Efeitos de dois protocolos de exercício nas alterações hepáticas induzidas pelo diabetes mellitus tipo 1

Abstract

Type 1 Diabetes Mellitus (DM1) is characterized by an absolute deficiency in insulin production, resulting in the development of chronic hyperglycemia, and is associated with various pathological conditions, including liver disease. New therapeutic strategies are needed to improve and/or prevent the progression of diabetic liver disease. This study investigated the effects of moderate-intensity physical exercise before and after the induction of diabetes mellitus on type 1 diabetes mellitus-induced liver changes in Wistar rats. To this end, 30 rats weighing between 290 and 310 g were divided into 5 groups: CS (Sedentary Control, n=6), CT (Trained Control, n=6), DS (Sedentary Diabetic, n=6), DT (Trained Diabetic, n=6), and DPT (Previously Trained Diabetic, n=6). Only the DPT group underwent 4 weeks of training before the induction of diabetes with streptozotocin (STZ/40mg/Kg). After confirmation of diabetes, the DPT, DS, and CT groups underwent 8 weeks of treadmill exercise, 5 times a week. The animals were euthanized, blood samples were collected for liver function assessment, and the liver was removed for histological, redox balance, and ELISA studies. Our results demonstrate a slight increase in serum AST and ALP levels in the DS group. However, only the DPT group showed reduced serum AST levels compared to the DS and DT groups (p<0.05) and ALP levels, although this difference was not statistically significant. Serum ALT, GGT, and bilirubin levels were elevated in the DS group compared to the controls (p<0.001 and p<0.05, respectively). Both exercise protocols prevented this increase in ALT, as the training reduced ALT levels compared to the DS group (p<0.001) and showed no significant change among the controls. GGT and bilirubin levels did not differ between the DS and DT groups. Only the DPT group prevented the changes in GGT and bilirubin, as preventive training reduced these levels compared to the DS group (p<0.05) and showed no significant change compared to the controls. Lipid peroxidation was increased in rats in the DS group compared to the CS and CT groups (p<0.05 and p<0.01, respectively). Both physical exercise protocols were able to prevent these alterations in lipid peroxidation induced by diabetes, since a reduction in lipid peroxidation was observed in the DT and DPT groups compared to the DS group, p<0.01, and they did not show statistical differences compared to the control groups. On the other hand, catalase enzyme activity was elevated in the liver tissue of DS rats when compared to that of the CS (p<0.001) and CT (p<0.05) groups. In contrast, training of rats in the DT and DPT groups promoted a reduction in catalase activity. Liver TNF-α levels were elevated in the DS and DT groups compared to controls (p<0.05). However, we observed a reduction in TNF-α levels only in the DPT group. Necrosis, edema, and increased hyperemic sinusoids in the liver tissue of the DS group were reduced by both exercise protocols, p<0.001. Steatosis was reduced in the trained diabetic groups, p<0.05, and we observed no difference in ballooning degeneration. In conclusion, moderate-intensity aerobic exercise improved liver enzyme levels, TNF-alpha, redox balance, and histological aspects in the liver tissue of rats with type 1 diabetes, with some additional beneficial effects induced by preventive training.