Relationship Between Nrf2/Keap1 and Exercise-Induced Modulation of Oxidative Stress in Hippocampal Tissue of Aged Diabetic Rats

Introduction: Diabetes mellitus is a common metabolic disorder known for reducing antioxidant levels and concurrently increasing the production of free radicals. The Nrf2/Keap1/ARE signaling pathway may relate to insulin resistance in the brain. Exercise training may activate the production of reactive oxygen species (ROS) and boost antioxidant signaling pathways such as Nrf2/ Keap1/ARE in the brain. Methods: Fifteen male Wistar rats were divided into three groups: diabetic endurance training (DET, n=5), diabetic resistance training (DRT, n=5), and diabetic control (DC, n=5). Diabetes was induced using streptozotocin (30 mg/kg, i.p.) and a high-fat diet (55% fat, 31% carbohydrate, and 14% protein). The DET group underwent eight weeks of training at 75–60% of velocity at maximal oxygen uptake (vVO2max), while the DRT group performed resistance exercises at 60% of their maximum voluntary carrying capacity (MVCC), with the rats climbing a ladder 14–20 times per session, five days a week. Results: In the DET group, Nrf2 expression correlated positively with MVCC3, whereas no significant correlations were found in the DRT group, and a negative correlation was observed in the DC group. Nrf2 and vVO2max showed a significant negative correlation at the second measurement (r = -0.728, P = 0.002), especially in the DC group (r = -0.85, P < 0.01). Keap1 levels exhibited weak to moderate positive correlations with vVO2max across groups and significant positive correlations with MVCC parameters, particularly in the DRT group (r = 0.92, p = 0.01). Conclusion: The analysis revealed varying correlations between Nrf2 and Keap1 levels with exercise performance metrics (vVO2max and MVCC parameters), with significant relationships observed only in specific experimental groups, highlighting the need for further investigation into the differential effects of these proteins on exercise outcomes.