Contribution of mast cells to the oedema induced by Bothrops moojeni snake venom and a pharmacological assessment of the inflammatory mediators involved.
The ability of Bothrops moojeni venom (BmV) to induce oedema in mice, the involvement of principal inflammatory mediators and mast cells (MCs) were investigated. The intraplantar injection of BmV (0.3-6 microg/paw) caused a dose- and time-dependent oedema with a peak between 30 and 60 min after venom injection (0.3-1 microg/paw), disappearing within 24h. Either MCs granule inhibition or depletion by cromoglycate or C48/80, respectively, markedly reduced BmV-induced oedema. MCs depletion by imatinib also reduced oedema. Intraperitoneal BmV injection (2.5-10 microg/site) induced MCs degranulation and release of PGD(2). Treatment with promethazine, cimetidine or thioperamide, histamine H1, H2 and H3/H4 receptor antagonists, respectively, markedly reduced the initial phase of oedema. Combined treatment with these antagonists further reduced, but not abrogated oedema. Indomethacin or eterocoxib (cyclooxygenase inhibitors) reduced oedema until 180 min, whereas zileuton (lipoxygenase inhibitor) affected this event until 60 min. Dexamethazone caused a long lasting reduction of oedema. However, L-NAME and aminoguanidine (NO synthase inhibitors) significantly increased BmV-induced oedema. In conclusion, BmV induces oedema, mediated by MCs degranulation, histamine by H1, H2, H3/H4 receptors, prostaglandins and leukotrienes, and down-regulated by NO. Partial neutralization of oedema was observed even when polyspecific bothropic antivenom was injected immediately after venom.
Galvão Nascimento
Neide
N
Laboratory of Pharmacology, Butantan Institute, São Paulo, SP, Brazil.
Sampaio
Marlos Cortez
MC
Amaral Olivo
Renata
R
Teixeira
Catarina
C
D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D017837:Bothrops; D015550:Cell Degranulation / Q000187:drug effects; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D005528:Foot / Q000473:pathology; D005612:Freeze Drying; D006632:Histamine / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism*; D007700:Kinetics; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D015230:Prostaglandin D2 / Q000378:metabolism
D000997:Antivenins; D003435:Crotalid Venoms; D018836:Inflammation Mediators; D009569:Nitric Oxide; D006632:Histamine; D015230:Prostaglandin D2