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

Author(s)

Rocha-e-Silva, Thomaz A. A. ^{[1, 2]} ; Linardi, Alessandra ^[2] ; Antunes, Edson ^[1] ; Hyslop, Stephen ^[1]

Affiliation

^[1] Univ Estadual Campinas, Fac Ciencias Med, Dept Farmacol, Campinas, SP - Brazil

^[2] Santa Casa Sao Paulo, Dept Ciencias Fisiol, Fac Ciencias Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Pharmacology and Experimental Therapeutics; v. 356, n. 1, p. 13-19, JAN 2016.
• Web of Science Citations: 0

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, non-aggressive 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 mu g/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-hydroxytryptamine(1/2) and histamine H-1 receptor antagonist), and N-omega-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor). In contrast, mepyramine (a histamine H-1 receptor antagonist), D-Arg-{[}Hyp(3), Thi(5), D-Tic(7), Oic(8)-]-BK (JE 049, a bradykinin B-2 receptor antagonist), and ((S)-N-methyl-N-{[}4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-di-chloro phenyl)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. (AU)