RT - Journal Article T1 - The effect of resistance training and endothelial stem cell injection on skeletal muscle antioxidant enzymes in type 1 diabetic rats JF - RJMS YR - 2021 JO - RJMS VO - 28 IS - 9 UR - http://rjms.iums.ac.ir/article-1-7000-en.html SP - 172 EP - 183 K1 - Resistance training K1 - Stem cells K1 - Catalase K1 - Glutathione K1 - Glutathione peroxidase K1 - Type 1 diabetes AB - Background & Aims: Type 1 diabetes is an autoimmune disease that destroys pancreatic β cells and accounts for 5-10% of all cases of diabetes. In type 1 diabetes, blood glucose levels are not sufficiently regulated and rise to abnormal levels for a long time. This chronic hyperglycemia is characteristic of diabetes and a major cause of many disease-related complications (1). Although many physiopathological aspects of diabetes are still unclear, it is well established that oxidative stress plays a major role in the development and spread of the disease (2). Catalase (CAT) is an antioxidant enzyme and is present in almost all living tissues that consume oxygen. This enzyme uses iron or manganese as a cofactor and catalyzes the degradation or reduction of hydrogen peroxide (H2O2) into water and molecular oxygen (4). The enzyme glutathione peroxidase plays an important role in inhibiting the process of lipid peroxidation and thus protects cells against oxidative stress (6). Recently, many attempts have been made to use stem cell transplantation in the treatment of type 1 diabetes (8-10). Recent studies have shown that stem cells reduce glucose levels further by acting on the paracrine glands rather than directly affecting insulin-producing cells (10, 12). On the other hand, the positive effects of regular exercise on various diseases such as type 1 diabetes have been identified (13). In the study of Pereira et al. (2016), the swimming exercise protocol for 8 weeks plays a role in controlling blood sugar and improves oxidative stress in the blood of diabetic rats by increasing the level of catalase (15). Also, a study showed that after 6 weeks of endurance training, glutathione peroxidase activity in the hippocampal tissue of rats with diabetes significantly increased (16). However, Farhangi et al. (2016) in a study investigated the effect of eight weeks of endurance training on the activity of some antioxidant enzymes and lipid peroxidation of cardiac tissue of streptozotocin-induced diabetic rats. Cardiac tissue catalase activity was not affected by endurance training (17). Recent studies have provided support for the use of resistance training to improve glucose control in type 1 diabetic patients (20). However, the effect of this type of exercise on skeletal muscle antioxidant factors has not been studied in type 1 diabetic subjects. On the other hand, in the field of changes in skeletal muscle antioxidant factors in response to endothelial stem cell injection, it can be said that no research has been done so far. Therefore, the aim of this study was to investigate the effect of resistance training and endothelial stem cell injection on skeletal muscle antioxidant enzymes in type 1 diabetic rats. Methods: In this experimental study, 36 male Wistar rats were divided into six groups of control (healthy), basal diabetic control, diabetic control, diabetes + stem cell injection, diabetes + resistance training and diabetes + stem cell injection + resistance training. In this study, rats became diabetic intraperitoneally using streptozotocin as a single dose of 40 mg/kg. Resistance exercises including climbing a one-meter ladder with weights hanging from the tail were performed for 17 sessions. 500,000 bone-derived stem cells were injected by a cell counter. Data were analyzed using independent t-test, 2-factor analysis of variance and Bonferroni hoc test at P<0.05. Results: The results showed that after the intervention, the levels of catalase, glutathione and glutathione peroxidase in the group of resistance training, stem cell injection and resistance training with stem cell injection were significantly higher than the control group (P<0.001). Also, the levels of catalase, glutathione and glutathione peroxidase in the rats of the resistance training group with simultaneous injection of stem cells were significantly higher than the resistance training and stem cell injection groups (P<0.001). Conclusion: The results of the present study showed that resistance training and endothelial stem cell injection resulted in an increase in skeletal muscle antioxidant enzymes in type 1 diabetic rats. The findings of this study were consistent with the results of Previous research (24, 25). A possible explanation for the increase in skeletal muscle antioxidant enzymes in post-exercise diabetic rats may be that the compensatory response to the combination of risk factors (diabetes-induced hyperglycemia) by overproduction of hydrogen peroxide by increasing the concentration of this Enzymes take place. This post-workout antioxidant enhancement is probably an attempt to balance the increase in reactive oxygen species under high blood sugar conditions. Therefore, exercise protects against oxidative stress by increasing the levels of catalase, superoxide dismutase and glutathione peroxidase in the skeletal muscle tissue of diabetic rats. The mechanism of changes caused by exercise has been investigated. The mechanism of change of antioxidant enzymes in training groups is to increase intracellular responses and reactions of different body tissues to oxidative stress produced during exercise and catabolism of synthetic components of proteins and cell defense structure (27). The results of our study show that stem cells with dose of 500,000 cells in rats muscle can significantly increase the protein level of catalase, glutathione and glutathione peroxidase in diabetic rats. The results can be elucidated by considering how STZ works, which increases reactive oxygen species, so that STZ causes cell DNA damage (29). stem cells have been shown to be resistant to oxidative stress production conditions such as ionizing radiation (34). In addition, stem cells are not susceptible to cell death due to oxidative stress. stem cells exposed to oxidative stress show low intracellular concentrations of reactive species with high expression of enzymes needed to control oxidative stress such as catalase and glutathione peroxidase (35). Because the definition of oxidative stress is the lack of an appropriate amount of ROS repellent tool (36) and previous research has shown that mesenchymal stem cells have the ability to reduce the severity of oxidative stress and increase the amount or activity of ROS neutralizing enzymes (35). It is thought that stem cell therapy may help increase antioxidant capacity in type 1 diabetes. There were some limitations in the present study, such as the lack of measurement of lipid peroxidation indices and antioxidant capacity of diabetic rats. Also, since the interactive effect of exercise and endothelial stem cells on the levels of antioxidant enzymes in type 1 diabetics, few studies have been performed, so more studies are needed to investigate the mechanisms affecting changes in these indices. Therefore, it is suggested that the interactive effect of other training methods and endothelial stem cells on the levels of antioxidant enzymes in type 1 diabetic subjects be investigated in future studies. It seems that the intervention of resistance training with simultaneous injection of stem cells can help improve the antioxidant enzymes of skeletal muscle in type 1 diabetes. LA eng UL http://rjms.iums.ac.ir/article-1-7000-en.html M3 ER -