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

The thiazolidinediones (TZDs) class comprises drugs with hypoglycemic effects, reducing insulin resistance in peripheral tissues. Our group has demonstrated in preliminary in vivo data 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 in Wistar rats. In insulin resistance context, GQ-11 treatment showed to upregulate expression of anti-inflammatory mediators, such as IL-10, TGF- and Arg-1, besides downregulating expression of pro-inflammatory cytokines both in db/db mice wounds and in macrophages, besides increasing re-epithelization and collagen deposition. In addition, the treatment also induced keratinocytes proliferation and fibroblasts differentiation in RHE. In ischemia-reperfusion model, same anti-inflammatory effect was observed along anti-oxidant properties through regulation of enzymes, such as catalase, GPx and TBARS formation decrease, besides 18F-FDG uptake decrease in Positron Emission Tomography (PET) imaging, suggesting decrease of inflammation process related to reperfusion after aorta clamping. Concluding, the treatment with a dual PPAR/ agonism, such as GQ-11, promotes a central anti-inflammatory effect, suggesting a new approach to tissue repair management in diabetes and in prevention of ischemia-reperfusion syndrome post-surgery.