Antioxidant defense responses to sleep loss and sleep recovery

Abstract

Sleep deprivation in humans is widely believed to impair health, and sleep is thought to have powerful restorative properties. The specific physical and biochemical factors and processes mediating these outcomes, however, are poorly elucidated. Sleep deprivation in the animal model produces a condition that eventually becomes highly lethal, lacks specific localization, and is reversible with sleep, implying mediation by a biochemical abnormality. Metabolic and immunological consequences of sleep deprivation point to a high potential for antioxidant imbalance. The objective, therefore, was to study glutathione content in the liver, heart, and lung, because glutathione is considered a major free radical scavenger that reflects the degree to which a tissue has been oxidatively challenged. We also investigated major enzymatic antioxidants, including catalase and glutathione peroxidase, as well as indexes of glutathione recycling. Catalase activity and glutathione content, which normally are tightly regulated, were both decreased in liver by 23-36% by 5 and 10 days of sleep deprivation. Such levels are associated with impaired health in other animal models of oxidative stress-associated disease. The decreases were accompanied by markers of generalized cell injury and absence of responses by the other enzymatic antioxidants under study. Enzymatic activities in the heart indicated an increased rate of oxidative pentose phosphate pathway activity during sleep deprivation. Recovery sleep normalized antioxidant content in liver and enhanced enzymatic antioxidant activities in both the liver and the heart. The present results link uncompensated oxidative stress to health effects induced by sleep deprivation and provide evidence that restoration of antioxidant balance is a property of recovery sleep.

Effects of 72 Hours Sleep Deprivation on Liver Circadian Clock Gene Expression and Oxidative Stress in Rats

“…In the liver tissue, GSH-Px also can accelerate the removal of free radicals to reduce liver injury. Everson et al found that GSH-Px activity in the liver was significantly lower than that in the control group after 5 days continuous SD [14]. Our experimental results showed that the activity of SOD and GSH-Px in the liver of the rats in the group SD was significantly lower than that in the control group, indicating that sleep deprivation could reduce the antioxidant stress ability.…”

Phagocyte migration and cellular stress induced in liver, lung, and intestine during sleep loss and sleep recovery

“…Sleep deprivation in rats was produced by the Bergmann-Rechtschaffen method (7, 24) for 5 or 10 days, which was tolerated and produced hyperphagia and a negative energy balance, as already reported (19). Two freely moving rats were studied at a time.…”

“…The 48-h period of measurement was based on previous findings of a return to near basal levels of energy expenditure (18) and normalization of the liver content of glutathione and catalase activity, which are principal free radical scavengers (19). Rats in the sleep recovery groups were injected 6 h before tissue harvest with 25 to 50 mg of bromodeoxyuridine (BrdU)/kg body wt for further studies of cell renewal.…”

Recurrent restriction of sleep and inadequate recuperation induce both adaptive changes and pathological outcomes

“…To produce chronic sleep restriction, the disk was rotated for 6 s according to a pattern of disk rotations that had reliably produced reduced and highly fragmented sleep under acute conditions (23,26). In these prior studies, the housing platform had been rotated for 6 s each time sleep onset was detected in a rat to be totally deprived of sleep, which reduced and fragmented the sleep of a paired rat housed on the same platform.…”

“…Each sleep-restriction period lasted 10 days, which is known to be tolerated in rats under acute sleep-loss conditions (2,18,20,21,24,28,53,55). Each intervening period of sleep ad libitum lasted 2 days, which previously has been shown to normalize energy expenditure and antioxidant parameters in totally sleepdeprived rats (22,23). The 10-day sleep-restriction and 2-day sleep-recuperation periods were repeated consecutively six times during 10 wk, which is a duration of 72 days determined a priori.…”