Pharmacological Characterization of Sephadex-lnduced 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 µg/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.

Pharmacological and histopathological characterization of Bothrops lanceolatus (Fer de lance) venom-induced edema

“…These hemorrhagins are zincdependent enzymes which hydrolyze proteins in the basal lamina of capillary vessels to produce hemorrhage [9][10][11]43]. Since hemorrhage appears soon after venom injection and interferes with the development of inflammatory edema, B. lanceolatus venom was treated with EDTA to reduce the local tissue damage caused by the venom.…”

“…The blockade of serotonin receptors by methysergide decreases the edematogenic effects of many phlogistic agents, such as Sephadex [43], polycations [45] and snake venoms [30]. Serotonin has an important role in the edema induced by B. lanceolatus venom since methysergide significantly reduced the increase in paw volume caused by venom which had or had not been treated with EDTA.…”

Tissue-selective inflammation in the oral cavity of the rat

“…Doses of all compounds were based on previous publications of the group (Francischi et al 1996;Pacheco et al 1997;PaivaLima et al 2014). …”

Alterações locais induzidas pela secreção tóxicas de Philodryas patagoniensis (Girard, 1857) (Serpentes: Colubridae)

“…Estas hemorraginas são enzimas zinco-dependentes que hidrolisam proteínas da lâmina basal de vasos capilares produzindo hemorragia (FRANCISCHI et al, 1993;BJARNASSON & FOX, 1994;KAMIGUTI et al, 1996;. Uma vez que a hemorragia é vista macroscopicamente logo após a injeção de veneno e possivelmente interfere com o desenvolvimento do edema inflamatório, o veneno de P. patagoniensis foi incubado com 5mM de EDTA e este foi capaz de reduzir em aproximadamente 45% o edema induzido pelo veneno.…”

“…Uma vez que a hemorragia é vista macroscopicamente logo após a injeção de veneno e possivelmente interfere com o desenvolvimento do edema inflamatório, o veneno de P. patagoniensis foi incubado com 5mM de EDTA e este foi capaz de reduzir em aproximadamente 45% o edema induzido pelo veneno. Esta redução muito provavelmente resultou da ação quelante do EDTA sobre cátions divalentes de metaloproteinases, uma vez que estas enzimas são dependentes de zinco ou cálcio (FRANCISCHI et al, 1993).…”