Effects of a new thiazolidine compound (GQ-11) on tissue repair process in models of insulin resistance and ischemia-reperfusion

• Ano de defesa: 2019
• Autor(a) principal: Silva, Jacqueline Cavalcante
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Inflamação; Inflammation; Ischemia/Reperfusion; Isquemia/Reperfusão; Reparo tecidual; Thiazolidinediones; Tiazolidinadionas; Tissue Repair
• Link de acesso: http://www.teses.usp.br/teses/disponiveis/9/9142/tde-03122019-115921/

The thiazolidinediones (TZDs) class comprises drugs with hypoglycemic effects, reducing insulin resistance in peripheral tissues. Our group has demonstrated in preliminary in vivo studies that a new TZD, GQ-11, improves insulin resistance as well as modulates cytokines involved in inflammatory process, suggesting an interesting approach for therapeutic alternatives in tissue repair, especially in metabolic decompensation cases, as insulin resistance and ischemia-reperfusion. In this context, the aim of this study was to investigate GQ-11 effects in tissue repair in three different models: insulin resistance in db/db mice, reconstructed human epidermis (RHE) in glycated collagen matrix and ischemia/reperfusion induced by aorta clamping in Wistar rats. In insulin resistance context, GQ-11 treatment upregulated the expression of anti-inflammatory mediators, such as IL-10, TGF-β and Arg-1, downregulated the expression of pro-inflammatory cytokines both in db/db mice wounds and in macrophage, besides increasing re-epithelization and collagen deposition. In addition, the treatment also induced keratinocytes proliferation and fibroblasts differentiation in RHE. In ischemia-reperfusion model, the same anti-inflammatory effect was observed along with anti-oxidant properties through regulation of enzymes, such as catalase and GPx, as well as by decreasing TBARS formation. Animals imaging by positron emission tomography (PET) indicated significant less 18F-FDG uptake in animal treated with GQ-11 compared to controls, suggesting decrease of the inflammation process related to reperfusion after aorta clamping. Concluding, the dual PPARα/γ agonist GQ-11 has an important antiinflammatory effect, suggesting a new approach to tissue repair management in diabetes and in prevention of ischemia-reperfusion syndrome post-surgery.