PHARMACOLOGICAL ASPECTS OF MOUSE HIND-PAW EDEMA 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 ve nom is dose dependent, with onset, peak and duration at 30, 60 and 180 min, respectively. Subplantar injection of 30 ng/g of Bothrops jarara ca (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 cours e. Systemic effects or haemorrhage were not observed with doses less t han 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 ve nom. 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 induc ed a significant reduction (56.19 +/- 6.8%) of the oedematogenic activ ity. The oedema induced by LMR venom is possibly induced by release of a pharmacological active substance at the site of injection. Histamin e, arachidonate metabolites, nitric oxide and serotonin may play impor tant roles in the oedematogenic effect of LMR venom since pre-treatmen t of mice with pyrilamine, indomethacin, dexamethasone, L-NAME and met hysergide 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) o f the oedema formation. The present results demonstrate that the oedem a induced by LMR and BJ venoms may be triggered and maintained by diff erent pharmacological mechanisms. Since methysergide and L-NAME were t he most active inhibitors of the oedema we can suggest that a link bet ween serotonin release by the venom and a NO synthase activation may b e an important step in the oedema formation induced by LMR venom. (C) 1998 Elsevier Science Ltd. All rights reserved.