Preventive Effects And Mechanisms Of Mitochondrial Targeting Nutrients On Endurance Exercise-induced Fatigue

Endurance exercise-induced fatigue is a common physiological response. The key point for improving exercise ability is having appropriate fatigue with quick recovery. It has been proven that the exercise-induced fatigue could result in over production of reactive oxygen species from mitochondria. Therefore, inhibiting oxidative damage and improving mitochondrial function might be a good strategy to reduce exercise induced-fatigue and accelerate recovery. We have identified a group of nutrients as mitochondrial targeting nutrients because they protect mitochondria from damage and maintain the function of mitochondria for normal physiological activities. In the present study, we have shown that an appropriately selected combination of mitochondrial nutrients is effective on reducing exercise-induced fatigue and accelerating recovery by synergistically improving mitochondrial structure and function through the actions on various pathways.Aims:Exhaustive exercise causes fatigue due to mitochondrial dysfunction and oxidative stress. In order to find an effective strategy to prevent fatigue and/or enhance recovery, we studied the effects of a combination of mitochondrial targeting nutrients on physical activity, mitochondrial function and oxidative stress in exhaustively exercised rats.Main methods:The present study was to investigate the effects of a combination of mitochondrial nutrients on physical performance and related biochemical parameters in rats during long-term exhaustive exercise. Rats were randomly divided into three groups:sedentary control (SC), exhaustive-exercise (EC) and exhaustive-exercise with nutrients (EN) which received a combination of mitochondrial nutrients supplementation for 12 weeks (4 week prior to the exercise program and 8 weeks during the exercise prohram). Rats in EC and EN groups were submitted to an exercise program, which contains four- week endurance training and four-week exhaustive exercise. Key findings:Examination of running distance over the 4-week period revealed that EC group rats ran less distance throughout the entire duration of the exhaustive exercise period compared with EN group rats. The activities of plasma alanine transaminase (ALT), lactate dehydrogenase (LDH) and creatine-kinase (CK) in the EC group were significantly higher than those in the SC group. However, nutrients supplementation attenuated the elevation of these enzyme activities in the plasma of rats. The rise in malondialdehyde (MDA) following the treadmill test was significantly less after nutrients supplementation. In addition, nutrients also inhibited the decrease of the activity of glutathione S-transferase (GST) and total antioxidant capacity (TOC) in plasma. The percentage of apoptotic cells increased significantly in spleen lympocytes and the generation of reactive oxygen species (ROS) also enhanced after 24h-recovery of the exhaustive exercise in the EC group. Nutrients supplementation also suppressed the elevation of ROS and apoptosis in the EN group. We found that the nutrient treatment significantly increased the running time, improved mitochondrial function and reduced oxidative stress in muscle.We also found that exhaustive exercise induced an increase in activities of mitochondrial complexes I, IV and V, an increase in GSH level and a decrease in ROS in liver mitochondria but no change in levels of ROS and MDA, or in activities of complexes II and III. Exercise also induced a significant increase in MDA and activities of glutathione S-transferase and NADPH-quinone-oxidoreductase 1 (NQO-1) in the liver homogenate. The nutrient treatment showed amelioration of the complex V and NQO-1 activities, but no effect on other parameters.Conclusions:We found that exhaustive exercise reduced the running time, increased the activities of ALT and LDH and the levels of red blood cells, hemoglobin and hemocrit, depressed kidney function (decreased levels of BUN and creatine) and immune function, decreased mitochondrial function in muscle and liver, elevated oxidative stress and decreased antioxidant defense in plasma, muscle, liver and spleen. We also found that the mitochondrial targeting nutrient treatment treatment significantly increased the running time, ameliorated the abnormality of plasma enzymes and oxygen transportation system, imporved the kidney function and immune function, protected the mitochondrial dysfunction in muscle and liver, enhanced antioxidant defense system and reduced oxidative stress in plasma, muscle, liver and spleen. In addition, we showed that, the nutrient treatment has less impact on exercise-induced oxidative and mitochondrial stress in the liver than in the muscle.