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

Oshima-Franco, Yoko; Leite, Gildo Bernardo; Silva, Gustavo H.; Cardoso, Débora Morais; Hyslop, Stephen; Giglio, José Roberto; Cruz‐Höfling, Maria Alice da; Rodrigues‐Simioni, Léa

doi:10.1016/s0041-0101(01)00107-6

Cited by 36 publications

(23 citation statements)

References 27 publications

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“…Bothropstoxin-I has a direct action on the muscle membrane (Heluany et al 1992;Melo et al 1993;RodriguesSimioni et al 1995;Oshima-Franco et al 2000& 2001, and our myographic results agree with this finding. However, pretreatment with Mn 2π protected against bothropstoxin-Iinduced neuromuscular blockade.…”

Section: Discussionsupporting

confidence: 91%

“…Bothropstoxin-I, the major myotoxin in B. jararacussu venom, inhibits muscle twitches evoked either through direct stimulation of the muscle or, indirectly, through the motor nerve in mouse, chick and frog neuromuscular preparations, with no pronounced neurotoxic effect in vivo (Rodrigues-Simioni et al 1983;Homsi-Brandeburgo et al 1988;Heluany et al 1992;Melo et al 1993;Rodrigues-Simioni et al 1995;Gutiérrez & Lomonte 1995;Oshima-Franco et al 2000& 2001. Several studies have shown that bothropstoxin-I is a lysine (Lys)-49 phospholipase A 2 that is homologous to other Bothrops myotoxic phospholipase A 2 (Cintra et al 1993), but has no detectable phospholipase A 2 activity on artificial substrates.…”

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confidence: 99%

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

Oshima-Franco¹,

Leite²,

Belo³

et al. 2004

Basic Clin Pharma Tox

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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.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

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

Oshima-Franco¹,

Leite²,

Belo³

et al. 2004

Basic Clin Pharma Tox

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“…The initial work on the neuromuscular blocking action of bothropic venoms by Rodrigues-Simioni et al (43) led to the discovery of bothropstoxin-I (21), a myotoxin that has since been widely studied (19,34,35). The presence of a presynaptic PLA 2 in B. n. pauloensis venom was expected, since several reports had already indicated that this venom had presynaptic neurotoxicity (4,5,12,44,53).…”

Section: Discussionmentioning

confidence: 99%

Purification and n-terminal sequencing of two presynaptic neurotoxic PLA2, neuwieditoxin-I and neuwieditoxin-II, from Bothrops neuwiedi pauloensis (jararaca pintada) venom

Oliveira¹,

Kassab²,

Soares³

et al. 2007

J. Venom. Anim. Toxins incl. Trop. Dis

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ABSTRACT:Two presynaptic phospholipases A 2 (PLA 2 ), neuwieditoxin-I (NeuTX-I) and neuwieditoxin-II (NeuTX-II), were isolated from the venom of Bothrops neuwiedi pauloensis (BNP). The venom was fractionated using molecular exclusion HPLC (Protein-Pak 300SW column), followed by reverse phase HPLC (μBondapak C18 column). Tricine-SDS-PAGE in the presence or absence of dithiothreitol showed that NeuTX-I and NeuTX-II had a molecular mass of approximately 14 kDa and 28kDa, respectively. At 10μg/ml, both toxins produced complete neuromuscular blockade in indirectly stimulated chick biventer cervicis isolated preparation without inhibiting the response to acetylcholine, but NeuTX-II reduced the response to KCl by 67.0±8.0% (n=3; p<0.05). NeuTX-I and NeuTX-II are probably responsible for the presynaptic neurotoxicity of BNP venom in vitro. In fact, using loose patch clamp technique for mouse phrenic nerve-diaphragm preparation, NeuTX-I produced a calcium-dependent blockade of acetylcholine release and caused appearance of giant miniature end-plate potentials (mepps), indicating a pure presynaptic action. The N-terminal sequence of NeuTX-I was DLVQFGQMILKVAGRSLPKSYGAYGCYCGWGGRGK (71% homology with bothropstoxin-II and 54% homology with caudoxin) and that of NeuTX-II was SLFEFAKMILEETKRLPFPYYGAYGCYCGWGGQGQPKDAT (92% homology with Basp-III and 62% homology with crotoxin PLA2). The fact that NeuTX-I has Q-4 (Gln-4) and both toxins have F-5 (Phe-5) and Y-28 (Tyr-28) strongly suggests that NeuTX-I and NeuTX-II are Asp49 PLA 2 .

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“…In addition to the extracts tested here, other substances with a facilitatory action on neuromuscular transmission, such as heparin (20) and manganese (a neuromuscular blocker that shows spontaneous reversion and post-wash facilitation) (18,19,27), also protect against neuromuscular blockade.…”

Section: Neutralization Assaysmentioning

confidence: 99%

Neutralization of the neuromuscular activity of bothropstoxin-i, a myotoxin from Bothrops jararacussu snake venom, by a hydroalcoholic extract of Casearia sylvestris Sw. (guaçatonga)

Oshima-Franco¹,

Alves²,

Andréo-Filho³

et al. 2005

J. Venom. Anim. Toxins incl. Trop. Dis

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Numerous plants are used as snakebite antidotes in Brazilian folk medicine, including Casearia sylvestris Swartz, popularly known as guaçatonga. In this study, we examined the action of a hydroalcoholic extract from C. sylvestris on the neuromuscular blockade caused by bothropstoxin-I (BthTX-I), a myotoxin from Bothrops jararacussu venom, in mouse isolated phrenic nerve-diaphragm (PND) preparations. Aqueous (8 and 12 mg/ml, n=4 and 5, respectively) and hydroalcoholic (12 mg/ml, n=12) extracts of the leaves of C. sylvestris caused facilitation in PND preparations followed by partial neuromuscular blockade. BthTX-I (20 µg/ml, n=4) caused 50% paralysis after 65±15 min (mean ± S.E.M). Preincubation (30 min at 37°C) of BthTX-I (20 µg/ml, n=4) with a concentration of the hydroalcoholic extract (4 mg/ml) that had no neuromuscular activity, such as the control (n=5), prevented the neuromuscular blockade caused by the toxin. This protection may be mediated by compounds such as flavonoids and phenols identified by thin-layer chromatography and colorimetric assays.

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

Cited by 36 publications

References 27 publications

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

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

Purification and n-terminal sequencing of two presynaptic neurotoxic PLA2, neuwieditoxin-I and neuwieditoxin-II, from Bothrops neuwiedi pauloensis (jararaca pintada) venom

Neutralization of the neuromuscular activity of bothropstoxin-i, a myotoxin from Bothrops jararacussu snake venom, by a hydroalcoholic extract of Casearia sylvestris Sw. (guaçatonga)

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