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1.
Cell Physiol Biochem ; 57(6): 426-451, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37967151

RESUMO

BACKGROUND/AIMS: Currently, it is proven that the cellular metabolism of nitric oxide is necessary to maintain optimal health and adaptation of the organism to the impact of various environmental factors. The aim of this work was to reveal the biological role of nitric oxide, its metabolic changes, and its mechanism of action in tissues under hypoxia, as well as the possibility of tissue metabolism correction through NO-dependent systems under the influence of Krebs cycle intermediates. METHODS: A systematic assessment of the effect of succinate (SC, 50 mg/kg b.w.) and α-ketoglutarate (KGL, 50 mg/kg b.w.) in the regulation of oxygendependent processes in rats (mitochondrial oxidative phosphorylation, microsomal oxidation, intensity of lipid peroxidation processes, and the state of the antioxidant defense system) depending on functional changes in nitric oxide production during hypoxia was evaluated. The state of the nitric oxide system was estimated spectrophotometrically by determination of the concentration of its stable nitrite anion metabolite (NO2 -). The levels of catecholamines were estimated from the content of epinephrine and norepinephrine using the differentially fluorescent method. The activity of cytochrome P450-dependent aminopyrine-N-demethylase was determined with the Nash reagent. RESULTS: Tissue hypoxia and metabolic disorders caused by this condition through changes in the content of catecholamines (epinephrine, norepinephrine, dopamine, DOPA) as well as the cholinesterase-related system (acetylcholine content and acetylcholinesterase activity) were the studied experimental parameters under acute hypoxia (AH, 7% O2 in N2, 30 min). The activation of lipid peroxidation and oxidatively modified proteins and an increase in the epinephrine content in AH are associated with an increased role of SC and a decrease in KGL as substrates of oxidation in mitochondria. A more pronounced effect of exogenous KGL, compared to SC, on the content of nitrite anion as a stable metabolite of nitric oxide in the liver under acute hypoxia against the background of a decrease in the intensity of lipid peroxidation processes was revealed. The activation of SC-dependent mitochondrial oxidative processes caused by AH was found to decrease in animals after an intermittent hypoxia training (IHT) course. IHT (7% O2 in N2, 15-min, 5 times daily, 14 days) prevented the activation of oxidative stress in tissues and blood after the AH impact and increased the efficiency of energy-related reactions in the functioning of hepatic mitochondria through increased oxidation of KGL. CONCLUSION: The studied effects of adaptation are mediated by an increase in the role of NO-dependent mechanisms, as assessed by changes in the pool of nitrates, nitrites, carbamides, and total polyamines.


Assuntos
Ciclo do Ácido Cítrico , Óxido Nítrico , Ratos , Animais , Ratos Wistar , Nitritos , Acetilcolinesterase/metabolismo , Hipóxia/metabolismo , Norepinefrina , Epinefrina , Catecolaminas , Oxigênio
2.
Exp Lung Res ; 46(10): 376-392, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32930002

RESUMO

AIM: Rapid ascent to high altitude and inability to acclimatize lead to high-altitude illnesses. Intermittent hypoxia (IH) conditioning has been hypothesized as a non-pharmacological strategy aiming to improve adaptive responses during high altitude ascent. In the recent years, IH training (IHT) has become increasingly popular among recreational and professional athletes owing to its ability to mitigate high altitude related problems. This study aimed at exploring the role of IHT in altitude acclimatization. METHODS: Male Sprague Dawley rats were subjected to IHT for 4 h consecutively for 5 days at 12% FiO2 under normobaric conditions. To assess the effect of IHT in hypoxic acclimatization, animals were further exposed to extreme hypoxia (EH) at 8% FiO2. Oxygen saturation (SpO2), respiratory rate and heart rate were recorded during the exposure. Oxidative stress (ROS, MDA, and 4-HNE) and histopathological examinations were studied in the lung tissue sections. Hypoxia biomarkers, HIF-1α, EPO, VEGF, and BPGM were evaluated through western blotting in the lung tissue. RESULTS: Assessment of the IHT showed that SpO2 levels were found to be higher in the IH trained rats with a statistical difference of p < 0.01 in the first hour of hypoxia exposure as compared to the untrained rats. There was a significantly higher (p < 0.001) generation of ROS and MDA in the untrained rats as compared to the trained rats. Lipid peroxidation markers and systemic inflammatory marker were found to be expressed at much higher level in the untrained rats. There was a higher expression of HIF-1α (1.24-fold ↑), VEGF (1.14-fold ↑) and decrease in EPO (1.43-fold ↓) in the untrained rats as compared to trained rats. CONCLUSIONS: Preconditioning with IHT resulted in the reduction in hypoxia induced oxidative stress during extreme hypoxia exposure and thus, maintaining redox balance as well as adjustment in the physiological changes in rats.


Assuntos
Altitude , Hipóxia , Animais , Masculino , Estresse Oxidativo , Saturação de Oxigênio , Ratos , Ratos Sprague-Dawley
3.
J Sport Rehabil ; 28(6): 540-543, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29584516

RESUMO

OBJECTIVE: To study the effect of intermittent hypoxia training (IHT) for dizziness. DESIGN: A single-blind, randomized controlled trial. All participants were recruited from a rehabilitation department in an acute university-affiliated hospital. INTERVENTION: Participants with dizziness were randomly assigned to 2 groups (IHT group and control group). The Dizziness Handicap Inventory, Activities-specific Balance Confidence Scale, and Vertigo Visual Analog Scale were conducted at baseline, end of the fourth week. RESULTS: Among 52 subjects, there were18 males and 34 females, ages 35 to 62 years old (mean [SD] = 46.9 [7.93]). Time length since onset ranged from 12 to 34 months (20.2 [7.15] mo). Dizziness Handicap Inventory, Activities-specific Balance Confidence Scale, Vertigo Visual Analog Scale scores, and attack frequencies of dizziness were improved after IHT intervention in the end of the fourth week. There were significant differences between the IHT group and the control group in the Dizziness Handicap Inventory, Activities-specific Balance Confidence Scale, Vertigo Visual Analog Scale scores, and attack frequencies of dizziness at the end of the fourth week (P < .05). No adverse events occurred during the study. CONCLUSION: IHT could improve dizziness after intervention at the end of the fourth week. IHT could be the effective method for treating dizziness.


Assuntos
Tontura/reabilitação , Hipóxia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Escala Visual Analógica
4.
Am J Physiol Regul Integr Comp Physiol ; 313(1): R10-R18, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28490448

RESUMO

Abrupt cessation of chronic alcohol consumption triggers signaling cascades that harm vulnerable brain regions and produce neurobehavioral deficits. We have demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in rats prevents brain damage and neurobehavioral impairment resulting from abrupt ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated protein kinase p38 and presenilin 1 (PS1), the catalytic subunit of γ-secretase that produces the neurotoxic amyloid-ß (Aß) peptides Aß40 and Aß42. We tested the hypotheses that 1) IHT limits EW-induced activation of the p38-PS1 axis, thereby attenuating γ-secretase activation and Aß accumulation, and 2) EW disables heat shock protein 25 (HSP25), a p38 substrate, molecular chaperone, and antioxidant, and provokes protein carbonylation in a manner suppressed by IHT. Adult male rats completed two cycles of a 4-wk ethanol diet (6.5% wt/vol) and a 3-wk EW or an isocaloric, dextrin-based control diet. A 20-day IHT program (5-8 daily cycles of 5-10 min of 9.5-10% fractional inspired O2 + 4 min of 21% fractional inspired O2) was administered during the first EW phase. After the second EW phase, the brain was excised and the prefrontal cortex extracted. PS1, phosphorylated p38 (p-p38), and HSP25 were analyzed by immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein carbonyl content by spectrometry, and Aß40 and Aß42 contents by enzyme-linked immunosorbent assay. IHT attenuated the EW-associated increases in PS1, p-p38, Aß40, Aß42, and protein carbonyl contents, but not that of PS1 messenger RNA, while preserving functionally competent HSP25 dimers in EW rats. Collectively, these findings suggest that IHT may attenuate EW-induced γ-secretase overactivation by suppressing activation of the p38-PS1 axis and by preventing oxidative protein damage.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/metabolismo , Etanol/toxicidade , Hipóxia/metabolismo , Presenilina-1/metabolismo , Animais , Córtex Cerebral/efeitos dos fármacos , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP27/metabolismo , Precondicionamento Isquêmico , Masculino , Oxigênio , Presenilina-1/genética , Ratos , Ratos Sprague-Dawley , Síndrome de Abstinência a Substâncias/fisiopatologia , Síndrome de Abstinência a Substâncias/prevenção & controle , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Wilderness Environ Med ; 26(1): 78-82, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25541511

RESUMO

OBJECTIVE: The purpose of this study was to determine the effects of different inspired oxygen fractions (Fio2) on average and peak power capacity during consecutive jumps to assess the effectiveness of a hypoxic explosive-strength program. METHODS: Eight physically active subjects (aged 33.62 ± 4.07 years; height, 1.77 ± 0.05 m; weight, 74.38 ± 6.86 kg) completed a Bosco jump test, consisting of a series of 15-second "all-out" jumps with 3 minutes of recovery, performed in a normoxia condition (N [Fio2 = 21%]) and in two hypoxic conditions: moderate hypoxia (MH [Fio2 16.5% o2]) and high hypoxia (HH [13.5% o2]). A force platform provided the average and the maximal power output (W) generated during consecutive jumps. Measurements were also taken of lactate, creatine kinase, arterial oxygen saturation, and perceived exertion using the Borg fatigue scale. RESULTS: The average power outputs throughout the entire sets were similar between N (3187 ± 46) and MH (3184 ± 15; P > .05), but slightly greater with HH (3285 ± 43) compared with N (P < .05). Values for lactate during N (7.5 ± 3.0), MH (7.7 ± 4.0), and HH (7.9 ± 3.0; P > .05), and for creatine kinase (values before, 69.8 ± 15; and 24 hours after in N [79.4 ± 15.60], MH [85.2 ± 26.7], and HH [84.3 ± 47.2]; P > .05) were similar for all conditions. Only during exercise in hypoxia were moderate and severe hypoxemia induced as the sets increased and Fio2 was lower (P < .05). At the same time, the perceived exertion reported by subjects was substantially higher at HH (8.9 ± 1.1) than at N (7.1 ± 1.9; P < .05). CONCLUSIONS: Jumping power output was not negatively affected by mild or high hypoxia in comparison with normoxia during an anaerobic workout despite having higher hypoxemia and a greater perception of exertion.


Assuntos
Consumo de Oxigênio , Oxigênio/análise , Resistência Física , Treinamento Resistido , Adulto , Humanos , Masculino
6.
Curr Res Physiol ; 5: 327-337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35880035

RESUMO

As the number of people travelling to altitude increases, the risk of life threatening medical emergencies also increases. It is important that we have effective strategies to minimize the risk of altitude illness. In this study, an attempt was made to investigate the combined effect of non-pharmacological (Intermittent hypoxia training; IHT) and pharmacological (acetazolamide; ACZ) intervention as a prophylactic strategy in order to minimize the risk of high altitude hypoxic related problems using rats as an animal model. Male Sprague Dawley rats were subjected to IHT for 4 h consecutively for 5 days at 12% FiO2 under normobaric conditions with and without oral ACZ administration at 25 mg/kg body weight. Validation of the intervention was performed by exposing the rats to extreme hypoxia (EH) at 8% FiO2 to further assess the effect of IHT and ACZ on hypoxic acclimatization. The principal findings of this study is that the combined effect of IHT and ACZ improves the arterial oxygenation by alterations in hemodynamics and in blood gasometry, thereby resulting into an increase in the oxygen carrying capacity of the blood with increase in SpO2 (peripheral oxygen saturation). The present study showed that the combined effect of IHT with ACZ could be refined as a prophylactic measure for better outcomes during altitude ascent and rapid altitude acclimatization rather than IHT or ACZ alone.

7.
Biology (Basel) ; 12(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36671699

RESUMO

Cyclooxygenase 2 (COX2) inhibitors have been demonstrated to protect against hypoxia pathogenesis in several investigations. It has also been utilized as an adjuvant therapy in the treatment of COVID-19. COX inhibitors, which have previously been shown to be effective in treating previous viral and malarial infections are strong candidates for improving the COVID-19 therapeutic doctrine. However, another COX inhibitor, ibuprofen, is linked to an increase in the angiotensin-converting enzyme 2 (ACE2), which could increase virus susceptibility. Hence, inhibiting COX2 via therapeutics might not always be protective and we need to investigate the downstream molecules that may be involved in hypoxia environment adaptation. Research has discovered that people who are accustomed to reduced oxygen levels at altitude may be protected against the harmful effects of COVID-19. It is important to highlight that the study's conclusions only applied to those who regularly lived at high altitudes; they did not apply to those who occasionally moved to higher altitudes but still lived at lower altitudes. COVID-19 appears to be more dangerous to individuals residing at lower altitudes. The downstream molecules in the (COX2) pathway have been shown to adapt in high-altitude dwellers, which may partially explain why these individuals have a lower prevalence of COVID-19 infection. More research is needed, however, to directly address COX2 expression in people living at higher altitudes. It is possible to mimic the gene-environment interaction of higher altitude people by intermittent hypoxia training. COX-2 adaptation resulting from hypoxic exposure at altitude or intermittent hypoxia exercise training (IHT) seems to have an important therapeutic function. Swimming, a type of IHT, was found to lower COX-2 protein production, a pro-inflammatory milieu transcription factor, while increasing the anti-inflammatory microenvironment. Furthermore, Intermittent Hypoxia Preconditioning (IHP) has been demonstrated in numerous clinical investigations to enhance patients' cardiopulmonary function, raise cardiorespiratory fitness, and increase tissues' and organs' tolerance to ischemia. Biochemical activities of IHP have also been reported as a feasible application strategy for IHP for the rehabilitation of COVID-19 patients. In this paper, we aim to highlight some of the most relevant shared genes implicated with COVID-19 pathogenesis and hypoxia. We hypothesize that COVID-19 pathogenesis and hypoxia share a similar mechanism that affects apoptosis, proliferation, the immune system, and metabolism. We also highlight the necessity of studying individuals who live at higher altitudes to emulate their gene-environment interactions and compare the findings with IHT. Finally, we propose COX2 as an upstream target for testing the effectiveness of IHT in preventing or minimizing the effects of COVID-19 and other oxygen-related pathological conditions in the future.

8.
Am J Transl Res ; 12(7): 4059-4065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774759

RESUMO

OBJECTIVE: To study the effect of intermittent hypoxia training (IHT) for migraine. DESIGN: A single-blind, randomized controlled trial. All participants were recruited from a rehabilitation department in an acute university-affiliated hospital. METHODS: Participants with migraines were randomly assigned to two groups (IHT group and control group). The Migraine Disability Assessment (MIDAS), Visual Analog Scale (VAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and cerebrovascular hemodynamic parameters were collected at baseline and end of the 8th week. The attack frequencies of migraines were evaluated at 3 months. RESULTS: Among the 48 subjects, five males and forty-three females, the ages ranged from 19 to 53 years old (mean ± SD = 31.3±7.78). MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters were improved after IHT intervention. There were significant differences between IHT group and the control group in MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters at the end of the 8th weeks (P<0.05). Attack frequencies were improved within 3 months after IH training intervention (P<0.01), but not in the control group (P>0.05). No adverse events occurred during the study. CONCLUSION: IHT could improve migraines after intervention up to three months. IHT could be an effective method for relieving a migraine.

9.
Exp Biol Med (Maywood) ; 245(8): 740-747, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32299228

RESUMO

IMPACT STATEMENT: The effects of intermittent hypoxic training or conditioning on many pathological conditions have been widely investigated. One of the pathological conditions dealt with intermittent hypoxic training is ischemic stroke. Well-known mechanisms of intermittent hypoxia-induced protection are related to increased energy metabolism and the enhanced antioxidant effects. In the last decades, the role of microglia in the progress of ischemic stroke-related brain damage has been focused. The dual-edge function of microglia indicates that the microglia-mediated inflammatory response is definitely beneficial in the early stage of ischemic stroke, but long-term activation of microglia is rather detrimental during the recovery process. The effect of IHT on microglia polarization is not investigated. This study focused on whether IHT regulates the polarization of microglia without dampening its classic phagocytic function. This study will provide pivotal information regarding the effects of IHT on the long-term effects on the recovery process from ischemic stroke.


Assuntos
Hipóxia Celular , Microglia/metabolismo , Fagocitose , Animais , Células Cultivadas , Citocinas/metabolismo , Glucose/deficiência , Camundongos , Oxigênio/metabolismo , Fenótipo , Espécies Reativas de Oxigênio/metabolismo
10.
Exp Biol Med (Maywood) ; 241(12): 1351-63, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27190276

RESUMO

Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso- and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Transtornos Cerebrovasculares/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Hipóxia , Animais , Humanos
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