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

2011 ◽  
Vol 122 (6) ◽  
pp. 299-311 ◽  
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.

scholarly journals Rhodiola crenulataExtract Alleviates Hypoxic Pulmonary Edema in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
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.

scholarly journals Hypericum perforatum (ethanolic extract) ameliorates simulated hypobaric hypoxia induced oxidative stress and neuronal damage in brains of Balb/c mice

2018 ◽  
Vol 9 (2) ◽  
pp. 1-8
Author(s):  
Amardeep Gautam ◽  
Rizwana Tabassum ◽  
Anju Katyal
Keyword(s):  
Oxidative Stress ◽  
High Altitude ◽  
Passive Avoidance ◽  
Hypobaric Hypoxia ◽  
Hypericum Perforatum ◽  
Elevated Plus Maze ◽  
Ethanolic Extract ◽  
Amnesic Effect ◽  
Plus Maze ◽  
High Altitude Illness

Background: Hypobaric hypoxia refers to lower oxygen availability at high altitudes and is the cause of high altitude illness. Drugs such as acetazolamide and dexamethasone provide symptomatic relief and are associated with undesired side effects. Plant extracts such as Hypericum perforatum, which are documented to have neuromodulatory role can be more beneficial in ameliorating high altitude illness. Aims and Objective: Progressive cognitive decline is the hallmark characteristic of hypobaric hypoxia induced neuropathology attributed to ensuing oxidative stress and subsequent hippocampal damage. We have explored the efficacy of ethanolic extracts of Hypericum perforatum in amelioration of hypobaric hypoxia induced oxidative stress and associated behavioral deficits in mice.Material and Methods: Male Balb/c mice were exposed to simulated altitude of 25,000 ft. for 7 days (6 hr. per day) in a specially designed chamber. Ethanolic extract of Hypericum perforatum (HPE)(25mg/kg of body weight) was given orally prior to hypoxia exposure and effects were compared to hypoxia and control groups.Results: Animals exposed to hypobaric hypoxia showed sign of cognitive deterioration at day 3 and day 7 in the Elevated Plus Maze and Passive Avoidance Step through behavioral paradigms as compare to normoxic animals. Administration of HPE was able to alleviate the amnesic effect in treatment group, indicated by reduction in transfer latencies at day 3(IR-3 = -0.66±0.07) and day 7 IR-7 = -0.81±0.06) in elevated plus maze task and increased passive avoidance step through latency at day 3, (IR-3 = 3.23±0.67),as compared to ±hypoxic mice. Hypoxia group of animals suffered significant oxidative stress compared to normoxic mice as indicated by up-regulated malondialdehyde and total nitrite levels in hippocampal homogenates. The plasma lactate dehydrogenase activity was also increased following hypoxia indicating tissue damage. Co-treatment with HPE in simulated hypobaric hypoxia insult for seven days resulted in significant reduction in malondialdehyde, total nitrites and plasma LDH levels in animals.Conclusion: Hypericum perforatum extract improves cognitive performance in hypobaric hypoxia exposed mice with a concomitant reduction in oxidative stress burden suggesting its plausible use for preventing high altitude illness.Asian Journal of Medical Sciences Vol.9(2) 2018 1-8

scholarly journals Oxidative Stress, Kinase Activation, and Inflammatory Pathways Involved in Effects on Smooth Muscle Cells During Pulmonary Artery Hypertension Under Hypobaric Hypoxia Exposure

2021 ◽  
Vol 12 ◽  
Author(s):  
Patricia Siques ◽  
Eduardo Pena ◽  
Julio Brito ◽  
Samia El Alam
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
High Altitude ◽  
Hypobaric Hypoxia ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Muscle Cells ◽  
Kinase Activation

High-altitude exposure results in hypobaric hypoxia, which affects organisms by activating several mechanisms at the physiological, cellular, and molecular levels and triggering the development of several pathologies. One such pathology is high-altitude pulmonary hypertension (HAPH), which is initiated through hypoxic pulmonary vasoconstriction to distribute blood to more adequately ventilated areas of the lungs. Importantly, all layers of the pulmonary artery (adventitia, smooth muscle, and endothelium) contribute to or are involved in the development of HAPH. However, the principal action sites of HAPH are pulmonary artery smooth muscle cells (PASMCs), which interact with several extracellular and intracellular molecules and participate in mechanisms leading to proliferation, apoptosis, and fibrosis. This review summarizes the alterations in molecular pathways related to oxidative stress, inflammation, kinase activation, and other processes that occur in PASMCs during pulmonary hypertension under hypobaric hypoxia and proposes updates to pharmacological treatments to mitigate the pathological changes in PASMCs under such conditions. In general, PASMCs exposed to hypobaric hypoxia undergo oxidative stress mediated by Nox4, inflammation mediated by increases in interleukin-6 levels and inflammatory cell infiltration, and activation of the protein kinase ERK1/2, which lead to the proliferation of PASMCs and contribute to the development of hypobaric hypoxia-induced pulmonary hypertension.

Susceptibility genes for gentamicin-induced vestibular dysfunction

2008 ◽  
Vol 18 (1) ◽  
pp. 59-68
Author(s):  
Stephen M. Roth ◽  
Scott M. Williams ◽  
Lan Jiang ◽  
Kalapurakkal S. Menon ◽  
John J. Jeka
Keyword(s):  
Oxidative Stress ◽  
Candidate Genes ◽  
Single Gene ◽  
Aminoglycoside Antibiotic ◽  
Susceptibility Genes ◽  
Vestibular Dysfunction ◽  
Gene Interactions ◽  
Risk Alleles ◽  
Stress Related Genes ◽  
Increased Susceptibility

Background: Approximately 5% of patients administered gentamicin (GM), an aminoglycoside antibiotic, experience vestibular ototoxicity resulting in balance dysfunction. In the present study, we sought to identify susceptibility genes associated with GM-induced vestibular dysfunction using a case/control design. Methods: White cases (n = 137; 55 men, 82 women) were recruited based on physician-confirmed unilateral or bilateral vestibular dysfunction attributed to GM administration. Controls (n = 126; 54 men, 72 women) were healthy, age-matched individuals without vestibular dysfunction or balance impairment. Buccal cell samples were obtained from all subjects and DNA was genotyped for 15 polymorphisms in 9 genes. Candidate genes were identified primarily for their roles in oxidative stress based on predicted mechanisms of gentamicin-induced ototoxicity. Statistical analyses included the multi-dimensionality reduction (MDR) method for identifying gene x gene interactions across multiple candidate genes. Results: Both single gene and MDR analyses revealed the NOS3 (ENOS) p.Glu298Asp polymorphism as significantly associated with GM-induced vestibular dysfunction (both p ⩽ 0.03). MDR analysis revealed a three-gene combination, consisting of NOS3 (p.Glu298Asp), GSTZ1 (p.Lys32Glu), and GSTP1 (p.Ile105Val), that provided the highest predictive model for GM-induced vestibular dysfunction (64% accuracy; p = 0.009). Conclusions: The results indicate that carriers of risk alleles at three oxidative stress-related genes have increased susceptibility to GM-induced vestibular dysfunction.

scholarly journals Blood Oxidative-Stress Markers During a High-Altitude Trek

2013 ◽  
Vol 23 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Lindsey E. Miller ◽  
Graham R. McGinnis ◽  
Brian Kliszczewicz ◽  
Dustin Slivka ◽  
Walter Hailes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Altitude ◽  
Hypobaric Hypoxia ◽  
Antioxidant Potential ◽  
Protein Carbonyls ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Lipid Hydroperoxides ◽  
Time Points ◽  
Trolox Equivalent ◽  
Base Elevation

Oxidative stress occurs as a result of altitude-induced hypobaric hypoxia and physical exercise. The effect of exercise on oxidative stress under hypobaric hypoxia is not well understood.Purpose:To determine the effect of high-altitude exercise on blood oxidative stress. Nine male participants completed a 2-d trek up and down Mt Rainer, in North America, at a peak altitude of 4,393 m. Day 1 consisted of steady-pace climbing for 6.25 hr to a final elevation of 3,000 m. The 4,393-m summit was reached on Day 2 in approximately 5 hr. Climb–rest intervals varied but were consistent between participants, with approximately 14 hr of total time including rest periods. Blood samples were assayed for biomarkers of oxidative stress and antioxidant potential at the following time points: Pre (before the trek), 3Kup (at ascent to 3,000 m), 3Kdown (at 3,000 m on the descent), and Post (posttrek at base elevation). Blood serum variables included ferric-reducing antioxidant potential (FRAP), Trolox equivalent antioxidant capacity (TEAC), protein carbonyls (PC), and lipid hydroperoxides. Serum FRAP was elevated at 3Kup and 3Kdown compared with Pre and Post values (p = .004, 8% and 11% increase from Pre). Serum TEAC values were increased at 3Kdown and Post (p = .032, 10% and 18% increase from Pre). Serum PC were elevated at 3Kup and 3Kdown time points (p = .034, 194% and 138% increase from Pre), while lipid hydroperoxides were elevated Post only (p = .004, 257% increase from Pre).Conclusions:Findings indicate that high-altitude trekking is associated with increased blood oxidative stress.

EFFECTS OF HYPOBARIC HYPOXIA AT HIGH ALTITUDE ON OXIDATIVE STRESS PARAMETERS. RESULTS OF THE HIGHCARE PROJECT

2011 ◽  
Vol 29 ◽  
pp. e55-e56
Author(s):  
E. Kaschina ◽  
T. Unger ◽  
M. Sommerfeld ◽  
G. Bilo ◽  
M. Revera ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Altitude ◽  
Hypobaric Hypoxia ◽  
Oxidative Stress Parameters ◽  
Stress Parameters

scholarly journals Intermittent Hypobaric Hypoxic Preconditioning Provides Neuroprotection by Increasing Antioxidant Activity, Erythropoietin Expression and Preventing Apoptosis and Astrogliosis in the Brain of Adult Rats Exposed to Acute Severe Hypoxia

2021 ◽  
Vol 22 (10) ◽  
pp. 5272
Author(s):  
Débora Coimbra-Costa ◽  
Fernando Garzón ◽  
Norma Alva ◽  
Tiago C. C. Pinto ◽  
Fernando Aguado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hypobaric Hypoxia ◽  
Hypoxic Preconditioning ◽  
Severe Hypoxia ◽  
Efficient Tool ◽  
Adult Rats ◽  
Therapeutic Benefits ◽  
Background Exposure ◽  
The Brain ◽  
Apoptotic Cascade

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.

scholarly journals Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Davide Di Bella ◽  
João P. S. Ferreira ◽  
Renee de Nazare O. Silva ◽  
Cinthya Echem ◽  
Aline Milan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gold Nanoparticles ◽  
Blood Vessels ◽  
Platelet Adhesion ◽  
Potential Candidate ◽  
Cerebral Blood Vessels ◽  
Cerebral Microvessels ◽  
Antibiotic Effect ◽  
Anti Inflammatory ◽  
20 Nm

Abstract Background Sepsis is an emergency medical condition that can lead to death and it is defined as a life-threatening organ dysfunction caused by immune dysregulation in response to an infection. It is considered the main killer in intensive care units. Sepsis associated-encephalopathy (SAE) is mostly caused by a sepsis-induced systemic inflammatory response. Studies report SAE in 14–63% of septic patients. Main SAE symptoms are not specific and usually include acute impairment of consciousness, delirium and/or coma, along with electroencephalogram (EEG) changes. For those who recover from sepsis and SAE, impaired cognitive function, mobility and quality of life are often observed months to years after hospital discharge, and there is no treatment available today to prevent that. Inflammation and oxidative stress are key players for the SAE pathophysiology. Gold nanoparticles have been demonstrated to own important anti-inflammatory properties. It was also reported 20 nm citrate-covered gold nanoparticles (cit-AuNP) reduce oxidative stress. In this context, we tested whether 20 nm cit-AuNP could alleviate the acute changes caused by sepsis in brain of mice, with focus on inflammation. Sepsis was induced in female C57BL/6 mice by cecal ligation and puncture (CLP), 20 nm cit-AuNP or saline were intravenously (IV) injected 2 h after induction of sepsis and experiments performed 6 h after induction. Intravital microscopy was used for leukocyte and platelet adhesion study in brain, blood brain barrier (BBB) permeability carried out by Evans blue assay, cytokines measured by ELISA and real time PCR, cell adhesion molecules (CAMs) by flow cytometry and immunohistochemistry, and transcription factors, by western blotting. Results 20 nm cit-AuNP treatment reduced leukocyte and platelet adhesion to cerebral blood vessels, prevented BBB failure, reduced TNF- concentration in brain, and ICAM-1 expression both in circulating polymorphonuclear (PMN) leukocytes and cerebral blood vessels of mice with sepsis. Furthermore, 20 nm cit-AuNP did not interfere with the antibiotic effect on the survival rate of mice with sepsis. Conclusions Cit-AuNP showed important anti-inflammatory properties in the brain of mice with sepsis, being a potential candidate to be used as adjuvant drug along with antibiotics in the treatment of sepsis to avoid SAE

Sign in / Sign up

Export Citation Format

Share Document