Chemical and Pharmacological Screening of <i>Rhinella icterica</i> (Spix 1824) Toad Parotoid Secretion in Avian Preparations
The biological activity of <i>Rhinella icterica</i> parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5<i&g...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/12/6/396 |
| _version_ | 1797565291135238144 |
|---|---|
| author | Raquel Soares Oliveira Bruna Trindade Borges Allan Pinto Leal Manuela Merlin Lailowski Karla de Castro Figueiredo Bordon Velci Queiróz de Souza Lúcia Vinadé Tiago Gomes dos Santos Stephen Hyslop Sidnei Moura Eliane Candiani Arantes Alexandre Pinto Corrado Cháriston A. Dal Belo |
| author_facet | Raquel Soares Oliveira Bruna Trindade Borges Allan Pinto Leal Manuela Merlin Lailowski Karla de Castro Figueiredo Bordon Velci Queiróz de Souza Lúcia Vinadé Tiago Gomes dos Santos Stephen Hyslop Sidnei Moura Eliane Candiani Arantes Alexandre Pinto Corrado Cháriston A. Dal Belo |
| author_sort | Raquel Soares Oliveira |
| collection | DOAJ |
| description | The biological activity of <i>Rhinella icterica</i> parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5<i>β</i>,12<i>β</i>)-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide, marinobufagin, bufogenin B, 11α,19-dihydroxy-telocinobufagin, bufotalin, monohydroxylbufotalin, 19-oxo-cinobufagin, 3α,12<i>β</i>,25,26-tetrahydroxy-7-oxo-5<i>β</i>-cholestane-26-<i>O</i>-sulfate, and cinobufagin-3-hemisuberate that were identified as alkaloid and steroid compounds, in addition to marinoic acid and <i>N</i>-methyl-5-hydroxy-tryptamine. In chick brain slices, all fractions caused a slight decrease in cell viability, as also seen with the highest concentration of RIPS tested. In chick <i>biventer cervicis</i> neuromuscular preparations, RIPS and all four fractions significantly inhibited junctional acetylcholinesterase (AChE) activity. In this preparation, only fraction RI23 completely mimicked the pharmacological profile of RIPS, which included a transient facilitation in the amplitude of muscle twitches followed by progressive and complete neuromuscular blockade. Mass spectrometric analysis showed that RI23 consisted predominantly of bufogenins, a class of steroidal compounds known for their cardiotonic activity mediated by a digoxin- or ouabain-like action and the blockade of voltage-dependent L-type calcium channels. These findings indicate that the pharmacological activities of RI23 (and RIPS) are probably mediated by: (1) inhibition of AChE activity that increases the junctional content of Ach; (2) inhibition of neuronal Na<sup>+</sup>/K<sup>+</sup>-ATPase, leading to facilitation followed by neuromuscular blockade; and (3) blockade of voltage-dependent Ca<sup>2+</sup> channels, leading to stabilization of the motor endplate membrane. |
| first_indexed | 2024-03-10T19:10:02Z |
| format | Article |
| id | doaj.art-475c0045fcd940508554b10dfafb681d |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T19:10:02Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-475c0045fcd940508554b10dfafb681d2023-11-20T03:52:14ZengMDPI AGToxins2072-66512020-06-0112639610.3390/toxins12060396Chemical and Pharmacological Screening of <i>Rhinella icterica</i> (Spix 1824) Toad Parotoid Secretion in Avian PreparationsRaquel Soares Oliveira0Bruna Trindade Borges1Allan Pinto Leal2Manuela Merlin Lailowski3Karla de Castro Figueiredo Bordon4Velci Queiróz de Souza5Lúcia Vinadé6Tiago Gomes dos Santos7Stephen Hyslop8Sidnei Moura9Eliane Candiani Arantes10Alexandre Pinto Corrado11Cháriston A. Dal Belo12Laboratório de Neurobiologia e Toxinologia, Programa de Pós-Graduação em Ciências Biológicas (PPGCB), Universidade Federal do Pampa (UNIPAMPA), Avenida Antônio Trilha 1847, São Gabriel RS 97300-000, BrazilLaboratório de Neurobiologia e Toxinologia, Programa de Pós-Graduação em Ciências Biológicas (PPGCB), Universidade Federal do Pampa (UNIPAMPA), Avenida Antônio Trilha 1847, São Gabriel RS 97300-000, BrazilLaboratório de Neurobiologia e Toxinologia, Programa de Pós-Graduação em Ciências Biológicas (PPGCB), Universidade Federal do Pampa (UNIPAMPA), Avenida Antônio Trilha 1847, São Gabriel RS 97300-000, BrazilLaboratório de Biotecnologia de Produtos Naturais e Sintéticos, Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), Rua Francisco Getúlio Vargas 1130, Caxias do Sul RS 95070-560, BrazilDepartamento de Ciências BioMoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto SP 14.040-903, BrazilLaboratório de Neurobiologia e Toxinologia, Programa de Pós-Graduação em Ciências Biológicas (PPGCB), Universidade Federal do Pampa (UNIPAMPA), Avenida Antônio Trilha 1847, São Gabriel RS 97300-000, BrazilLaboratório de Neurobiologia e Toxinologia, Programa de Pós-Graduação em Ciências Biológicas (PPGCB), Universidade Federal do Pampa (UNIPAMPA), Avenida Antônio Trilha 1847, São Gabriel RS 97300-000, BrazilLaboratório de Estudos em Biodiversidade Pampiana, Universidade Federal do Pampa (UNIPAMPA), Avenida Antônio Trilha 1847, São Gabriel RS 97300-000, BrazilDepartamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas SP 13083-887, BrazilLaboratório de Biotecnologia de Produtos Naturais e Sintéticos, Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), Rua Francisco Getúlio Vargas 1130, Caxias do Sul RS 95070-560, BrazilDepartamento de Ciências BioMoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Avenida do Café, s/n, Ribeirão Preto SP 14.040-903, BrazilDepartamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Avenida Bandeirantes 3900, Ribeirão Preto SP 14040-030, BrazilLaboratório de Neurobiologia e Toxinologia, Programa de Pós-Graduação em Ciências Biológicas (PPGCB), Universidade Federal do Pampa (UNIPAMPA), Avenida Antônio Trilha 1847, São Gabriel RS 97300-000, BrazilThe biological activity of <i>Rhinella icterica</i> parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5<i>β</i>,12<i>β</i>)-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide, marinobufagin, bufogenin B, 11α,19-dihydroxy-telocinobufagin, bufotalin, monohydroxylbufotalin, 19-oxo-cinobufagin, 3α,12<i>β</i>,25,26-tetrahydroxy-7-oxo-5<i>β</i>-cholestane-26-<i>O</i>-sulfate, and cinobufagin-3-hemisuberate that were identified as alkaloid and steroid compounds, in addition to marinoic acid and <i>N</i>-methyl-5-hydroxy-tryptamine. In chick brain slices, all fractions caused a slight decrease in cell viability, as also seen with the highest concentration of RIPS tested. In chick <i>biventer cervicis</i> neuromuscular preparations, RIPS and all four fractions significantly inhibited junctional acetylcholinesterase (AChE) activity. In this preparation, only fraction RI23 completely mimicked the pharmacological profile of RIPS, which included a transient facilitation in the amplitude of muscle twitches followed by progressive and complete neuromuscular blockade. Mass spectrometric analysis showed that RI23 consisted predominantly of bufogenins, a class of steroidal compounds known for their cardiotonic activity mediated by a digoxin- or ouabain-like action and the blockade of voltage-dependent L-type calcium channels. These findings indicate that the pharmacological activities of RI23 (and RIPS) are probably mediated by: (1) inhibition of AChE activity that increases the junctional content of Ach; (2) inhibition of neuronal Na<sup>+</sup>/K<sup>+</sup>-ATPase, leading to facilitation followed by neuromuscular blockade; and (3) blockade of voltage-dependent Ca<sup>2+</sup> channels, leading to stabilization of the motor endplate membrane.https://www.mdpi.com/2072-6651/12/6/396Anti-AChE activityavianchick neurobiological preparationscytotoxicityneuromuscular blockadetoad poison |
| spellingShingle | Raquel Soares Oliveira Bruna Trindade Borges Allan Pinto Leal Manuela Merlin Lailowski Karla de Castro Figueiredo Bordon Velci Queiróz de Souza Lúcia Vinadé Tiago Gomes dos Santos Stephen Hyslop Sidnei Moura Eliane Candiani Arantes Alexandre Pinto Corrado Cháriston A. Dal Belo Chemical and Pharmacological Screening of <i>Rhinella icterica</i> (Spix 1824) Toad Parotoid Secretion in Avian Preparations Toxins Anti-AChE activity avian chick neurobiological preparations cytotoxicity neuromuscular blockade toad poison |
| title | Chemical and Pharmacological Screening of <i>Rhinella icterica</i> (Spix 1824) Toad Parotoid Secretion in Avian Preparations |
| title_full | Chemical and Pharmacological Screening of <i>Rhinella icterica</i> (Spix 1824) Toad Parotoid Secretion in Avian Preparations |
| title_fullStr | Chemical and Pharmacological Screening of <i>Rhinella icterica</i> (Spix 1824) Toad Parotoid Secretion in Avian Preparations |
| title_full_unstemmed | Chemical and Pharmacological Screening of <i>Rhinella icterica</i> (Spix 1824) Toad Parotoid Secretion in Avian Preparations |
| title_short | Chemical and Pharmacological Screening of <i>Rhinella icterica</i> (Spix 1824) Toad Parotoid Secretion in Avian Preparations |
| title_sort | chemical and pharmacological screening of i rhinella icterica i spix 1824 toad parotoid secretion in avian preparations |
| topic | Anti-AChE activity avian chick neurobiological preparations cytotoxicity neuromuscular blockade toad poison |
| url | https://www.mdpi.com/2072-6651/12/6/396 |
| work_keys_str_mv | AT raquelsoaresoliveira chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT brunatrindadeborges chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT allanpintoleal chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT manuelamerlinlailowski chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT karladecastrofigueiredobordon chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT velciqueirozdesouza chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT luciavinade chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT tiagogomesdossantos chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT stephenhyslop chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT sidneimoura chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT elianecandianiarantes chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT alexandrepintocorrado chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations AT charistonadalbelo chemicalandpharmacologicalscreeningofirhinellaictericaispix1824toadparotoidsecretioninavianpreparations |