Neutralization of the pharmacological effects of bothropstoxin-I from Bothrops jararacussu (jararacucu) venom by crotoxin antiserum and heparin

Bothropstoxin-I (BthTX-1), the principal myotoxin of Bothrops jararacussu v enom, is devoid of phospholipase A(2) (PLA(2)) activity but capable of bloc king neuromuscular transmission in mouse nerve-muscle preparations. In this study, the ability of crotoxin antiserum and heparin in preventing the neu rotoxic and myotoxic effects of BthTX-I was investigated. Phrenic nerve-dia phragm preparations (PND) stimulated indirectly with supramaximal stimuli ( 0.2 ms, 0.1 Hz) were incubated with BthTX-I (20 mug/ml) alone or with BthTX -I preincubated with antiserum or heparin for 30 min at 37 degreesC prior t o testing. Control preparations were incubated with Tyrode solution, antise rum or heparin alone. BthTX-I (20 mug/ml) produced 50% neuromuscular blocka de in the PND preparations in 31 +/- 4 min, with complete blockade occurrin g in 120 min. The antiserum and heparin significantly prevented the neuromu scular blockade caused by BthTX-I (84 +/- 4% and 100% protection, respectiv ely). Light microscopy examination of the muscles at the end of the 120 min incubation showed that BthTX-I damaged 48 +/- 6% of the fibers. Preincubat ing the toxin with antivenom significantly reduced the extent of this damag e (only 15 +/- 4% of fibers affected, corresponding to 69% protection, P < 0.01) whereas heparin offered no protection (34 +/- 7% of fibers affected, not significantly different from that seen with toxin alone). These results show that the antivenom was more effective in neutralizing the myotoxic ef fects of BthTX-I than was heparin. (C) 2001 Elsevier Science Ltd. All right s reserved.