The Implications of Combined Metformin and Atorvastatin Treatment on Oxidative Stress/ Antioxidant Status in the Gastrocnemius Muscle of Treadmill Exercised STZ-Diabetic Rats


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Tunçyürekli M., Tülüce Y., Lermioğlu Erciyas F.

8th World Congress of Oxidative Stress, Calcium Signaling and TRP Channels, Isparta, Türkiye, 5 - 08 Eylül 2023, cilt.15, sa.3, ss.53

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 15
  • Basıldığı Şehir: Isparta
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.53
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

In patients with uncontrolled type 1 diabetes (T1DM), hyperglycemia increases reactive oxygen radical (ROS) production and oxidative stress (OS), especially in skeletal muscle. Excess OS damages striated muscle tissues and reduces physical activity, resulting in a decline in the patient's quality of life. Regular physical activity is thought to enhance the respiratory capacity of muscles. It can also mitigate the harmful impact of diabetes by facilitating the adaptation of the body to exercise. This process involves the activation of antioxidant systems and related mechanisms to counteract the rise in ROS production. On the other hand, some studies suggest that exercise could potentially increase OS. Metformin and atorvastatin are frequently-used drugs to regulate disease and prevent cardiovascular complications in T1DM. In addition, they have some impact on oxidative stress and skeletal muscle functions. Currently, there is no research on the effects of the simultaneous use of these medications on T1DM patients who exercise. This study aimed to explore the impact of administering metformin and atorvastatin in combination on skeletal muscle oxidant/antioxidant parameters in T1DM rats undergoing moderate intensity treadmill training. Male Wistar rats were divided into six groups for this study: a sedentary control group (naive; 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). Diabetes was induced by administering Streptozotocin (STZ) at a dose of 45 mg/kg intraperitoneally. The study included rats whose glucose levels in the tail vein blood were greater than 250 mg/dL after ten days. The exercise groups of rats engaged in treadmill running for five days per week, while the administration of drugs was conducted seven days per week. At the conclusion of the fourth week, samples of the rats' gastrocnemius muscle were obtained while under ketamine anaesthesia (100 mg/kg; i.p.). Superoxide dismutase (SOD) activity, reduced glutathione (GSH), and malondialdehyde (MDA) levels were assessed as indicators of oxidative stress/antioxidant status. Analyses of total oxidative capacity (TOS) and total antioxidant capacity (TAS) were conducted to determine the oxidative stress index (OSI). At the end of the study, the MDA levels, an indicator of oxidative stress, were found to have increased, whereas GSH levels were found to have decreased in group D. There was not any significant effect of drugs on these parameters. Although the combination of drugs decreased OSI, metformin alone was proven to be more effective. The drugs showed an increase in SOD activity. In conclusion, to evaluate the effects of drug combinations with greater precision, more comprehensive analyses are necessary.