Banca de DEFESA: Alessandra Rodrigues Silva Rossi

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Alessandra Rodrigues Silva Rossi
DATE: 20/12/2022
TIME: 08:00
LOCAL: A definir
TITLE:

EVALUATION OF THE TOXICITY OF GQ-16, A NEW AGONIST LIGAND OF PEROXYSOME GAMMA PROLIFERATOR-ACTIVATED RECEPTORS (PPARy), COMPARED TO OTHER THIAZOLIDINEDIONES IN ZEBRA FISH (DANIO RERIO)

KEY WORDS:

Thiazolidinediones, PPARy, Danio Rerio, GQ-16

PAGES: 100
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

The increase in sedentary lifestyle and obesity in society has increasingly highlighted an important public health problem, Type 2 Diabetes Mellitus (Type 2 DM). Only two drug classes with insulin-sensitizing action are available, biguanides (metformin) and thiazolidinediones (TZD) or glitazones (pioglitazone and rosiglitazone). TZDs exert their hypoglycemic effects by binding to the peroxisomal proliferator-activated receptor gamma (PPARγ), a nuclear receptor expressed in different tissues, however these drugs have been linked to serious adverse effects such as congestive heart failure and bladder cancer. Since total PPARγ agonists caused greater adverse effects, the efforts of the scientific community turned to the development of molecules with partial activity in these receptors. OBJECTIVE: To analyze the toxicity of GQ-16, in comparison with other TZDs (rosiglitazone and pioglitazone), using zebrafish as an animal model. METHOD: Acute toxicity test in zebrafish embryos (FET) was performed with rosiglitazone, pioglitazone and GQ-16 at different concentrations. Subsequently, the PCR test was performed to evaluate the gene expression of the PPARy and FABP4 receptors, in addition to the microarray technique for the evaluation of the gene expression of several genes at the same time. Result: GQ-16 and pioglitazone were not toxic to the embryos in the FET, unlike Rosiglitazone which led to 100% embryo mortality at the highest concentration. At lower concentrations, it showed a high rate of changes in embryonic development, of the surviving larvae at a concentration of 25uM, 43.8% had pericardial edema, 16.6% had tail deformity and 1.6% had developmental delay. Gene expression analysis showed that GQ-16 increased expression of FABP4 and also PPARy but did not reach statistical significance for PPARy. Pioglitazone and rosiglitazone increased PPARy and FABP4 expression. CONCLUSION: The findings support that GQ16, a new PPARy partial agonist, has lower toxicity than other thiazolidinediones, but further studies are needed to elucidate potential benefits and adverse effects of this new ligand”

BANKING MEMBERS:
Externo à Instituição - ALEXANDRE DE GÓES MARTINI - UVir
Interna - 2329402 - ANGELICA AMORIM AMATO
Externa à Instituição - CINTHIA GABRIEL MEIRELES - MS
Presidente - 186.580.591-20 - FRANCISCO DE ASSIS ROCHA NEVES - UNIFESP
Externa ao Programa - 1529483 - MARIA DE FATIMA BORIN