title: Pharmacological characterization of Sephadex-induced oedema in rat paws: predominant role of serotonin and platelet-activating factor.
abstract: An intravenous injection of Sephadex beads has been used to induce lung inflammation and bronchial hyperreactivity in small animals. In the present study, we injected Sephadex beads (0.3-5.5 mg/paw) into rat paws and followed the resulting inflammation plethysmometrically. Our results show that Sephadex beads induced a significant and dose-dependent increase in the hindpaw volume at 5 min; it was maximal at 30-60 min and declined at 4 h. However, the paw volume remained significantly increased for up to 21 days. The initial 4-hour-oedema was confirmed by histopathology of the paw tissues, but the persistent increase in paw volume was related to a chronic inflammatory (granulomatous) response. The Sephadex-induced oedema was predominantly due to serotonin (5-HT) release since specific antagonists such as methysergide (1 mg/kg) and pizotifen (0.1-2 mg/kg) administered both systemically and locally were able to inhibit the oedema (10-100 microgram/paw) as could pretreatment with compound 48/80. In addition, platelet-activating factor (PAF) was also shown to be involved, since systemic pretreatment using the specific PAF antagonist BN 52021 (1 mg/kg) was able to inhibit the increase in paw volume induced by Sephadex. Effective doses of indomethacin (2 mg/kg), L-NAME (1 mg/kg), pyrilamine (1-2 mg/kg), ondansetron (1 mg/kg) and HOE 140 (1 mg/kg) did not affect the Sephadex-induced oedema, thus ruling out the participation of prostaglandins, nitric oxide, histamine, 5-HT3 receptors and bradykinin in its development. Since the late increases in paw volume induced by Sephadex were reduced by pretreatment of the animals with the immunosuppressive drugs rapamycin and dexamethasone but not cyclosporin, our results also suggested that distinct immunological pathways may be involved in the modulation of the chronic phase of inflammation induced by Sephadex beads in rat paws.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil.
authors.forename: J N
authors.initials: JN
authors.lastname: Francischi
authors.forename: M F
authors.initials: MF
authors.lastname: Dias
authors.forename: O A
authors.initials: OA
authors.lastname: Rocha
authors.forename: M S
authors.initials: MS
authors.lastname: de Abreu Castro
authors.forename: M A
authors.initials: MA
authors.lastname: Kiyomi Funayama Tatsuo
authors.forename: P
authors.initials: P
authors.lastname: Farinelli
authors.forename: C M
authors.initials: CM
authors.lastname: Pacheco
authors.forename: D L
authors.initials: DL
authors.lastname: Ferreira-Alves
authors.forename: P
authors.initials: P
authors.lastname: Sirois
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D003911:Dextrans / Q000008:administration & dosage; D004224:Diterpenes; D004487:Edema / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D046934:Ginkgolides; D006632:Histamine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018836:Inflammation Mediators / Q000502:physiology; D007275:Injections, Intravenous; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011090:Polyenes / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D020123:Sirolimus; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D003911:Dextrans; D004224:Diterpenes; D046934:Ginkgolides; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D007783:Lactones; D010972:Platelet Activating Factor; D011090:Polyenes; D012702:Serotonin Antagonists; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D003907:Dexamethasone; D006632:Histamine; D016572:Cyclosporine; C025614:sephadex; C045856:ginkgolide B; D001920:Bradykinin; D020123:Sirolimus; D008784:Methysergide