Atividade antioxidante in vitro e in vivo de análogos sintéticos da curcumina e compostos heterocíclicos

Abstract

Diabetes mellitus is a chronic disease characterized by hyperglycemia, metabolic imbalance, resulting in oxidative stress that promotes tissue damage. The appearance of this disease is highly related to lifestyle and food of the population, being of great interest to search for a dietary supplement that can also act by preventing or reducing oxidative alterations in diabetic individuals. Based on the known antioxidant action of curcumin, aimed in this work to evaluate the in vitro antioxidant activity of a series of synthetic analogs of the curcumin as well as new tiazólicas heterocyclic chemical structures and select the most promising substance for further studies in vivo. In vitro analyzes were performed by ABTS, radical DPPH capture and FRAP methods. From the results obtained, a synthetic heterocyclic thiazole, RI46, was selected for in vivo studies, considering potency, ease of synthesis and low cytotocixity. For comparison purposes, curcumin was used as positive control both in vitro and in vivo studies. In in vivo experiments, the liver extracts of healthy and diabetic Wistar rats were used, with analysis to determine the enzymatic activity of SOD, CAT, GPx and GR, and determination of lipid peroxidation by TBARS assay; finally, in the blood of these animals, biochemical parameters: hemoglobin, total cholesterol, HDL cholesterol, triglycerides, ALT, AST, alkaline phosphatase, urea, total protein, creatinine, magnesium, uric acid, and albumin amylase were evaluated. The results were submitted to ANOVA analysis of variance and the treatment means were compared by Tukey test (0.05). With regard to in vivo studies, it was not detected statistical evidence of changes caused in liver enzymes and lipid peroxidation, after treatment with RI46 and curcumin, however, these parameters also were not changed between control groups with and without diabetes. On the other hand, concerning on biochemical parameters, it was detected significant differences in uric acid, alkaline phosphatase, ALT, urea, indicating a possible antioxidant protective role of such substances in the liver and kidney of diabetic animals, that could be acting by other means than the commonly reported in the literature.