Effects of manganese (Mn2+) on neurotoxic and myotoxic activities induced by Crotalus durissus terrificus and Bothrops jararacussu venoms in chick biventer cervicis preparations

In the present study, manganese (Mn2+), a neuromuscular blocker with pre and postsynaptic actions, was used to verify the neurotoxicity and myotoxicity induced by Crotalus durissus terrificus (Cdt) and Bothrops jararacussu (Bjssu) venoms in biventer cervicis preparations (BCp). Preparations pretreated with 0.66 and 1.6mM Mn2+ did not affect Cdt venom-induced blockage nor change KCl-induced contracture but partially reduced ACh-induced contracture. However, both Mn2+ concentrations partially hindered Bjssu venom-induced blockage after washing the preparations with Krebs solution, and only 1.6mM Mn2+ preparations significantly recovered ACh-induced contracture. The effect of Cdt venom myotoxicity on contractile responses was different from that of Bjssu venom myotoxicity. Pretreatment with 1.6mM Mn2+ partially reduced muscle damage percentage and creatine kinase (CK) activity (U/l) induced by both venoms. In conclusion, Mn2+ interfered in ACh-induced contracture of the nicotinic receptor; did not prevent Cdt venom neurotoxicity but partially reduced its myotoxicity in vitro due to the stabilizing action of this venom on the sarcolemmal membrane; and partially attenuated myotoxicity and neuromuscular blockage induced by Bjssu venom. The Mn2+ dual action (pre and postsynaptic) is useful to study snake venoms since most of them present one or both of these actions; besides, Mn2+ allowed recovering coherent interpretation of experimental versus clinical results.

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

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 mg/ml, n=4) caused 50% paralysis after 65±15 min (mean ± S.E.M). Preincubation (30 min at 37°C) of BthTX-I (20 mg/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

Rabbit antivenom efficacy against myotoxic and neurotoxic activities of Bothrops jararacussu venom and Bothropstoxin-I

Bothrops jararacussu venom and its major toxin bothropstoxin-I (BthTX-I) possess myotoxic and neurotoxic properties. The efficacy of a rabbit antivenom raised against B. jararacussu venom in the neutralization of physiological, biochemical, and morphological changes induced by the venom and its major toxin BthTX-I was studied in mouse isolated phrenic nerve-diaphragm (PND) and extensor digitorum longus (EDL) preparations. The times required for 50 per cent neuromuscular blockade in PND and EDL preparations for venom were 70ñ11.5 (S.E.M., n=5) min and 58ñ8 (n=16) (50 µ/mL), and for BthTX-I 31ñ6 (n=3) min and 30ñ3 (n=5) min (20 µg/mL), respectively. After 120 min incubation, creatine kinase (CK) concentrations in solution containing the EDL preparations were 3464ñ346 U/L after exposure to venom (50 µg/mL, n=5) and 3422ñ135 U/L to BthTX-I (20µg/mL, n=4), respectively. Rabbit antivenom dose-dependently neutralized venom and toxin-induced neuromuscular blockade in both preparations and effectively prevented venom and toxin-induced CK release from EDL. Histological analysis showed that rabbit antivenom neutralized morphological damage caused by B.jararacussu venom and BthTX-I in EDL preparations. these results indicate that rabbit antivenom effectively neutralized the biological activities of B.jararacussu venom and BthTX-I.