Alcohol-induced deterioration in primary antioxidant and glutathione family enzymes reversed by exercise training in the liver of old rats.

Chronic alcohol consumption causes severe hepatic oxidative damage, particularly to old subjects by decreasing various antioxidant enzymes. In this study, we test the hypothesis that exercise training can protect the aging liver against alcohol-induced oxidative damage. Two different age groups of Wistar albino rats (3 months young, n=24; 18 months old, n=24) were evenly divided into four groups: control (Con), exercise trained (Tr, 23 m/min 30 min/day, 5 days/week for 2 months), ethanol drinking/treated (Et, 2.0 g/kg b.w. orally), and exercise training plus ethanol drinking/treated (Tr+Et). We found significantly (P<.001) lowered hepatic antioxidant enzymes including superoxide dismutase, catalase, selenium (Se)-dependent glutathione peroxidase (Se-GSH-Px), Se-non-dependent glutathione peroxidase (non-Se-GSH-Px), glutathione reductase, and glutathione S-transferase activities in aged rats compared with young. Age-related decrease in antioxidant enzyme status was further exacerbated with ethanol drinking, which indicates liver in aged rats is more susceptible to oxidative damage because of decreased free radical scavenging system in aged/old ethanol-drinking rats. However, the decrease in liver antioxidant enzymes status with ethanol consumption was ameliorated by 2 months exercise training in old and young rats. These results demonstrate that age-associated decrease in hepatic free radical scavenging system exacerbated by ethanol drinking. For the first time, we found that this deterioration was significantly reversed by exercise training in aging liver, thus protects against alcohol-induced oxidative damage.

Effect of mild intermittent hypoxia on glucose tolerance, muscle morphology and AMPK-PGC-1alpha signaling.

The main goal of this study was to investigate the long-term effect of daily 8-hour mild intermittent hypoxia (14-15% O2) on glucose tolerance and muscle morphology of Sprague-Dawley rats. The involvement of AMPK-PGC-1alpha-VEGF signaling pathways in the skeletal muscle was also determined during the first 8 hours of hypoxia. We found that mRNA levels of VEGF and PGC-1alpha were significantly increased above control after 8-h mild hypoxia without a change in AMPK phosphorylation. After 8 weeks of mild intermittent hypoxia treatment, plasma glucose and insulin levels in oral glucose tolerance test (OGTT), epididymal fat mass, and body weight were significantly lower compared to the control group. While soleus muscle weight was not changed, capillary and fiber densities in the hypoxia group were 33% and 35% above the control suggesting reorganization of muscle fibers. In conclusion, our data provide strong evidence that long-term mild intermittent hypoxia decreases the diffusion distance of glucose and insulin across muscle fibers, and decreases adiposity in rats. These changes may account for the improved glucose tolerance observed following the 8-week hypoxia treatment, and provides grounds for investigating the development of a mild non-pharmacological intervention in the treatment of obesity and type 2 diabetes.