Intermittent cold and hypobaric hypoxia treatment modulates oxidative stress in injured muscles of rats

Background: Exposure to intermittent hypoxia has been demonstrated to be an efficient tool for hypoxic preconditioning, preventing damage to cells and demonstrating therapeutic benefits. We aimed to evaluate the effects of respiratory intermittent hypobaric hypoxia (IHH) to avoid brain injury caused by exposure to acute severe hypoxia (ASH). Methods: biomarkers of oxidative damage, mitochondrial apoptosis, and transcriptional factors in response to hypoxia were assessed by Western blot and immunohistochemistry in brain tissue. Four groups of rats were used: (1) normoxic (NOR), (2) exposed to ASH (FiO2 7% for 6 h), (3) exposed to IHH for 3 h per day over 8 days at 460 mmHg, and (4) ASH preconditioned after IHH. Results: ASH animals underwent increased oxidative-stress-related parameters, an upregulation in apoptotic proteins and had astrocytes with phenotype forms compatible with severe diffuse reactive astrogliosis. These effects were attenuated and even prevented when the animals were preconditioned with IHH. These changes paralleled the inhibition of NF-κB expression and the increase of erythropoietin (EPO) levels in the brain. Conclusions: IHH exerted neuroprotection against ASH-induced oxidative injury by preventing oxidative stress and inhibiting the apoptotic cascade, which was associated with NF-κB downregulation and EPO upregulation.

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Mitochondrial DNA mutations contribute to high altitude pulmonary edema via increased oxidative stress and metabolic reprogramming during hypobaric hypoxia

Biochimica et Biophysica Acta (BBA) - Bioenergetics ◽

10.1016/j.bbabio.2021.148431 ◽

2021 ◽

Vol 1862 (8) ◽

pp. 148431

Author(s):

Swati Sharma ◽

Yamini Singh ◽

Rajat Sandhir ◽

Sayar Singh ◽

Lilly Ganju ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dna ◽

Pulmonary Edema ◽

High Altitude ◽

Hypobaric Hypoxia ◽

Metabolic Reprogramming ◽

Mitochondrial Dna Mutations ◽

Dna Mutations ◽

High Altitude Pulmonary Edema

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Huperzine A Ameliorates Cognitive Deficits and Oxidative Stress in the Hippocampus of Rats Exposed to Acute Hypobaric Hypoxia

Neurochemical Research ◽

10.1007/s11064-012-0826-x ◽

2012 ◽

Vol 37 (9) ◽

pp. 2042-2052 ◽

Cited By ~ 23

Author(s):

Qinghai Shi ◽

Jianfeng Fu ◽

Di Ge ◽

Yan He ◽

Jihua Ran ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Deficits ◽

Hypobaric Hypoxia ◽

Huperzine A ◽

Acute Hypobaric Hypoxia ◽

And Oxidative Stress

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Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia

International Journal of Molecular Sciences ◽

10.3390/ijms21176421 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6421

Author(s):

Eduardo Pena ◽

Julio Brito ◽

Samia El Alam ◽

Patricia Siques

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Right Ventricular ◽

Hypobaric Hypoxia ◽

Ventricular Hypertrophy ◽

Current Knowledge ◽

Right Heart Failure ◽

Right Ventricular Hypertrophy ◽

Therapeutic Approaches ◽

Inflammatory Molecules

High altitude (hypobaric hypoxia) triggers several mechanisms to compensate for the decrease in oxygen bioavailability. One of them is pulmonary artery vasoconstriction and its subsequent pulmonary arterial remodeling. These changes can lead to pulmonary hypertension and the development of right ventricular hypertrophy (RVH), right heart failure (RHF) and, ultimately to death. The aim of this review is to describe the most recent molecular pathways involved in the above conditions under this type of hypobaric hypoxia, including oxidative stress, inflammation, protein kinases activation and fibrosis, and the current therapeutic approaches for these conditions. This review also includes the current knowledge of long-term chronic intermittent hypobaric hypoxia. Furthermore, this review highlights the signaling pathways related to oxidative stress (Nox-derived O2.- and H2O2), protein kinase (ERK5, p38α and PKCα) activation, inflammatory molecules (IL-1β, IL-6, TNF-α and NF-kB) and hypoxia condition (HIF-1α). On the other hand, recent therapeutic approaches have focused on abolishing hypoxia-induced RVH and RHF via attenuation of oxidative stress and inflammatory (IL-1β, MCP-1, SDF-1 and CXCR-4) pathways through phytotherapy and pharmacological trials. Nevertheless, further studies are necessary.

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CYBA and GSTP1 variants associate with oxidative stress under hypobaric hypoxia as observed in high-altitude pulmonary oedema

Clinical Science ◽

10.1042/cs20110205 ◽

2011 ◽

Vol 122 (6) ◽

pp. 299-311 ◽

Cited By ~ 14

Author(s):

Aastha Mishra ◽

Zahara Ali ◽

Arpana Vibhuti ◽

Rahul Kumar ◽

Perwez Alam ◽

...

Keyword(s):

Oxidative Stress ◽

High Altitude ◽

Pulmonary Oedema ◽

Hypobaric Hypoxia ◽

Glutathione Transferase ◽

Prostaglandin F2α ◽

Gene Interactions ◽

Potential Candidate ◽

Genotype Distribution ◽

Risk Alleles

HAPE (high-altitude pulmonary oedema) is characterized by pulmonary hypertension, vasoconstriction and an imbalance in oxygen-sensing redox switches. Excess ROS (reactive oxygen species) contribute to endothelial damage under hypobaric hypoxia, hence the oxidative-stress-related genes CYBA (cytochrome b−245 α polypeptide) and GSTP1 (glutathione transferase Pi 1) are potential candidate genes for HAPE. In the present study, we investigated the polymorphisms −930A/G and H72Y (C/T) of CYBA and I105V (A/G) and A114V (C/T) of GSTP1, individually and in combination, in 150 HAPE-p (HAPE patients), 180 HAPE-r (HAPE-resistant lowland natives) and 180 HLs (healthy highland natives). 8-Iso-PGF2α (8-iso-prostaglandin F2α) levels were determined in plasma and were correlated with individual alleles, genotype, haplotype and gene–gene interactions. The relative expression of CYBA and GSTP1 were determined in peripheral blood leucocytes. The genotype distribution of −930A/G, H72Y (C/T) and I105V (A/G) differed significantly in HAPE-p compared with HAPE-r and HLs (P≤0.01). The haplotypes G-C of −930A/G and H72Y (C/T) in CYBA and G-C and G-T of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-p; in contrast, haplotypes A-T of −930A/G and H72Y (C/T) in CYBA and A-C of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-r and HLs. 8-Iso-PGF2α levels were significantly higher in HAPE-p and in HLs than in HAPE-r (P=2.2×10−16 and 1.2×10−14 respectively) and the expression of CYBA and GSTP1 varied differentially (P<0.05). Regression analysis showed that the risk alleles G, C, G and T of −930A/G, H72Y (C/T), I105V (A/G) and A114V (C/T) were associated with increased 8-iso-PGF2α levels (P<0.05). Interaction between the two genes revealed over-representation of most of the risk-allele-associated genotype combinations in HAPE-p and protective-allele-associated genotype combinations in HLs. In conclusion, the risk alleles of CYBA and GSTP1, their haplotypes and gene–gene interactions are associated with imbalanced oxidative stress and, thereby, with high-altitude adaptation and mal-adaptation.

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Effects of Prolonged Exposure to Hypobaric Hypoxia on Oxidative Stress, Inflammation and Gluco-Insular Regulation: The Not-So-Sweet Price for Good Regulation

PLoS ONE ◽

10.1371/journal.pone.0094915 ◽

2014 ◽

Vol 9 (4) ◽

pp. e94915 ◽

Cited By ~ 32

Author(s):

Mario Siervo ◽

Heather L. Riley ◽

Bernadette O. Fernandez ◽

Carl A. Leckstrom ◽

Daniel S. Martin ◽

...

Keyword(s):

Oxidative Stress ◽

Hypobaric Hypoxia ◽

Prolonged Exposure

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Rhodiola crenulataExtract Alleviates Hypoxic Pulmonary Edema in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/718739 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Shih-Yu Lee ◽

Min-Hui Li ◽

Li-Shian Shi ◽

Hsin Chu ◽

Cheng-Wen Ho ◽

...

Keyword(s):

Oxidative Stress ◽

Pulmonary Edema ◽

High Altitude ◽

Hypobaric Hypoxia ◽

Capillary Barrier ◽

Lung Water ◽

Stress Markers ◽

Rhodiola Crenulata ◽

High Altitude Illness ◽

Alveolar Capillary

Sudden exposure of nonacclimatized individuals to high altitude can easily lead to high altitude illnesses. High altitude pulmonary edema (HAPE) is the most lethal form of high altitude illness. The present study was designed to investigate the ability ofRhodiola crenulataextract (RCE), an herbal medicine traditionally used as an antiacute mountain sickness remedy, to attenuate hypoxia-induced pulmonary injury. Exposure of animals to hypobaric hypoxia led to a significant increase in pathological indicators for pulmonary edema, including the lung water content, disruption of the alveolar-capillary barrier, and protein-rich fluid in the lungs. In addition, hypobaric hypoxia also increased oxidative stress markers, including (ROS) production, (MDA) level, and (MPO) activity. Furthermore, overexpression of plasma (ET-1), (VEGF) in (BALF), and (HIF-1α) in lung tissue was also found. However, pretreatment with RCE relieved the HAPE findings by curtailing all of the hypoxia-induced lung injury parameters. These findings suggest that RCE confers effective protection for maintaining the integrity of the alveolar-capillary barrier by alleviating the elevated ET-1 and VEGF levels; it does so by reducing hypoxia-induced oxidative stress. Our results offer substantial evidence to support arguments in favor of traditional applications ofRhodiola crenulatafor antihigh altitude illness.

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