Normal adaptations to exercise despite protection against oxidative stress

Abstract

It has been reported that supplementation with the antioxidant vitamins C and E prevents the adaptive increases in mitochondrial biogenesis and GLUT4 expression induced by endurance exercise. We reevaluated the effects of these antioxidants on the adaptive responses of rat skeletal muscle to swimming in a short-term study consisting of 9 days of vitamins C and E with exercise during the last 3 days and a longer-term study consisting of 8 wk of antioxidant vitamins with exercise during the last 3 wk. The rats in the antioxidant groups were given 750 mg·kg body wt(-1)·day(-1) vitamin C and 150 mg·kg body wt(-1)·day(-1) vitamin E. In rats euthanized immediately after exercise, plasma TBARs were elevated in the control rats but not in the antioxidant-supplemented rats, providing evidence for an antioxidant effect. In rats euthanized 18 h after exercise there were large increases in insulin responsiveness of glucose transport in epitrochlearis muscles mediated by an approximately twofold increase in GLUT4 expression in both the short- and long-term treatment groups. The protein levels of a number of mitochondrial marker enzymes were also increased about twofold. Superoxide dismutases (SOD) 1 and 2 were increased about twofold in triceps muscle after 3 days of exercise, but only SOD2 was increased after 3 wk of exercise. There were no differences in the magnitudes of any of these adaptive responses between the control and antioxidant groups. These results show that very large doses of antioxidant vitamins do not prevent the exercise-induced adaptive responses of muscle mitochondria, GLUT4, and insulin action to exercise and have no effect on the level of these proteins in sedentary rats.

Fig. 1.

The antioxidant vitamin supplementation prevented an exercise-induced increase in thiobarbituric acid-reactive substances (TBARs) in plasma. Values are means ± SE for 3 rats in each of the sedentary (Sed) groups and for 6 rats in each of the exercised (Ex) groups. *P < 0.05 vs. other groups.

Fig. 2.

A: expression of superoxide dismutase (SOD)1 and SOD2 proteins increased in response to 3 days of exercise training in both the antioxidant (AO) and control groups. Values are means ± SE for 3 rats in each of the Sed groups and 6 rats in each of the Ex groups. *P < 0.05 vs. sedentary groups. B: expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) increased to the same extent in the AO and V groups in response to 3 days of exercise training. C: expression of mitochondrial enzyme proteins increased to the same extent in the AO-supplemented and control groups in response to 3 days of exercise training. Values are means ± SE for 3 rats in each of the Sed groups and 6 rats in each of the Ex groups. V, vehicle. *P < 0.05 vs. Sed groups. LCAD, long-chain acyl-CoA dehydrogenase; NADH-UO, NADH-ubiquinone oxidoreductase; SUO, succinate-ubiquinone oxidoreductase 30-kDa subunit; COX-I and -IV, cytochrome oxidase subunits I and IV, respectively.

Fig. 3.

A: glucose transporter 4 (GLUT4) protein expression increased to the same extent in triceps muscles of the AO vitamin supplemented and control rats in response to the 3 days of exercise. *Exercised vs. sedentary, P < 0.05. B: insulin responsiveness of 2-deoxyglucose transport increased similarly in the AO vitamin supplemented and control groups in response to the 3 days of exercise training. Values are means ± SE for 3 rats in each of the Sed groups and 6 rats in each of the Ex groups. *Insulin-treated vs. basal, P < 0.05 for both the AO and V groups. †Insulin-treated Ex vs. insulin-treated Sed, P < 0.05 for both the AO and the V groups.

Fig. 4.

A: effects of 3 wk of exercise and 8 wk of AO supplementation on expression of SOD1 and SOD2 proteins in triceps muscles of the control and AO groups. B: effects of 3 wk of exercise on expression of mitochondrial proteins in triceps muscles of the control and AO groups. Values are means ± SE for 6 animals/group. *P < 0.05 vs. Sed groups.

Fig. 5.

A: GLUT4 expression. *Exercise vs. sedentary, P < 0.01. B: insulin responsiveness of glucose transport in soleus muscles of control and AO groups after 8 wk of AO supplementation and 3 wk of exercise. *Insulin vs. basal, P < 0.01. †Exercised vs. sedentary, P < 0.05. Values are means ± SE for 6 muscles/group.