Inflammatory events induced by brown spider venom and its recombinant dermonecrotic toxin: A pharmacological investigation

Paludo, Kátia Sabrina; Biscaia, Stellee Marcela Petris; Chaim, Olga Meiri; Otuki, Michel Fleith; Naliwaiko, Katya; Dombrowski, Patrícia A.; Franco, Célia Regina Cavichiolo; Veiga, Sílvio Sanches

doi:10.1016/j.cbpc.2008.08.009

Cited by 29 publications

(23 citation statements)

References 46 publications

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“…Based on these data, it is possible to suggest that L. intermedia TCTP may act as a histamine release factor. The presence of a component in L. intermedia venom related to the histaminergic activity of venom supports with this hypothesis [149]. Recently, some authors have called attention to the role of histamine and its receptors in the development of edema, involving increased vascular permeability and vasodilatation [150], which occurs in Loxoscelism.…”

Section: Translationally Controlled Tumor Protein (Tctp)mentioning

confidence: 79%

Brown Spider (Loxosceles genus) Venom Toxins: Tools for Biological Purposes

Chaim

Trevisan-Silva

Chaves-Moreira

et al. 2011

Toxins

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Venomous animals use their venoms as tools for defense or predation. These venoms are complex mixtures, mainly enriched of proteic toxins or peptides with several, and different, biological activities. In general, spider venom is rich in biologically active molecules that are useful in experimental protocols for pharmacology, biochemistry, cell biology and immunology, as well as putative tools for biotechnology and industries. Spider venoms have recently garnered much attention from several research groups worldwide. Brown spider (Loxosceles genus) venom is enriched in low molecular mass proteins (5–40 kDa). Although their venom is produced in minute volumes (a few microliters), and contain only tens of micrograms of protein, the use of techniques based on molecular biology and proteomic analysis has afforded rational projects in the area and permitted the discovery and identification of a great number of novel toxins. The brown spider phospholipase-D family is undoubtedly the most investigated and characterized, although other important toxins, such as low molecular mass insecticidal peptides, metalloproteases and hyaluronidases have also been identified and featured in literature. The molecular pathways of the action of these toxins have been reported and brought new insights in the field of biotechnology. Herein, we shall see how recent reports describing discoveries in the area of brown spider venom have expanded biotechnological uses of molecules identified in these venoms, with special emphasis on the construction of a cDNA library for venom glands, transcriptome analysis, proteomic projects, recombinant expression of different proteic toxins, and finally structural descriptions based on crystallography of toxins.

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Section: Translationally Controlled Tumor Protein (Tctp)mentioning

confidence: 79%

Brown Spider (Loxosceles genus) Venom Toxins: Tools for Biological Purposes

Chaim

Trevisan-Silva

Chaves-Moreira

et al. 2011

Toxins

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“…This notion is strengthened by evidence observed in the course of loxoscelism, which includes itch, morbilliform erythema, cutaneous rash and petechial eruption [1], [2], [31], [61], [62]. It might also suggest the involvement of the immune system [63], [64]. Cutaneous rashes respond to treatment with systemic steroids [31], [63].…”

Section: Discussionmentioning

confidence: 94%

A Novel Hyaluronidase from Brown Spider (Loxosceles intermedia) Venom (Dietrich's Hyaluronidase): From Cloning to Functional Characterization

et al. 2013

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Loxoscelism is the designation given to clinical symptoms evoked by Loxosceles spider's bites. Clinical manifestations include skin necrosis with gravitational spreading and systemic disturbs. The venom contains several enzymatic toxins. Herein, we describe the cloning, expression, refolding and biological evaluation of a novel brown spider protein characterized as a hyaluronidase. Employing a venom gland cDNA library, we cloned a hyaluronidase (1200 bp cDNA) that encodes for a signal peptide and a mature protein. Amino acid alignment revealed a structural relationship with members of hyaluronidase family, such as scorpion and snake species. Recombinant hyaluronidase was expressed as N-terminal His-tag fusion protein (∼45 kDa) in inclusion bodies and activity was achieved using refolding. Immunoblot analysis showed that antibodies that recognize the recombinant protein cross-reacted with hyaluronidase from whole venom as well as an anti-venom serum reacted with recombinant protein. Recombinant hyaluronidase was able to degrade purified hyaluronic acid (HA) and chondroitin sulfate (CS), while dermatan sulfate (DS) and heparan sulfate (HS) were not affected. Zymograph experiments resulted in ∼45 kDa lytic zones in hyaluronic acid (HA) and chondroitin sulfate (CS) substrates. Through in vivo experiments of dermonecrosis using rabbit skin, the recombinant hyaluronidase was shown to increase the dermonecrotic effect produced by recombinant dermonecrotic toxin from L. intermedia venom (LiRecDT1). These data support the hypothesis that hyaluronidase is a “spreading factor”. Recombinant hyaluronidase provides a useful tool for biotechnological ends. We propose the name Dietrich's Hyaluronidase for this enzyme, in honor of Professor Carl Peter von Dietrich, who dedicated his life to studying proteoglycans and glycosaminoglycans.

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“…Edema formation has also been observed for nontheraphosid spiders such as P. nigriventer (Antunes et al, 1992Bento et al, 1995;Costa et al, 1997) and Loxosceles spp. (Rattmann et al, 2008;Paludo et al, 2009;Barbaro et al, 2010;Guimarães et al, 2013;Ribeiro et al, 2015), and a variety of Australian spiders (Atkinson, 1986;Korszniak and Story, 1995). Unlike envenoming by Loxosceles spp.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats

Silva

Linardi

Antunes

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Bites by tarantulas (Theraphosidae, Mygalomorphae) in humans can result in mild clinical manifestations such as local pain, erythema, and edema. Vitalius dubius is a medium-sized, nonaggressive theraphosid found in southeastern Brazil. In this work, we investigated the mediators involved in the plasma extravasation caused by V. dubius venom in rats. The venom caused dose-dependent (0.1-100 mg/site) edema in rat dorsal skin. This edema was significantly inhibited by butyl]benzamide) (SR48968, a neurokinin NK 2 receptor antagonist) had no effect on the venom-induced increase in vascular permeability. In rat hind paws, the venom-induced edema was attenuated by ketoprofen (a nonselective COX inhibitor) administered 15 minutes postvenom. Preincubation of venom with commercial antiarachnid antivenom attenuated the venom-induced edema. These results suggest that the enhanced vascular permeability evoked by V. dubius venom involves serotonin, COX products, neurokinin NK 1 receptors, and nitric oxide formation. The attenuation of hind paw edema by ketoprofen suggests that COX inhibitors could be useful in treating the local inflammatory response to bites by these spiders.

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Inflammatory events induced by brown spider venom and its recombinant dermonecrotic toxin: A pharmacological investigation

Cited by 29 publications

References 46 publications

Brown Spider (Loxosceles genus) Venom Toxins: Tools for Biological Purposes

Brown Spider (Loxosceles genus) Venom Toxins: Tools for Biological Purposes

A Novel Hyaluronidase from Brown Spider (Loxosceles intermedia) Venom (Dietrich's Hyaluronidase): From Cloning to Functional Characterization

Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats

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