title: Anticonvulsant Effects of Fractions Isolated from Dinoponera quadriceps (Kempt) Ant Venom (Formicidae: Ponerinae).
abstract: 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 antDinoponera 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 fromD. quadricepsvenom 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.
authors.affiliation: Physiology Department, University Federal of Rio Grande of Norte, Natal, RN 59078-970, Brazil. dy_2012@hotmail.com.
authors.forename: Diana Aline Morais Ferreira
authors.initials: DA
authors.lastname: Nôga
authors.affiliation: Physiology Department, University Federal of Rio Grande of Norte, Natal, RN 59078-970, Brazil. lemb.89@gmail.com.
authors.forename: Luiz Eduardo Mateus
authors.initials: LE
authors.lastname: Brandão
authors.affiliation: Physiology Department, University Federal of Rio Grande of Norte, Natal, RN 59078-970, Brazil. nandacagni@hotmail.com.
authors.forename: Fernanda Carvalho
authors.initials: FC
authors.lastname: Cagni
authors.affiliation: Physiology Department, University Federal of Rio Grande of Norte, Natal, RN 59078-970, Brazil. delanoanibal@gmail.com.
authors.forename: Delano
authors.initials: D
authors.lastname: Silva
authors.affiliation: Physiology Department, University Federal of Rio Grande of Norte, Natal, RN 59078-970, Brazil. dinalillia@gmail.com.
authors.forename: Dina Lilia Oliveira
authors.initials: DL
authors.lastname: de Azevedo
authors.affiliation: Physiology Department, University Federal of Rio Grande of Norte, Natal, RN 59078-970, Brazil. arrilton@gmail.com.
authors.forename: Arrilton
authors.initials: A
authors.lastname: Araújo
authors.affiliation: Biology Department, University of São Paulo, Ribeirao Preto, SP 14040-901, Brazil. wagnerf@usp.br.
authors.forename: Wagner Ferreira
authors.initials: WF
authors.lastname: Dos Santos
authors.affiliation: Biophysics Department, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil. miranda.unifesp@gmail.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
authors.affiliation: Pharmacology Department, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil. reginahsilva@gmail.com.
authors.forename: Regina Helena
authors.initials: RH
authors.lastname: da Silva
authors.affiliation: Biosciences Department, Federal University of São Paulo, Santos, SP 11015-020, Brazil. alemrib@gmail.com.
authors.forename: Alessandra Mussi
authors.initials: AM
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D000862:Ant Venoms / Q000737:chemistry / Q000494:pharmacology*; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology*; D001000:Ants; D001640:Bicuculline; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000862:Ant Venoms; D000927:Anticonvulsants; D001640:Bicuculline
keywords: ant venom; bicuculline; natural product; neuroactive compounds; peptide fraction; tonic-clonic seizures