title: Inflammatory events induced by brown spider venom and its recombinant dermonecrotic toxin: a pharmacological investigation.
abstract: Accidents involving Brown spider (Loxosceles sp.) venom produce a massive inflammatory response in injured region. This venom has a complex mixture of different toxins, and the dermonecrotic toxin is the major contributor to toxic effects. The ability of Loxosceles intermedia venom and a recombinant isoform of dermonecrotic toxin to induce edema and increase in vascular permeability was investigated. These toxins were injected into hind paws and caused a marked dose and time-dependent edema and increase in vascular permeability in mice. Furthermore, the enzymatic activity of venom toxins may be primal for these effects. A mutated recombinant isoform of dermonecrotic toxin, that has only residual enzymatic activity, was not able to induce these inflammatory events. Besides the previous heating of toxins markedly reduced the paw edema and vascular permeability showing that thermolabile constituents can trigger these effects. In addition, the ability of these venom toxins to evoke inflammatory events was partially reduced in compound 48/80-pretreated animals, suggesting that mast cells may be involved in these responses. Pretreating mice with histamine (prometazine and cetirizine) and serotonin (methysergide) receptor antagonists significantly attenuated toxins induced edema and vascular permeability. Moreover, HPLC analysis of whole venom showed the presence of histamine sufficient to induce inflammatory responses. In conclusion, these inflammatory events may result from the activation of mast cells, which in turn release bioamines and may be related to intrinsic histamine content of venom.
authors.affiliation: Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Katia Sabrina
authors.initials: KS
authors.lastname: Paludo
authors.forename: Stellee Marcela Petris
authors.initials: SM
authors.lastname: Biscaia
authors.forename: Olga Meiri
authors.initials: OM
authors.lastname: Chaim
authors.forename: Michel Fleith
authors.initials: MF
authors.lastname: Otuki
authors.forename: Katya
authors.initials: K
authors.lastname: Naliwaiko
authors.forename: Patrícia Andréia
authors.initials: PA
authors.lastname: Dombrowski
authors.forename: Célia Regina Cavichiolo
authors.initials: CR
authors.lastname: Franco
authors.forename: Silvio Sanches
authors.initials: SS
authors.lastname: Veiga
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D015550:Cell Degranulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced* / Q000276:immunology; D006632:Histamine / Q000032:analysis; D006633:Histamine Antagonists / Q000494:pharmacology; D006358:Hot Temperature; D007279:Injections, Subcutaneous; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D009154:Mutation; D010739:Phospholipase D / Q000008:administration & dosage / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity*; D010727:Phosphoric Diester Hydrolases / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000633:toxicity; D012701:Serotonin / Q000032:analysis; D012702:Serotonin Antagonists / Q000494:pharmacology; D013111:Spider Venoms / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity*; D013112:Spiders; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D006633:Histamine Antagonists; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D013111:Spider Venoms; C516323:dermonecrotic toxin, Loxosceles intermedia; C055161:loxosceles venom; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D010727:Phosphoric Diester Hydrolases; D010739:Phospholipase D