Abstract
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 μg/site) edema in rat dorsal skin. This edema was significantly inhibited by ((S)1-{2-[3(3-4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)piperidine-3-yl]ethyl}-4-phenyl-1-azoniabicyclo[2.2.2]octone, chloride) (SR140333, a neurokinin NK1 receptor antagonist), indomethacin [a nonselective cyclooxygenase (COX) inhibitor], cyproheptadine (a serotonin 5-hydroxytryptamine1/2 and histamine H1 receptor antagonist), and Nω-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor). In contrast, mepyramine (a histamine H1 receptor antagonist), D-Arg-[Hyp3,Thi5,D-Tic7,Oic8-]-BK (JE 049, a bradykinin B2 receptor antagonist), and ((S)-N-methyl-N-[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-di-chlorophenyl)butyl]benzamide) (SR48968, a neurokinin NK2 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 NK1 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.
Footnotes
- Received June 14, 2015.
- Accepted October 14, 2015.
During part of this work, T.A.A.R.S. was supported by a PhD studentship from the São Paulo State Research Foundation [FAPESP, Grant 03/10453-0]. E.A. and S.H. are supported by research fellowships from the Brazilian National Council for Scientific and Technological Development (CNPq). This work was partly supported by the Research Support Fund of the Faculdade de Ciências Médicas da Santa Casa de São Paulo [FAP-FCMSCSP (to T.A.A.R.S.)].
The authors have no financial conflicts of interest.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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