Efeito neuroprotetor da formononetina em modelo animal para estudo da doença de Parkinson

• Ano de defesa: 2016
• Autor(a) principal: Oliveira, Juciele Valéria Ribeiro de
• Orientador(a): Gomes, Margarete Zanardo
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Sergipe
• Programa de Pós-Graduação: Pós-Graduação em Biotecnologia (RENORBIO-SE)
• País: Brasil
• Palavras-chave em Português: Biotecnologia; Biotecnologia farmacêutica; Doença de Parkinson; Antioxidantes; Formononetina; Isoflavonas; Agentes anti-inflamatórios; Agentes neuroprotetores; Neuroproteção; Flavonoids; Anti-inflammatory agents; Antioxidants
• Palavras-chave em Inglês: Nerve degeneration
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS
• Link de acesso: https://ri.ufs.br/handle/riufs/3267

This study aimed to evaluate the antioxidant activity in vitro, as well as and the possible neuroprotective effect in vivo of the isoflavonoid formononetin (FORM) in an experimental model for the study of Parkinson's disease (PD). Among the methods used to determine the antioxidant activity of FORM in vitro, they were elected the DPPH, ABTS and FRAP. In the in vivo assays, FORM was evaluated for its biological activity on experimental PD induced by 6- hydroxydopamine (6-OHDA, 10 μg in 2 μL) injection in the right striatum. Control groups received saline containing 0.02% of ascorbic acid. The animals were subjected to the open field behavioral test after 21 days of surgery. The immunohistochemical analysis of tyrosine hydroxylase TH was performed in the substantia nigra pars compacta (SNc) and the inflammatory response was evaluated at the striatum (hystochemical for hematoxylin eosin) after sacrifice 28 days of surgery. Statistical analysis was performed by one way analysis of variance or, in the case of graduated inflammatory response, by the Kruskal-Wallis test with Dunn's extension. The in vitro results of DPPH, ABTS and FRAP showed significant antioxidant action of FORM, similar to that of the vitamins A and E (p > 0.05) and synergism between FORM and vitamin A (for equivalent vitamin C and Trolox, p < 0.001). In the open field test the rearing, crossings, ambulation (to the right and left), the immobility time and latency to onset the movement were similar between the group treated with FORM 20 mg/kg and the lesioned group and different from the groups treated with vehicle and FORM 10 mg/kg. In immunostaining for TH SNc, it was observed that 6-OHDA caused a decrease in the mean number of dopaminergic neurons (22% remaining) in the lesioned group, whereas the treatment with FORM 10 mg/kg promoted an increase to 51% and FORM 20 mg/kg in 79%, p < 0.0001. The data were also indicative of anti-inflammatory action of FORM evidenced in histopatholological analysis and by the reduction in the microglial inflammatory infiltrate. It was found that lesioned rats treated with vehicle exhibited severe grade of inflammatory response (more than 50% of the microglial infiltrate) while in the group without lesion less than 10% of inflammatory infiltrate. On the other hand, in the groups treated with FORM (10 and 20 mg/kg), there was a moderate inflammatory response, (10 to 50% infiltrate p < 0.0001). Therefore, the treatment with FORM promoted a neuroprotective and anti-inflammatory effects, which may be associated with high antioxidant activity.