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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Ferraz, Miriele C. [1] ; Yoshida, Edson H. [1] ; Tavares, Renata V. S. [2] ; Cogo, Jose C. [3] ; Cintra, Adelia C. O. [4] ; Dal Belo, Chariston A. [5] ; Franco, Luiz M. [6] ; dos Santos, Marcio G. [7] ; Resende, Flavia A. [8] ; Varanda, Eliana A. [8] ; Hyslop, Stephen [9] ; Puebla, Pilar [10] ; Feliciano, Arturo San [10] ; Oshima-Franco, Yoko [1]
Total Authors: 14
Affiliation:
[1] Univ Sorocaba UNISO, Postgrad Program Pharmaceut Sci, BR-18023000 Sorocaba, SP - Brazil
[2] Univ Sorocaba UNISO, Postgrad Program Technol & Environm Proc, BR-18023000 Sorocaba, SP - Brazil
[3] Serpentarium Vale do Paraiba Univ CEN UNIVAP, BR-12244000 Sao Jose Dos Campos, SP - Brazil
[4] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin Toxicol & Bromatol Anal, BR-14040903 Ribeirao Preto, SP - Brazil
[5] Fed Univ Pampa UNIPAMPA, LANETOX, BR-97300000 Sao Gabriel, RS - Brazil
[6] Univ Metodista Piracicaba, BR-13423170 Piracicaba, SP - Brazil
[7] UFT, Postgrad Course Environm Sci, BR-77001090 Palmas, TO - Brazil
[8] Sao Paulo State Univ UNESP, Fac Pharmaceut Sci, BR-14801902 Araraquara, SP - Brazil
[9] State Univ Campinas UNICAMP, Dept Pharmacol, Fac Med Sci, BR-13083887 Campinas, SP - Brazil
[10] Univ Salamanca, Dept Pharmaceut Chem, CIETUS, IBSAL, Salamanca 37007 - Spain
Total Affiliations: 10
Document type: Journal article
Source: Molecules; v. 19, n. 5, p. 5790-5805, MAY 2014.
Web of Science Citations: 7
Abstract

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. (AU)

FAPESP's process: 08/11005-5 - Dipteryx alata Vogel: antiophidian action and toxicity
Grantee:Yoko Oshima Franco
Support Opportunities: Scholarships abroad - Research