Potencial terapêutico de flavonoides na síndrome dos ovários policísticos e complicações clínicas associadas

• Ano de defesa: 2022
• Autor(a) principal: Oliveira, Anne Karoline de Souza
• Orientador(a): Quintans, Jullyana de Souza Siqueira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Ciências da Saúde
• Palavras-chave em Português: Síndrome dos ovários policísticos (SOP); Flavonoides; Hiperandrogenismo; Disfunção ovulatória; Tecido adiposo
• Palavras-chave em Inglês: Polycystic ovary syndrome (PCOS); Flaavonoids; Hiperandrogenism; Ovulatory disfunctions; Adipose tissue
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: https://ri.ufs.br/jspui/handle/riufs/18471

Polycystic Ovary Syndrome (PCOS) is an endocrinopathy that commonly affects women of reproductive age and is associated with hyperandrogenism, ovarian dysfunction, insulin resistance, cardiometabolic complications and infertility. Hesperitin (HST) is a flavonoid with biological potential and stands out for its ability to modulate genes involved in the inflammatory process and redox homeostasis. Therefore, the objective of the present work was to gather scientific evidence on the biological properties and molecular targets of flavonoids in endocrine and metabolic disorders associated with PCOS, through systematic reviews, and to evaluate the effect of the HST-OH-γ-CD complex ( hesperitin-hydroxypropyl-γ-cyclodextrin) in the modulation of PCOS in an animal model. The first systematic review showed that the antiobesogenic properties of flavonoids are associated with modulation of proteins, transcription factors and target genes involved in adipogenesis, lipolysis, glucose metabolism, inflammation and oxidative stress. The findings described in the second review highlight that the mechanisms underlying the therapeutic potential of flavonoids are associated with their anti-inflammatory, antioxidant, lipid-lowering, anti-apoptotic, and regulatory target genes involved in steroidogenesis and intracellular insulin signaling. The effect of the HST-OH-γ-CD complex on PCOS modulation was evaluated in a letrozole-induced model. Initially, the antioxidant activity of HST was evaluated by different models in vitro and, in cell culture of macrophages against the production of ROS (reactive oxygen species), induced by hydrogen peroxide. The antioxidant action of the flavonoid HST was mainly associated with its potential to donate hydrogens, neutralizing radical species. For induction of PCOS, adult Wistar rats received letrozole (1mg/kg of body weight, orally) for 21 days. After induction of PCOS, confirmed by the presence of irregular estrous cycles, the animals were treated with free and complexed HST (200 mg/kg of body weight, orally) for another 21 days. At the end of the treatment, the rats were euthanized. Blood was collected for quantification of biochemical parameters. Ovaries, uterus, liver, periovarian adipose tissue and retroperitoneal measurement were collected for weight measurement. Ovarian tissues were collected for histological analysis and for the analysis of oxidative stress markers and quantification of proteins involved in folliculogenesis. For tabulation and statistical analysis of the data, the Prism 7 software (GraphPad) with analysis of variance (ANOVA) was used, followed by the Tukey test. The results of the preclinical trial showed that complexed HST aided in tissue weight loss of fat pads and restored the architecture of ovarian follicular cells. This effect was associated with a reduction in serum levels of total testosterone and body fat deposition, in addition to the maintenance of p-Akt/Akt indices in ovarian tissue. It is worth noting here the relevance of the complexation of hydrophobic molecules in cyclodextrins, which in the present study, potentiated the pharmacological effects of the flavonoid HST. As far as we know, our study is the first to demonstrate the promising potential of complexed HST against endocrine, reproductive and metabolic disorders characteristic of PCOS, providing support for pre-clinical and clinical trials that use complexed HST as an alternative therapeutic strategy in the management of PCOS.