allopurinol and Apnea

Based on the fact that erythropoietin (Epo) administration in rodents protects against spatial learning and cognitive deficits induced by chronic intermittent hypoxia (CIH)-mediated oxidative damage, here we tested the hypothesis that Epo in the brain protects against cardiorespiratory disorders and oxidative stress induced by CIH in adult mice.. Adult control and transgenic mice overexpressing Epo in the brain only (Tg21) were exposed to CIH (21%-10% O2-10 cycles/hour-8 hours/day-7 days) or room air. After CIH exposure, we used the tail cuff method to measure arterial pressure, and whole-body plethysmography to assess the frequency of apneic episodes at rest, minute ventilation, and ventilatory responses to hypoxia and hypercapnia. Finally, the activity of pro-oxidant (XO-xanthine oxidase, and NADPH) and antioxidant (super oxide dismutase) enzymes was evaluated in the cerebral cortex and brainstem.. Exposure of control mice to CIH significantly increased the heart rate and arterial pressure, the number of apneic events, and the ventilatory response to hypoxia and hypercapnia. Furthermore, CIH increased the ratio of pro-oxidant to antioxidant enzymes in cortex and brainstem tissues. Both physiological and molecular changes induced by CIH were prevented in transgenic Tg21 mice.. We conclude that the neuroprotective effect of Epo prevents oxidative damage in the brain and cardiorespiratory disorders induced by CIH. Considering that Epo is used in clinics to treat chronic kidney disease and stroke, our data show convincing evidence suggesting that Epo may be a promising alternative drug to treat sleep-disorder breathing.

Topics: Animals; Apnea; Arterial Pressure; Brain; Brain Stem; Cerebral Cortex; Erythropoietin; Heart Rate; Hypercapnia; Hypoxia; Male; Mice; Mice, Transgenic; NADP; Oxidative Stress; Plethysmography, Whole Body; Pulmonary Ventilation; Reactive Oxygen Species; Rest; Sleep Apnea Syndromes; Superoxide Dismutase; Xanthine Oxidase

The aim was evaluating the effects of hypoxia/reoxygenation repetitive episodes during 5 days of apnea diving (3-day training/2-day competition) on peripheral blood mononuclear cells (PBMCs) antioxidant defenses, oxidative damage, and plasma xanthine oxidase activity. Blood samples, from seven professional apnea divers, were taken under basal conditions the previous morning to the first training session (pre-diving basal), 4 h after ending the competition (4 h post-diving) and the following morning (15 h after last dive) in basal conditions (post-diving basal). Glucose levels significantly decreased whereas triglycerides increased at 4 h post-diving, both returning to basal values at post-diving basal. Glutathione reductase and catalase activity significantly increased after 4 h post-diving remaining elevated at post-diving basal. Glutathione peroxidase and superoxide dismutase activities and catalase protein levels progressively increased after diving with significant differences respect to initial values at post-diving basal. No significant differences were observed in circulating PBMCs and oxidative damage markers. Plasma xanthine oxidase activity and nitrite levels, but not the inducible nitric oxide synthetase, significantly increased 4 h post-diving, returning to the basal values after 15 h. In conclusion, chronic and repetitive episodes of diving apnea during five consecutive days increased plasma xanthine oxidase activity and nitric oxide production which could enhance the signalling role of reactive oxygen and nitrogen species for PBMCs antioxidant adaptation against hypoxia/reoxygenation.

Topics: Adaptation, Physiological; Adult; Antioxidants; Apnea; Athletes; Catalase; Competitive Behavior; Diving; Humans; Lymphocytes; Male; Nitric Oxide Synthase Type II; Oxidative Stress; Xanthine Oxidase