scholarly journals Curcumin prevents chronic intermittent hypoxia-induced myocardial injury

2020 ◽  
Vol 11 ◽  
pp. 204062232092210 ◽  
Author(s):  
Sophie Moulin ◽  
Claire Arnaud ◽  
Sophie Bouyon ◽  
Jean-Louis Pépin ◽  
Diane Godin-Ribuot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Er Stress ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Sleep Apnoea ◽  
Cardiac Response ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep

Background: Chronic intermittent hypoxia (IH), the hallmark feature of obstructive sleep apnoea syndrome, contributes to infarct size enhancement after myocardial ischemia–reperfusion (I/R). Curcumin (Curc), the natural pigment of Curcuma longa, has been demonstrated to be beneficial in the context of myocardial injury. In this study, we assessed the effects of Curc on the maladaptive cardiac response to IH, and particularly on IH-induced hypoxia inducible factor-1 (HIF-1) expression, oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis. Methods: Swiss/SV129 mice were exposed to normoxia or IH (21–5% FiO2, 60 s cycles, 8 h per day, for 21 days) and treated orally with Curc (100 mg kg−1 day−1, oral gavage) or its vehicle. Mice were then either euthanised for heart sampling in order to perform biochemical and histological analysis, or subjected to an in vivo ischemia-reperfusion protocol in order to measure infarct size. Results: IH increased nuclear HIF-1α expression and superoxide anion (O2.–) production as well as nuclear factor kappa B (NF-kB) p65, glucose-regulated protein (Grp78) and C/EBP homologous protein (CHOP) expression. IH also induced apoptosis and increased infarct size after I/R . The IH-induced HIF-1 activation, oxidative stress, inflammation, ER stress and apoptosis were abolished by chronic Curc treatment. Curc also significantly decreased infarct size only in mice exposed to IH. Conclusion: Curc prevents IH-induced myocardial cell death signalling. Curc might be used as a combined therapy with continuous positive airway pressure in sleep apnoea patients with high cardiovascular risk.

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 Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation:The Role of Hydrogen Peroxide

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Xia Yin ◽  
Yang Zheng ◽  
Quan Liu ◽  
Jun Cai ◽  
Lu Cai
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Intermittent Hypoxia ◽  
Cardiac Response ◽  
Chronic Intermittent Hypoxia ◽  
Critical Element ◽  
Respiratory Disorder ◽  
Obstructive Sleep ◽  
Antioxidative Therapy

Obstructive sleep apnea (OSA) is a highly prevalent respiratory disorder of sleep, and associated with chronic intermittent hypoxia (CIH). Experimental evidence indicates that CIH is a unique physiological state with potentially “adaptive” and “maladaptive” consequences for cardio-respiratory homeostasis. CIH is also a critical element accounting for most of cardiovascular complications of OSA. Cardiac response to CIH is time-dependent, showing a transition from cardiac compensative (such as hypertrophy) to decompensating changes (such as failure). CIH-provoked mild and transient oxidative stress can induce adaptation, but severe and persistent oxidative stress may provoke maladaptation. Hydrogen peroxide as one of major reactive oxygen species plays an important role in the transition of adaptive to maladaptive response to OSA-associated CIH. This may account for the fact that although oxidative stress has been recognized as a driver of cardiac disease progression, clinical interventions with antioxidants have had little or no impact on heart disease and progression. Here we focus on the role of hydrogen peroxide in CIH and OSA, trying to outline the potential of antioxidative therapy in preventing CIH-induced cardiac damage.

scholarly journals Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Thomas Gille ◽  
Morgane Didier ◽  
Cécile Rotenberg ◽  
Eva Delbrel ◽  
Dominique Marchant ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Fibrosis ◽  
Pulmonary Edema ◽  
Cell Apoptosis ◽  
Lung Fibrosis ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep ◽  
The Impact ◽  
Lung Oxidative Stress

Background. Severe obstructive sleep apnea (OSA) with chronic intermittent hypoxia (IH) is common in idiopathic pulmonary fibrosis (IPF). Here, we evaluated the impact of IH on bleomycin- (BLM-) induced pulmonary fibrosis in mice. Methods. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day) or intermittent air (IA). In the four experimental groups, we evaluated (i) survival; (ii) alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii) lung cell apoptosis; and (iv) pulmonary fibrosis. Results. Survival at day 21 was lower in the BLM-IH group (p<0.05). Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content (p=0.02) and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, (p<0.001). Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice (p<0.05 versus BLM-IA group). At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. Conclusion. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.

scholarly journals Silencing MR-1 Protects against Myocardial Injury Induced by Chronic Intermittent Hypoxia by Targeting Nrf2 through Antioxidant Stress and Anti-Inflammation Pathways

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Qixue Wang ◽  
Yue Wang ◽  
Jiner Zhang ◽  
Shuo Pan ◽  
Shaofeng Liu
Keyword(s):  
Oxidative Stress ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Cardiac Insufficiency ◽  
Inflammatory Factors ◽  
Chronic Intermittent Hypoxia ◽  
Heme Oxygenase 1 ◽  
Stress System ◽  
Antioxidant Stress ◽  
And Oxidative Stress

Background. Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) often have cardiac insufficiency mainly due to hypoxia/reperfusion injury caused by chronic intermittent hypoxia (CIH). Inflammation and oxidative stress are involved in the cardiovascular events of OSAHS patients. Studies have found that myofibrillation regulator-1 (MR-1) participates in the pathological process of OSAHS-induced myocardial injury, but the specific mechanism is still unclear. Methods. We used a CIH-induced rat model to simulate the process of OSAHS disease. Indices of myocardial injury, inflammation, and oxidative stress were detected using quantitative PCR and enzyme-linked immunosorbent assay (ELISA). After administration of adenoassociated viral vector (AAV) encoding silencing RNA against MR-1, we examined expression of the classic antioxidant stress pathway protein NF-E2-related factor 2 (Nrf2) using western blotting. Results. We found that levels of serum inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 were increased, and we further observed disturbance of the oxidative stress system, in which the content of reactive oxygen species (ROS), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) was enhanced in CIH-induced rats. Subsequently, we detected that expression of Nrf2 and heme oxygenase-1 (HO-1) was slightly increased, while the expression of Kelch-like ECH-associated protein 1 (Keap-1) was significantly increased in the CIH model. Interestingly, after administration of silencing MR-1 AAV, the elevated levels of inflammatory factors were reduced, and the disordered oxidative stress system was corrected. Additionally, the expression of Nrf2 and HO-1 was distinctly increased, but the high expression of Keap-1 was decreased. Conclusions. Our research results demonstrate that silencing MR-1 rescued the myocardium the injury from inflammatory and oxidative stress in CIH-induced rats by administration of the Nrf2 signaling pathway.

High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size

2016 ◽  
Vol 310 (2) ◽  
pp. H279-H289 ◽  
Author(s):  
Guillaume Bourdier ◽  
Patrice Flore ◽  
Hervé Sanchez ◽  
Jean-Louis Pepin ◽  
Elise Belaidi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Infarct Size ◽  
Er Stress ◽  
High Intensity ◽  
Intermittent Hypoxia ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
High Intensity Training ◽  
Intensity Training

Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 × 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 ± 3.2% vs. 22.7 ± 1.7% of ventricles in IH + sedenary and normoxia + sedentary groups, respectively, P < 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 ± 3.9% and 21.0 ± 5.1% in IH + HIT and normoxia + HIT groups, respectively, P = 0.28). In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IH-induced myocardial ischemia-reperfusion damages in OSA patients.

scholarly journals Nitration of MnSOD in the Carotid Body and Adrenal Gland Induced by Chronic Intermittent Hypoxia

2018 ◽  
Vol 66 (10) ◽  
pp. 753-765
Author(s):  
Esteban A. Moya ◽  
Paulina Arias ◽  
Rodrigo Iturriaga
Keyword(s):  
Oxidative Stress ◽  
Adrenal Gland ◽  
Enzymatic Activity ◽  
Adrenal Medulla ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Sprague Dawley ◽  
Obstructive Sleep ◽  
Key Enzyme

Chronic intermittent hypoxia (CIH), main feature of obstructive sleep apnea, produces nitro-oxidative stress, which contributes to potentiate carotid body (CB) chemosensory discharges and sympathetic-adrenal-axis activity, leading to hypertension. The MnSOD enzymatic activity, a key enzyme on oxidative stress control, is reduced by superoxide-induced nitration. However, the effects of CIH-induced nitration on MnSOD enzymatic activity in the CB and adrenal gland are not known. We studied the effects of CIH on MnSOD protein and immunoreactive (MnSOD-ir) levels in the CB, adrenal gland and superior cervical ganglion (SCG), and on 3-nitrotyrosine (3-NT-ir), CuZnSOD (CuZnSOD-ir), MnSOD nitration, and its enzymatic activity in the CB and adrenal gland from male Sprague-Dawley rats exposed to CIH for 7 days. CIH increased 3-NT-ir in CB and adrenal gland, whereas MnSOD-ir increased in the CB and in adrenal cortex, but not in the whole adrenal medulla or SCG. CIH nitrated MnSOD in the CB and adrenal medulla, but its activity decreased in the adrenal gland. CuZnSOD-ir remained unchanged in both tissues. All changes observed were prevented by ascorbic acid treatment. Present results show that CIH for 7 days produced MnSOD nitration, but failed to reduce its activity in the CB, because of the increased protein level.

scholarly journals Human concentrations of uric acid scavenges adaptive and maladaptive reactive oxygen species in isolated rat hearts subjected to ischemic stress

2020 ◽  
Vol 98 (3) ◽  
pp. 139-146 ◽  
Author(s):  
Neoma T. Boardman ◽  
Aleksander Tank Falck ◽  
Trine Lund ◽  
Xi Chu ◽  
Montserrat Martin-Armas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Uric Acid ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Cardiac Response ◽  
Oxygen Species

Uric acid is a purine degradation product but also an important antioxidant and reactive oxygen species (ROS) scavenger. Experimental settings that mimic myocardial ischemia–reperfusion have not included uric acid despite that it is always present in human extracellular fluid and plasma. We hypothesized that uric acid has an important role in myocardial ROS scavenging. Here, we tested the cardiac response to uric acid on infarct size following ischemia–reperfusion with and without exacerbated oxidative stress due to acute pressure overload and during preconditioning. We also examined mitochondrial respiration and ROS-induced mitochondrial permeability transition pore opening. Under exacerbated ROS stress induced by high-pressure perfusion, uric acid lowered oxidative stress and reduced infarct size. In contrast, uric acid blocked cardioprotection induced by ischemic preconditioning. However, this effect was reversed by probenecid, an inhibitor of cellular uptake of uric acid. In accordance, in intact cardiomyocytes, extracellular uric acid reduced the susceptibility of mitochondria towards opening of the permeability transition pore, suggesting that uric acid may prevent ischemia–reperfusion injury due to scavenging of maladaptive ROS. Moreover, as uric acid also scavenges adaptive ROS, this may interfere with preconditioning. Altogether, uric acid might be a confounder when translating preclinical experimental results into clinical treatment.

scholarly journals Chronic Intermittent Hypoxia Induces Early-Stage Metabolic Dysfunction Independently of Adipose Tissue Deregulation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1233
Author(s):  
Fátima O. Martins ◽  
Joana F. Sacramento ◽  
Elena Olea ◽  
Bernardete F. Melo ◽  
Jesus Prieto-Lloret ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Intermittent Hypoxia ◽  
Early Stage ◽  
Tissue Hypoxia ◽  
Whole Body ◽  
Chronic Intermittent Hypoxia ◽  
Adipose Tissue Dysfunction ◽  
Obstructive Sleep

Several studies demonstrated a link between obstructive sleep apnea (OSA) and the development of insulin resistance. However, the main event triggering insulin resistance in OSA remains to be clarified. Herein, we investigated the effect of mild and severe chronic intermittent hypoxia (CIH) on whole-body metabolic deregulation and visceral adipose tissue dysfunction. Moreover, we studied the contribution of obesity to CIH-induced dysmetabolic states. Experiments were performed in male Wistar rats submitted to a control and high-fat (HF) diet. Two CIH protocols were tested: A mild CIH paradigm (5/6 hypoxic (5% O2) cycles/h, 10.5 h/day) during 35 days and a severe CIH paradigm (30 hypoxic (5% O2) cycles, 8 h/day) during 15 days. Fasting glycemia, insulinemia, insulin sensitivity, weight, and fat mass were assessed. Adipose tissue hypoxia, inflammation, angiogenesis, oxidative stress, and metabolism were investigated. Mild and severe CIH increased insulin levels and induced whole-body insulin resistance in control animals, effects not associated with weight gain. In control animals, CIH did not modify adipocytes perimeter as well as adipose tissue hypoxia, angiogenesis, inflammation or oxidative stress. In HF animals, severe CIH attenuated the increase in adipocytes perimeter, adipose tissue hypoxia, angiogenesis, and dysmetabolism. In conclusion, adipose tissue dysfunction is not the main trigger for initial dysmetabolism in CIH. CIH in an early stage might have a protective role against the deleterious effects of HF diet on adipose tissue metabolism.

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