Neutralization of the oedematogenic activity of Bothrops Jararaca venom on the mouse paw by an antibothropic fraction isolated from Opossum (Didelphis Marsupialis) serum

Abstract

The pharmacological modulation of mice paw oedema produced by Bothrops jararaca venom (BJV) has been studied. Intraplantar injection of BJV (1-30 micrograms/paw) produced a dose- and time-related oedema, which was maximal 30 min after injection, reduced gradually thereafter and disappeared over 48 h. BJV heated at 100 degrees C for 5 or 15 min blocked local hemorrhage and caused partial inhibition of its oedematogenic activity. The BJV oedema was not inhibited by the anti-histamine meclizine, the inhibitor of histamine and serotonin, cyproheptadine, PAF-acether antagonist WEB 2170 or by the anti-leukotrienes C4/D4, LY 171883. Dexamethasone, aspirin, indomethacin, and the dual cyclooxygenase and lipoxygenase inhibitor BW 755C inhibited BJV-induced oedema indicating that arachidonic acid metabolism products via the cyclooxygenase pathway participate in its genesis and/or maintenance. The antibothropic fraction (ABF) (25-200 micrograms/paw) isolated from Didelphis marsupialis serum neutralized the oedema induced by the venom with and without heating, the hemorrhage induced by BJV and partially blocked the oedema induced by bradykinin and by cellulose sulphate. The oedema produced by histamine, serotonin, PAF-acether or leukotriene C4 was not inhibited.

Effect of dexamethasone associated with serum therapy on treatment of Bothrops jararaca venom-induced paw edema in mice

“…In human beings, edema at the site of the bite has a rapid onset and can reach great proportions of the affected limb [1,3]. Experimental studies have shown that edema induced by Bothrops jararaca venom is of infl ammatory origin and primarily mediated by arachidonic acid metabolites [7][8][9]. The rapid manifestation of edema and its modulation by endogenous mediators decrease the effi cacy of serum therapy, inasmuch as antivenom neutralizes venom toxins, but not the infl ammatory mediators released by them.…”

“…Some studies have shown that pretreatment of animals with anti-infl ammatory drugs can result in a signifi cant reduction of Bothrops venom-induced paw edema [7][8][9][14][15][16]. Despite such evidences, the use of anti-infl ammatory drugs in combination with serum therapy is not a usual practice to treat patients bitten by Bothrops snakes in Brazil [17].…”

Structural and Functional Analyses of DM43, a Snake Venom Metalloproteinase Inhibitor from Didelphis marsupialisSerum

“…It showed antihemorrhagic, antilethal, antimyonecrotic, and antiedematogenic properties (27)(28)(29)(30) and was active neither on snake venom serine proteinases nor on proteinases from other sources (31). Recently, two antihemorrhagic proteins, DM40 and DM43, were isolated from the antibothropic factor and characterized as SVMP inhibitors from the immunoglobulin supergene family.…”

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

“…Prostaglandina E 2 (PGE 2 ) é o principal PERALES et al, 1992) e pela miotoxina I do veneno de B. asper (GUTIÉRREZ et al, 1986b). Entretanto, outros venenos como o da lagarta Lonomia obliqua (BASTOS et al, 2004), do escorpião Tityus serrulatus (NASCIMENTO Jr. et al, 2005), Bothrops asper em ratos (CHACUR et al, 2001), e Bothrops lanceolatus em ratos ) não contam com a participação desta via na formação do edema.…”

“…(BASU et al, 1990) e Tityus serrulatus (NASCIMENTO Jr. et al, 2005). No entanto, a serotonina parece não estar envolvida na formação do edema induzido pelo veneno, semelhante aos venenos de Bothrops asper em camundongos (CHAVES et al, 1995) Bothrops insularis (BARBOSA et al, 2003) e Bothrops jararaca em ratos (TREBIEN & CALIXTO, 1989) e camundongos (PERALES et al, 1992). et al, 1992), Bothrops asper em ratos (CHACUR et al, 2001) e camundongos (CHAVES et al, 1995) e Tityus serrulatus (NASCIMENTO Jr. et al, 2005).…”