Poster 092 - Effects of manganese (Mn2+) against the myotoxic and neurotoxic actions of BthTX-I

Poster 92. Congresso da Sociedade Brasileira de Toxinologia, 8., Symposium of the Pan American Section of the International Society on Toxinology, 8., 2004, Angra dos Reis, Brasil. Abstracts... J. Venom. Anim. Toxins incl.Trop. Dis., 2004, 10, 3, p.451.

Effects OfManganese (Mn²⁺) Against The MyotoxicAnd NeurotoxicActions Of BthTX-I From Bothrops jararacussuVenom

¹Randazzo-Moura, P.; ¹Leite, G.B.; ¹Silva, G.H.; ²Paffaro, V.A.Jr.; ³Cintra, A.C.O.; ²Cruz-Höfling, M.A.; ¹Oshima-Franco, Y. and ¹Rodrigues-Simioni, L.

Deptos. de ¹Farmacologia, FCM e ²Histologia e Embriologia, IB, UNICAMP/SP, ³Depto de Bioquímica, FMRP, USP/SP.

Bothropstoxin-I (BthTX-I), a myotoxin from Bothrops jararacussu venom, induces irreversible neuromuscular blockade. We evaluated the ability of Mn²⁺ to prevent the myotoxicity and neurotoxicity of BthTX-I. The release of creatine kinase (CK) and light microscopy were used to assess myotoxicity. Neurotoxicity was evaluated by conventional myography. The time to 50% paralysis in mouse phrenic nerve-diaphragm (PND) and extensor digitorum longus (EDL) preparations was, respectively, 32.8 ± 3.3 min (n=6) and 32.9 ± 3.2 min (n=11) for 1.4 mM BthTX-I. The CK release from EDL preparations was 1261 ± 113 U/L with 1.4 mM BthTX-I (n=20) and 94.5 ± 17.5 U/L (n=17) for Mn²⁺ 0.9 mM followed by 1.4 mM BthTX-I (p<0.05). Mn²⁺ significantly prevented the blockade and the CK release induced by BthTX-I in both preparations. However, the morphological changes caused by BthTX-I in these muscles was about 40% prevented by Mn²⁺. Morphologically the muscle fibers were unchanged, in both controls. In addition, different levels of damage were observed in both preparations, respectively after: BthTX-I (1.4 mM), 82 ± 3.1% and 68.5 ± 2.9% (p<0.05); Mn²⁺ 0.9 mM followed by 1.4 mM BthTX-I, 49.2 ± 4.5% and 41.3 ± 2.9% (n=6). Morphometric measurements of cross-sections of muscle fibers treated with BthTX-I (1.4 mM) were of 3.885 ± 140.9 mm² (PND) and 1.574 ± 58.0 mm² (EDL) (p<0.05). At the same experimental condition the results of Mn²⁺ (0.9 mM) followed by BthTX-I (1.4 mM) were 3.107 ± 109.4 mm² (PND) and 1.346 ± 47.72 mm² (EDL) (p<0.05). These results show that whereas Mn²⁺abolished the neurotoxicity of BthTX-I, it only partially prevented the myotoxicity, indicating that these activities can be dissociated.

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