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
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,...
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2014-05-01
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| author | Miriéle C. Ferraz Edson H. Yoshida Renata V.S. Tavares José C. Cogo Adélia C.O. Cintra Cháriston A. Dal Belo Luiz M. Franco Márcio G. dos Santos Flávia A. Resende Eliana A. Varanda Stephen Hyslop Pilar Puebla Arturo San Feliciano Yoko Oshima-Franco |
| author_facet | Miriéle C. Ferraz Edson H. Yoshida Renata V.S. Tavares José C. Cogo Adélia C.O. Cintra Cháriston A. Dal Belo Luiz M. Franco Márcio G. dos Santos Flávia A. Resende Eliana A. Varanda Stephen Hyslop Pilar Puebla Arturo San Feliciano Yoko Oshima-Franco |
| author_sort | Miriéle C. Ferraz |
| collection | DOAJ |
| 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 μg/mL) did not alter the muscle twitch tension whereas incubation with venom (40 μg/mL) caused irreversible paralysis. Preincubation of TM (200 μg/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 PLA2 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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| spelling | doaj.art-854d119539cb41f8b00ba595d39dd8462022-12-22T01:14:29ZengMDPI AGMolecules1420-30492014-05-011955790580510.3390/molecules19055790molecules19055790An 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 MyonecrosisMiriéle C. Ferraz0Edson H. Yoshida1Renata V.S. Tavares2José C. Cogo3Adélia C.O. Cintra4Cháriston A. Dal Belo5Luiz M. Franco6Márcio G. dos Santos7Flávia A. Resende8Eliana A. Varanda9Stephen Hyslop10Pilar Puebla11Arturo San Feliciano12Yoko Oshima-Franco13Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO), Rodovia Raposo Tavares, Km 92.5, 18023-000 Sorocaba, SP, BrazilPost-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO), Rodovia Raposo Tavares, Km 92.5, 18023-000 Sorocaba, SP, BrazilPost-Graduate Program in Technological and Environmental Processes, University of Sorocaba (UNISO), Rodovia Raposo Tavares, Km 92.5, 18023-000 Sorocaba, SP, BrazilSerpentarium of the Vale do Paraíba University (CEN—UNIVAP), Av Shishima Hifumi 2911, 12244-000 São José dos Campos, SP, BrazilDepartment of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences, São Paulo University (USP), Via do Café S/N, 14040-903 Ribeirão Preto, SP, BrazilLANETOX, Federal University of Pampa (UNIPAMPA), Avenida Antonio Trilha 1847, 97300-000 São Gabriel, RS, BrazilMethodist University of Piracicaba, Rodovia do Açucar, Km 156, 13423-170 Piracicaba, SP, BrazilPost-Graduate Course in Environmental Sciences, Federal University of Tocantins (UFT), Av NS 15 ALC NO 14, 109 Norte, 77001-090 Palmas, TO, BrazilFaculty of Pharmaceutical Sciences, São Paulo State University (UNESP), Rodovia Araraquara-Jau, Km 1, 14801-902 Araraquara, SP, BrazilFaculty of Pharmaceutical Sciences, São Paulo State University (UNESP), Rodovia Araraquara-Jau, Km 1, 14801-902 Araraquara, SP, BrazilDepartment of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, 13083-887 Campinas, SP, BrazilDepartment of Pharmaceutical Chemistry, Salamanca University, CIETUS, IBSAL, Salamanca 37007, SpainDepartment of Pharmaceutical Chemistry, Salamanca University, CIETUS, IBSAL, Salamanca 37007, SpainPost-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (UNISO), Rodovia Raposo Tavares, Km 92.5, 18023-000 Sorocaba, SP, BrazilSnakebite 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 μg/mL) did not alter the muscle twitch tension whereas incubation with venom (40 μg/mL) caused irreversible paralysis. Preincubation of TM (200 μg/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 PLA2 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.http://www.mdpi.com/1420-3049/19/5/5790ames testbothropstoxin-I7,8,3'-trihydroxy-4'-methoxyisoflavoneneuromuscular junctionSalmonella mutagenicitysnake venoms |
| spellingShingle | Miriéle C. Ferraz Edson H. Yoshida Renata V.S. Tavares José C. Cogo Adélia C.O. Cintra Cháriston A. Dal Belo Luiz M. Franco Márcio G. dos Santos Flávia A. Resende Eliana A. Varanda Stephen Hyslop Pilar Puebla Arturo San Feliciano Yoko Oshima-Franco 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 Molecules ames test bothropstoxin-I 7,8,3'-trihydroxy-4'-methoxyisoflavone neuromuscular junction Salmonella mutagenicity snake venoms |
| 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 |
| 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_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_sort | 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 |
| topic | ames test bothropstoxin-I 7,8,3'-trihydroxy-4'-methoxyisoflavone neuromuscular junction Salmonella mutagenicity snake venoms |
| url | http://www.mdpi.com/1420-3049/19/5/5790 |
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