Neutralisation of the pharmacological activities of Bothrops alternatus venom by anti-PLA2 IgGs

Denegri, Maria Emília Garcia; Maruñak, Silvana; Todaro, Juan Santiago; Ponce-Soto, Luis Alberto; Acosta, Ofelia; Leiva, Laura

doi:10.1016/j.toxicon.2014.05.016

Cited by 6 publications

(4 citation statements)

References 22 publications

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“…The anti-PLA 2 IgGs developed from Ba spII RP4 PLA 2 (a non-toxic PLA 2 from Bothrops alternates venom) could inhibit haemolysis and myotoxicity of the crude venom, and also decreased 50% of mortality of mice dosed with four times the LD 50 . The protection effect of the anti-PLA 2 IgGs suggested Ba SpII RP4 PLA2 had a synergistic effect on whole-venom toxicity [ 22 ]. Therefore, PLA 2 became a valuable target in solving snakebite envenomation.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, Garcia et al used a non-toxic PLA 2 derived from B. alternatus venom as an antigen to immunize rabbits, and applied the resulting anti-PLA 2 IgG to mice that were injected with B. alternates venom. The hemorrhagic and myotoxic effects were completely inhibited by anti-PLA 2 IgG, and all mice survived over 48 h after they were administered four times the LD 50 dose venom and anti-PLA 2 IgG [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Wang

Zhang

et al. 2018

Molecules

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Phospholipase A2s (PLA2) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA2s, and was recently repurposed to a broad-spectrum inhibitor of PLA2 in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA2, which was estimated by IC50 in vitro and ED50 in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Wang

Zhang

et al. 2018

Molecules

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“…Despite in vivo evidence demonstrating the capacity of humoral adaptive immunity to neutralize myotoxins and other compounds responsible for local and systemic venom symptoms [39][40][41], the delayed timeframe between venom inoculation and the production of sufficient quantities of antibodies for toxin neutralization poses a limitation for an immediate beneficial effect of the humoral response following snakebite envenomation. In fact, venom effects initiate immediately after the snakebite and are subsequently intensified by the body's inflammatory response, resulting in significant symptoms within a few hours and potentially leading to fatality.…”

Section: Evidence Of Humoral Memory Response Following Snakebite Enve...mentioning

confidence: 99%

The State-of-the-Art of the Humoral Memory Response to Snakebites: Insights from the Yanomami Population

Jati,

dos Anjos Martins,

Rocha

et al. 2023

Toxins

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Snakebite envenomation (SBE)-induced immunity refers to individuals who have been previously bitten by a snake and developed a protective immune response against subsequent envenomations. The notion stems from observations of individuals, including in the indigenous population, who present only mild signs and symptoms after surviving multiple SBEs. Indeed, these observations have engendered scientific interest and prompted inquiries into the potential development of a protective immunity from exposure to snake toxins. This review explores the evidence of a protective immune response developing following SBE. Studies suggest that natural exposure to snake toxins can trigger protection from the severity of SBEs, mediated by specific antibodies. However, the evaluation of the immune memory response in SBE patients remains challenging. Further research is needed to elucidate the immune response dynamics and identify potential targets for therapeutic interventions. Furthermore, the estimation of the effect of previous exposures on SBE epidemiology in hyperendemic areas, such as in the indigenous villages of the Amazon region (e.g., the Yanomami population) is a matter of debate.

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“…Unlike the common antivenins of venom proteome, Garcia Denegri et al developed a poly-antibody using a nontoxic PLA 2 (BaSpII RP4) from Bothrops alternatus as antigen [ 91 ]. This antibody showed a specific and sensitive inhibition of the venom PLA 2 s' enzymatic activity.…”

Section: Pla 2 Inhibitors Attenuate Morbidimentioning

confidence: 99%

Snake Venom PLA₂, a Promising Target for Broad-Spectrum Antivenom Drug Development

Xiao

Hong

Liao

et al. 2017

BioMed Research International

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Snakebite envenomation is a neglected global health problem, causing substantial mortality, disability, and psychological morbidity, especially in rural tropical and subtropical zones. Antivenin is currently the only specific medicine for envenomation. However, it is restricted by cold storage, snakebite diagnosis, and high price. Snake venom phospholipase A2s (svPLA2s) are found in all kinds of venomous snake families (e.g., Viperidae, Elapidae, and Colubridae). Along with their catalytic activity, svPLA2s elicit a wide variety of pharmacological effects that play a pivotal role in envenomation damage. Hence, neutralization of the svPLA2s could weaken or inhibit toxic damage. Here we overviewed the latest knowledge on the distribution, pathophysiological effects, and inhibitors of svPLA2s to elucidate the potential for a novel, wide spectrum antivenom drug targeting svPLA2s.

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Neutralisation of the pharmacological activities of Bothrops alternatus venom by anti-PLA2 IgGs

Cited by 6 publications

References 22 publications

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

The State-of-the-Art of the Humoral Memory Response to Snakebites: Insights from the Yanomami Population

Snake Venom PLA₂, a Promising Target for Broad-Spectrum Antivenom Drug Development

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Neutralisation of the pharmacological activities of Bothrops alternatus venom by anti-PLA2 IgGs

Cited by 6 publications

References 22 publications

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

The State-of-the-Art of the Humoral Memory Response to Snakebites: Insights from the Yanomami Population

Snake Venom PLA2, a Promising Target for Broad-Spectrum Antivenom Drug Development

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Product

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Snake Venom PLA₂, a Promising Target for Broad-Spectrum Antivenom Drug Development