Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia

Zambelli, Vanessa O.; Picolo, Gisele; Fernandes, Carlos A. H.; Fontes, Marcos R.M.; Cury, Yara

doi:10.3390/toxins9120406

Cited by 56 publications

(44 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secreted PLA2 has been found in several animal venoms [ 49 ] and probably contributes to the development of pain, inflammation, and cell lysis consequent to the envenomation [ 12 ].…”

Section: Components Of Scyphozoan Venom and Their Activitymentioning

confidence: 99%

Impact of Scyphozoan Venoms on Human Health and Current First Aid Options for Stings

Costa

Morabito

Spada

et al. 2018

Toxins

View full text Add to dashboard Cite

Cnidaria include the most venomous animals of the world. Among Cnidaria, Scyphozoa (true jellyfish) are ubiquitous, abundant, and often come into accidental contact with humans and, therefore, represent a threat for public health and safety. The venom of Scyphozoa is a complex mixture of bioactive substances—including thermolabile enzymes such as phospholipases, metalloproteinases, and, possibly, pore-forming proteins—and is only partially characterized. Scyphozoan stings may lead to local and systemic reactions via toxic and immunological mechanisms; some of these reactions may represent a medical emergency. However, the adoption of safe and efficacious first aid measures for jellyfish stings is hampered by the diffusion of folk remedies, anecdotal reports, and lack of consensus in the scientific literature. Species-specific differences may hinder the identification of treatments that work for all stings. However, rinsing the sting site with vinegar (5% acetic acid) and the application of heat (hot pack/immersion in hot water) or lidocaine appear to be substantiated by evidence. Controlled clinical trials or reliable models of envenomation are warranted to confirm the efficacy and safety of these approaches and identify possible species-specific exceptions. Knowledge of the precise composition of Scyphozoa venom may open the way to molecule-oriented therapies in the future.

show abstract

“…Secreted PLA2 has been found in several animal venoms [ 49 ] and probably contributes to the development of pain, inflammation, and cell lysis consequent to the envenomation [ 12 ].…”

Section: Components Of Scyphozoan Venom and Their Activitymentioning

confidence: 99%

Impact of Scyphozoan Venoms on Human Health and Current First Aid Options for Stings

Costa

Morabito

Spada

et al. 2018

Toxins

View full text Add to dashboard Cite

show abstract

“…A number of PLA2s exert strong myotoxic effects which often lead to severe necrosis (Harris and Maltin, 1982;Gutierrez and Ownby, 2003), and many of these toxins also promote inflammation, including edema formation, cytokine production and leukocyte recruitment, pain by inducing thermal allodynia and mechanical hyperalgesia, paralysis through block of neuromuscular transmission and intensify hemorrhage by inhibiting coagulation (Table 1) (Camara et al, 2003;Chacur et al, 2003;Camargo et al, 2008;Teixeira et al, 2011;Lomonte and Rangel, 2012;Harris and Scott-Davey, 2013;Casais-E-Silva et al, 2016;Costa et al, 2017;Zambelli et al, 2017b;Zhang et al, 2017). Neurotoxic effects caused by these toxins, as well as some of their proinflammatory effects, occurs via the modulation of pre-synaptic terminals as well as sensory nerveendings (Camara et al, 2003;Harris and Scott-Davey, 2013;Sribar et al, 2014;Zhang et al, 2017).…”

Section: Phospholipases (Pla2s)mentioning

confidence: 99%

“…The pain induced by PLA2s is driven by inflammatory processes and sensory neuronal activation. Bradykinin is an important mediator of the inflammatory pain induced by PLA2s (Moreira et al, 2014;Urs et al, 2014;Mamede et al, 2016;Zambelli et al, 2017b). It induces mechanical hyperalgesia dependent on the production of TNF-α, IL-1β, and prostaglandins (Cunha et al, 1992).…”

Section: Phospholipases (Pla2s)mentioning

confidence: 99%

“…Furthermore, SVSPs and SVMPs induce hemostatic and cardiovascular effects as coagulopathy, hypotension and hemorrhage (Slagboom et al, 2017). Interestingly, some PLA2s, SVSPs, and SVMPs are also capable of triggering severe pain by modulating pain pathways through activation of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1) and acid-sensing ion channel (ASIC) (Bohlen et al, 2011;Zhang et al, 2017); and/or by pain sensitization through inflammatory mediators (Zychar et al, 2010;Menaldo et al, 2013;Ferraz et al, 2015;Mamede et al, 2016;Zambelli et al, 2017b). The inflammation induced by the elapid and viper venoms is widely reported to produce pain or hyperalgesia in human and in experimental models (Hifumi et al, 2015;Bucaretchi et al, 2016;Kleggetveit et al, 2016;Mamede et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

et al. 2019

View full text Add to dashboard Cite

Animal venoms have evolved over millions of years for prey capture and defense from predators and rivals. Snake venoms, in particular, have evolved a wide diversity of peptides and proteins that induce harmful inflammatory and neurotoxic effects including severe pain and paralysis, hemotoxic effects, such as hemorrhage and coagulopathy, and cytotoxic/myotoxic effects, such as inflammation and necrosis. If untreated, many envenomings result in death or severe morbidity in humans and, despite advances in management, snakebite remains a major public health problem, particularly in developing countries. Consequently, the World Health Organization recently recognized snakebite as a neglected tropical disease that affects ∼2.7 million p.a. The major protein classes found in snake venoms are phospholipases, metalloproteases, serine proteases, and three-finger peptides. The mechanisms of action and pharmacological properties of many snake venom toxins have been elucidated, revealing a complex multifunctional cocktail that can act synergistically to rapidly immobilize prey and deter predators. However, despite these advances many snake toxins remain to be structurally and pharmacologically characterized. In this review, the multifunctional features of the peptides and proteins found in snake venoms, as well as their evolutionary histories, are discussed with the view to identifying novel modes of action and improving snakebite treatments.

show abstract

“…Among the main components of animal venoms are the secreted PLA₂ that belong to distinct PLA₂s groups. Snake venom PLA₂s from Elapidae and Viperidae families belong, respectively, to the IA and IIA/IIB groups [15,16]. For instance, snake venoms are rich sources of PLA 2 enzymes that are frequently found as a large number of isozymes [17].…”

Section: Introductionmentioning

confidence: 99%

Effects of Mlx-8, a phospholipase A2 from Brazilian coralsnake Micrurus lemniscatus venom, on muscarinic acetylcholine receptors in rat hippocampus

Santos

Silva

Porto

et al. 2020

J. Venom. Anim. Toxins incl. Trop. Dis

View full text Add to dashboard Cite

Background: Here, we described the presence of a neurotoxin with phospholipase A 2 activity isolated from Micrurus lemniscatus venom (Mlx-8) with affinity for muscarinic acetylcholine receptors (mAChRs). Methods: The purification, molecular mass determination, partial amino acid sequencing, phospholipase A 2 activity determination, inhibition of the binding of the selective muscarinic ligand [ 3 H]QNB and inhibition of the total [ 3 H]inositol phosphate accumulation in rat hippocampus of the Mlx-8 were determined. Results: Thirty-one fractions were collected from HPLC chromatography, and the Mlx-8 toxin was used in this work. The molecular mass of Mlx-8 is 13.628 Da. Edman degradation yielded the following sequence: NLYQFKNMIQCTNTRSWL-DFADYG-CYCGRGGSGT. The Mlx-8 had phospholipase A 2 enzymatic activity. The pK i values were determined for Mlx-8 toxin and the M 1 selective muscarinic antagonist pirenzepine in hippocampus membranes via [ 3 H]QNB competition binding assays. The pK i values obtained from the analysis of Mlx-8 and pirenzepine displacement curves were 7.32 ± 0.15, n = 4 and 5.84 ± 0.18, n = 4, respectively. These results indicate that Mlx-8 has affinity for mAChRs. There was no effect on the inhibition ability of the [ 3 H]QNB binding in hippocampus membranes when 1 µM Mlx-8 was incubated with 200 µM DEDA, an inhibitor of phospholipase A 2. This suggests that the inhibition of the phospholipase A 2 activity of the venom did not alter its ability to bind to displace [ 3 H]QNB binding. In addition, the Mlx-8 toxin caused a blockade of 43.31 ± 8.86%, n = 3 and 97.42 ± 2.02%, n = 3 for 0.1 and 1 µM Mlx-8, respectively, on the total [ 3 H]inositol phosphate content induced by 10 µM carbachol. This suggests that Mlx-8 inhibits the intracellular

show abstract

Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia

Cited by 56 publications

References 145 publications

Impact of Scyphozoan Venoms on Human Health and Current First Aid Options for Stings

Impact of Scyphozoan Venoms on Human Health and Current First Aid Options for Stings

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

Effects of Mlx-8, a phospholipase A2 from Brazilian coralsnake Micrurus lemniscatus venom, on muscarinic acetylcholine receptors in rat hippocampus

Contact Info

Product

Resources

About