Efeito do tratamento conjunto com quercetina, glutamina e α-tocoferol sobre a morfologia do miocárdio de ratos diabéticos

Abstract

Diabetic cardiomyopathy (CM) is one of the major causes of morbidity and mortality in diabetic patients and is characterized by hypertrophy and cardiac fibrosis. This work aimed to analyze the effects of the joint treatment of antioxidants in the myocardium of rats with diabetes mellitus (DM). Twenty-nine male rats with 90 days of subdivision were used in four groups (n = 5): N (normoglycemic); D (diabetic); NT (normoglycemic treated with antioxidants) and; DT (diabetic treated with antioxidants). DM was induced by streptozotocin (35mg / kg body weight). The antioxidative treatment was performed via gavage with quercetin (100mg / kg body weight), 1% L-glutamine and 1% α-tocopherol and the experimental period was 60 days. The animals' body weight, water consumption and feed intake were analyzed. The analysis of the final glycemia, MDA, GSH, IL-1β, NTF-α, IL-10 and MPO, were performed in the blood tissue while the quantitative analyzes of collagen fibers and expression of SOD-1, GPX-1, IL -1β, TGF-β and FGF-2 were performed in 3-m thick sections of the myocardium. Fisher's test was used with level of significance when p <0.05%. The results showed a reduction in body weight in D and DT compared to normoglycemics, and an increase in heart weight / final body weight (PC / PF), an indication of cardiac hypertrophy, was observed in groups D, DT and NT in relation to N (p <0.05). The water and feed intake was higher in D, NT and DT compared to N, and DT group presented higher mean values than the others (p <0.05). Hyperglycemia was confirmed in the D and DT animals in relation to nondiabetics, being higher in DT than in D (p <0.05). In relation to systemic oxidative stress there was an increase in the plasma levels of MDA in NT and DT compared to N and D (p <0.05) and, increase of GSH in DT in relation to D (p <0.001) and NT in compared to N (p <0.001). At the tissue level, there was an increase in the expression of SOD-1 in the myocardium of the animals of group D in relation to N (p <0.001), whereas GPX was higher in D and in NT compared to N (p <0.001) and lower in DT with respect to D (p <0.001). In the analysis of systemic inflammation there was an increase in the level of MPO in NT compared to N (p <0.001), levels of IL-1β and TNF-α were similar between groups and IL-10 was higher in DT than in D (p <0.01) and lower in NT compared to N (p <0.01). At the tissue level there was an increase in the expression of IL-1β in D when compared to N (p <0.001). In relation to tissue development there was an increase in the expression of TGF-β in group D compared to N (p <0.001), increase in FGF-2 in DT in relation to the other groups (p <0.001) and increase in fiber deposition collagen in D and NT compared to N (p <0.001). The findings indicate that the antioxidant combination treatment proposed in this study was not able to reverse or decrease DM changes in relation to body weight, heart weight / body weight ratio, plasma glucose levels, amount of water and ingested ration. Treatment was not beneficial in normoglycemic animals since cardiac hypertrophy and increased water and feed consumption were also observed. At the systemic level DM reduced IL-10 levels while the treatment promoted higher oxidative stress (MDA levels) and inflammation (MPO levels) in the DT group, while stimulating the increase in GSH and IL-10 that have antioxidant and anti-inflammatory action, respectively. However, in NT the stress findings were similar to DT, but in relation to inflammation markers there was an increase in MPO and a reduction in IL-10, indicating that the treatment was harmful in normal animals. In the myocardium the DM promoted increased expression of SOD-1, GPX, IL-1β, TGF-β and in collagen deposition. The antioxidant treatment in DT did not promote reduction of SOD-1, IL-1β and TGF-β, but it reduced oxidative stress (expression of GPX-1) by the greater activation of the glutathione pathway, which led to greater expression of FGF -2 and reduction of collagen deposition. In the NT group, however, there was an increase in oxidative stress (GPX-1), which led to higher collagen deposition in relation to the other groups, again demonstrating that the use of antioxidants in a normal condition is not indicated. Thus, treatment with quercetin, L-glutamine and α-tocopherol promoted reduction of oxidative stress and fibrosis in the myocardium of rats with induced diabetes mellitus.