title: Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats.
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 N(ω)-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor). In contrast, mepyramine (a histamine H1 receptor antagonist), D-Arg-[Hyp(3),Thi(5),D-Tic(7),Oic(8)-]-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.
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, Brazil (T.A.A.R.S., E.A., S.H.); and Departamento de Ciências Fisiológicas, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil (T.A.A.R.S., A.L.) thomaz.silva@fcmsantacasasp.edu.br hyslop@fcm.unicamp.br.
authors.forename: Thomaz A A
authors.initials: TA
authors.lastname: Rocha-E-Silva
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, Brazil (T.A.A.R.S., E.A., S.H.); and Departamento de Ciências Fisiológicas, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil (T.A.A.R.S., A.L.).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Linardi
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, Brazil (T.A.A.R.S., E.A., S.H.); and Departamento de Ciências Fisiológicas, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil (T.A.A.R.S., A.L.).
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, Brazil (T.A.A.R.S., E.A., S.H.); and Departamento de Ciências Fisiológicas, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil (T.A.A.R.S., A.L.).
authors.forename: Stephen
authors.initials: S
authors.lastname: Hyslop
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D003533:Cyproheptadine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*; D005528:Foot / Q000473:pathology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D007660:Ketoprofen / Q000627:therapeutic use; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D064729:Neurokinin-1 Receptor Antagonists / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000627:therapeutic use*; D011812:Quinuclidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000187:drug effects; D012702:Serotonin Antagonists / Q000627:therapeutic use; D012867:Skin / Q000473:pathology; D013111:Spider Venoms / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006634:Histamine H1 Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; D012702:Serotonin Antagonists; D013111:Spider Venoms; C085215:SR 140333; D003533:Cyproheptadine; D007660:Ketoprofen; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin