Abstract
Obstructive sleep apnea is a common disorder associated with aging and obesity. Apneas cause repeated arousals, intermittent hypoxia, and oxidative stress. Changes in glucolipidic profile occur in apnea patients, independently of obesity. Animal models of sleep apnea induce hyperglycemia. This study aims to evaluate the effect of the antioxidants melatonin and N-acetylcysteine on glucose, triglyceride, and cholesterol levels in animals exposed to intermittent hypoxia. Two groups of Balb/c mice were exposed to intermittent hypoxia (n = 36) or sham intermittent hypoxia (n = 36) for 35 days. The intermittent hypoxia group underwent a total of 480 cycles of 30 seconds reducing the inspired oxygen fraction from 21% to 7 ± 1% followed by 30 seconds of normoxia, during 8 hours daily. Melatonin or N-acetylcysteine were injected intraperitonially daily from day 21 on. At day 35, glucose levels were significantly higher in the intermittent hypoxia group than in the control group. The intermittent hypoxia groups receiving N-acetylcysteine and vehicle showed higher glucose levels than the group receiving melatonin. The lipid profile was not affected by intermittent hypoxia or antioxidant administration. The present results suggest that melatonin prevents the well-recognized increase in glucose levels that usually follows exposure to intermittent hypoxia. Further exploration of the role of melatonin in sleep apnea is warranted.
Highlights
Obstructive sleep apnea causes repeated arousals and intermittent hypoxia
The repeated hypoxic episodes seen in obstructive sleep apnea (OSA) in crease oxidative stress [5], which may represent a link between apneas and diabetes [6,7,8]
The intermittent hypoxia procedure has been described previously in adult male mice [18,19], a mixture of 90% N2 and 10% CO2 was released into the cages over a period of 30 seconds, gradually reducing the oxy gen fraction to 7 ± 1% and increasing the CO2 fraction to approximately 5 ± 1%; fans were operated for 30 seconds so as to introduce room air into the cage
Summary
Obstructive sleep apnea causes repeated arousals and intermittent hypoxia. Such events lead to sympathetic hyperactivity, oxidative stress, and insulin resistance [1]. The repeated hypoxic episodes seen in OSA in crease oxidative stress [5], which may represent a link between apneas and diabetes [6,7,8]. Intermittent hy poxia, a mod el of OSA, induces acute insulin resistance in healthy humans [9] and animals [10]. Mice recei ving obesity-inducing diets showed a greater increase of the HOMA index under intermittent hypoxia than lean mice [11]
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