis induced krait venoms mice, which also mediated. The venom from Bungarus species representative class neurotoxic snakes (including taipans, coral some Alpine vipers addition other kraits) was chosen. functional NMJ demonstrated using electrophysiological, imaging lung detection methods. According present results, propose Agomelatine should be tested human bitten acting presynaptically promote their health. Noticeably, these drugs commercially available, safe, non-expensive, have bench life can administered snakebite places far away health facilities.

Language: Английский

Citations

2