Evaluation of the toxicity potential of exercise and atorvastatin/metformin combination therapy on STZ-diabetic rats

Exercise is recommended for individuals with diabetes, and metformin and atorvastatin are commonly prescribed to diabetic patients. However, these two drugs have potential effects that may lead to toxicity in the skeletal muscle system. Therefore, the effects and potential interactions of combining these two drugs on skeletal muscle performance and structure were investigated in vivo in an experimental diabetes model. Male Wistar rats were divided into six groups: a sedentary control group (N) and five treatment groups—exercise (C), diabetes (D), diabetes with metformin (MET), diabetes with atorvastatin (ATO), and diabetes with metformin and atorvastatin (MET + ATO). In the diabetes model experimentally created with streptozotocin (STZ; 45 mg/kg, i.p.) and metformin (300 mg/kg/day), atorvastatin (10 mg/kg/day) was administered to drug groups by gavage during the 4-week study period. The rats were allowed to run (at moderate level) for 30 min, 5 days a week, on the treadmill. At the end of the study, blood samples and gastrocnemius muscle tissues of the rats were obtained under ketamine anesthesia (100 mg/kg; i.p). The effects of combining exercise and medication on skeletal muscle were assessed by examining the levels of significant biomarkers including PGC-1α, UCP-3, and MyHCs, as well as analyzing oxidative stress/antioxidant capacity parameters in muscle tissue samples. Additionally, relevant biochemical indicators were determined in serum samples. The quantity and morphology of mitochondria in muscle tissue were assessed using transmission electron microscopy. It was observed in the study that some toxic effects associated with the use of drugs alone were reduced by combination therapy. It is thought that this study will contribute to the literature in the evaluation of the effects of drugs and their combined use in Type 1 diabetes under exercise conditions. Graphical Abstract: (Figure presented.)