Efeitos bioquímicos e metabólicos da administração de farinha do bagaço de uvas em modelo animal de Diabetes Mellitus tipo 2

Abstract

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder associated withobesity, genetic factors, physical inactivity, and inadequate diet, which can lead to cardiovascular diseases (CVD), oxidative imbalance, and cognitive disorders. Many compounds have been studied as potential resources in the treatment and/or prevention of this disease, such as grape derivatives. In this context, grape pomace flour (GPF), obtained after processing grape pomace, has been evaluated. It contains nutrients, soluble and insoluble fibers, and antioxidant compounds. The aim of this study was to investigate the effects of administering GPF from the 'Arinto' and 'Touriga Nacional' grape varieties on serum biochemical, oxidative, behavioral, and histological parameters in adult male Wistar rats. We assessed the potential protective effect of 10% GPF supplementation in a preclinical model of T2DM induced by a high-fat diet (HFD) for 28 days and a single dose of streptozotocin (35 mg/kg) on the 21st day. After performing the oral glucose tolerance test (OGTT) on the 24th day, and the open field test (OFT) and elevated plus maze (EPM) test on the 28th day, the animals were euthanized, and serum, cerebral cortex, hippocampus, liver, and pancreas were collected for further analyses. The experimental induction of T2DM resulted in various metabolic disturbances, as evidenced by OGTT, area under the curve, and serum glucose levels. Additionally, polyuria and a significant increase in body weight, elevation in serum levels of triglycerides (TG), total cholesterol (TC), and TyG index were observed. Induction of anxiety-like behavior was also observed in the EPM. When assessing oxidative stress parameters, increased levels of reactive oxygen species (ROS) were observed in the hippocampus, elevated levels of nitrites and decreased catalase (CAT) enzyme activity in the cortex, increased levels of thiobarbituric acid reactive substances (TBARS) and nitrites, as well as decreased superoxide dismutase (SOD) enzyme activity in the liver. Vacuoles in acinar cells and congested vessels were observed in the pancreas. On the other hand, treatment with GPF from 'Arinto' and 'Touriga Nacional' grapes showed protective effects on glycemic and lipid metabolism disorders, reduction in uric acid and creatinine levels, as well as in the transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, anxiety-like behavior was attenuated, and there was a decrease in TBARS and ROS levels in the cerebral cortex, with enhanced CAT enzyme activity. The treatments also provided protection against increased TBARS in the liver, and protected pancreatic beta cells from cytotoxicity observed in the context of insulin resistance. The results suggest that grape byproducts may offer a promising approach to mitigate the deleterious effects of T2DM, contributing to therapeutic and dietary strategies for health.