Agregação de proteínas como consequência da glicação não enzimática: investigação in vitro da mitigação de seus efeitos por piceatanol

Abstract

Advanced glycation end products (AGEs) can induce diverse effects on human health, such as neurodegenerative diseases including Alzheimer's and Parkinson's, as well as other metabolic disorders such as diabetes, heart disease, including cancer. In this work, we investigated the progression of hemoglobin (Hb) glycation through the formation of AGEs, structural changes in the Soret band, degradation products of the heme group and the formation of Hb aggregates, using glucose and fructose as reducing sugars in the process of glycation of human hemoglobin. Piceatannol (PIC) was used to evaluate the inhibition of AGEs formation and other effects mentioned. Therefore, PIC was used in different concentrations (10 – 300 μM). PIC was able to inhibit the formation of AGEs in a dose-dependent manner. At the concentration of 300 μM, in the glucose reaction system, it inhibited 89%, with IC50 of 74.51 μM; in the glucose+fructose system, it inhibited 78%, with IC50 of 127 μM and in the presence of fructose, inhibited 73%, with IC30 of 153 μM. In addition, the formation of β amyloid fibrils decreased as the concentration of PIC increased, reaching 52% inhibition to the fructose system, at a concentration of 300 μM. PIC also exerted a protective effect on the changes in the heme group of Hb, where a reduction in maximum absorption was observed, compared to the first day of glycation of 36, 26 and 29% for the glucose, glucose+fructose and fructose systems, respectively, referring to the last week of glycation at the maximum concentration. The protective effect of PIC against changes in the heme group of Hb and in the formation of amyloid fibrils were evident, and the assays suggested the potential use of PIC in the control of carbonyl stress.