ANÁLISE HISTOLÓGICA DA MIOTOXICIDADE DO VENENO DE MICRURUS SPIXII (COBRA CORAL AMAZÔNICA) EM MÚSCULO BIVENTER CERVICIS DE PINTAINHO E SUA NEUTRALIZAÇÃO POR SORO ANTIELAPÍDICO

Autores

  • Fernanda Ruis Passos Autor
  • Wanessa Regis da Costa Autor
  • Nathalia Margarida Cantuária Autor
  • Patricia Lius Melo Alves Autor
  • Jonas Eligio Garcia de Azevedo Autor
  • Stephen Hylop Autor
  • Yoko Oshima-Franco Autor

DOI:

https://doi.org/10.56238/arev8n2-068

Palavras-chave:

Biventer cervicis, Microscopia de Luz, Micrurus spixii, Soro Antielapídico, Veneno de Serpente

Resumo

Os venenos de cobras corais (Micrurus spp.) são neurotóxicos e miotóxicos. Microscopia de luz foi utilizada para avaliar a miotoxicidade do veneno de Micrurus spixii e o potencial de neutralização do dano celular pelo soro antielapídico. Foram estudados músculos provenientes de preparações de biventer cervicis de pintainho estimulados indiretamente durante 2 h, expostas a (n=3 cada) solução nutritiva de Krebs (controle negativo), veneno (10 µg/mL) e pré-incubação (30 min, 37 oC) de veneno (10 µg/mL) com 0,03 mL de soro antielapídico. Os músculos fixados em formalina 10% e mantidos em álcool 70% foram processados e emblocados em parafina para análise histológica. Cortes de 4 μm foram corados com hematoxilina-eosina e analisados em duplo-cego para verificar a presença de edema, vacúolos, condensação de miofibrilas e células ghost. A incubação com veneno reduziu drasticamente a proporção de células saudáveis, de 66,0 ± 0,1% no grupo controle para 0,92 ± 0,08% no grupo veneno (p<0,05). A pré-incubação do veneno com soro antielapídico protegeu parcialmente contra esta redução (4,8 ± 0,42% de células saudáveis; p<0,05 comparado ao veneno). O veneno aumentou a proporção de células com: edema, condensação de miofibrilas e células ghost, e dobrou a proporção de células vacuoladas. As alterações diminuíram em graus variados após pré-incubação com soro antielapídico. Os resultados mostram que o veneno causou alterações histomorfológicas em músculo biventer cervicis e que o soro antielapídico protegeu significativamente, em diferentes níveis, contra o dano celular na proporção testada de soro antielapídico:veneno.

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Referências

AIRD, S. D.; SILVA JR., N. J. Chemistry of coralsnake venoms. In: SILVA JR., N. J.; PORRAS, L. W.; AIRD, S. D.; PRUDENTE, A. L. C. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021. p. 399-484.

AIRD, S. D. et al. Coralsnake Venomics: Analyses of Venom Gland Transcriptomes and Proteomes of Six Brazilian Taxa. Toxins, v. 9, n. 6, 1 jun. 2017. https://doi.org/10.3390/toxins9060187

Barros, A. C. et al. Local effects induced by venoms from five species of genus Micrurus sp. (coral snakes). Toxicon : official journal of the International Society on Toxinology, v. 32, n. 4, p. 445–452,1994. https://doi.org/10.1016/0041-0101(94)90296-8

BAUDOU, F. G. et al. South American snake venoms with abundant neurotoxic components. Composition and toxicological properties. A literature review. Acta Tropica, v. 224, p. 106119, 1 dez. 2021. https://doi.org/10.1016/j.actatropica.2021.106119

BUCARETCHI, F. et al. Coral snake bites (Micrurus spp.) in Brazil: a review of literature reports. Clinical toxicology (Philadelphia, Pa.), v. 54, n. 3, p. 222–234, 15 mar. 2016. https://doi.org/10.3109/15563650.2015.1135337

BUCARETCHI, F.; DE CAPITANI, E. M.; HYSLOP, S. Coralsnake envenomation in Brazil. In: SILVA JR., N. J.; PORRAS, L. W.; AIRD, S. D.; PRUDENTE, A. L. C. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021. p. 703-744.

BUONONATO, M. A.; MELGAREJO, A. R.; PUORTO, G.; SILVA JR., N. J. Coralsnakes of medical interest in Brazil. In: SILVA JR., N. J.; PORRAS, L. W.; AIRD, S. D.; PRUDENTE, A. L. C. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021. p. 651-676.

CANTUÁRIA, N. M. Influência da presença de crotamina na composição do veneno de Crotalus durissus terrificus sob abordagem neurobloqueadora e histológica. 2022. Trabalho de Conclusão de Curso (Graduação) – Universidade de Sorocaba (UNISO), Sorocaba, 2022. Acesso em: 25 ago. 2025.

CANTUÁRIA, N. M. Avaliação das diferentes atividades tóxicas do veneno de Micrurus spixii, e a eficácia de neutralização do soro antielapídico, varespladib e neostigmina através de estudo in vitro, in vivo e ex vivo. 2024. Dissertação (Mestrado) – Universidade de Sorocaba (UNISO), Sorocaba, 2024. Disponível em: <https://uniso.br/mestrado-doutorado/farmacia/dissertacoes/2024/nathalia-margarida.pdf>. Acesso em: 3 jul. 2025.

CARBAJAL-SAUCEDO, A. et al. Neuromuscular activity of Micrurus laticollaris (Squamata: Elapidae) venom in vitro. Toxins, v. 6, n. 1, p. 359–370, 2014. https://doi.org/10.3390/toxins6010359

CASAIS-E-SILVA, L. L.; DA CRUZ-HOFLING, Maria Alice; TEIXEIRA, Catarina F. P. The edematogenic effect of Micrurus lemniscatus venom is dependent on venom phospholipase A2 activity and modulated by non-neurogenic factors. Toxicology Letters, v. 369, p. 12–21, 1 out. 2022. https://doi.org/10.1016/j.toxlet.2022.08.003

CASAIS-E-SILVA, L. L. et al. Micrurus lemniscatus venom stimulates leukocyte functions in vivo. Archives of toxicology, v. 99, n. 4, p. 1591–1603, 1 abr. 2025. https://doi.org/10.1007/s00204-025-03970-z

CASEWELL, N. R. et al. Causes and Consequences of Snake Venom Variation. Trends in Pharmacological Sciences, v. 41, n. 8, p. 570–581, 1 ago. 2020. https://doi.org/10.1016/j.tips.2020.05.006

CHIPPAUX, J. P.; WILLIAMS, V.; WHITE, J. Snake venom variability: methods of study, results and interpretation. Toxicon, v. 29, n. 11, p. 1279–1303, 1991. https://doi.org/10.1016/0041-0101(91)90116-9

CHOUDHURY, M.; DAS, M. Snake Venom Three-Finger Neurotoxins and Neurotoxin-Like Proteins: Insights Into Their Structural and Functional Aspects Along With Their Pharmacological Potential. Basic & clinical pharmacology & toxicology, v. 137, n. 6, 1 dez. 2025. https://doi.org/10.1111/bcpt.70144

DASHEVSKY, D. et al. Red-on-Yellow Queen: Bio-Layer Interferometry Reveals Functional Diversity Within Micrurus Venoms and Toxin Resistance in Prey Species. Journal of molecular evolution, v. 92, n. 3, p. 317–328, 1 jun. 2024. https://doi.org/10.1007/s00239-024-10176-x

de BARROS, N. Fosfolipase Asp-49 de Bothrops jararacussu encapsulada em lipossomas como terapia alternativa para leishmaniose cutânea. 2017. Tese (Doutorado) – Universidade Federal do Amazonas, Manaus, 2017. Disponível em: <https://tede.ufam.edu.br/bitstream/tede/6298/5/Tese_Neuza%20B.%20Barros.pdf>. Acesso em: 9 jun. 2025.

de ROODT, A. R. et al. Cross-reactivity of some Micrurus venoms against experimental and therapeutic anti-Micrurus antivenoms. Toxicon : official journal of the International Society on Toxinology, v. 200, p. 153–164, 1 set. 2021. https://doi.org/10.1016/j.toxicon.2021.07.011

FERRAZ, M. C. Estudo biomonitorado de compostos isolados da planta Dipteryx alata Vogel contra venenos ofídicos. 2013. Dissertação (Mestrado) – Universidade de Sorocaba, Sorocaba, 2013. Disponível em: <https://repositorio.uniso.br/handle/uniso/589>. Acesso em: 28 set. 2025.

FLORIANO, R. S.; SCHEZARO-RAMOS, R.; HYSLOP, S. Neuropharmacology of coralsnake (Micrurus) venoms. In: SILVA JR., N. J.; PORRAS, L. W.; AIRD, S. D.; PRUDENTE, A. L. C. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021. p. 535-635.

GUTIÉRREZ, J. M.; OWNBY, C. L. Skeletal muscle degeneration induced by venom phospholipases A 2: Insights into the mechanisms of local and systemic myotoxicity. Toxicon, v. 42, n. 8, p. 915–931, 2003. https://doi.org/10.1016/j.toxicon.2003.11.005

GUTIÉRREZ, J. M.; LOMONTE, B.; AIRD, S. D.; SILVA JR., N. J. Biological activities and action mechanisms of coralsnake venoms. In: SILVA JR., N. J.; PORRAS, L. W.; AIRD, S. D.; PRUDENTE, A. L. C. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021. p. 519-533.

GUTIÉRREZ, J. M. et al. Experimental myonecrosis induced by the venoms of South American Micrurus (coral snakes). Toxicon, v. 30, n. 10, p. 1299–1302, 1992. https://doi.org/10.1016/0041-0101(92)90446-c

HIGASHI, H. G. et al. Antigenic cross-reactivity among components of Brazilian Elapidae snake venoms. Brazilian journal of medical and biological research, v. 28, n. 7, p. 767-771, 1995.

HIREMATH, K. et al. Three finger toxins of elapids: structure, function, clinical applications and its inhibitors. Molecular diversity, v. 28, n. 5, p. 3409–3426, 1 out. 2024. https://doi.org/10.1007/s11030-023-10734-3

HO, P. L.; YAMAGUCHI, I. K.; TAMBOURGI, D. V. Immunology of coralsnake venoms and antivenom production. In: SILVA JR., N. J.; PORRAS, L. W.; AIRD, S. D.; PRUDENTE, A. L. C. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021. p. 637-650.

KINI, R. M.; KOH, C. Y. Variations in “Functional Site” Residues and Classification of Three-Finger Neurotoxins in Snake Venoms. Toxins, v. 17, n. 8, 1 ago. 2025. https://doi.org/10.3390/toxins17080364

KLEIZ-FERREIRA, J. M. et al. Three-Finger Toxins from Brazilian Coral Snakes: From Molecular Framework to Insights in Biological Function. Toxins, v. 13, n. 5, 1 maio 2021. https://doi.org/10.3390/toxins13050328

KOH, C. Y.; KINI, R. M. Orphan Three-Finger Toxins from Snake Venoms: Unexplored Library of Novel Biological Ligands with Potential New Structures and Functions. International journal of molecular sciences, v. 26, n. 18, 1 set. 2025. https://doi.org/10.3390/ijms26188792

LOMONTE, B. Lys49 myotoxins, secreted phospholipase A2-like proteins of viperid venoms: A comprehensive review. Toxicon, v. 224, 1 mar. 2023. https://doi.org/10.1016/j.toxicon.2023.107024

LOMONTE, B. et al. Venomous snakes of Costa Rica: biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics. Journal of proteomics, v. 105, p. 323–339, 13 jun. 2014. https://doi.org/10.1016/j.jprot.2014.02.020

LOMONTE, B. et al. Venomic analyses of coralsnakes. In: SILVA JR., N. J.; PORRAS, L. W.; AIRD, S. D.; PRUDENTE, A. L. C. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021. p. 485-518.

LÓPEZ-DÁVILA, A. J.; LOMONTE, B.; GUTIÉRREZ, J. M. Alterations of the skeletal muscle contractile apparatus in necrosis induced by myotoxic snake venom phospholipases A2: a mini-review. Journal of muscle research and cell motility, v. 45, n. 2, p. 69–77, 1 jun. 2024. https://doi.org/10.1007/s10974-023-09662-4

LUNA, K. P. O. Avaliação da resposta imune relacionada à ação dos venenos das serpentes Bothrops erythromelas e Crotalus durissus cascavella. 2010. Tese (Doutorado em Saúde Pública) – Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Recife, 2010. Disponível em: <https://www.cpqam.fiocruz.br/bibpdf/2010luna-kpo.pdf>. Acesso em: 15 jun. 2025.

MARQUES, O. A. V.; SAZIMA, I. The natural history of New World coralsnakes. In: SILVA JR., N. J.; PORRAS, L. W.; AIRD, S. D.; PRUDENTE, A. L. C. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021. p. 275-289.

Ministério da Saúde. Manual de diagnóstico e tratamento de acidentes por animais peçonhentos. 2. ed. Brasília, DF: Fundação Nacional de Saúde, 2001.

Ministério da Saúde. Secretaria de Vigilância em Saúde. Vigilância em saúde no Brasil 2003|2019: Da criação da Secretaria de Vigilância em Saúde aos dias atuais. Boletim Epidemiológico, [Brasília, DF], v. 50, n. esp., p. 1-154, 2019. Disponível em: <http://www.saude.gov.br/boletins-epidemiologicos>. Acesso em: 17 ago. 2025.

Ministério da Saúde. Tratamento de acidentes ofídicos. [S. l.]: Ministério da Saúde, 2024. Disponível em: <https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/a/animais-peconhentos/acidentes-ofidicos/tratamento>. Acesso em: 14 ago. 2025.

MONTECUCCO, C.; GUTIÉRREZ, J. M.; LOMONTE, B. Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action. Cellular and molecular life sciences : CMLS, v. 65, n. 18, p. 2897–2912, set. 2008. https://doi.org/10.1007/s00018-008-8113-3

NIRTHANAN, S. Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine. Biochemical pharmacology, v. 181, 1 nov. 2020. https://doi.org/10.1016/j.bcp.2020.114168

PINHO, F. M.; PEREIRA, I. D. [Snake bites]. Revista da Associação Médica Brasileira (1992), v. 47, n. 1, p. 24–29, 2001. https://doi.org/10.1590/S0104-42302001000100026

PRIETO DA SILVA, A. R. et al. Cross reactivity of different specific Micrurus antivenom sera with homologous and heterologous snake venoms. Toxicon, v. 39, n. 7, p. 949-953, 2001. https://doi.org/10.1016/s0041-0101(00)00233-6.

REY-SUÁREZ, P. et al. Assessment of venom variation and phylogenetic relationships of Micrurus dumerilii from three different regions of Colombia. Biochimie, v. 235, p. 93–105, 1 ago. 2025. https://doi.org/10.1016/j.biochi.2025.06.003

RODRÍGUEZ-VARGAS, A. et al. Immunological Cross-Reactivity and Preclinical Assessment of a Colombian Anticoral Antivenom against the Venoms of Three Micrurus Species. Toxins, v. 16, n. 2, 1 fev. 2024. https://doi.org/10.3390/toxins16020104

SANZ, L. et al. Comparative venomics of Brazilian coral snakes: Micrurus frontalis, Micrurus spixii spixii, and Micrurus surinamensis. Toxicon : official journal of the International Society on Toxinology, v. 166, p. 39–45, (2019a) https://doi.org/10.1016/j.toxicon.2019.05.001

SANZ, L. et al. New insights into the phylogeographic distribution of the 3FTx/PLA 2 venom dichotomy across genus Micrurus in South America. Journal of Proteomics, v. 200, p. 90–101, (2019b). https://doi.org/10.1016/j.jprot.2019.03.014

SEIFERT, S. A.; ARMITAGE, J. O.; SANCHEZ, E. E. Snake Envenomation. The New England journal of medicine, v. 386, n. 1, p. 68–78, 6 jan. 2022. https://doi.org/10.1056/nejmra2105228

SETÚBAL, S. da S. et al. Unveiling the inflammatory response in macrophages induced by Micrurus lemniscatus venom. Toxicon, v. 268, 1 dez. 2025. https://doi.org/10.1016/j.toxicon.2025.108634

SILVA-CARVALHO, R. et al. In vivo treatment with varespladib, a phospholipase A2 inhibitor, prevents the peripheral neurotoxicity and systemic disorders induced by Micrurus corallinus (coral snake) venom in rats. Toxicology letters, v. 356, p. 54–63, (2022a). https://doi.org/10.1016/j.toxlet.2021.11.003

SILVA-CARVALHO, R. et al. Partial efficacy of a Brazilian coralsnake antivenom and varespladib in neutralizing distinct toxic effects induced by sublethal Micrurus dumerilii carinicauda envenoming in rats. Toxicon : official journal of the International Society on Toxinology, v. 213, p. 99–104, (2022b). https://doi.org/10.1016/J.TOXICON.2022.04.014

SILVA JR., N. J.; AIRD, S. D. Prey specificity, comparative lethality and compositional differences of coral snake venoms. Comparative Biochemistry and Physiology - Part C Toxicology & Pharmacology, v. 128, n. 3, p. 425-456, 2001.

SILVA JR., N. J. et al. New World coralsnakes: an overview. In: SILVA JR., N. J. et al. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021a. p. 115-139.

SILVA JR., N. J. et al. Coralsnake diversity in Brazil. In: SILVA JR., N. J. et al. (Org.). Advances in Coralsnake Biology: With an Emphasis on South America. Eagle Mountain, UT: Eagle Mountain Publishing LC, 2021b. p. 141-251.

SOUSA, L. F. et al. Individual Variability in Bothrops atrox Snakes Collected from Different Habitats in the Brazilian Amazon: New Findings on Venom Composition and Functionality. Toxins, v. 13, n. 11, art. 814, 2021. https://doi.org/10.3390/toxins13110814

TANAKA, G. D. et al. Diversity of Micrurus snake species related to their venom toxic effects and the prospective of antivenom neutralization. PLoS neglected tropical diseases, v. 4, n. 3, mar. 2010. https://doi.org/10.1371/journal.pntd.0000622

TANAKA, G. D. et al. Micrurus snake species: venom immunogenicity, antiserum cross-reactivity and neutralization potential. Toxicon, v. 117, p. 59-68, 2016. https://doi.org/10.1016/j.toxicon.2016.03.020

TASOULIS, T.; ISBISTER, G. K. A current perspective on snake venom composition and constituent protein families. Archives of toxicology, v. 97, n. 1, p. 133–153, 1 jan. 2023. https://doi.org/10.1007/s00204-022-03420-0.

TERRA, A. L. C. et al. Biological characterization of the Amazon coral Micrurus spixii snake venom: isolation of a new neurotoxic phospholipase A2. Toxicon, v. 103, p. 1-11, 2015. https://doi.org/10.1016/J.TOXICON.2015.06.011

VALERIANO-ZAPANA, J. A. et al. Purificación y caracterización de una nueva PLA2 del veneno total de Micrurus spixii. ECIPeru: Revista del Encuentro Científico Internacional, v. 9, n. 2, p. 27-32, 2013.

VÉLEZ, S. T. et al. Standard quality characteristics and efficacy of a new third-generation antivenom developed in Colombia covering Micrurus spp. venoms. Toxins, v. 16, n. 4, art. 183, 2024. https://doi.org/10.3390/toxins16040183

VITAL BRAZIL, O.; FONTANA, M. D.; HELUANY, N. F. Mode of action of the coral snake Micrurus spixii venom at the neuromuscular junction. Journal of Natural Toxins, v. 4, p. 19-33, 1995.

WORLD HEALTH ORGANIZATION. Snakebite envenoming: a strategy for prevention and control. Geneva: WHO, 2019. Disponível em: https://www.who.int/publications/i/item/9789241515641. Acesso em: 26 jul. 2025.

YU, C.; YU, H.; LI, P. Highlights of animal venom research on the geographical variations of toxin components, toxicities and envenomation therapy. International Journal of Biological Macromolecules, v. 165, n. B, p. 2994-3006, 2020. https://doi.org/10.1016/j.ijbiomac.2020.10.190

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2026-02-12

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PASSOS, Fernanda Ruis; DA COSTA, Wanessa Regis; CANTUÁRIA, Nathalia Margarida; ALVES, Patricia Lius Melo; DE AZEVEDO, Jonas Eligio Garcia; HYLOP, Stephen; OSHIMA-FRANCO, Yoko. ANÁLISE HISTOLÓGICA DA MIOTOXICIDADE DO VENENO DE MICRURUS SPIXII (COBRA CORAL AMAZÔNICA) EM MÚSCULO BIVENTER CERVICIS DE PINTAINHO E SUA NEUTRALIZAÇÃO POR SORO ANTIELAPÍDICO . ARACÊ , [S. l.], v. 8, n. 2, p. e12172, 2026. DOI: 10.56238/arev8n2-068. Disponível em: https://periodicos.newsciencepubl.com/arace/article/view/12172. Acesso em: 16 fev. 2026.