The Presynaptic Activity of Bothropstoxin‐I, a Myotoxin from Bothrops jararacussu Snake Venom

Abstract

Bothropstoxin-I from Bothrops jararacussu snake venom is a lysine-49 phospholipase A 2 with myotoxic and neurotoxic activities. In this study, we used mouse phrenic nerve-diaphragm preparations in the absence and presence of manganese (Mn 2π ), a presynaptic blocker, to investigate a possible presynaptic action of bothropstoxin-I. At concentrations of 0.9 mM and 1.8 mM, Mn 2π produced 50% neuromuscular blockade in less than 4 min., which was spontaneously reversible at the lower concentration. Bothropstoxin-I (1.4 mM) irreversibly inhibited neuromuscular blockade by 50% in 31∫4 min. (mean∫S.E.M., nΩ9). Pretreating preparations with 0.9 mM Mn 2π prevented the blockade by bothropstoxin-I. When added after bothropstoxin-I, Mn 2π produced its characteristic blockade and, after washing, the twitch tension returned to pre-Mn 2π levels, indicating that bothropstoxin-I caused irreversible damage before the addition of Mn 2π . Electrophysiological measurements showed that a concentration of bothropstoxin-I (0.35 mM), which did not produce neuromuscular blockade, caused the appearance of giant miniature end-plate potentials with no change in the membrane resting potential but increased the quantal content. Preparations preincubated with Mn 2π (0.9 mM, 30 min.) were protected against the depolarizing action of bothropstoxin-I (0.7 mM). These results show that, in addition to its well-known myotoxic effect, bothropstoxin-I also has a presynaptic action.

Evaluation of the Safety of Three Phenolic Compounds from <i>Dipteryx alata</i> Vogel with Antiophidian Potential

“…BthTX-I is considered the main myotoxin from the venom since it is able to reproduce in vitro the neurotoxicity and the myonecrosis of the crude venom [43], being this characteristic the main reason of the interest in the myotoxin. BthTX-I has a presynaptic nature at 0.35 µM, which is not sufficient to cause muscle fiber depolarization [46]. The Asp49 to Lys49 substitution in the catalytic center (only in the calcium-binding loop) explains the lack of enzymatic action in BthTX-I, due to the loss of ability to bind Ca 2+ [47].…”

Bothrops jararacussu venom-induced neuromuscular blockade inhibited by Casearia gossypiosperma Briquet hydroalcoholic extract

“…Crude Bjssu venom induces neurotoxicity in vitro and causes muscle necrosis in vivo, resulting in irreversible tissue loss and limb amputation in severe accidents (29,30). Muscle necrosis is usually attributed to bothropstoxin-I, which is a myotoxic Lys49 PLA 2 homologue and the main toxic component of Bjssu venom (41). The myotoxic components of snake venoms can reduce the initiation of muscle contractures, muscle response after direct stimulation or elevated potassium exposure (42).…”

Antibothropic Action of Camellia sinensis Extract Against the Neuromuscular Blockade by Bothrops jararacussu Snake Venom and Its Main Toxin, Bothropstoxin-I

“…Oshima-Franco et al (2004) have shown that BthTX-I, at a concentration that does not produce neuromuscular blockade (0.35 mM) caused the appearance of giant miniature endplate potentials, without affecting the resting membrane potential. The authors suggested that the toxin would act through Ca 2+ channels, since Mn 2+ antagonized both neurotoxic and myotoxic actions of the myotoxin and are related to Ca 2+ fluxes.…”

“…Different mechanisms have been proposed for BthTX-I myotoxic effect such as altering the bilayer membrane integrity (Lomonte et al, 2003), binding to the Ca 2+ -binding region in the pore of Ca 2+ channels (Oshima-Franco et al, 2004), activating membrane acceptors (CintraFrancischinelli et al, 2009) or causing a general membrane-destabilizing (Gallacci & Cavalcante, 2009). In order to explain the rationale of this study more details will be given about these mechanisms.…”

“…The well-successful experience between C. sinensis leaf extract and presynaptic neurotoxins, and while bothropstoxin-I (BthTX-I) isolated from Bothrops jararacussu venom exhibits an earlier presynaptic action (Oshima-Franco et al, 2004) before its well-known myotoxic effect, the same experimental procedure was carried out using C. sinensis extract, which protected 100% the neuromuscular blockade (Fig. 1).…”