Pharmacological aspects of mouse hind-paw oedema induced by Lachesis muta rhombeata venom.
Pharmacological aspects of mouse hind-paw oedema induced by subplantar injections of Lachesis muta rhombeata (LMR) venom were investigated. The oedema induced by subplantar injections of 10 to 50 ng/g of LMR venom is dose dependent, with onset, peak and duration at 30, 60 and 180 min, respectively. Subplantar injection of 30 ng/g of Bothrops jararaca (BJ) venom induced oedema that has the same intensity as 30 ng/g of LMR venom but lasts for more than 4 h suggesting different time course. Systemic effects or haemorrhage were not observed with doses less than 50 ng/g. Oedema is not due to the presence of oedematogenic amines since dialysis did not change the oedema induced by 30 ng/g of LMR venom. Part of the oedema induced by LMR venom is due to a thermolabile fraction since pre-heating the venom at 100 degrees C for 15 min induced a significant reduction (56.19 +/- 6.8%) of the oedematogenic activity. The oedema induced by LMR venom is possibly induced by release of a pharmacological active substance at the site of injection. Histamine, arachidonate metabolites, nitric oxide and serotonin may play important roles in the oedematogenic effect of LMR venom since pre-treatment of mice with pyrilamine, indomethacin, dexamethasone, L-NAME and methysergide induced a significant reduction (49.86 +/- 10%; 51.06 +/- 5.9%; 77.66 +/- 3.6%; 73.30 +/- 6.1% and 93.77 +/- 2.8%, respectively) of the oedema formation. The present results demonstrate that the oedema induced by LMR and BJ venoms may be triggered and maintained by different pharmacological mechanisms. Since methysergide and L-NAME were the most active inhibitors of the oedema we can suggest that a link between serotonin release by the venom and a NO synthase activation may be an important step in the oedema formation induced by LMR venom.
Soares de Moura
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Departamento de Farmacologia IB-Centro Biomédico, Universidade do Estado do Rio de Janeiro, Brasil.
Aguiar
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Melgarejo
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AR
de Carvalho
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D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy / Q000209:etiology*; D010450:Endopeptidases / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006614:Hindlimb; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006358:Hot Temperature; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000627:therapeutic use; D013256:Steroids
D000893:Anti-Inflammatory Agents; D003435:Crotalid Venoms; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; C072644:Lachesis venom; D012702:Serotonin Antagonists; D013256:Steroids; D019001:Nitric Oxide Synthase; D010450:Endopeptidases