Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom

Toni, Lanuze G. B. de; Menaldo, Danilo L.; Cintra, Adélia Cristina Oliveira; Figueiredo, Maria José; Souza, Anderson R. de; Maximiano, William Marcatti Amarú; Jamur, Maria Célia; Souza, Glória Emília Petto de; Sampaio, Suely Vilela

doi:10.1016/j.intimp.2015.06.001

Cited by 44 publications

(28 citation statements)

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“…jararaca venom, the present results showed that this therapeutic combination caused a significant reduction of the edema in the second hour and subsequently after envenomation [27]. These data suggest that in addition to eicosanoids, other endogenous mediators such as histamine may participate in the snake venom-induced inflammatory edema [32]. …”

Section: Discussionmentioning

confidence: 63%

Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone

et al. 2017

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Bothrops atrox snakes are the leading cause of snake bites in Northern Brazil. The venom of this snake is not included in the antigen pool used to obtain the Bothrops antivenom. There are discrepancies in reports on the effectiveness of this antivenom to treat victims bitten by B. atrox snakes. However, these studies were performed using a pre-incubation of the venom with the antivenom and, thus, did not simulate a true case of envenomation treatment. In addition, the local lesions induced by Bothrops venoms are not well resolved by antivenom therapy. Here, we investigated the efficacy of the Bothrops antivenom in treating the signs and symptoms caused by B. atrox venom in mice and evaluated whether the combination of dexamethasone and antivenom therapy enhanced the healing of local lesions induced by this envenomation. In animals that were administered the antivenom 10 minutes after the envenomation, we observed an important reduction of edema, dermonecrosis, and myonecrosis. When the antivenom was given 45 minutes after the envenomation, the edema and myonecrosis were reduced, and the fibrinogen levels and platelet counts were restored. The groups treated with the combination of antivenom and dexamethasone had an enhanced decrease in edema and a faster recovery of the damaged skeletal muscle. Our results show that Bothrops antivenom effectively treats the envenomation caused by Bothrops atrox and that the use of dexamethasone as an adjunct to the antivenom therapy could be useful to improve the treatment of local symptoms observed in envenomation caused by Bothrops snakes.

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Section: Discussionmentioning

confidence: 63%

Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone

et al. 2017

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“…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%

“…The mechanisms on how neurogenic inflammation is triggered by the snake venom components and how it participates in the hemorrhagic process are still not understood. Pain induced by SVMPs is characterized by hyperalgesia and inflammatory pain, which is dependent on the production of cytokines, nitric oxide, prostaglandins, histamine, leukotrienes, and migration of leukocytes, mast cell degranulation and NFkB activation (Fernandes et al, 2007;Bernardes et al, 2015;De Toni et al, 2015;Ferraz et al, 2015). However, the mechanisms underlying SVMP-induced pain are still poorly understood, with neurogenic inflammation and neuronal excitatory properties still underexplored.…”

Section: Not Describedmentioning

confidence: 99%

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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“…The edema formation is a two phase process; the initial phase of edema involves the action of inflammatory mediators on the vascular permeability, including histamine, serotonin and bradykinin (Toni et al, 2015). The second or the later phase involves the pain mediators like prostaglandins (Chao et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

In-vivo evaluation of analgesic, anti-inflammatory and anti-pyretic activity of aqueous methanolic extract of Jatropha gossypifolia

Ghauri¹,

Khan²,

Khan³

et al. 2017

Afr. J. Pharm. Pharmacol.

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Many pathological conditions are associated with pain, fever and inflammation. Synthetic drugs available for the treatment of these ailments accompany many unwanted side effect; most prominent of which is the gastric ulcer. Present study was thus aimed at evaluating the analgesic, anti-pyretic and anti-inflammatory potential of aqueous methanolic extract of leaves of plant Jatropha gossypifolia. Antiinflammatory activity was evaluated using carrageenan induced paw edema. Acetic acid induced writhing test and hot plate method was used to assess the analgesic activity. Anti-pyretic activity was ascertained using brewer's yeast induced pyrexia. The aqueous methanolic extract of the plant J. gassypifolia have demonstrated significant analgesic, anti-pyretic and anti-inflammatory activity at 200 mg/kg dose. The data was statistically analyzed by one way ANOVA followed by post hoc Dunnett's test for multiple comparisons. It has thus concluded that aqueous methanolic extract of leaves of plant J. gassypifolia possess analgesic, anti-inflammatory and anti-pyretic properties. These results strongly support the ethno-pharmacological use of this plant as anti-pyretic, analgesic and anti-inflammatory agent.

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Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom

Cited by 44 publications

References 73 publications

Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone

Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone

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

In-vivo evaluation of analgesic, anti-inflammatory and anti-pyretic activity of aqueous methanolic extract of Jatropha gossypifolia

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