An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/molecules19055790 http://hdl.handle.net/11449/112066 |
Resumo: | Snakebite is a neglected disease and serious health problem in Brazil, with most bites being caused by snakes of the genus Bothrops. Although serum therapy is the primary treatment for systemic envenomation, it is generally ineffective in neutralizing the local effects of these venoms. In this work, we examined the ability of 7,8,3'-trihydroxy-4'-methoxyisoflavone (TM), an isoflavone from Dipteryx alata, to neutralize the neurotoxicity (in mouse phrenic nerve-diaphragm preparations) and myotoxicity (assessed by light microscopy) of Bothrops jararacussu snake venom in vitro. The toxicity of TM was assessed using the Salmonella microsome assay (Ames test). Incubation with TM alone (200 mu g/mL) did not alter the muscle twitch tension whereas incubation with venom (40 mu g/mL) caused irreversible paralysis. Preincubation of TM (200 mu g/mL) with venom attenuated the venom-induced neuromuscular blockade by 84% +/- 5% (mean +/- SEM; n = 4). The neuromuscular blockade caused by bothropstoxin-I (BthTX-I), the major myotoxic PLA(2) of this venom, was also attenuated by TM. Histological analysis of diaphragm muscle incubated with TM showed that most fibers were preserved (only 9.2% +/- 1.7% were damaged; n = 4) compared to venom alone (50.3% +/- 5.4% of fibers damaged; n = 3), and preincubation of TM with venom significantly attenuated the venom-induced damage (only 17% +/- 3.4% of fibers damaged; n = 3; p < 0.05 compared to venom alone). TM showed no mutagenicity in the Ames test using Salmonella strains TA98 and TA97a with (+S9) and without (-S9) metabolic activation. These findings indicate that TM is a potentially useful compound for antagonizing the neuromuscular effects (neurotoxicity and myotoxicity) of B. jararacussu venom. |
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An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosisames testbothropstoxin-I7,8,3'-trihydroxy-4'-methoxyisoflavoneneuromuscular junctionSalmonella mutagenicitysnake venomsSnakebite is a neglected disease and serious health problem in Brazil, with most bites being caused by snakes of the genus Bothrops. Although serum therapy is the primary treatment for systemic envenomation, it is generally ineffective in neutralizing the local effects of these venoms. In this work, we examined the ability of 7,8,3'-trihydroxy-4'-methoxyisoflavone (TM), an isoflavone from Dipteryx alata, to neutralize the neurotoxicity (in mouse phrenic nerve-diaphragm preparations) and myotoxicity (assessed by light microscopy) of Bothrops jararacussu snake venom in vitro. The toxicity of TM was assessed using the Salmonella microsome assay (Ames test). Incubation with TM alone (200 mu g/mL) did not alter the muscle twitch tension whereas incubation with venom (40 mu g/mL) caused irreversible paralysis. Preincubation of TM (200 mu g/mL) with venom attenuated the venom-induced neuromuscular blockade by 84% +/- 5% (mean +/- SEM; n = 4). The neuromuscular blockade caused by bothropstoxin-I (BthTX-I), the major myotoxic PLA(2) of this venom, was also attenuated by TM. Histological analysis of diaphragm muscle incubated with TM showed that most fibers were preserved (only 9.2% +/- 1.7% were damaged; n = 4) compared to venom alone (50.3% +/- 5.4% of fibers damaged; n = 3), and preincubation of TM with venom significantly attenuated the venom-induced damage (only 17% +/- 3.4% of fibers damaged; n = 3; p < 0.05 compared to venom alone). TM showed no mutagenicity in the Ames test using Salmonella strains TA98 and TA97a with (+S9) and without (-S9) metabolic activation. These findings indicate that TM is a potentially useful compound for antagonizing the neuromuscular effects (neurotoxicity and myotoxicity) of B. jararacussu venom.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)PROBIC/UnisoUniv Sorocaba UNISO, Postgrad Program Pharmaceut Sci, BR-18023000 Sorocaba, SP, BrazilUniv Sorocaba UNISO, Postgrad Program Technol & Environm Proc, BR-18023000 Sorocaba, SP, BrazilSerpentarium Vale do Paraiba Univ CEN UNIVAP, BR-12244000 Sao Jose Dos Campos, SP, BrazilUniv Sao Paulo, Fac Pharmaceut Sci, Dept Clin Toxicol & Bromatol Anal, BR-14040903 Ribeirao Preto, SP, BrazilFed Univ Pampa UNIPAMPA, LANETOX, BR-97300000 Sao Gabriel, RS, BrazilUniv Metodista Piracicaba, BR-13423170 Piracicaba, SP, BrazilUFT, Postgrad Course Environm Sci, BR-77001090 Palmas, TO, BrazilSao Paulo State Univ UNESP, Fac Pharmaceut Sci, BR-14801902 Araraquara, SP, BrazilState Univ Campinas UNICAMP, Dept Pharmacol, Fac Med Sci, BR-13083887 Campinas, SP, BrazilUniv Salamanca, Dept Pharmaceut Chem, CIETUS, IBSAL, Salamanca 37007, SpainSao Paulo State Univ UNESP, Fac Pharmaceut Sci, BR-14801902 Araraquara, SP, BrazilFAPESP: 04/09705-8FAPESP: 07/53883-6FAPESP: 08/50669-6FAPESP: 08/52643-4FAPESP: 08/11005-5USAL:18KAC9/463AC01Mdpi AgUniv Sorocaba UNISOSerpentarium Vale do Paraiba Univ CEN UNIVAPUniversidade de São Paulo (USP)Universidade Federal do Pampa (UNIPAMPA)Univ Metodista PiracicabaUFTUniversidade Estadual Paulista (Unesp)Universidade Estadual de Campinas (UNICAMP)Univ SalamancaFerraz, Miriele C.Yoshida, Edson H.Tavares, Renata V. S.Cogo, Jose C.Cintra, Adelia C. O.Dal Belo, Chariston A.Franco, Luiz M.Santos, Marcio G. dosResende, Flavia A. [UNESP]Varanda, Eliana Aparecida [UNESP]Hyslop, StephenPuebla, PilarFeliciano, Arturo SanOshima-Franco, Yoko2014-12-03T13:09:12Z2014-12-03T13:09:12Z2014-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5790-5805application/pdfhttp://dx.doi.org/10.3390/molecules19055790Molecules. Basel: Mdpi Ag, v. 19, n. 5, p. 5790-5805, 2014.1420-3049http://hdl.handle.net/11449/11206610.3390/molecules19055790WOS:000337113000022WOS000337113000022.pdf7501930236496670Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMolecules3.0980,855info:eu-repo/semantics/openAccess2024-06-24T13:06:44Zoai:repositorio.unesp.br:11449/112066Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-06-24T13:06:44Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis |
title |
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis |
spellingShingle |
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis Ferraz, Miriele C. ames test bothropstoxin-I 7,8,3'-trihydroxy-4'-methoxyisoflavone neuromuscular junction Salmonella mutagenicity snake venoms |
title_short |
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis |
title_full |
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis |
title_fullStr |
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis |
title_full_unstemmed |
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis |
title_sort |
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis |
author |
Ferraz, Miriele C. |
author_facet |
Ferraz, Miriele C. Yoshida, Edson H. Tavares, Renata V. S. Cogo, Jose C. Cintra, Adelia C. O. Dal Belo, Chariston A. Franco, Luiz M. Santos, Marcio G. dos Resende, Flavia A. [UNESP] Varanda, Eliana Aparecida [UNESP] Hyslop, Stephen Puebla, Pilar Feliciano, Arturo San Oshima-Franco, Yoko |
author_role |
author |
author2 |
Yoshida, Edson H. Tavares, Renata V. S. Cogo, Jose C. Cintra, Adelia C. O. Dal Belo, Chariston A. Franco, Luiz M. Santos, Marcio G. dos Resende, Flavia A. [UNESP] Varanda, Eliana Aparecida [UNESP] Hyslop, Stephen Puebla, Pilar Feliciano, Arturo San Oshima-Franco, Yoko |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Univ Sorocaba UNISO Serpentarium Vale do Paraiba Univ CEN UNIVAP Universidade de São Paulo (USP) Universidade Federal do Pampa (UNIPAMPA) Univ Metodista Piracicaba UFT Universidade Estadual Paulista (Unesp) Universidade Estadual de Campinas (UNICAMP) Univ Salamanca |
dc.contributor.author.fl_str_mv |
Ferraz, Miriele C. Yoshida, Edson H. Tavares, Renata V. S. Cogo, Jose C. Cintra, Adelia C. O. Dal Belo, Chariston A. Franco, Luiz M. Santos, Marcio G. dos Resende, Flavia A. [UNESP] Varanda, Eliana Aparecida [UNESP] Hyslop, Stephen Puebla, Pilar Feliciano, Arturo San Oshima-Franco, Yoko |
dc.subject.por.fl_str_mv |
ames test bothropstoxin-I 7,8,3'-trihydroxy-4'-methoxyisoflavone neuromuscular junction Salmonella mutagenicity snake venoms |
topic |
ames test bothropstoxin-I 7,8,3'-trihydroxy-4'-methoxyisoflavone neuromuscular junction Salmonella mutagenicity snake venoms |
description |
Snakebite is a neglected disease and serious health problem in Brazil, with most bites being caused by snakes of the genus Bothrops. Although serum therapy is the primary treatment for systemic envenomation, it is generally ineffective in neutralizing the local effects of these venoms. In this work, we examined the ability of 7,8,3'-trihydroxy-4'-methoxyisoflavone (TM), an isoflavone from Dipteryx alata, to neutralize the neurotoxicity (in mouse phrenic nerve-diaphragm preparations) and myotoxicity (assessed by light microscopy) of Bothrops jararacussu snake venom in vitro. The toxicity of TM was assessed using the Salmonella microsome assay (Ames test). Incubation with TM alone (200 mu g/mL) did not alter the muscle twitch tension whereas incubation with venom (40 mu g/mL) caused irreversible paralysis. Preincubation of TM (200 mu g/mL) with venom attenuated the venom-induced neuromuscular blockade by 84% +/- 5% (mean +/- SEM; n = 4). The neuromuscular blockade caused by bothropstoxin-I (BthTX-I), the major myotoxic PLA(2) of this venom, was also attenuated by TM. Histological analysis of diaphragm muscle incubated with TM showed that most fibers were preserved (only 9.2% +/- 1.7% were damaged; n = 4) compared to venom alone (50.3% +/- 5.4% of fibers damaged; n = 3), and preincubation of TM with venom significantly attenuated the venom-induced damage (only 17% +/- 3.4% of fibers damaged; n = 3; p < 0.05 compared to venom alone). TM showed no mutagenicity in the Ames test using Salmonella strains TA98 and TA97a with (+S9) and without (-S9) metabolic activation. These findings indicate that TM is a potentially useful compound for antagonizing the neuromuscular effects (neurotoxicity and myotoxicity) of B. jararacussu venom. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-12-03T13:09:12Z 2014-12-03T13:09:12Z 2014-05-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/molecules19055790 Molecules. Basel: Mdpi Ag, v. 19, n. 5, p. 5790-5805, 2014. 1420-3049 http://hdl.handle.net/11449/112066 10.3390/molecules19055790 WOS:000337113000022 WOS000337113000022.pdf 7501930236496670 |
url |
http://dx.doi.org/10.3390/molecules19055790 http://hdl.handle.net/11449/112066 |
identifier_str_mv |
Molecules. Basel: Mdpi Ag, v. 19, n. 5, p. 5790-5805, 2014. 1420-3049 10.3390/molecules19055790 WOS:000337113000022 WOS000337113000022.pdf 7501930236496670 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Molecules 3.098 0,855 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
5790-5805 application/pdf |
dc.publisher.none.fl_str_mv |
Mdpi Ag |
publisher.none.fl_str_mv |
Mdpi Ag |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1803649280860225536 |