scholarly journals Atorvastatin attenuates intermittent hypoxia-induced myocardial oxidative stress in a mouse obstructive sleep apnea model

Aging ◽  
2021 ◽  
Author(s):  
Xiao-Bin Zhang ◽  
Hui-Juan Cheng ◽  
Ya-Ting Yuan ◽  
Yan Chen ◽  
Yi-Yuan Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Myocardial Oxidative Stress ◽  
Obstructive Sleep

scholarly journals Obstructive Sleep Apnea and Circulating Biomarkers of Oxidative Stress: A Cross-Sectional Study

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 476
Author(s):  
Bernardo U. Peres ◽  
AJ Hirsch Allen ◽  
Aditi Shah ◽  
Nurit Fox ◽  
Ismail Laher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Smoking History ◽  
Obstructive Sleep ◽  
History Of ◽  
Statin Usage ◽  
The Impact

Oxidative stress (OS) drives cardiometabolic diseases. Intermittent hypoxia consistently increases oxidative stress markers. Obstructive sleep apnea (OSA) patients experience intermittent hypoxia and an increased rate of cardiovascular disease, however, the impact of OSA on OS markers is not clear. The objective was to assess relationships between OSA severity and biomarker levels. Patients with suspected OSA referred for a polysomnogram (PSG) provided fasting blood sample. Plasma levels of 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were measured. The relationship between OSA and OS was assessed both before and after controlling for confounders (age, sex, smoking history, history of cardiovascular disease, ethnicity, diabetes, statin usage, body mass index (BMI)). 402 patients were studied (68% male, mean age ± SD = 50.8 ± 11.8 years, apnea-hypopnea index (AHI) = 22.2 ± 21.6 events/hour, BMI = 31.62 ± 6.49 kg/m2). In a multivariable regression, the AHI significantly predicted 8-isoprostane levels (p = 0.0008) together with age and statin usage; AHI was not a predictor of 8-OHdG or SOD. Female sex (p < 0.0001) and no previous history of cardiovascular disease (p = 0.002) were associated with increased antioxidant capacity. Circulating 8-isoprostane levels may be a promising biomarker of the severity of oxidative stress in OSA patients. Prospective studies are needed to determine whether this biomarker is associated with long-term cardiometabolic complications in OSA.

Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice

2007 ◽  
Vol 102 (5) ◽  
pp. 1806-1814 ◽  
Author(s):  
Ah-Mee Park ◽  
Yuichiro J. Suzuki
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Damage ◽  
Obstructive Sleep ◽  
Increased Risk

Obstructive sleep apnea is associated with increased risk for cardiovascular diseases. As obstructive sleep apnea is characterized by episodic cycles of hypoxia and normoxia during sleep, we investigated effects of intermittent hypoxia (IH) on ischemia-reperfusion-induced myocardial injury. C57BL/6 mice were subjected to IH (2 min 6% O2 and 2 min 21% O2) for 8 h/day for 1, 2, or 4 wk; isolated hearts were then subjected to ischemia-reperfusion. IH for 1 or 2 wk significantly enhanced ischemia-reperfusion-induced myocardial injury. However, enhanced cardiac damage was not seen in mice treated with 4 wk of IH, suggesting that the heart has adapted to chronic IH. Ischemia-reperfusion-induced lipid peroxidation and protein carbonylation were enhanced with 2 wk of IH, while, with 4 wk, oxidative stress was normalized to levels in animals without IH. H2O2 scavenging activity in adapted hearts was higher after ischemia-reperfusion, suggesting the increased antioxidant capacity. This might be due to the involvement of thioredoxin, as the expression level of this protein was increased, while levels of other antioxidant enzymes were unchanged. In the heart from mice treated with 2 wk of IH, ischemia-reperfusion was found to decrease thioredoxin. Ischemia-reperfusion injury can also be enhanced when thioredoxin reductase was inhibited in control hearts. These results demonstrate that IH changes the susceptibility of the heart to oxidative stress in part via alteration of thioredoxin.

scholarly journals Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia

2015 ◽  
Vol 118 (5) ◽  
pp. 544-557 ◽  
Author(s):  
Diane C. Lim ◽  
Daniel C. Brady ◽  
Pengse Po ◽  
Li Pang Chuang ◽  
Laise Marcondes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mouse Model ◽  
Mouse Models ◽  
Intermittent Hypoxia ◽  
Molecular Signatures ◽  
Rodent Models ◽  
Obstructive Sleep ◽  
And Oxidative Stress

Mouse models of cyclical intermittent hypoxia (CIH) are used to study the consequences of both hypoxia and oxidative stress in obstructive sleep apnea (OSA). Whether or not a mouse model of CIH that simulates OSA patients' oxygenation characteristics would translate into improved patient care remains unanswered. First we identified oxygenation characteristics using the desaturation and resaturation time in 47 OSA subjects from the Molecular Signatures of Obstructive Sleep Apnea Cohort (MSOSA). We observe that a cycle of intermittent hypoxia is not sinusoidal; specifically, desaturation time increases in an almost linear relationship to the degree of hypoxia (nadir), whereas resaturation time is somewhat constant (∼15 s), irrespective of the nadir. Second, we modified the Hycon mouse model of CIH to accommodate a 15-s resaturation time. Using this modified CIH model, we explored whether a short resaturation schedule (15 s), which includes the characteristics of OSA patients, had a different effect on levels of oxidative stress (i.e., urinary 8,12- iso-iPF2α-VI levels) compared with sham and a long resaturation schedule (90 s), a schedule that is not uncommon in rodent models of CIH. Results suggest that shorter resaturation time may result in a higher level of 8,12- iso-iPF2α-VI compared with long resaturation or sham conditions. Therefore, simulating the rodent model of CIH to reflect this and other OSA patients' oxygenation characteristics may be worthy of consideration to better understand the effects of hypoxia, oxidative stress, and their interactions.

scholarly journals Edaravone mitigates cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome via regulation of cAMP/PKACREB pathway

2021 ◽  
Vol 20 (11) ◽  
pp. 2299-2304
Author(s):  
Yongmei Zhao ◽  
Hongli Li ◽  
Yong Chen ◽  
Kexing Li ◽  
Sufei Yang
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Cognitive Impairment ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
New Drugs ◽  
Juvenile Rats ◽  
Protein Levels ◽  
Obstructive Sleep ◽  
Hypopnea Syndrome

Purpose: To investigate the influence of edaravone on cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome (OSAHS), and the mechanism involved.Methods: Fifty-four young Wistar rats were randomly selected into control, intermittent hypoxia and edaravone groups. The contents of the antioxidants CAT, Mn-SOD, Cu/Zn SOD and oxidative stress products malondialdehyde (MDA) in hippocampus were assayed and compared. The expressions of brain-derived neurotrophic factor (BDNF), Bcl-2, CREB, p-CREB and PKAc were determined.Results: The times taken to cross the target quadrant and the platform; levels of CAT and Mn-SOD, as well as protein levels of BNDF, Bcl-2, p-CREB and PKAc were markedly lower in intermittent hypoxia group than in controls; and MDA contents, 8-OHdG and protein hydroxyl were markedly higher in intermittent hypoxic rats group than in controls. Time taken to cross the platform and quadrant; activities of CAT and Mn-SOD, and protein concentrations of BDNF, Bcl-2, p-CREB and PKAc were markedly higher in the edaravone-treated rats than in intermittent hypoxia rats.Conclusion: Edaravone significantly mitigated cognitive damage and hippocampal lesions in OSAHS rats via a mechanism related to alleviation of oxidative stress and up-regulation of the expressions of p-CREB and its downstream proteins BDNF and Bcl-2. This finding provides a theoretical basis for research and development of new drugs against OSAHS.

Impact of obstructive sleep apnea and intermittent hypoxia on blood rheology – a translational study

2021 ◽  
pp. 2100352
Author(s):  
Xavier Waltz ◽  
Andrew E. Beaudin ◽  
Elise Belaidi ◽  
Jill Raneri ◽  
Jean-Louis Pépin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Blood Viscosity ◽  
Intermittent Hypoxia ◽  
Redox Balance ◽  
Erythrocyte Deformability ◽  
Erythrocyte Aggregation ◽  
Control Group ◽  
Obstructive Sleep

RationaleHemorheological alterations are reported in obstructive sleep apnea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress.ObjectiveTo investigate whether IH causes hemorheological alterations viaoxidative stress.MethodsWistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days. Twenty-three moderate-to-severe OSA patients were assessed at three time points: baseline, after randomisation to either 2 weeks of nocturnal oxygen (n=13) or no treatment (n=10), and after 1-month of CPAP treatment (n=17). Further, an OSA-free control group (n=13) was assessed at baseline and after time-matched follow-up.MeasurementsWe measured hemorheological parameters [hematocrit, blood viscosity, plasma viscosity (rats only), erythrocyte aggregation and deformability (humans only)] and redox balance (SOD, GPX, protein oxidation [AOPP] and lipid peroxidation [MDA]). We also tested erythrocytes hemorheological sensitivity to reactive oxygen species (ROS) in our human participants using the oxidant t-butyl hydroperoxide (TBHP).ResultsIn rats, IH increased blood viscosity by increasing hematocrit without altering erythrocytes hemorheological properties. IH also reduced SOD activity and increased AOPP. In humans, baseline hemorheological properties were similar between patients and controls, and properties were unaltered following oxygen and CPAP, except erythrocyte deformability was reduced following oxygen therapy. Redox balance was comparable between patients and controls. At baseline, TBHP induced a greater reduction of erythrocyte deformability in patients while CPAP reduced TBHP-induced increase in aggregation strength.ConclusionIH and OSA per se do not cause hemorheological alterations despite the presence of oxidative stress or higher sensitivity to ROS, respectively.

scholarly journals Cardiovascular Complications of Sleep Apnea: Role of Oxidative Stress

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Mohammad Badran ◽  
Najib Ayas ◽  
Ismail Laher
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Animal Models ◽  
Intermittent Hypoxia ◽  
Cardiovascular Complications ◽  
Middle Aged ◽  
Cellular Mechanisms ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) occurs in 2% of middle-aged women and 4% of middle-aged men with a higher prevalence among obese subjects. This condition is considered as an independent risk factor for cerebrovascular and cardiovascular diseases. One of the major pathophysiological characteristics of OSA is intermittent hypoxia. Hypoxia can lead to oxidative stress and overproduction of reactive oxygen species, which can lead to endothelial dysfunction, a hallmark of atherosclerosis. Many animal models, such as the rodent model of intermittent hypoxia, mimic obstructive sleep apnea in human patients and allow more in-depth investigation of biological and cellular mechanisms of this condition. This review discusses the role of oxidative stress in cardiovascular disease resulting from OSA in humans and animal models.

scholarly journals Intermittent hypoxia has organ-specific effects on oxidative stress

2008 ◽  
Vol 295 (4) ◽  
pp. R1274-R1281 ◽  
Author(s):  
Jonathan Jun ◽  
Vladimir Savransky ◽  
Ashika Nanayakkara ◽  
Shannon Bevans ◽  
Jianguo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Nadph Oxidase ◽  
Intermittent Hypoxia ◽  
Upper Airway ◽  
Oxidase Inhibitor ◽  
Enzyme Activation ◽  
Systemic Oxidative Stress ◽  
Obstructive Sleep

Obstructive sleep apnea is characterized by upper airway collapse, leading to intermittent hypoxia (IH). It has been postulated that IH-induced oxidative stress may contribute to several chronic diseases associated with obstructive sleep apnea. We hypothesize that IH induces systemic oxidative stress by upregulating NADPH oxidase, a superoxide-generating enzyme. NADPH oxidase is regulated by a cytosolic p47phox subunit, which becomes phosphorylated during enzyme activation. Male C57BL/6J mice were exposed to IH with an inspired O2 fraction nadir of 5% 60 times/h during the 12-h light phase (9 AM–9 PM) for 1 or 4 wk. In the aorta and heart, IH did not affect lipid peroxidation [malondialdehyde (MDA) level], nitrotyrosine level, or p47phox expression and phosphorylation. In contrast, in the liver, exposure to IH for 1 wk resulted in a trend to an increase in MDA levels, whereas IH for 4 wk resulted in a 38% increase in MDA levels accompanied by upregulation of p47phox expression and phosphorylation. Administration of an NADPH oxidase inhibitor, apocynin, during IH exposure attenuated IH-induced increases in hepatic MDA. In p47phox-deficient mice, MDA levels were higher at baseline and, unexpectedly, decreased during IH. In conclusion, oxidative stress levels and pathways under IH conditions are organ and duration specific.

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