Effect of Aerobic Exercise Combined With Stevia Extract Supplementation on Selected Liver Enzymes in Diabetic Rats

Extended Abstract


Introduction
he high prevalence of liver disease in people with diabetes has already been reported. Although the exact mechanism of liver damage in diabetes is unclear, hyperglycemia increases glucose production by autooxidation of glucose, which leads to the destruction of liver cells, followed by the increase of alanine Aminotransferase (ALT), aspartate aminotransferase (AST) enzymes production from liver cells. According to reports, increased insulin level and resis-T tance to this hormone leads to fibrosis and necrosis of hepatic lobules and the subsequent increase in ALT and AST enzymes. Oxidative stress, which causes the production of free radicals is also plays an important role in diabetes. Free radicals are highly toxic to cells, including the liver, and cause many side effects in the body. Exercises, including moderate-intensity aerobic exercise (reducing inflammation, oxidative stress, and the amount of fat in liver cells), and anti-diabetic drugs such as Stevia Rebaudiana have been suggested for fighting the negative effects of diabetes on the liver. Studies have shown that both leaf powder and extracted fibers from Stevia Rebaudiana have lowering effects on blood sugar and also play an important role in reducing liver damage. Therefore, it seems that the combination of Stevia herbal medicine and aerobic exercise can treat and prevent the progression of liver disease caused by diabetes and reduce the levels of transaminases.

Materials and Methods
In this study, 40 Wistar rats were studied. After overnight fasting (except for rats in the healthy control group), 32 rats with 50 mg/kg weight received intraperitoneal injection of Streptozotocin (STZ). 5 days after injection and by measurement of blood glucose using a glucometer, rats with blood glucose >300 mg/dl entered into the study. The remaining diabetic rats were randomly divided into 4 groups of diabetic control (n=7), diabetic + exercise (n=7), diabetic + Stevia (n=7) and diabetic + Stevia + exercise (n=7). Rats in the control and diabetic control groups did not have any particular activity during the experiments. The diabetic + exercise group performed aerobic exercise for 6 weeks (5 days per week). The diabetic + Stevia group received 250 mg/kg of Stevia extract orally (5 days per week, once a day). Rats in the diabetic + exercise+ Stevia group, while performing aerobic exercise, received 250 mg /kg of Stevia extract orally at the end of each exercise session for 5 days per week. After 6 weeks, the rats were anesthetized by intraperitoneal injection of a mixture of ketamine and xylazine, and then their blood samples were collected. Blood samples were centrifuged and their serums were prepared. Liver enzymes (ALT and AST) were measured using special kits. Aerobic exercise intensity was controlled using the treadmill. The exercise protocol was designed with increasing intensity based on ACSM principles (Table 1). Stevia extract was prepared by maceration (soaking). For statistical analysis, Shapiro-Wilk test, ANOVA and Tukey's post hoc test were used. Table 2 presents the characteristics of samples mean serum levels of ALT and AST. The results of ANOVA presented in Table 3 and Figure 1, indicated a significant difference between the mean ALT and AST levels in the five study groups (P=0.00). Tukey's Post Hoc test results in Table 4 indicates where the differences between the groups was reported.

Conclusion
Stevia extract and aerobic exercise, either alone or in combination, cause a decrease in the number of damaging serum biomarkers in the liver of diabetic rats with streptozotocin. The reduction rate was more significant in the exercise group with the extract, which was probably achieved through hypoglycemic, antioxidant, and aerobic exercise. Therefore, it can be concluded that the use of stevia extract and aerobic training can have a double effect on reducing the risk of liver damage.
The dosage of stevia extract in this study is one of the limitations of the study. Stevia's hypoglycemic and antioxidant effects in people with diabetes likely depend on its dose; thus, further research in this area with different quantities of stevia dose can help better understand the results. It is suggested that in a similar study, the number of oxidative damage indices following stevia extract and exercise in diabetic rats should be investigated.
Overall, although being animals, the subjects were to be identified with human subjects. All of the results of this study showed that they effectively reduced the value of the currency. However, more biochemical researches should be done to use it.

Compliance with ethical guidelines
All ethical principles were considered in this article. The participants were informed about the purpose of the research and its implementation stages; they were also assured about the confidentiality of their information; Moreover, They were allowed to leave the study whenever they wish, and if desired, the results of the research would be available to them.

Funding
This study was extracted from the PhD. thesis of first author approved by Islamic Azad University of Kermanshah Branch.

Authors' contributions
All authors contributed equally in preparing all parts of the research.