Inflammatory Action of Secretory Phospholipases A2 from Snake Venoms

Costa, Soraia K.P.; Camargo, E E; Antunes, Edson

doi:10.1007/978-94-007-6452-1_10

Cited by 9 publications

(16 citation statements)

References 71 publications

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“…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 inflammation induced by PLA2s has non-neurogenic and neurogenic (substance-P dependent) components (Camara et al, 2003;Camargo et al, 2008;Costa et al, 2017;Zhang et al, 2017). The non-neurogenic component is mostly caused by the hydrolysis of membrane lipids that generate potent pro-inflammatory lipid mediators .…”

Section: Phospholipases (Pla2s)mentioning

confidence: 99%

“…Acute pain through ASIC1 activation (Bohlen et al, 2011) Inflammatory pain, thermal hypersalgesia and mechanical allodynia (Zhang et al, 2017) Excitation of sensory neurons (Bohlen et al, 2011;Zhang et al, 2017) Neurogenic inflammation (Camara et al, 2003;Camargo et al, 2008) Non-neurogenic inflammation Endematogenic and pro-inflammatory (Camara et al, 2003;Casais-E-Silva et al, 2016;Costa et al, 2017) Inhibits platelet aggregation (Teixeira et al, 2011) Phospholipase activity (Gutierrez and Ownby, 2003) Myotoxic (Harris and Maltin, 1982) Pre-synaptic toxin, block of neuromuscular transmission leading to muscle paralysis (Sribar et al, 2014;Gutierrez et al, 2017) SVMP Inflammatory hyperalgesia (Fernandes et al, 2007;Bernardes et al, 2015;De Toni et al, 2015;Ferraz et al, 2015) Endematogenic activity independent of pro-inflammatory mediators (Laing et al, 2003) Cleavage of basement membrane of capillary vessels and endothelial cells adhesion proteins (Gutierrez et al, 2005;Escalante et al, 2011) Procoagulant through activation of prothrombin and Factor X (Takeda et al, 2012;Ainsworth et al, 2018) Inhibition of platelet aggregation (Kamiguti, 2005) Dermonecrotic activity dependent on TNF signaling (Laing et al, 2003) Potential paralysis through inhibition of α-7 neuronal AChR by the cysteine-rich and disintregin-like domains complex (Brust et al, 2013) SVSP Mild mechanical hyperalgesia (Menaldo et al, 2013) Leucocyte migration (Menaldo et al, 2013) Mild edema (Zychar et al, 2010) Procoagulant through activation of prothrombin and factors VII and X (Kini, 2005) Anti-coagulant through activation of Prot...…”

Section: Pla2smentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2019

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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.

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Section: Phospholipases (Pla2s)mentioning

confidence: 99%

Section: Phospholipases (Pla2s)mentioning

confidence: 99%

Section: Pla2smentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2019

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“…Phospholipases A 2 (PLA 2 s) are key enzymes involved in many events in cellular signaling and act by cleaving ester bonds in phospholipids to generate fatty acids (hydrolysis reactions) [1][2][3]. They are pervasive in the mammalian pancreas and are highly abundant in many animal venoms [4,5]. Venom PLA 2 enzymes show a wide variety of functional activities, and thus can contribute to several distinct pathologies in envenomed prey/people, as well as potentially helping with prey digestion [4,5].…”

Section: Introductionmentioning

confidence: 99%

Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes

et al. 2020

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Phospholipase A2 (PLA2) enzymes are important toxins found in many snake venoms, and they can exhibit a variety of toxic activities including causing hemolysis and/or anticoagulation. In this study, the inhibiting effects of the small molecule PLA2 inhibitor varespladib on snake venom PLA2s was investigated by nanofractionation analytics, which combined chromatography, mass spectrometry (MS), and bioassays. The venoms of the medically important snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus, Echis ocellatus, and Oxyuranus scutellatus were separated by liquid chromatography (LC) followed by nanofractionation and interrogation of the fractions by a coagulation assay and a PLA2 assay. Next, we assessed the ability of varespladib to inhibit the activity of enzymatic PLA2s and the coagulopathic toxicities induced by fractionated snake venom toxins, and identified these bioactive venom toxins and those inhibited by varespladib by using parallel recorded LC-MS data and proteomics analysis. We demonstrated here that varespladib was not only capable of inhibiting the PLA2 activities of hemotoxic snake venoms, but can also effectively neutralize the coagulopathic toxicities (most profoundly anticoagulation) induced by venom toxins. While varespladib effectively inhibited PLA2 toxins responsible for anticoagulant effects, we also found some evidence that this inhibitory molecule can partially abrogate procoagulant venom effects caused by different toxin families. These findings further emphasize the potential clinical utility of varespladib in mitigating the toxic effects of certain snakebites.

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“…Snake venom PLA 2 s are proteins that hydrolyze phospholipids at the sn-2 position, generating lysophospholipids and free fatty acids, including arachidonic acid [ 9 , 10 ]. Arachidonic acid functions as substrate for the synthesis of various proinflammatory mediators, such as leukotrienes (LT), thromboxane A 2 (TXA 2 ), prostacyclin, and prostaglandins (PG).…”

Section: Introductionmentioning

confidence: 99%

Effect of Vipera ammodytes ammodytes Snake Venom on the Human Cytokine Network

Boda

Banfai

Garai

et al. 2018

Toxins

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Local inflammation is a well-known symptom of envenomation by snakes of the family Viperidae, attributed primarily to the phospholipase A2s, metalloproteinases and L-amino acid oxidases contained in their venom. The inflammatory effect of snake venoms has been associated with a marked increase of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α. To determine the impact of Vipera ammodytes ammodytes snake venom on the expression of inflammation-related genes, we incubated human U937 monocyte cells with dilutions of snake venom. Gene expression was quantified for 28 different genes using a TaqMan® Array Human Cytokine Network 96-well Plate in a RT-qPCR system. Our results have demonstrated that 1.0 μg/mL Vipera ammodytes ammodytes venom solution induces a notable change in the expression of several cytokine network genes. Among the upregulated genes, there were several that encode interleukins, interferons, and tumor necrosis factors. We further report the downregulation of three interleukin-related genes. Our findings come as supportive information for the known complex effect of snake venoms on the human cytokine network. It also provides relevant new information regarding the expression of genes that have not been previously associated with the effect of snake venoms.

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Inflammatory Action of Secretory Phospholipases A2 from Snake Venoms

Cited by 9 publications

References 71 publications

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

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

Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes

Effect of Vipera ammodytes ammodytes Snake Venom on the Human Cytokine Network

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