Interação entre exercício físico e o tratamento com resveratrol nas alterações hepáticas induzidas pelo diabetes mellitus em um modelo de pós-menopausa experimental

Abstract

Type 1 diabetes mellitus (T1DM) is characterized by hypoinsulinemia resulting from autoimmune destruction of pancreatic beta cells. Hyperglycemia can induce alterations in liver function and structure associated with increased oxidative stress and inflammation. However, liver alterations in T1DM have been less documented, especially in postmenopausal women with T1DM. The search for new strategies is necessary to improve or delay the progression of liver lesions induced by T1DM in the postmenopausal period. In this context, we evaluated the isolated and combined effects of physical exercise and resveratrol (RES) on liver enzyme levels, morphology, redox balance, and inflammation in hepatocytes of ovariectomized (OVX) rats with T1DM. Twenty-four rats were OVX, and diabetes was induced by injection of streptozotocin (STZ/40 mg/kg). Next, the rats were divided into 4 groups (n=6/each): OSD, sedentary diabetic OVX rats; OTD, trained diabetic OVX rats; OSD+RES, sedentary diabetic OVX rats + RES; OTD+RES, trained diabetic OVX rats + RES. The OTD and OTD+RES groups underwent 8 weeks of exercise. Treatment with RES was performed by intraperitoneal injection, at a dose of 5 mg/kg/day, 5 days/week, for 8 weeks in the OSD+RES and OTD+RES groups. The rats were euthanized and the liver was removed for histological, morphometric, immunohistochemical, and oxidative stress studies. The results demonstrate that the interaction of RES with physical training preserved the structure of the liver tissue and reduced total nitrite levels, hepatic expression of NF-κB, nitrotyrosine, and TGF-β. However, in isolation, RES and physical training increased glycogen content, GPx enzyme activity, and reduced laminin immunostaining in the liver tissue of rats in the SDO+RES and OTD groups. RES alone decreased TBARS levels and increased SOD enzyme activity in the liver of OSD+RES rats. In conclusion, our results show that exercise and RES, separately, have hepatoprotective effects, but the interaction of these therapeutic strategies induced additional beneficial effects in the liver of OVX rats with T1DM.