Ácido elágico e hesperidina como potenciais terapêuticos em desordens neuroinflamatórias

• Ano de defesa: 2020
• Autor(a) principal: Dornelles, Guilherme Lopes
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Medicina Veterinária; UFSM; Programa de Pós-Graduação em Medicina Veterinária; Centro de Ciências Rurais
• Palavras-chave em Português: Polifenóis; Antioxidantes; Anti-inflamatório; Estreptozotocina; Lipopolissacarídeos; Polyphenols; Antioxidants; Anti-inflammatory; Streptozotocin; Lipopolysaccharides; CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA
• Link de acesso: http://repositorio.ufsm.br/handle/1/22221

Neuroinflammation can negatively impact the process of neurogenesis in adult mammals in addition to being considered a risk factor for cognitive impairment and dementia. Among the experimental models of neuroinflammation, we highlight the models that use intraperitoneal (IP) applications of lipopolysaccharides (LPS) or intracerebroventricular administration (ICV) of streptozotocin (STZ). Several types of research have been carried out to search for therapeutic alternatives for neuroinflammatory disorders. Flavonoids, such as ellagic acid (EA) and hesperidin (HES), found mainly in fruits, have several beneficial effects on the body, such as antioxidant and anti-inflammatory properties, as well as reduced toxicity. In this context, this research aimed to evaluate the therapeutic potential of EA or HES in experimental models of neuroinflammation. This study was divided into two experiments. In the first one (MANUSCRIPT I), the objective of the study was to evaluate the potential of EA in an experimental model of neuroinflammation induced by multiple applications of LPS. Thirty-two male Wistar rats were used, distributed in 4 groups (n = 8): controls (CTRL+SAL) and control-treated with EA (CTRL+EA), and the groups of animals that received LPS (LPS+SAL) and (LPS+EA). The LPS groups received eight daily IP injections of LPS for eight consecutive days at a dose of 250mg/kg of body weight, dissolved in 0.9% saline while the CTRL and EA groups received only 0.9% saline vehicle in the same volume. Two hours after applications (IP), animals in the EA and LPS+EA group were treated with EA at a dose of 100mg/kg orally during the eight days of treatment. The open-field test and object recognition were performed at sixth, seventh, and eighth days of the experimental period. In the second experiment (MANUSCRIPT II), the study aimed to evaluate the effects of HES and its association with rivastigmine (RIV) on memory and oxidative parameters in a sporadic model of Alzheimer's Disease (AD) induced by ICV-STZ injection. 64 Wistar rats were used, divided into eight groups (n = 8): control (CTRL), RIV, HES, RIV+HES, STZ, STZ+RIV, and STZ, HES, STZ+RIV+HES. The rats received an ICV-STZ injection or saline solution (3 mg/kg) and were treated daily, from the fourth day, with 100 mg/kg of HES orally, for 30 days. Twenty-one days after ICV-STZ injection, oral treatment was started with 2 mg/kg of IVR that lasted for 13 days. Behavioral testing was performed by the Morris water maze 30 days after the ICV-STZ injection. In both studies, the antioxidants used (EA or HES) demonstrated the potential to reverse the harmful effects of LPS or STZ by reducing oxidative damage, increasing the antioxidant system, reducing reactive oxygen species (ROS), and improving in the animals' cognitive potential. Also, in MANUSCRIPT I, EA demonstrated immunomodulatory potential, from reduced expression of glial cells, as well as the ability to reduce acetylcholinesterase (AChE) activity and Tau phosphorylation. These results demonstrate the therapeutic potential of EA and HES in cognitive disorders secondary to neuroinflammation, which makes these antioxidants potential candidates for the treatment of neurodegenerative diseases.