Anticonvulsant Effects of Fractions Isolated from Dinoponera quadriceps (Kempt) Ant Venom (Formicidae: Ponerinae)

Natural products, sources of new pharmacological substances, have large chemical diversity and architectural complexity. In this context, some toxins obtained from invertebrate venoms have anticonvulsant effects. Epilepsy is a neurological disorder that affects about 65 million people worldwide, and approximately 30% of cases are resistant to pharmacological treatment. Previous studies from our group show that the denatured venom of the ant Dinoponera quadriceps (Kempt) protects mice against bicuculline (BIC)-induced seizures and death. The aim of this study was to investigate the anticonvulsant activity of compounds isolated from D. quadriceps venom against seizures induced by BIC in mice. Crude venom was fractionated by high-performance liquid chromatography (HPLC) resulting in six fractions referred to as DqTx1-DqTx6. A liquid chromatography-mass spectrometry (LC/MS) analysis revealed a major 431 Da compound in fractions DqTx1 and DqTx2. Fractions DqTx3 and DqTx4 showed a compound of 2451 Da and DqTx5 revealed a 2436 Da compound. Furthermore, the DqTx6 fraction exhibited a major component with a molecular weight of 13,196 Da. Each fraction (1 mg/mL) was microinjected into the lateral ventricle of mice, and the animals were observed in an open field. We did not observe behavioral alterations when the fractions were given alone. Conversely, when the fractions were microinjected 20 min prior to the administration of BIC (21.6 nM), DqTx1, DqTx4, and DqTx6 fractions increased the latency for onset of tonic-clonic seizures. Moreover, all fractions, except DqTx5, increased latency to death. The more relevant result was obtained with the DqTx6 fraction, which protected 62.5% of the animals against tonic-clonic seizures. Furthermore, this fraction protected 100% of the animals from seizure episodes followed by death. Taken together, these findings indicate that compounds from ant venom might be a potential source of new anticonvulsants molecules.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Pró-reitoria de Pesquisa da Universidade Federal do Rio Grande do Norte (PROPESQ/UFRN)Fundaçao de Apoio à Pesquisa do Estado do Rio Grande do Norte (FAPERN)Univ Fed Rio Grande do Norte, Dept Physiol, BR-59078970 Natal, RN, BrazilUniv Sao Paulo, Dept Biol, BR-14040901 Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Dept Biophys, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biosci, BR-11015020 Sao Paulo, SP, BrazilBiophysics Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-062, BrazilPharmacology Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-062, BrazilBiosciences Department, Universidade Federal de São Paulo (UNIFESP), Santos, SP 11015-020, BrazilWeb of Scienc