Modulation of Inflammation and angiogenesis by a new thiazolidine compound (GQ-11) in visceral ischemia.

Abstract

The thiazolidinediones (TZDs) class comprises drugs with hypoglycemic effects by activation of alpha/gamma peroxisome proliferator-activated receptor isoforms (PPAR±, PPAR³ and PPAR ²/´). Besides insulin sensitizer effect, some clinical studies have linked TZDs treatment to anti-inflammatory potential probably due to PPAR³ agonism. Although these beneficial effects, prolonged use of TZDs was associated to important side effects such as fluid retention, body weight gain, peripheral edema, severe hepatotoxicity and cardiovascular risk what led to removal of some full PPAR agonists - as troglitazone from the drug market. At the same time, the search for new thiazolidine compounds that show the desirable beneficial effects without the reported side effects has been encouraged. Preliminary in vivo data showed that GQ-11 - a new thiazolidine compound - besides hypoglycemic effects, modulates important cytokines involved not only in inflammatory process but in angiogenesis, indicating promising effects on tissue repair, especially in metabolic decompensation - what occurs in insulin resistance - and also preventing complications from inflammatory process caused by cardiovascular surgery. Thus, in this project two different important collaborations in two different institutions are proposed. In the first stage we suggest a collaboration with Dr. Timothy Koh, in University of Illinois at Chicago - United States - which would allow us to evaluate GQ-11 effects on tissue repair in a model of wound healing in insulin resistance with db/db mice (FAPESP 2016/16850-1). In the second stage, we suggest a collaboration with Dr. Domenico Palombo, in Università degli studi de Genova - Italy - which would allow us to evaluate GQ-11 effects in a visceral ischemia model with Wistar rats, by image techniques (PET/MRI). Both animal models are required and foreseen to accomplish the entailed PhD project previously approved.