Reduced resistance to oxidative stress during reproduction as a cost of early-life stress.

PubMed

Zimmer, Cédric; Spencer, Karen A

2015-05-01

Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underlying the trade-off between self-maintenance and investment in reproduction, it is necessary to look at the consequences of early-life stress on oxidative status during reproduction. Here, we investigated the effects of exposure to pre- and/or post-natal stress on oxidative balance during reproduction under benign or stressful environmental conditions in an avian model species, the Japanese quail. We determined total antioxidant status (TAS), total oxidant status (TOS) and resistance to a free-radical attack in individual exposed to pre-natal stress, post-natal stress or both and in control individuals exposed to none of the stressors. TAS levels decreased over time in all females that reproduced under stressful conditions. TOS decreased between the beginning and the end of reproductive period in pre-natal control females. In all females, resistance to a free-radical attack decreased over the reproductive event but this decrease was more pronounced in females from a pre-natal stress development. Our results suggest that pre-natal stress may be associated with a higher cost of reproduction in terms of oxidative stress. These results also confirm that early-life stress can be associated with both benefits and costs depending of the life-history stage or environmental context. Copyright © 2014 Elsevier Inc. All rights reserved.

Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches

PubMed Central

Balmus, Ioana Miruna; Dobrin, Romeo; Timofte, Daniel

2016-01-01

The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context. PMID:27563374

Examining the relationships between egg cortisol and oxidative stress in developing wild sockeye salmon (Oncorhynchus nerka).

PubMed

Taylor, Jessica J; Sopinka, Natalie M; Wilson, Samantha M; Hinch, Scott G; Patterson, David A; Cooke, Steven J; Willmore, William G

2016-10-01

Maternally-derived hormones in oocytes, such as glucocorticoids (GCs), play a crucial role in embryo development in oviparous taxa. In fishes, maternal stressor exposure increases circulating and egg cortisol levels, the primary GC in fishes, as well as induces oxidative stress. Elevated egg cortisol levels modify offspring traits but whether maternal oxidative stress correlates with circulating and egg cortisol levels, and whether maternal/egg cortisol levels correlate with offspring oxidative stress have yet to be determined. The objective of this study was to examine the relationships among maternal and egg cortisol, and maternal and offspring oxidative stress to provide insight into the potential intergenerational effects of stressor exposure in sockeye salmon (Oncorhynchus nerka). Antioxidant concentration and oxidative stress were measured in maternal tissues (plasma, brain, heart and liver) as well as offspring developmental stages (pre-fertilization, 24h post-fertilization, eyed, and hatch), and were compared to both naturally-occurring and experimentally-elevated (via cortisol egg bath) levels of cortisol in eggs. Oxygen radical absorptive capacity of tissues from maternal sockeye salmon was measured spectrophotometrically and was not correlated with maternal or egg cortisol concentrations. Also, naturally-occurring and experimentally-elevated cortisol levels in eggs (to mimic maternal stress) did not affect oxidative stress or antioxidant capacity of the offspring. We conclude that the metrics of maternal stress examined in sockeye salmon (i.e., maternal/egg cortisol, maternal oxidative stress) are independent of each other, and that egg cortisol content does not influence offspring oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

PubMed

Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

2016-04-01

Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs. Copyright © 2015 John Wiley & Sons, Ltd.

Free radicals, reactive oxygen species, oxidative stress and its classification.

PubMed

Lushchak, Volodymyr I

2014-12-05

Reactive oxygen species (ROS) initially considered as only damaging agents in living organisms further were found to play positive roles also. This paper describes ROS homeostasis, principles of their investigation and technical approaches to investigate ROS-related processes. Especial attention is paid to complications related to experimental documentation of these processes, their diversity, spatiotemporal distribution, relationships with physiological state of the organisms. Imbalance between ROS generation and elimination in favor of the first with certain consequences for cell physiology has been called "oxidative stress". Although almost 30years passed since the first definition of oxidative stress was introduced by Helmut Sies, to date we have no accepted classification of oxidative stress. In order to fill up this gape here classification of oxidative stress based on its intensity is proposed. Due to that oxidative stress may be classified as basal oxidative stress (BOS), low intensity oxidative stress (LOS), intermediate intensity oxidative stress (IOS), and high intensity oxidative stress (HOS). Another classification of potential interest may differentiate three categories such as mild oxidative stress (MOS), temperate oxidative stress (TOS), and finally severe (strong) oxidative stress (SOS). Perspective directions of investigations in the field include development of sophisticated classification of oxidative stresses, accurate identification of cellular ROS targets and their arranged responses to ROS influence, real in situ functions and operation of so-called "antioxidants", intracellular spatiotemporal distribution and effects of ROS, deciphering of molecular mechanisms responsible for cellular response to ROS attacks, and ROS involvement in realization of normal cellular functions in cellular homeostasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus

PubMed Central

Tangvarasittichai, Surapon

2015-01-01

Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus (T2DM) and this appears to underlie the development of cardiovascular disease, T2DM and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM. PMID:25897356

A coupled mechanical-chemical model for reflecting the influence of stress on oxidation reactions in thermal barrier coating

NASA Astrophysics Data System (ADS)

Chen, Lin; Yueming, Li

2018-06-01

In this paper, a coupled mechanical-chemical model is established based on the thermodynamic framework, in which the contribution of chemical expansion to free energy is introduced. The stress-dependent chemical potential equilibrium at the gas-solid interface and the stress gradient-dependent diffusion equation as well as a so-called generalized force which is conjugate to the oxidation rate are derived from the proposed model, which could reflect the influence of stresses on the oxidation reaction. Based on the proposed coupled mechanical-chemical model, a user element subroutine is developed in ABAQUS. The numerical simulation of the high temperature oxidation in the thermal barrier coating is carried out to verify the accuracy of the proposed model, and then the influence of stresses on the oxidation reaction is investigated. In thermally grown oxide, the considerable stresses would be induced by permanent volumetric swelling during the oxidation. The stresses play an important role in the chemical potential equilibrium at the gas-solid interface and strongly affect the oxidation reaction. The gradient of the stresses, however, only occurs in the extremely thin oxidation front layer, which plays a very limited role in the oxidation reaction. The generalized force could be divided into the stress-dependent and the stress-independent parts. Comparing with the stress-independent part, the stress-dependent part is smaller, which has little influence on oxidation reaction.

Oxidative Stress in Placenta: Health and Diseases

PubMed Central

Wu, Fan; Tian, Fu-Ju; Lin, Yi

2015-01-01

During pregnancy, development of the placenta is interrelated with the oxygen concentration. Embryo development takes place in a low oxygen environment until the beginning of the second trimester when large amounts of oxygen are conveyed to meet the growth requirements. High metabolism and oxidative stress are common in the placenta. Reactive oxidative species sometimes harm placental development, but they are also reported to regulate gene transcription and downstream activities such as trophoblast proliferation, invasion, and angiogenesis. Autophagy and apoptosis are two crucial, interconnected processes in the placenta that are often influenced by oxidative stress. The proper interactions between them play an important role in placental homeostasis. However, an imbalance between the protective and destructive mechanisms of autophagy and apoptosis seems to be linked with pregnancy-related disorders such as miscarriage, preeclampsia, and intrauterine growth restriction. Thus, potential therapies to hold oxidative stress in leash, promote placentation, and avoid unwanted apoptosis are discussed. PMID:26693479

The Impact of Oxidative Stress on the Bone System in Response to the Space Special Environment.

PubMed

Tian, Ye; Ma, Xiaoli; Yang, Chaofei; Su, Peihong; Yin, Chong; Qian, Ai-Rong

2017-10-12

The space special environment mainly includes microgravity, radiation, vacuum and extreme temperature, which seriously threatens an astronaut's health. Bone loss is one of the most significant alterations in mammalians after long-duration habitation in space. In this review, we summarize the crucial roles of major factors-namely radiation and microgravity-in space in oxidative stress generation in living organisms, and the inhibitory effect of oxidative stress on bone formation. We discussed the possible mechanisms of oxidative stress-induced skeletal involution, and listed some countermeasures that have therapeutic potentials for bone loss via oxidative stress antagonism. Future research for better understanding the oxidative stress caused by space environment and the development of countermeasures against oxidative damage accordingly may facilitate human beings to live more safely in space and explore deeper into the universe.

The Impact of Oxidative Stress on the Bone System in Response to the Space Special Environment

PubMed Central

Tian, Ye; Ma, Xiaoli; Yang, Chaofei; Su, Peihong; Yin, Chong

2017-01-01

The space special environment mainly includes microgravity, radiation, vacuum and extreme temperature, which seriously threatens an astronaut’s health. Bone loss is one of the most significant alterations in mammalians after long-duration habitation in space. In this review, we summarize the crucial roles of major factors—namely radiation and microgravity—in space in oxidative stress generation in living organisms, and the inhibitory effect of oxidative stress on bone formation. We discussed the possible mechanisms of oxidative stress-induced skeletal involution, and listed some countermeasures that have therapeutic potentials for bone loss via oxidative stress antagonism. Future research for better understanding the oxidative stress caused by space environment and the development of countermeasures against oxidative damage accordingly may facilitate human beings to live more safely in space and explore deeper into the universe. PMID:29023398

Integrated Approaches to Drug Discovery for Oxidative Stress-Related Retinal Diseases.

PubMed

Nishimura, Yuhei; Hara, Hideaki

2016-01-01

Excessive oxidative stress induces dysregulation of functional networks in the retina, resulting in retinal diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy. Although various therapies have been developed to reduce oxidative stress in retinal diseases, most have failed to show efficacy in clinical trials. This may be due to oversimplification of target selection for such a complex network as oxidative stress. Recent advances in high-throughput technologies have facilitated the collection of multilevel omics data, which has driven growth in public databases and in the development of bioinformatics tools. Integration of the knowledge gained from omics databases can be used to generate disease-related biological networks and to identify potential therapeutic targets within the networks. Here, we provide an overview of integrative approaches in the drug discovery process and provide simple examples of how the approaches can be exploited to identify oxidative stress-related targets for retinal diseases.

Integrated Approaches to Drug Discovery for Oxidative Stress-Related Retinal Diseases

PubMed Central

Hara, Hideaki

2016-01-01

Excessive oxidative stress induces dysregulation of functional networks in the retina, resulting in retinal diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy. Although various therapies have been developed to reduce oxidative stress in retinal diseases, most have failed to show efficacy in clinical trials. This may be due to oversimplification of target selection for such a complex network as oxidative stress. Recent advances in high-throughput technologies have facilitated the collection of multilevel omics data, which has driven growth in public databases and in the development of bioinformatics tools. Integration of the knowledge gained from omics databases can be used to generate disease-related biological networks and to identify potential therapeutic targets within the networks. Here, we provide an overview of integrative approaches in the drug discovery process and provide simple examples of how the approaches can be exploited to identify oxidative stress-related targets for retinal diseases. PMID:28053689

Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy.

PubMed

Hassanzadeh, Parichehr; Arbabi, Elham; Atyabi, Fatemeh; Dinarvand, Rassoul

2017-06-15

Some conventional antiepileptic drugs induce oxidative stress and cognitive impairment which may limit their clinical applications. Ferulic acid is a phenolic phytochemical with antioxidant and neuroprotective properties that prompted us to evaluate its therapeutic potential in epilepsy which is usually associated with oxidative stress and cognitive decline. Male Wistar rats received 30mg/kg of pentylenetetrazole (PTZ) intraperitoneally (i.p.) once every alternate day until the development of kindling. The locomotor activity, elevated plus maze, and passive avoidance tests were performed. Oxidative stress was evaluated by the determination of brain malondialdehyde and reduced glutathione. The effects of pre-treatment with ferulic acid (25, 50, 75, and 100mg/kg, i.p.) against PTZ-kindled seizures, cognitive impairment, and oxidative stress were investigated. Kindling was developed 34.18±1.54days after PTZ treatment which was associated with generalized tonic-clonic seizures (GTCS), myoclonic jerks, cognitive deficit, and oxidative stress. Ferulic acid at doses of 75 and 100mg/kg significantly reduced the seizure score, number of myoclonic jerks, cognitive decline and oxidative stress. Spontaneous locomotor activity did not significantly differ between the groups. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment induced by PTZ kindling. Therefore, this phenolic phytochemical appears as a promising adjuvant for antiepileptic drugs. Meanwhile, further experimental and clinical studies are required to provide insights into the cellular/molecular mechanism(s) underlying the action of ferulic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

Micro-encapsulated sensors for in vivo assessment of the oxidative stress in aquatic organisms

NASA Astrophysics Data System (ADS)

Sadovoy, Anton; Teh, Cathleen; Escobar, Marco; Meglinski, Igor; Korzh, Vladimir

2011-10-01

Oxidative stress results from an imbalance between the production and detoxification of reactive oxygen spices (ROS). ROS are natural byproducts of normal metabolism of oxygen and have important roles in cell signaling and homeostasis. Many heart related diseases like heart failure and myocardial infarction develop as a result of oxidative stress. Current treatment cannot improve the progressive decline in heart function experienced by all patients. Therefore heart failure is the cause of around 25% of all deaths in the Asia Pacific region. Thus any step taken to address the oxidative stress problem is essential for enhancing human health and improve their quality of life. Current approach is dedicated to develop micron-size oxidation stress-sensor for in-vivo measuring level of ROS in KillerRed expressing transgenic zebrafish larvae. Central to our investigation is the light-inducible heart failure animal model we developed in zebrafish that expressed KillerRed in the heart. By utilizing the photosensitizer properties of KillerRed to produce ROS upon green light illumination, heart failure can be repeatedly induced in a non-invasive manner. Importantly, the use of this biological platform permits the development of physiologically sensitive ROS sensor and identifies efficient antioxidants that improve heart contractility. The biosensor approach is based on utilizing biocompatible polyelectrolyte microcapsules as a carry of fluorescent dyes sensitive to amount of reactive oxygen spices. Microcapsule prevents dye diffusion in tissue that makes use toxic dyes possible. Microcapsule's wall is permeable for environment with size less than 500 Da. The oxidation stress-sensors are injected directly in zebrafish pericardium with further circulation along blood system. Detecting of ROS is obtained by using laser scanning microscopy by illuminating oxidation stress-sensors and detecting changing excitation signal from the fluorescent dye.

Micro-encapsulated sensors for in vivo assessment of the oxidative stress in aquatic organisms

NASA Astrophysics Data System (ADS)

Sadovoy, Anton; Teh, Cathleen; Escobar, Marco; Meglinski, Igor; Korzh, Vladimir

2012-03-01

Oxidative stress results from an imbalance between the production and detoxification of reactive oxygen spices (ROS). ROS are natural byproducts of normal metabolism of oxygen and have important roles in cell signaling and homeostasis. Many heart related diseases like heart failure and myocardial infarction develop as a result of oxidative stress. Current treatment cannot improve the progressive decline in heart function experienced by all patients. Therefore heart failure is the cause of around 25% of all deaths in the Asia Pacific region. Thus any step taken to address the oxidative stress problem is essential for enhancing human health and improve their quality of life. Current approach is dedicated to develop micron-size oxidation stress-sensor for in-vivo measuring level of ROS in KillerRed expressing transgenic zebrafish larvae. Central to our investigation is the light-inducible heart failure animal model we developed in zebrafish that expressed KillerRed in the heart. By utilizing the photosensitizer properties of KillerRed to produce ROS upon green light illumination, heart failure can be repeatedly induced in a non-invasive manner. Importantly, the use of this biological platform permits the development of physiologically sensitive ROS sensor and identifies efficient antioxidants that improve heart contractility. The biosensor approach is based on utilizing biocompatible polyelectrolyte microcapsules as a carry of fluorescent dyes sensitive to amount of reactive oxygen spices. Microcapsule prevents dye diffusion in tissue that makes use toxic dyes possible. Microcapsule's wall is permeable for environment with size less than 500 Da. The oxidation stress-sensors are injected directly in zebrafish pericardium with further circulation along blood system. Detecting of ROS is obtained by using laser scanning microscopy by illuminating oxidation stress-sensors and detecting changing excitation signal from the fluorescent dye.

Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology

PubMed Central

Jaquet, Vincent; Trabace, Luigia; Krause, Karl-Heinz

2013-01-01

Abstract Significance: Severe life stress (SLS), as opposed to trivial everyday stress, is defined as a serious psychosocial event with the potential of causing an impacting psychological traumatism. Recent Advances: Numerous studies have attempted to understand how the central nervous system (CNS) responds to SLS. This response includes a variety of morphological and neurochemical modifications; among them, oxidative stress is almost invariably observed. Oxidative stress is defined as disequilibrium between oxidant generation and the antioxidant response. Critical Issues: In this review, we discuss how SLS leads to oxidative stress in the CNS, and how the latter impacts pathophysiological outcomes. We also critically discuss experimental methods that measure oxidative stress in the CNS. The review covers animal models and human observations. Animal models of SLS include sleep deprivation, maternal separation, and social isolation in rodents, and the establishment of hierarchy in non-human primates. In humans, SLS, which is caused by traumatic events such as child abuse, war, and divorce, is also accompanied by oxidative stress in the CNS. Future Directions: The outcome of SLS in humans ranges from resilience, over post-traumatic stress disorder, to development of chronic mental disorders. Defining the sources of oxidative stress in SLS might in the long run provide new therapeutic avenues. Antioxid. Redox Signal. 18, 1475–1490. PMID:22746161

Classification of oxidative stress based on its intensity

PubMed Central

Lushchak, Volodymyr I.

2014-01-01

In living organisms production of reactive oxygen species (ROS) is counterbalanced by their elimination and/or prevention of formation which in concert can typically maintain a steady-state (stationary) ROS level. However, this balance may be disturbed and lead to elevated ROS levels called oxidative stress. To our best knowledge, there is no broadly acceptable system of classification of oxidative stress based on its intensity due to which proposed here system may be helpful for interpretation of experimental data. Oxidative stress field is the hot topic in biology and, to date, many details related to ROS-induced damage to cellular components, ROS-based signaling, cellular responses and adaptation have been disclosed. However, it is common situation when researchers experience substantial difficulties in the correct interpretation of oxidative stress development especially when there is a need to characterize its intensity. Careful selection of specific biomarkers (ROS-modified targets) and some system may be helpful here. A classification of oxidative stress based on its intensity is proposed here. According to this classification there are four zones of function in the relationship between “Dose/concentration of inducer” and the measured “Endpoint”: I – basal oxidative stress (BOS); II – low intensity oxidative stress (LOS); III – intermediate intensity oxidative stress (IOS); IV – high intensity oxidative stress (HOS). The proposed classification will be helpful to describe experimental data where oxidative stress is induced and systematize it based on its intensity, but further studies will be in need to clear discriminate between stress of different intensity. PMID:26417312

Nutrients and Oxidative Stress: Friend or Foe?

PubMed Central

Tan, Bee Ling; Liew, Winnie-Pui-Pui

2018-01-01

There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF-κB-) mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs). Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders. PMID:29643982

Nutrients and Oxidative Stress: Friend or Foe?

PubMed

Tan, Bee Ling; Norhaizan, Mohd Esa; Liew, Winnie-Pui-Pui

2018-01-01

There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF- κ B-) mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs). Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.

The effect of oxidative stress on the progression of Hashimoto's thyroiditis.

PubMed

Ates, Ihsan; Arikan, Mehmet Fettah; Altay, Mustafa; Yilmaz, Fatma Meric; Yilmaz, Nisbet; Berker, Dilek; Guler, Serdar

2017-11-29

We aimed to investigate the effects of oxidative stress in the pathogenesis and progression of Hashimoto's thyroiditis (HT). Forty euthyroid and 40 subclinical hypothyroid patients older than 18 years and not yet had received treatment were enrolled in the study. In the 9 months follow-up, 14 of the HT patients developed overt hypothyroidism. The mean total oxidant status (TOS) and oxidative stress index (OSI) were higher in patients who developed overt hypothyroidism than those who did not (p < .001). And no significant difference was found between the two groups in terms of paraoxanase-1 and arylesterase (p > .05). Multivariable Cox regression model showed thyroid stimulating hormone level (HR = 1.348, p < .001), free-thyroxine level (HR = 0.481, p = .017) and OSI ratio (HR = 2.349, p < .001) to be independent predictors of development of overt hypothyroidism. OSI level, being over 2.96 with 92.9% sensitivity and 62.5% specificity, predicts the risk of hypothyroidism. Oxidative stress may be an effective risk factor in the development of overt hypothyroidism in HT.

Biomarkers and Brain Mechanisms of Gulf War Illness

DTIC Science & Technology

2017-09-01

serve as biomarkers of the disorder. 15. SUBJECT TERMS Gulf War illness, neuroinflammation, oxidative stress , mitochondrial dysfunction, magnetic...Oxidative Stress , Mitochondrial Dysfunction; Magnetic Resonance Imaging, Positron Emission Tomography Page | 5 Subtask 2: Develop complementary or...30 Major Task 3: To conduct 1H and 31P MRS studies for assessment of oxidative stress and mitochondrial dysfunction in vivo. Assess cerebral blood

Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress.

PubMed

Dehdashtian, Ehsan; Mehrzadi, Saeed; Yousefi, Bahman; Hosseinzadeh, Azam; Reiter, Russel J; Safa, Majid; Ghaznavi, Habib; Naseripour, Masood

2018-01-15

Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus (DM), remains as one of the major causes of vision loss worldwide. The release of pro-inflammatory cytokines and the adhesion of leukocytes to retinal capillaries are initial events in DR development. Inflammation, ER stress, oxidative stress and autophagy are major causative factors involved in the pathogenesis of DR. Diabetes associated hyperglycemia leads to mitochondrial electron transport chain dysfunction culminating in a rise in ROS generation. Since mitochondria are the major source of ROS production, oxidative stress induced by mitochondrial dysfunction also contributes to the development of diabetic retinopathy. Autophagy increases in the retina of diabetic patients and is regulated by ER stress, oxidative stress and inflammation-related pathways. Autophagy functions as a double-edged sword in DR. Under mild stress, autophagic activity can lead to cell survival while during severe stress, dysregulated autophagy results in massive cell death and may have a role in initiation and exacerbation of DR. Melatonin and its metabolites play protective roles against inflammation, ER stress and oxidative stress due to their direct free radical scavenger activities and indirect antioxidant activity via the stimulation antioxidant enzymes including glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. Melatonin also acts as a cell survival agent by modulating autophagy in various cell types and under different conditions through amelioration of oxidative stress, ER stress and inflammation. Herein, we review the possible effects of melatonin on diabetic retinopathy, focusing on its ability to regulate autophagy processes. Copyright © 2017. Published by Elsevier Inc.

Oxidative stress-induced autophagy: Role in pulmonary toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu

2014-03-01

Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injurymore » associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.« less

Oxidative Stress Status and Placental Implications in Diabetic Rats Undergoing Swimming Exercise After Embryonic Implantation

PubMed Central

Damasceno, Débora Cristina; Sinzato, Yuri Karen; Ribeiro, Viviane Maria; Rudge, Marilza Vieira Cunha; Calderon, Iracema Mattos Paranhos

2015-01-01

The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control—nondiabetic sedentary rats, control exercised—nondiabetic exercised rats, diabetic—diabetic sedentary rats, and diabetic exercised—diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR. PMID:25361551

[Defects in TOR regulatory complexes retard aging and carbonyl/oxidative stress development in yeast Saccharomyces cerevisiae].

PubMed

Homza, B V; Vasyl'kovs'ka, R A; Semchyshyn, H M

2014-01-01

TOR signaling pathway first described in yeast S. cerevisiae is the highly conserved regulator of eukaryotic cell growth, aging and stress resistance. The effect of nitrogen sources, in particular amino acids, on the activity of TOR signaling pathway is well studied, however its relation to carbohydrates is poor understood. The aim of the present study is expanding of our understanding of potential role of TOR regulatory complexes in development of carbonyl/oxidative stress that can result from yeast cultivation on glucose and fructose. It has been shown that the level of alpha-dicarbonyl compounds and protein carbonyl groups increased with time of yeast cultivation and was higher in cells grown on fructose that demonstrated their accelerated aging and carbonyl/oxidative stress development as compared with cells grown on glucose. The strains defective in TOR proteins cultivated in the presence of glucose as well as fructose demonstrated lower markers of the stress and aging than parental strain. Thus these data confirmed the previous conclusion on fructose more potent ability to cause carbonyl/oxidative stress and accelerated aging in S. cerevisiae as compared with glucose. However, defects in TOR regulatory complexes retard aging and development of the stress in yeast independent on the type of carbohydrate in the cultivation medium.

Microbial oxidative stress response: Novel insights from environmental facultative anaerobic bacteria.

PubMed

Fu, Huihui; Yuan, Jie; Gao, Haichun

2015-10-15

Facultative bacteria can grow under either oxic or anoxic conditions. While oxygen provides substantial advantages in energy yield by respiration, it can become life-threatening because of reactive oxygen species that derive from the molecule naturally. Thus, to survive and thrive in a given niche, these bacteria have to constantly regulate physiological processes to make maximum benefits from oxygen respiration while restraining oxidative stress. Molecular mechanisms and physiological consequences of oxidative stress have been under extensive investigation for decades, mostly on research model Escherichia coli, from which our understanding of bacterial oxidative stress response is largely derived. Nevertheless, given that bacteria live in enormously diverse environments, to cope with oxidative stress different strategies are conceivably developed. Copyright © 2015 Elsevier Inc. All rights reserved.

Honey Bee (Apis mellifera) Drones Survive Oxidative Stress due to Increased Tolerance instead of Avoidance or Repair of Oxidative Damage

PubMed Central

Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K.; Tarpy, David R.; Rueppell, Olav

2016-01-01

Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. PMID:27422326

Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage.

PubMed

Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K; Tarpy, David R; Rueppell, Olav

2016-10-01

Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. Copyright © 2016 Elsevier Inc. All rights reserved.

High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production

PubMed Central

Ruggiero, Christine; Ehrenshaft, Marilyn; Cleland, Ellen

2011-01-01

Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases. PMID:21386058

Oxidative stress in Alzheimer disease

PubMed Central

Durany, Nuria

2009-01-01

Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress (e.g., protein oxidation, lipid oxidation, DNA oxidation and glycoxidation) during the course of the disease. Advanced glycation endproducts (AGEs) are present in amyloid plaques in AD, and its extracellular accumulation may be caused by an accelerated oxidation of glycated proteins. AGEs participate in neuronal death causing direct (chemical) and indirect (cellular) free radical production and consequently increase oxidative stress. The development of drugs for the treatment of AD that breaks the vicious cycles of oxidative stress and neurodegeneration offer new opportunities. These approaches include AGE-inhibitors, antioxidants and anti-inflammatory substances, which prevent free radical production. PMID:19372765

Oxidative stress in Alzheimer disease.

PubMed

Gella, Alejandro; Durany, Nuria

2009-01-01

Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress (e.g., protein oxidation, lipid oxidation, DNA oxidation and glycoxidation) during the course of the disease. Advanced glycation endproducts (AGEs) are present in amyloid plaques in AD, and its extracellular accumulation may be caused by an accelerated oxidation of glycated proteins. AGEs participate in neuronal death causing direct (chemical) and indirect (cellular) free radical production and consequently increase oxidative stress. The development of drugs for the treatment of AD that breaks the vicious cycles of oxidative stress and neurodegeneration offer new opportunities. These approaches include AGE-inhibitors, antioxidants and anti-inflammatory substances, which prevent free radical production.

"Cumulative Stress": The Effects of Maternal and Neonatal Oxidative Stress and Oxidative Stress-Inducible Genes on Programming of Atopy.

PubMed

Manti, Sara; Marseglia, Lucia; D'Angelo, Gabriella; Cuppari, Caterina; Cusumano, Erika; Arrigo, Teresa; Gitto, Eloisa; Salpietro, Carmelo

2016-01-01

Although extensive epidemiological and laboratory studies have been performed to identify the environmental and immunological causes of atopy, genetic predisposition seems to be the biggest risk factor for allergic diseases. The onset of atopic diseases may be the result of heritable changes of gene expression, without any alteration in DNA sequences occurring in response to early environmental stimuli. Findings suggest that the establishment of a peculiar epigenetic pattern may also be generated by oxidative stress (OS) and perpetuated by the activation of OS-related genes. Analyzing the role of maternal and neonatal oxidative stress and oxidative stress-inducible genes, the purpose of this review was to summarize what is known about the relationship between maternal and neonatal OS-related genes and the development of atopic diseases.

Trehalose ameliorates oxidative stress-mediated mitochondrial dysfunction and ER stress via selective autophagy stimulation and autophagic flux restoration in osteoarthritis development.

PubMed

Tang, Qian; Zheng, Gang; Feng, Zhenhua; Chen, Yu; Lou, Yiting; Wang, Chenggui; Zhang, Xiaolei; Zhang, Yu; Xu, Huazi; Shang, Ping; Liu, Haixiao

2017-10-05

Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, we explored the potential protective effects of trehalose, a novel Mammalian Target of Rapamycin (mTOR)-independent autophagic inducer, in TBHP-treated mouse chondrocytes and a destabilized medial meniscus (DMM) mouse OA model. We found aberrant p62 accumulation and increased apoptosis in human OA cartilage and chondrocytes. Consistently, p62 and cleaved caspase-3 levels increased in mouse chondrocytes under oxidative stress. Furthermore, trehalose restored oxidative stress-induced autophagic flux disruption and targeted autophagy selectively by activating BCL2 interacting protein 3 (BNIP3) and Phosphoglycerate mutase family member 5 (PGAM5). Trehalose could ameliorate oxidative stress-mediated mitochondrial membrane potential collapse, ATP level decrease, dynamin-related protein 1 (drp-1) translocation into the mitochondria, and the upregulation of proteins involved in mitochondria and endoplasmic reticulum (ER) stress-related apoptosis pathway. In addition, trehalose suppressed the cleavage of caspase 3 and poly(ADP-ribose) polymerase (PARP) and prevented DNA damage under oxidative stress. However, the anti-apoptotic effects of trehalose in TBHP-treated chondrocytes were partially abolished by autophagic flux inhibitor chloroquine and BNIP3- siRNA. The protective effect of trehalose was also found in mouse OA model. Taken together, these results indicate that trehalose has anti-apoptotic effects through the suppression of oxidative stress-induced mitochondrial injury and ER stress which is dependent on the promotion of autophagic flux and the induction of selective autophagy. Thus, trehalose is a promising therapeutic agent for OA.

Transcriptional Modulation of Ethylene Response Factor Protein JERF3 in the Oxidative Stress Response Enhances Tolerance of Tobacco Seedlings to Salt, Drought, and Freezing1[C][W][OA

PubMed Central

Wu, Lijun; Zhang, Zhijin; Zhang, Haiwen; Wang, Xue-Chen; Huang, Rongfeng

2008-01-01

Abiotic stresses such as drought, cold, and salinity affect normal growth and development in plants. The production and accumulation of reactive oxygen species (ROS) cause oxidative stress under these abiotic conditions. Recent research has elucidated the significant role of ethylene response factor (ERF) proteins in plant adaptation to abiotic stresses. Our earlier functional analysis of an ERF protein, JERF3, indicated that JERF3-expressing tobacco (Nicotiana tabacum) adapts better to salinity in vitro. This article extends that study by showing that transcriptional regulation of JERF3 in the oxidative stress response modulates the increased tolerance to abiotic stresses. First, we confirm that JERF3-expressing tobacco enhances adaptation to drought, freezing, and osmotic stress during germination and seedling development. Then we demonstrate that JERF3-expressing tobacco imparts not only higher expression of osmotic stress genes compared to wild-type tobacco, but also the activation of photosynthetic carbon assimilation/metabolism and oxidative genes. More importantly, this regulation of the expression of oxidative genes subsequently enhances the activities of superoxide dismutase but reduces the content of ROS in tobacco under drought, cold, salt, and abscisic acid treatments. This indicates that JERF3 also modulates the abiotic stress response via the regulation of the oxidative stress response. Further assays indicate that JERF3 activates the expression of reporter genes driven by the osmotic-responsive GCC box, DRE, and CE1 and by oxidative-responsive as-1 in transient assays, suggesting the transcriptional activation of JERF3 in the expression of genes involved in response to oxidative and osmotic stress. Our results therefore establish that JERF3 activates the expression of such genes through transcription, resulting in decreased accumulation of ROS and, in turn, enhanced adaptation to drought, freezing, and salt in tobacco. PMID:18945933

Defective Hematopoietic Stem Cell and Lymphoid Progenitor Development in the Ts65Dn Mouse Model of Down Syndrome: Potential Role of Oxidative Stress

PubMed Central

Lorenzo, Laureanne Pilar E.; Chen, Haiyan; Shatynski, Kristen E.; Clark, Sarah; Yuan, Rong; Harrison, David E.; Yarowsky, Paul J.

2011-01-01

Abstract Aims Down Syndrome (DS), a genetic disease caused by a triplication of chromosome 21, is characterized by increased markers of oxidative stress. In addition to cognitive defects, patients with DS also display hematologic disorders and increased incidence of infections and leukemia. Using the Ts65Dn mouse model of DS, the goal of this study was to examine hematopoietic stem and lymphoid progenitor cell function in DS. Results Analysis of hematopoietic progenitor populations showed that Ts65Dn mice possessed fewer functional hematopoietic stem cells and a significantly decreased percentage of bone marrow lymphoid progenitors. Increased reactive oxygen species and markers of oxidative stress were detected in hematopoietic stem cell populations and were associated with a loss of quiescence. Bone marrow progenitor populations expressed diminished levels of the IL-7Rα chain, which was associated with decreased proliferation and increased apoptosis. Modulating oxidative stress in vitro suggested that oxidative stress selectively leads to decreased IL-7Rα expression, and inhibits the survival of IL-7Rα-expressing hematopoietic progenitors, potentially linking increased reactive oxygen species and immunopathology. Innovation The study results identify a link between oxidative stress and diminished IL-7Rα expression and function. Further, the data suggest that this decrease in IL-7Rα is associated with defective hematopoietic development in Down Syndrome. Conclusion The data suggest that hematopoietic stem and lymphoid progenitor cell defects underlie immune dysfunction in DS and that increased oxidative stress and reduced cytokine signaling may alter hematologic development in Ts65Dn mice. Antioxid. Redox Signal. 15, 2083–2094. PMID:21504363

A theoretical model and phase field simulation on the evolution of interface roughness in the oxidation process

NASA Astrophysics Data System (ADS)

Yang, Fan; Fang, Dai-Ning; Liu, Bin

2012-01-01

An oxidation kinetics model is developed to account for the effects of the oxidation interface curvature and the oxidation-induced volume change or Pilling-Bedworth ratio. For the oxidation of Fe-Cr-Al-Y alloy fiber, the predictions agree well with experimental results. By considering the influence of the oxidation interface curvature on oxidation rates, the evolution of fluctuant oxidation interface is predicted. We also developed the phase field method (PFM) to simulate the evolution of the interface roughness. Both the theoretical model and the PFM results show that the interface will become smooth during high temperature oxidation. Stress distribution and evolution are calculated by PFM, which indicates that the stress level decreases as the interface morphology evolves.

Nitrative and Oxidative Stress in Toxicology and Disease

PubMed Central

Roberts, Ruth A.; Laskin, Debra L.; Smith, Charles V.; Robertson, Fredika M.; Allen, Erin M. G.; Doorn, Jonathan A.; Slikker, William

2009-01-01

Persistent inflammation and the generation of reactive oxygen and nitrogen species play pivotal roles in tissue injury during disease pathogenesis and as a reaction to toxicant exposures. The associated oxidative and nitrative stress promote diverse pathologic reactions including neurodegenerative disorders, atherosclerosis, chronic inflammation, cancer, and premature labor and stillbirth. These effects occur via sustained inflammation, cellular proliferation and cytotoxicity and via induction of a proangiogenic environment. For example, exposure to the ubiquitous air pollutant ozone leads to generation of reactive oxygen and nitrogen species in lung macrophages that play a key role in subsequent tissue damage. Similarly, studies indicate that genes involved in regulating oxidative stress are altered by anesthetic treatment resulting in brain injury, most notable during development. In addition to a role in tissue injury in the brain, inflammation, and oxidative stress are implicated in Parkinson's disease, a neurodegenerative disease characterized by the loss of dopamine neurons. Recent data suggest a mechanistic link between oxidative stress and elevated levels of 3,4-dihydroxyphenylacetaldehyde, a neurotoxin endogenous to dopamine neurons. These findings have significant implications for development of therapeutics and identification of novel biomarkers for Parkinson's disease pathogenesis. Oxidative and nitrative stress is also thought to play a role in creating the proinflammatory microenvironment associated with the aggressive phenotype of inflammatory breast cancer. An understanding of fundamental concepts of oxidative and nitrative stress can underpin a rational plan of treatment for diseases and toxicities associated with excessive production of reactive oxygen and nitrogen species. PMID:19656995

Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

PubMed Central

Hosseini, Asieh; Abdollahi, Mohammad

2013-01-01

Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

Role of oxidative stress in diabetic retinopathy and the beneficial effects of flavonoids.

PubMed

Ola, Mohammad Shamsul; Al-Dosari, Dalia; Alhomida, Abdullah S

2018-05-15

Diabetic retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious changes through dysregulation of cellular physiology that damages both neuronal and vascular cells. Here in this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contributes to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by us and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the potential beneficial effects of the six major flavonoid families, such as flavonones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flanonoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in the diabetic retina. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.

PubMed

Findeisen, Hannes M; Pearson, Kevin J; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; de Cabo, Rafael; Bruemmer, Dennis

2011-04-14

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G(1)→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction.

Oxidative Stress Accumulates in Adipose Tissue during Aging and Inhibits Adipogenesis

PubMed Central

Findeisen, Hannes M.; Pearson, Kevin J.; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L.; Cohn, Dianne; Heywood, Elizabeth B.; de Cabo, Rafael; Bruemmer, Dennis

2011-01-01

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G1→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction. PMID:21533223

The progress of inflammation and oxidative stress in patients with chronic kidney disease.

PubMed

Xu, Gaosi; Luo, Kaiping; Liu, Huixin; Huang, Tianlun; Fang, Xiangdong; Tu, Weiping

2015-02-01

The variations and their correlation of inflammation and oxidative stress in chronic kidney disease (CKD) have not been thoroughly understood. Biomarkers of inflammation and oxidative stress were measured in a cohort of 176 patients with CKD ranging from stage 1 to 5 and 67 healthy controls. Correlation analysis in levels between inflammation and oxidative stress was also performed with estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. Concentrations of serum creatinine (Scr), hs-CRP (hypersensitive C reactive protein) and MDA (malondialdehyde) of these participants were measured again after 12 month follow-up. In the present study, with the development of CKD, serum levels of hs-CRP, interleukin-6 (IL-6) and MDA were significantly increased, and the serum levels of SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase) were significantly decreased in these participants. eGFR was inversely associated with MDA and positively with SOD and GSH-PX when adjusting for age and hypertension therapy. IL-6 and hs-CRP were positively correlated with MDA, and negatively associated with SOD and GSH-PX. Notably, after 12-month follow-up, the increase in Scr was positively associated with the increase in hs-CRP (p < 0.01) and MDA (p < 0.05), respectively. Inflammation and oxidative stress interacted with each other and played pivotal roles in the development of CKD. Variation in eGFR was parallel with the changes of oxidative stress and inflammation when CKD developing.

The Role of Oxidative Stress and Antioxidants in Liver Diseases

PubMed Central

Li, Sha; Tan, Hor-Yue; Wang, Ning; Zhang, Zhang-Jin; Lao, Lixing; Wong, Chi-Woon; Feng, Yibin

2015-01-01

A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed. PMID:26540040

Targeting oxidant-dependent mechanisms for the treatment of COPD and its comorbidities.

PubMed

Bernardo, Ivan; Bozinovski, Steven; Vlahos, Ross

2015-11-01

Chronic obstructive pulmonary disease (COPD) is an incurable global health burden and is characterised by progressive airflow limitation and loss of lung function. In addition to the pulmonary impact of the disease, COPD patients often develop comorbid diseases such as cardiovascular disease, skeletal muscle wasting, lung cancer and osteoporosis. One key feature of COPD, yet often underappreciated, is the contribution of oxidative stress in the onset and development of the disease. Patients experience an increased burden of oxidative stress due to the combined effects of excess reactive oxygen species (ROS) and nitrogen species (RNS) generation, antioxidant depletion and reduced antioxidant enzyme activity. Currently, there is a lack of effective treatments for COPD, and an even greater lack of research regarding interventions that treat both COPD and its comorbidities. Due to the involvement of oxidative stress in the pathogenesis of COPD and many of its comorbidities, a unique therapeutic opportunity arises where the treatment of a multitude of diseases may be possible with only one therapeutic target. In this review, oxidative stress and the roles of ROS/RNS in the context of COPD and comorbid cardiovascular disease, skeletal muscle wasting, lung cancer, and osteoporosis are discussed and the potential for therapeutic benefit of anti-oxidative treatment in these conditions is outlined. Because of the unique interplay between oxidative stress and these diseases, oxidative stress represents a novel target for the treatment of COPD and its comorbidities. Copyright © 2015. Published by Elsevier Inc.

Pulsatile Hyperglycaemia Induces Vascular Oxidative Stress and GLUT 1 Expression More Potently than Sustained Hyperglycaemia in Rats on High Fat Diet

PubMed Central

Rakipovski, Günaj; Lykkesfeldt, Jens; Raun, Kirsten

2016-01-01

Introduction Pulsatile hyperglycaemia resulting in oxidative stress may play an important role in the development of macrovascular complications. We investigated the effects of sustained vs. pulsatile hyperglycaemia in insulin resistant rats on markers of oxidative stress, enzyme expression and glucose metabolism in liver and aorta. We hypothesized that liver’s ability to regulate the glucose homeostasis under varying states of hyperglycaemia may indirectly affect oxidative stress status in aorta despite the amount of glucose challenged with. Methods Animals were infused with sustained high (SHG), low (SLG), pulsatile (PLG) glucose or saline (VEH) for 96 h. Oxidative stress status and key regulators of glucose metabolism in liver and aorta were investigated. Results Similar response in plasma lipid oxidation was observed in PLG as in SHG. Likewise, in aorta, PLG and SHG displayed increased expression of glucose transporter 1 (GLUT1), gp-91PHOX and super oxide dismutase (SOD), while only the PLG group showed increased accumulation of oxidative stress and oxidised low density lipoprotein (oxLDL) in aorta. Conclusion Pulsatile hyperglycaemia induced relatively higher levels of oxidative stress systemically and in aorta in particular than overt sustained hyperglycaemia thus supporting the clinical observations that pulsatile hyperglycaemia is an independent risk factor for diabetes related macrovascular complications. PMID:26790104

Pulsatile Hyperglycaemia Induces Vascular Oxidative Stress and GLUT 1 Expression More Potently than Sustained Hyperglycaemia in Rats on High Fat Diet.

PubMed

Rakipovski, Günaj; Lykkesfeldt, Jens; Raun, Kirsten

2016-01-01

Pulsatile hyperglycaemia resulting in oxidative stress may play an important role in the development of macrovascular complications. We investigated the effects of sustained vs. pulsatile hyperglycaemia in insulin resistant rats on markers of oxidative stress, enzyme expression and glucose metabolism in liver and aorta. We hypothesized that liver's ability to regulate the glucose homeostasis under varying states of hyperglycaemia may indirectly affect oxidative stress status in aorta despite the amount of glucose challenged with. Animals were infused with sustained high (SHG), low (SLG), pulsatile (PLG) glucose or saline (VEH) for 96 h. Oxidative stress status and key regulators of glucose metabolism in liver and aorta were investigated. Similar response in plasma lipid oxidation was observed in PLG as in SHG. Likewise, in aorta, PLG and SHG displayed increased expression of glucose transporter 1 (GLUT1), gp-91PHOX and super oxide dismutase (SOD), while only the PLG group showed increased accumulation of oxidative stress and oxidised low density lipoprotein (oxLDL) in aorta. Pulsatile hyperglycaemia induced relatively higher levels of oxidative stress systemically and in aorta in particular than overt sustained hyperglycaemia thus supporting the clinical observations that pulsatile hyperglycaemia is an independent risk factor for diabetes related macrovascular complications.

Cardiovascular and renal manifestations of glutathione depletion induced by buthionine sulfoximine.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Pérez-Abud, Rocío; Vargas Tendero, Pablo; Baca, Yolanda; Wangensteen, Rosemary

2012-06-01

Oxidative stress contributes to the development of several cardiovascular diseases, including diabetes, renal insufficiency, and arterial hypertension. Animal studies have evidenced the association between higher blood pressure (BP) and increased oxidative stress, and treatment with antioxidants has been shown to reduce BP, while BP reduction due to antihypertensive drugs is associated with reduced oxidative stress. In 2000, it was first reported that oxidative stress and arterial hypertension were produced in normal Sprague-Dawley rats by oral administration of buthionine sulfoximine (BSO), which induces glutathione (GSH) depletion, indicating that oxidative stress may induce hypertension. The contribution of several potential pathogenic factors has been evaluated in the BSO rat model, the prototype of oxidative stress-induced hypertension, including vascular reactivity, endothelium-derived factors, renin-angiotensin system activity, TXA(2)-PGH(2) production, sodium sensitivity, renal dopamine-induced natriuresis, and sympathetic tone. This review summarizes the main factors implicated in the pathogenesis of BSO-induced hypertension and the alterations associated with GSH depletion that are related to renal function or BP control.

Stress generation in thermally grown oxide films. [oxide scale spalling from superalloy substrates

NASA Technical Reports Server (NTRS)

Kumnick, A. J.; Ebert, L. J.

1981-01-01

A three dimensional finite element analysis was conducted, using the ANSYS computer program, of the stress state in a thin oxide film thermally formed on a rectangular piece of NiCrAl alloy. The analytical results indicate a very high compressive stress in the lateral directions of the film (approximately 6200 MPa), and tensile stresses in the metal substrate that ranged from essentially zero to about 55 MPa. It was found further that the intensity of the analytically determined average stresses could be approximated reasonably well by the modification of an equation developed previously by Oxx for stresses induced into bodies by thermal gradients.

The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications.

PubMed

Hu, Jianmin; Li, Hongde; Luo, Xiangjian; Li, Yueshuo; Bode, Ann; Cao, Ya

2017-11-01

Epstein-Barr virus (EBV) is an important cancer causing virus. Cancer associated with EBV account for approximately 1.5% of all cancers, and represent 1.8% of all cancer deaths worldwide. EBV reactivation plays an important role in the development of EBV-related diseases and is closely related with patients' survival and clinical stages of EBV-related cancers. The therapy regarding to EBV-related cancers is very urgent, especially in endemic areas. Generating oxidative stress is a critical mechanism by which host cells defend against infection by virus. In addition, ROS-mediated oxidative stress plays a significant but paradoxical role acting as a "double-edged sword" to regulate cellular response to radiation, which is the main therapy strategy for EBV-related cancers, especially nasopharyngeal carcinoma. Therefore, in this review we primarily discuss the possible interplay among the oxidative stress, EBV lytic reactivation and radioresistance. Understanding the role of oxidative stress in EBV lytic reactivation and radioresistance will assist in the development of effective strategies for prevention and treatment of EBV-related cancers. © 2017 UICC.

Oxidative stress differentially impacts male and female bovine embryos depending on the culture medium and the stress condition.

PubMed

Dallemagne, Matthew; Ghys, Emmanuelle; De Schrevel, Catalina; Mwema, Ariane; De Troy, Delphine; Rasse, Catherine; Donnay, Isabelle

2018-09-01

Male and female embryos are known to differ for their metabolism and response to environmental factors very early in development. The present study aimed to evaluate the response to oxidative stress of male and female bovine embryos at the morula-blastocyst stages in terms of developmental rates, total cell number and apoptotic rates in two culture conditions. Embryos where cultured in a medium supplemented with either 5% fetal calf serum (FCS) or 4 mg/mL bovine serum albumin and a mixture of insulin, transferrin and selenium (BSA-ITS). Oxidative stress was applied at Day-5 post insemination (pi) by adding either AAPH or menadione to the culture medium, and blastocysts were analyzed at Day-7pi. The impact on development and blastocyst quality was dependent on the culture medium and the stress inducer but differed between male and female embryos. Male embryos resisted better to oxidative stress in FCS supplemented medium, no matter the stress inducer. Accordingly, the impact on blastocyst cell number tended to be higher in female blastocysts after stress induction with AAPH in FCS supplemented medium. On the other hand, in BSA-ITS supplemented medium, female embryos were more resistant to AAPH induced stress, while menadione had no impact on sex ratio. The weaker resistance of males to AAPH in this medium is in accordance with their trend to show a higher increase in apoptotic rates than females in this condition. In conclusion, this study shows that oxidative stress has differential impact on male and female bovine blastocysts depending on the culture condition and on the way oxidative stress is induced. Copyright © 2018 Elsevier Inc. All rights reserved.

Substance P promotes the recovery of oxidative stress-damaged retinal pigmented epithelial cells by modulating Akt/GSK-3β signaling.

PubMed

Baek, Sang-Min; Yu, Seung-Young; Son, Youngsook; Hong, Hyun Sook

2016-01-01

Senescence of the retina causes an accumulation of reactive oxygen species (ROS). Oxidative stress associated with ROS can damage RPE cells, leading to neovascularization and severe ocular disorders, including age-related macular degeneration (AMD). Thus, the early treatment of the damage caused by oxidative stress is critical for preventing the development of ocular diseases such as AMD. In this study, we examined the role of substance P (SP) in the recovery of RPE cells damaged by oxidative stress. To induce oxidative stress, RPE cells were treated with H2O2 at various doses. Recovery from oxidative stress was studied following treatment with SP by analyzing cell viability, cell proliferation, cell apoptosis, and Akt/glycogen synthase kinase (GSK)-3β activation in RPE cells in vitro. H2O2 treatment reduced cellular viability in a dose-dependent manner. SP inhibited the reduction of cell viability due to H2O2 and caused increased cell proliferation and decreased cell apoptosis. Cell survival under oxidative stress requires the activation of Akt signaling that enables cells to resist oxidative stress-induced damage. SP treatment activated Akt/GSK-3β signaling in RPE cells, which were damaged due to oxidative stress, and the inhibition of Akt signaling in SP-treated RPE cells prevented SP-induced recovery. Pretreatment with the neurokinin 1 receptor (NK1R) antagonist reduced the recovery effect of SP on damaged RPE cells. SP can protect RPE cells from oxidant-induced cell death by activating Akt/GSK-3β signaling via NK1R. This study suggests the possibility of SP as a treatment for oxidative stress-related diseases.

Oxidative stress-induced autophagy: Role in pulmonary toxicity

PubMed Central

Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

2015-01-01

Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. PMID:24398106

Roles of Melatonin in Fetal Programming in Compromised Pregnancies

PubMed Central

Chen, Yu-Chieh; Sheen, Jiunn-Ming; Tiao, Miao-Meng; Tain, You-Lin; Huang, Li-Tung

2013-01-01

Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms. PMID:23466884

Dietary Modulation of Oxidative Stress in Alzheimer's Disease.

PubMed

Thapa, Arjun; Carroll, Nick J

2017-07-21

Cells generate unpaired electrons, typically via oxygen- or nitrogen-based by-products during normal cellular respiration and under stressed situations. These pro-oxidant molecules are highly unstable and may oxidize surrounding cellular macromolecules. Under normal conditions, the reactive oxygen or nitrogen species can be beneficial to cell survival and function by destroying and degrading pathogens or antigens. However, excessive generation and accumulation of the reactive pro-oxidant species over time can damage proteins, lipids, carbohydrates, and nucleic acids. Over time, this oxidative stress can contribute to a range of aging-related degenerative diseases such as cancer, diabetes, macular degeneration, and Alzheimer's, and Parkinson's diseases. It is well accepted that natural compounds, including vitamins A, C, and E, β-carotene, and minerals found in fruits and vegetables are powerful anti-oxidants that offer health benefits against several different oxidative stress induced degenerative diseases, including Alzheimer's disease (AD). There is increasing interest in developing anti-oxidative therapeutics to prevent AD. There are contradictory and inconsistent reports on the possible benefits of anti-oxidative supplements; however, fruits and vegetables enriched with multiple anti-oxidants (e.g., flavonoids and polyphenols) and minerals may be highly effective in attenuating the harmful effects of oxidative stress. As the physiological activation of either protective or destructive pro-oxidant behavior remains relatively unclear, it is not straightforward to relate the efficacy of dietary anti-oxidants in disease prevention. Here, we review oxidative stress mediated toxicity associated with AD and highlight the modulatory roles of natural dietary anti-oxidants in preventing AD.

Alpha-1 Antitrypsin Prevents the Development of Preeclampsia Through Suppression of Oxidative Stress.

PubMed

Feng, Yaling; Xu, Jianjuan; Zhou, Qin; Wang, Rong; Liu, Nin; Wu, Yanqun; Yuan, Hua; Che, Haisha

2016-01-01

Preeclampsia (PE) and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT) played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS, and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

[Oxidative stress. Should it be measured in the diabetic patient?].

PubMed

Villa-Caballero, L; Nava-Ocampo, A A; Frati-Munari, A C; Ponce-Monter, H

2000-01-01

Oxidative stress has been defined as a loss of counterbalance between free radical or reactive oxygen species production and the antioxidant systems, with negative effects on carbohydrates, lipids, and proteins. It is also involved in the progression of different chronic diseases and apoptosis. Diabetes mellitus is associated to a high oxidative stress level through different biochemical pathways, i.e. protein glycosylation, glucose auto-oxidation, and the polyol pathway, mainly induced by hyperglycemia. Oxidative stress could also be involved in the pathogenesis of atherosclerotic lesions and other chronic diabetic complications. Measurement of oxidative stress could be useful to investigate its role in the initiation and development processes of chronic diabetic complications and also to evaluate preventive actions, including antioxidative therapy. Different attempts have been made to obtain a practical, accurate, specific, and sensitive method to evaluate oxidative stress in clinical practice. However, this ideal method is not currently available to date and the usefulness of the current methods needs to be confirmed in daily practice. We suggest quantifying oxidated and reduced glutation (GSSG/GSH) and the thiobarbituric reactive substances (TBARS) with currently alternatives. Currently available alternative methods while we await better options.

Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

PubMed Central

Elnakish, Mohammad T.; Ahmed, Amany A. E.; Mohler, Peter J.; Janssen, Paul M. L.

2015-01-01

Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models. PMID:26146529

[Oxidative stress and infectious pathology].

PubMed

Romero Alvira, D; Guerrero Navarro, L; Gotor Lázaro, M A; Roche Collado, E

1995-03-01

Pathogenic organism can be considered as pro-oxidant agents because they produce cell death and tissue damage. In addition organism can be eliminated by specific cell defense mechanism which utilize in part, reactive oxygen radicals formed by oxidative stress responses. The cause of the necessarily defense process results in cell damage thereby leading to development of inflammation, a characteristic oxidative stress situation. This fact shows the duality of oxidative stress in infections and inflammation: oxygen free radicals protect against microorganism attack and can produce tissue damage during this protection to trigger inflammation. Iron, a transition metal which participates generating oxygen free radicals, displays also this duality in infection. We suggest also that different infectious pathologies, such as sickle cell anemia/malaria and AIDS, may display in part this duality. In addition, it should be noted that oxidative damage observed in infectious diseases is mostly due the inflammatory response than to the oxidative potential of the pathogenic agent, this last point is exemplified in cases of respiratory distress and in glomerulonephritis. This review analyzes these controversial facts of infectious pathology in relation with oxidative stress.

Metabolic and oxidative stress markers in Wistar rats after 2 months on a high-fat diet.

PubMed

Auberval, Nathalie; Dal, Stéphanie; Bietiger, William; Pinget, Michel; Jeandidier, Nathalie; Maillard-Pedracini, Elisa; Schini-Kerth, Valérie; Sigrist, Séverine

2014-01-01

Metabolic syndrome is associated with an increased risk of cardiovascular and hepatic complications. Oxidative stress in metabolic tissues has emerged as a universal feature of metabolic syndrome and its co-morbidities. We aimed to develop a rapidly and easily induced model of metabolic syndrome in rats to evaluate its impact on plasma and tissue oxidative stress. Metabolic syndrome was induced in rats using a high-fat diet (HFD), and these rats were compared to rats fed a normal diet (ND) for 2 months. Metabolic control was determined by measuring body weight, blood glucose, triglycerides, lipid peroxidation and protein carbonylation in plasma. Insulinemia was evaluated through the measure of C-peptide. Histological analysis was performed on the pancreas, liver and blood vessels. After 2 months, the HFD induced an increase in body weight, insulin and triglycerides. Liver steatosis was also observed in the HFD group, which was associated with an increase in glycogen storage. In the pancreas, the HFD induced islet hyperplasia. Tissue oxidative stress was also increased in the liver, pancreas and blood vessels, but plasma oxidative stress remained unchanged. This paper reports the development of a fast and easy model of rat metabolic syndrome associated with tissue oxidative stress. This model may be a good tool for the biological validation of drugs or antioxidants to limit or prevent the complications of metabolic syndrome.

Electron Paramagnetic Resonance Measurements of Reactive Oxygen Species by Cyclic Hydroxylamine Spin Probes.

PubMed

Dikalov, Sergey I; Polienko, Yuliya F; Kirilyuk, Igor

2018-05-20

Oxidative stress contributes to numerous pathophysiological conditions such as development of cancer, neurodegenerative, and cardiovascular diseases. A variety of measurements of oxidative stress markers in biological systems have been developed; however, many of these methods are not specific, can produce artifacts, and do not directly detect the free radicals and reactive oxygen species (ROS) that cause oxidative stress. Electron paramagnetic resonance (EPR) is a unique tool that allows direct measurements of free radical species. Cyclic hydroxylamines are useful and convenient molecular probes that readily react with ROS to produce stable nitroxide radicals, which can be quantitatively measured by EPR. In this work, we critically review recent applications of various cyclic hydroxylamine spin probes in biology to study oxidative stress, their advantages, and the shortcomings. Recent Advances: In the past decade, a number of new cyclic hydroxylamine spin probes have been developed and their successful application for ROS measurement using EPR has been published. These new state-of-the-art methods provide improved selectivity and sensitivity for in vitro and in vivo studies. Although cyclic hydroxylamine spin probes EPR application has been previously described, there has been lack of translation of these new methods into biomedical research, limiting their widespread use. This work summarizes "best practice" in applications of cyclic hydroxylamine spin probes to assist with EPR studies of oxidative stress. Additional studies to advance hydroxylamine spin probes from the "basic science" to biomedical applications are needed and could lead to better understanding of pathological conditions associated with oxidative stress. Antioxid. Redox Signal. 28, 1433-1443.

Stable expression of mtlD gene imparts multiple stress tolerance in finger millet.

PubMed

Hema, Ramanna; Vemanna, Ramu S; Sreeramulu, Shivakumar; Reddy, Chandrasekhara P; Senthil-Kumar, Muthappa; Udayakumar, Makarla

2014-01-01

Finger millet is susceptible to abiotic stresses, especially drought and salinity stress, in the field during seed germination and early stages of seedling development. Therefore developing stress tolerant finger millet plants combating drought, salinity and associated oxidative stress in these two growth stages is important. Cellular protection through osmotic adjustment and efficient free radical scavenging ability during abiotic stress are important components of stress tolerance mechanisms in plants. Mannitol, an osmolyte, is known to scavenge hydroxyl radicals generated during various abiotic stresses and thereby minimize stress damage in several plant species. In this study transgenic finger millet plants expressing the mannitol biosynthetic pathway gene from bacteria, mannitol-1-phosphate dehydrogenase (mtlD), were developed through Agrobacterium tumefaciens-mediated genetic transformation. mtlD gene integration in the putative transgenic plants was confirmed by Southern blot. Further, performance of transgenic finger millet under drought, salinity and oxidative stress was studied at plant level in T1 generation and in T1 and T2 generation seedlings. Results from these experiments showed that transgenic finger millet had better growth under drought and salinity stress compared to wild-type. At plant level, transgenic plants showed better osmotic adjustment and chlorophyll retention under drought stress compared to the wild-type. However, the overall increase in stress tolerance of transgenics for the three stresses, especially for oxidative stress, was only marginal compared to other mtlD gene expressing plant species reported in the literature. Moreover, the Agrobacterium-mediated genetic transformation protocol developed for finger millet in this study can be used to introduce diverse traits of agronomic importance in finger millet.

Association between oxidative stress and vascular reactivity in children with sickle cell anaemia and sickle haemoglobin C disease.

PubMed

Möckesch, Berenike; Connes, Philippe; Charlot, Keyne; Skinner, Sarah; Hardy-Dessources, Marie-Dominique; Romana, Marc; Jumet, Stéphane; Petras, Marie; Divialle-Doumdo, Lydia; Martin, Cyril; Tressières, Benoît; Tarer, Vanessa; Hue, Olivier; Etienne-Julan, Maryse; Antoine, Sophie; Pialoux, Vincent

2017-08-01

Oxidative stress and haemolysis-associated nitric oxide (NO) depletion plays a crucial role in the development of vasculopathy in sickle cell anaemia (SS). However it remains unknown whether oxidative stress and haemolysis levels influence vascular function in patients with sickle haemoglobin C disease (SC). Microvascular response to heat (using Laser Doppler flowmetry on finger), oxidative stress biomarkers, NO metabolites, endothelin-1 and haematological parameters were compared between patients with SS and SC. Vascular function, oxidative and nitrosative markers were also measured in healthy (AA) children. SS and SC had increased plasma advanced oxidation protein products (AOPP), malondialdehyde, plasma antioxidant activities and NO end products, compared to AA. SC had lower catalase activity compared to AA and SS. Haemolytic rate, glutathione peroxidase and nitrotyrosine concentrations were significantly increased in children with SS compared to SC and AA. SS and SC had impaired microvascular reactivity compared to AA. In SS, the plateau phase of the response to local thermal heating was negatively associated with nitrotyrosine and AOPP. No association between vascular function parameters and oxidative stress markers was observed in SC. Mild haemolysis in SC, compared to SS, may limit oxidative and nitrosative stress and could explain the better preserved microvascular function in this group. © 2017 John Wiley & Sons Ltd.

Oxidative stress and skin diseases: possible role of physical activity.

PubMed

Kruk, Joanna; Duchnik, Ewa

2014-01-01

The skin is the largest body organ that regulates excretion of metabolic waste products, temperature, and plays an important role in body protection against environmental physical and chemical, as well as biological factors. These include agents that may act as oxidants or catalysts of reactions producing reactive oxygen species (ROS), reactive nitrogen species (RNS), and other oxidants in skin cells. An increased amount of the oxidants, exceeding the antioxidant defense system capacity is called oxidative stress, leading to chronic inflammation, which, in turn, can cause collagen fragmentation and disorganization of collagen fibers and skin cell functions, and thus contribute to skin diseases including cancer. Moreover, research suggests that oxidative stress participates in all stages of carcinogenesis. We report here a summary of the present state of knowledge on the role of oxidative stress in pathogenesis of dermatologic diseases, defensive systems against ROS/RNS, and discuss how physical activity may modulate skin diseases through effects on oxidative stress. The data show duality of physical activity actions: regular moderate activity protects against ROS/RNS damage, and endurance exercise with a lack of training mediates oxidative stress. These findings indicate that the redox balance should be considered in the development of new antioxidant strategies linked to the prevention and therapy of skin diseases.

Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia: a novel role of oxidative stress and therapeutic implications.

PubMed

Hamada, Yasuhiro; Fujii, Hideki; Kitazawa, Riko; Yodoi, Junji; Kitazawa, Sohei; Fukagawa, Masafumi

2009-05-01

Diabetes mellitus is associated with increased risk of osteopenia and bone fracture. However, the mechanisms accounting for diabetic bone disorder are unclear. We have previously reported that streptozotocin-induced diabetic mice develop low turnover osteopenia associated with increased oxidative stress in the diabetic condition. To determine the role of oxidative stress in the development of diabetic osteopenia, we presently investigated the effect of overexpression of thioredoxin-1 (TRX), a major intracellular antioxidant, on the development of diabetic osteopenia, using TRX transgenic mice (TRX-Tg). TRX-Tg are C57BL/6 mice that carry the human TRX transgene under the control of beta-actin promoter. Eight-week-old male TRX-Tg mice and wild type (WT) littermates were intraperitoneally injected with either streptozotocin or vehicle. Mice were grouped as 1) non-diabetic WT, 2) non-diabetic TRX-Tg, 3) diabetic WT, and 4) diabetic TRX-Tg. After 12 weeks of streptozotocin treatment, oxidative stress on the whole body and bone was evaluated, and the physical properties of the femora, and histomorphometry parameters of the tibiae were assessed. TRX overexpression did not affect either body weight or hemoglobin A1c levels. There were no significant differences in renal function and in serum levels of calcium, phosphate, and intact parathyroid hormone among the four groups. On the other hand, urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was significantly elevated in diabetic WT and attenuated in diabetic TRX-Tg. Immunohistochemical staining for 8-OHdG revealed marked intensity in the bone tissue of diabetic WT compared with non-diabetic WT, while staining was attenuated in diabetic TRX-Tg. TRX overexpression partially restored reduced bone mineral density and prevented the suppression of bone formation observed in diabetic WT. Increased oxidative stress in diabetic condition contributes to the development of diabetic osteopenia. Suppression of increased oxidative stress by TRX induction could be a potential therapeutic approach for diabetic osteopenia.

Antioxidant effects of statins in the management of cardiometabolic disorders.

PubMed

Lim, Soo; Barter, Philip

2014-01-01

Redox systems are key players in vascular health. A shift in redox homeostasis-that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems. Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD+/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidation and the adiponectin levels. It is possible that the antioxidant properties of statins contribute to their protective cardiovascular effects, independent of the lipid-lowering actions of these agents. However, possible adverse effects of statins on glucose homeostasis may be related to the redox system. Therefore, studies investigating the modulation of redox signaling by statins are warranted.

Pharmacological models and approaches for pathophysiological conditions associated with hypoxia and oxidative stress.

PubMed

Farías, Jorge G; Herrera, Emilio A; Carrasco-Pozo, Catalina; Sotomayor-Zárate, Ramón; Cruz, Gonzalo; Morales, Paola; Castillo, Rodrigo L

2016-02-01

Hypoxia is the failure of oxygenation at the tissue level, where the reduced oxygen delivered is not enough to satisfy tissue demands. Metabolic depression is the physiological adaptation associated with reduced oxygen consumption, which evidently does not cause any harm to organs that are exposed to acute and short hypoxic insults. Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability of endogenous antioxidant systems to scavenge ROS, where ROS overwhelms the antioxidant capacity. Oxidative stress plays a crucial role in the pathogenesis of diseases related to hypoxia during intrauterine development and postnatal life. Thus, excessive ROS are implicated in the irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Here, we describe several pathophysiological conditions and in vivo and ex vivo models developed for the study of hypoxic and oxidative stress injury. We reviewed existing literature on the responses to hypoxia and oxidative stress of the cardiovascular, renal, reproductive, and central nervous systems, and discussed paradigms of chronic and intermittent hypobaric hypoxia. This systematic review is a critical analysis of the advantages in the application of some experimental strategies and their contributions leading to novel pharmacological therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone)

PubMed Central

Hara, Hideaki

2017-01-01

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress. PMID:28194256

Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone).

PubMed

Masuda, Tomomi; Shimazawa, Masamitsu; Hara, Hideaki

2017-01-01

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress.

Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

PubMed Central

Parker, Lewan; Shaw, Christopher S.; Stepto, Nigel K.; Levinger, Itamar

2017-01-01

Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis. PMID:28529499

Protective effects of a novel sea buckthorn wine on oxidative stress and hypercholesterolemia.

PubMed

Negi, Bharti; Kaur, Rajdeep; Dey, Gargi

2013-02-01

We developed a novel sea buckthorn wine containing significant in vitro free radical-scavenging activity. High-performance liquid chromatographic analysis of the sea buckthorn wine revealed that it contains high rutin, myricetin and quercetin levels compared to Cabernet Shiraz wine. In this study, we evaluated the protective effects of sea buckthorn wine against phorone-induced oxidative stress and high-cholesterol diet induced hypercholesterolemia in male LACA mice. Oral administration of sea buckthorn wine increased the redox ratio accompanied by reduction of oxidized glutathione levels leading to attenuation of phorone-induced oxidative stress. Furthermore, the sea buckthorn wine supplementation reduced hepatic lipid peroxidation and increased the superoxide dismutase activity indicating improved resistance to oxidative stress. In addition, high-cholesterol-fed mice administered with sea buckthorn wine exhibited a 197% increase in the HDL-C/LDL-C ratio compared to high-cholesterol diet treated mice. These studies provide important evidence that sea buckthorn wine exerts protective effects against oxidative stress and hypercholesterolemia.

Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring.

PubMed

Saad, M I; Abdelkhalek, T M; Haiba, M M; Saleh, M M; Hanafi, M Y; Tawfik, S H; Kamel, M A

2016-06-01

The effect of in-utero environment on fetal health and survival is long-lasting, and this is known as the fetal origin hypothesis. The oxidative stress state during gestation could play a pivotal role in fetal programming and development of diseases such as diabetes. In this study, we investigated the effect of intra-uterine obesity and malnutrition on oxidative stress markers in pancreatic and peripheral tissues of F1 offspring both prenatally and postnatally. Furthermore, the effect of postnatal diet on oxidative stress profile was evaluated. The results indicated that intra-uterine obesity and malnourishment significantly increased oxidative stress in F1 offspring. Moreover, the programming effect of obesity was more pronounced and protracted than malnutrition. The obesity-induced programming of offspring tissues was independent of high-caloric environment that the offspring endured; however, high-caloric diet potentiated its effect. In addition, pancreas and liver were the most affected tissues by fetal reprogramming both prenatally and postnatally. In conclusion, maternal obesity and malnutrition-induced oxidative stress could predispose offspring to insulin resistance and diabetes.

Oxidative stress in Nipah virus-infected human small airway epithelial cells.

PubMed

Escaffre, Olivier; Halliday, Hailey; Borisevich, Viktoriya; Casola, Antonella; Rockx, Barry

2015-10-01

Nipah virus (NiV) is a zoonotic emerging pathogen that can cause severe and often fatal respiratory disease in humans. The pathogenesis of NiV infection of the human respiratory tract remains unknown. Reactive oxygen species (ROS) produced by airway epithelial cells in response to viral infections contribute to lung injury by inducing inflammation and oxidative stress; however, the role of ROS in NiV-induced respiratory disease is unknown. To investigate whether NiV induces oxidative stress in human respiratory epithelial cells, we used oxidative stress markers and monitored antioxidant gene expression. We also used ROS scavengers to assess their role in immune response modulation. Oxidative stress was confirmed in infected cells and correlated with the reduction in antioxidant enzyme gene expression. Infected cells treated by ROS scavengers resulted in a significant decrease of the (F2)-8-isoprostane marker, inflammatory responses and virus replication. In conclusion, ROS are induced during NiV infection in human respiratory epithelium and contribute to the inflammatory response. Understanding how oxidative stress contributes to NiV pathogenesis is crucial for therapeutic development.

Oxidative Stress and Nucleic Acid Oxidation in Patients with Chronic Kidney Disease

PubMed Central

Sung, Chih-Chien; Hsu, Yu-Chuan; Lin, Yuh-Feng

2013-01-01

Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS) production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate), deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies. PMID:24058721

Oxidative stress reduces levels of dysbindin-1A via its PEST domain.

PubMed

Yap, Mei-Yi Alicia; Lo, Yew-Long; Talbot, Konrad; Ong, Wei-Yi

2014-12-01

Oxidative stress resulting from the generation of reactive oxygen species has been proposed as an etiological factor in schizophrenia. The present study tests the hypothesis that oxidative stress can affect levels of dysbindin-1A, encoded by Dtnbp1, a genetic risk factor for schizophrenia, via its PEST domain. In vitro studies on SH-SY5Y cells indicate that oxidative stress triggers proteasomal degradation of dysbindin-1A, and that this requires interactions with its PEST domain, which may be a TRIM32 target. We specifically found (a) that oxidative stress induced in SH-SY5Y cells by 500 µM hydrogen peroxide reduced levels of full-length dysbindin-1, but did not reduce levels of that protein lacking its PEST domain and (b) that levels of full-length dysbindin-1, but not dysbindin-1 lacking its PEST domain, were higher in cells treated with the proteasome inhibitor MG132. Oxidative stress thus emerges as the first known cellular factor regulating dysbindin-1 isoforms with PEST domains. These findings are consistent with the previously noted fact that phosphorylation of PEST domains often marks proteins for proteasomal degradation, and raises the possibility that treatments reducing oxidative stress in the brain, especially during development, may lower schizophrenia risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of the Oxidative Stress Status in Nonspecific Vaginitis and Its Role in Vaginal Epithelial Cells Apoptosis

PubMed Central

Chen, Zhaojie; Zhang, Zhen; Zhang, Haiyan; Xie, Beibei

2015-01-01

Nonspecific vaginitis (NSV), also named bacterial vaginosis, is one of the most common genital system diseases in women during their reproductive years. The specific pathogenic mechanism of NSV is not clear yet. Upon the balance alteration, large amount of reactive oxidant species (ROS) is generated and accumulated in the genital tract, and thus resulting in oxidative stress, which has been reported to be an important trigger of mitochondrial pathway cell apoptosis. In this study, the antioxidant secretion level and antioxidant enzyme activity in the vaginal discharge were evaluated to analyze the oxidative status in the vaginal tract of NSV patients. The effect of oxidative stress on the vaginal mucosa epithelial cell apoptosis was then studied. The role of oxidative stress on NSV development was uncovered; thus open new direction for the prevention and treatment of NSV by providing antiradical agents was revealed. PMID:26558281

Oxidative stress-induced telomeric erosion as a mechanism underlying airborne particulate matter-related cardiovascular disease

PubMed Central

2012-01-01

Particulate matter (PM) pollution is responsible for hundreds of thousands of deaths worldwide, the majority due to cardiovascular disease (CVD). While many potential pathophysiological mechanisms have been proposed, there is not yet a consensus as to which are most important in causing pollution-related morbidity/mortality. Nor is there consensus regarding which specific types of PM are most likely to affect public health in this regard. One toxicological mechanism linking exposure to airborne PM with CVD outcomes is oxidative stress, a contributor to the development of CVD risk factors including atherosclerosis. Recent work suggests that accelerated shortening of telomeres and, thus, early senescence of cells may be an important pathway by which oxidative stress may accelerate biological aging and the resultant development of age-related morbidity. This pathway may explain a significant proportion of PM-related adverse health outcomes, since shortened telomeres accelerate the progression of many diseases. There is limited but consistent evidence that vehicular emissions produce oxidative stress in humans. Given that oxidative stress is associated with accelerated erosion of telomeres, and that shortened telomeres are linked with acceleration of biological ageing and greater incidence of various age-related pathology, including CVD, it is hypothesized that associations noted between certain pollution types and sources and oxidative stress may reflect a mechanism by which these pollutants result in CVD-related morbidity and mortality, namely accelerated aging via enhanced erosion of telomeres. This paper reviews the literature providing links among oxidative stress, accelerated erosion of telomeres, CVD, and specific sources and types of air pollutants. If certain PM species/sources might be responsible for adverse health outcomes via the proposed mechanism, perhaps the pathway to reducing mortality/morbidity from PM would become clearer. Not only would pollution reduction imperatives be more focused, but interventions which could reduce oxidative stress would become all the more important. PMID:22713210

Increased Neuronal DNA/RNA Oxidation in the Frontal Cortex of Mice Subjected to Unpredictable Chronic Mild Stress.

PubMed

Maluach, Alfred M; Misquitta, Keith A; Prevot, Thomas D; Fee, Corey; Sibille, Etienne; Banasr, Mounira; Andreazza, Ana C

2017-01-01

Chronic stress is implicated in the development of various psychiatric illnesses including major depressive disorder. Previous reports suggest that patients with major depressive disorder have increased levels of oxidative stress, including higher levels of DNA/RNA oxidation found in postmortem studies, especially within brain regions responsible for the cognitive and emotional processes disrupted in the disorder. Here, we aimed to investigate whether unpredictable chronic mild stress in mice induces neuronal DNA/RNA oxidation in the prelimbic, infralimbic, and cingulate cortices of the frontal cortex and the basolateral amygdala and to explore potential associations with depressive-like behaviors. We expected that animals subjected to unpredictable chronic mild stress will present higher levels of DNA/RNA oxidation, which will be associated with anxiety-/depressive-like behaviors. C57BL/6J mice were assigned to unpredictable chronic mild stress or nonstress conditions (n = 10/group, 50% females). Following five weeks of unpredictable chronic mild stress exposure, mice were tested in a series of behavioral tests measuring anxiety- and depressive-like behaviors. Frontal cortex and amygdala sections were then immunolabeled for neuronal nuclei, a marker of post-mitotic neurons and anti-8-hydroxy-2-deoxyguanosine/8-oxo-7,8-dihydroguanosine, which reflects both DNA and RNA oxidation. Levels of neuronal DNA/RNA oxidation were increased in the frontal cortex of mice subjected to unpredictable chronic mild stress ( p = 0.0207). Levels of neuronal DNA/RNA oxidation in the frontal cortex were positively correlated with z-emotionality scores for latency to feed in the novelty-suppressed feeding test ( p = 0.0031). Statistically significant differences were not detected in basolateral amygdala levels of neuronal DNA/RNA oxidation between nonstress- and unpredictable chronic mild stress-exposed mice, nor were correlations found with behavioral performances for this region. Our results demonstrate that unpredictable chronic mild stress induces a significant increase in neuronal DNA/RNA oxidation in the frontal cortex that correlate with behavioral readouts of the stress response. A lack of DNA/RNA oxidation alterations in the basolateral amygdala suggests greater vulnerability of frontal cortex neurons to DNA/RNA oxidation in response to unpredictable chronic mild stress. These findings add support to the hypothesis that chronic stress-induced damage to DNA/RNA may be an additional molecular mechanism underlying cellular dysfunctions associated with chronic stress and present in stress-related disorders.

Role of Bacopa monnieri in the temporal regulation of oxidative stress in clock mutant (cryb) of Drosophila melanogaster.

PubMed

Subramanian, Perumal; Prasanna, Vinoth; Jayapalan, Jaime Jacqueline; Abdul Rahman, Puteri Shafinaz; Hashim, Onn Haji

2014-06-01

Accruing evidences imply that circadian organization of biochemical, endocrinological, cellular and physiological processes contribute to wellness of organisms and in the development of pathologies such as malignancy, sleep and endocrine disorders. Oxidative stress is known to mediate a number of diseases and it is notable to comprehend the orchestration of circadian clock of a model organism of circadian biology, Drosophila melanogaster, under oxidative stress. We investigated the nexus between circadian clock and oxidative stress susceptibility by exposing D. melanogaster to hydrogen peroxide (H2O2) or rotenone; the reversibility of rhythms following exposure to Bacopa monnieri extract (ayurvedic medicine rich in antioxidants) was also investigated. Abolishment of 24h rhythms in physiological response (negative geotaxis), oxidative stress markers (protein carbonyl and thiobarbituric acid reactive substances) and antioxidants (superoxide dismutase, catalase, glutathione-S-transferase and reduced glutathione) were observed under oxidative stress. Furthermore, abolishment of per mRNA rhythm in H2O2 treated wild type flies and augmented susceptibility to oxidative stress in clock mutant (cry(b)) flies connotes the role of circadian clock in reactive oxygen species (ROS) homeostasis. Significant reversibility of rhythms was noted following B. monnieri treatment in wild type flies than cry(b) flies. Our experimental approach revealed a relationship involving oxidative stress and circadian clock in fruit fly and the utility of Drosophila model in screening putative antioxidative phytomedicines prior to their use in mammalian systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

A tale of two toxicities: malformed selenoproteins and oxidative stress both contribute to selenium stress in plants

PubMed Central

Van Hoewyk, Doug

2013-01-01

Background Despite selenium's toxicity in plants at higher levels, crops supply most of the essential dietary selenium in humans. In plants, inorganic selenium can be assimilated into selenocysteine, which can replace cysteine in proteins. Selenium toxicity in plants has been attributed to the formation of non-specific selenoproteins. However, this paradigm can be challenged now that there is increasingly abundant evidence suggesting that selenium-induced oxidative stress also contributes to toxicity in plants. Scope This Botanical Briefing summarizes the evidence indicating that selenium toxicity in plants is attributable to both the accumulation of non-specific selenoproteins and selenium-induced oxidative stress. Evidence is also presented to substantiate the claim that inadvertent selenocysteine replacement probably impairs or misfolds proteins, which supports the malformed selenoprotein hypothesis. The possible physiological ramifications of selenoproteins and selenium-induced oxidative stress are discussed. Conclusions Malformed selenoproteins and oxidative stress are two distinct types of stress that drive selenium toxicity in plants and could impact cellular processes in plants that have yet to be thoroughly explored. Although challenging, deciphering whether the extent of selenium toxicity in plants is imparted by selenoproteins or oxidative stress could be helpful in the development of crops with fortified levels of selenium. PMID:23904445

The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress.

PubMed

Pomatto, Laura C D; Carney, Caroline; Shen, Brenda; Wong, Sarah; Halaszynski, Kelly; Salomon, Matthew P; Davies, Kelvin J A; Tower, John

2017-01-09

Multiple human diseases involving chronic oxidative stress show a significant sex bias, including neurodegenerative diseases, cancer, immune dysfunction, diabetes, and cardiovascular disease. However, a possible molecular mechanism for the sex bias in physiological adaptation to oxidative stress remains unclear. Here, we report that Drosophila melanogaster females but not males adapt to hydrogen peroxide stress, whereas males but not females adapt to paraquat (superoxide) stress. Stress adaptation in each sex requires the conserved mitochondrial Lon protease and is associated with sex-specific expression of Lon protein isoforms and proteolytic activity. Adaptation to oxidative stress is lost with age in both sexes. Transgenic expression of transformer gene during development transforms chromosomal males into pseudo-females and confers the female-specific pattern of Lon isoform expression, Lon proteolytic activity induction, and H 2 O 2 stress adaptation; these effects were also observed using adult-specific transformation. Conversely, knockdown of transformer in chromosomal females eliminates the female-specific Lon isoform expression, Lon proteolytic activity induction, and H 2 O 2 stress adaptation and produces the male-specific paraquat (superoxide) stress adaptation. Sex-specific expression of alternative Lon isoforms was also observed in mouse tissues. The results develop Drosophila melanogaster as a model for sex-specific stress adaptation regulated by the Lon protease, with potential implications for understanding sexual dimorphism in human disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidant-antioxidant imbalance in horses infected with equine infectious anaemia virus.

PubMed

Bolfă, Pompei Florin; Leroux, Caroline; Pintea, Adela; Andrei, Sanda; Cătoi, Cornel; Taulescu, Marian; Tăbăran, Flaviu; Spînu, Marina

2012-06-01

This study assesses the impact of equine infectious anaemia virus (EIAV) infection on the oxidant/antioxidant equilibrium of horses. Blood samples from 96 Romanian horses aged 1-25 years, were divided into different groups according to their EIAV-infection status, age, and time post-seroconversion. The effect of infection on oxidative stress was estimated by measuring enzymatic antioxidants (superoxide dismutase [SOD], glutathione peroxidase [GPx] and catalase), non-enzymatic antioxidants (uric acid and carotenoids), and lipid peroxidation (malondialdehyde [MDA]). Infection modified the oxidant/antioxidant equilibrium in the horses, influencing GPx and uric acid levels (P<0.05). Time post-seroconversion also contributed to oxidative stress imbalance, exhibiting a significant influence on both SOD and MDA concentrations in the blood (P<0.05). Animal age did not have a significant influence on oxidative stress. Recently infected horses (<1 year following seroconversion), and horses >5 years old, represented the most vulnerable category in terms of oxidative stress, followed by recently infected animals <5 years old. The results of this study are novel in implicating EIAV infection in the development of oxidative stress in horses. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stable Expression of mtlD Gene Imparts Multiple Stress Tolerance in Finger Millet

PubMed Central

Hema, Ramanna; Vemanna, Ramu S.; Sreeramulu, Shivakumar; Reddy, Chandrasekhara P.; Senthil-Kumar, Muthappa; Udayakumar, Makarla

2014-01-01

Finger millet is susceptible to abiotic stresses, especially drought and salinity stress, in the field during seed germination and early stages of seedling development. Therefore developing stress tolerant finger millet plants combating drought, salinity and associated oxidative stress in these two growth stages is important. Cellular protection through osmotic adjustment and efficient free radical scavenging ability during abiotic stress are important components of stress tolerance mechanisms in plants. Mannitol, an osmolyte, is known to scavenge hydroxyl radicals generated during various abiotic stresses and thereby minimize stress damage in several plant species. In this study transgenic finger millet plants expressing the mannitol biosynthetic pathway gene from bacteria, mannitol-1-phosphate dehydrogenase (mtlD), were developed through Agrobacterium tumefaciens-mediated genetic transformation. mtlD gene integration in the putative transgenic plants was confirmed by Southern blot. Further, performance of transgenic finger millet under drought, salinity and oxidative stress was studied at plant level in T1 generation and in T1 and T2 generation seedlings. Results from these experiments showed that transgenic finger millet had better growth under drought and salinity stress compared to wild-type. At plant level, transgenic plants showed better osmotic adjustment and chlorophyll retention under drought stress compared to the wild-type. However, the overall increase in stress tolerance of transgenics for the three stresses, especially for oxidative stress, was only marginal compared to other mtlD gene expressing plant species reported in the literature. Moreover, the Agrobacterium-mediated genetic transformation protocol developed for finger millet in this study can be used to introduce diverse traits of agronomic importance in finger millet. PMID:24922513

Cardiopulmonary Bypass and Oxidative Stress

PubMed Central

Zakkar, Mustafa; Guida, Gustavo; Suleiman, M-Saadeh; Angelini, Gianni D.

2015-01-01

The development of the cardiopulmonary bypass (CPB) revolutionized cardiac surgery and contributed immensely to improved patients outcomes. CPB is associated with the activation of different coagulation, proinflammatory, survival cascades and altered redox state. Haemolysis, ischaemia, and perfusion injury and neutrophils activation during CPB play a pivotal role in oxidative stress and the associated activation of proinflammatory and proapoptotic signalling pathways which can affect the function and recovery of multiple organs such as the myocardium, lungs, and kidneys and influence clinical outcomes. The administration of agents with antioxidant properties during surgery either intravenously or in the cardioplegia solution may reduce ROS burst and oxidative stress during CPB. Alternatively, the use of modified circuits such as minibypass can modify both proinflammatory responses and oxidative stress. PMID:25722792

Oxidative Stress, Unfolded Protein Response, and Apoptosis in Developmental Toxicity

PubMed Central

Kupsco, Allison; Schlenk, Daniel

2016-01-01

Physiological development requires precise spatiotemporal regulation of cellular and molecular processes. Disruption of these key events can generate developmental toxicity in the form of teratogenesis or mortality. The mechanism behind many developmental toxicants remains unknown. While recent work has focused on the unfolded protein response (UPR), oxidative stress, and apoptosis in the pathogenesis of disease, few studies have addressed their relationship in developmental toxicity. Redox regulation, UPR, and apoptosis are essential for physiological development and can be disturbed by a variety of endogenous and exogenous toxicants to generate lethality and diverse malformations. This review examines the current knowledge of the role of oxidative stress, UPR, and apoptosis in physiological development as well as in developmental toxicity, focusing on studies and advances in vertebrates model systems. PMID:26008783

Effect of Sophora subprosrate polysaccharide on oxidative stress induced by PCV2 infection in RAW264.7 cells.

PubMed

Su, Zi-Jie; Wei, Ying-Yi; Yin, Dan; Shuai, Xue-Hong; Zeng, Yun; Hu, Ting-Jun

2013-11-01

In this study, an oxidative stress model was first developed in a mouse macrophage cell line (RAW264.7 cells) by infecting the cells with porcine circovirus type 2 (PCV2). The regulatory effect of Sophora subprosrate polysaccharide (SSP) on PCV2-induced oxidative stress was investigated. The results showed that after infection with PCV2, reactive oxygen species (ROS) and nitric oxide (NO) production, myeloperoxidase (MPO) activity, and inducible nitric oxide synthase (iNOS) expression were significantly increased. Meanwhile, the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and hydroxyl radical prevention capacity were greatly reduced. These data indicate successful creation of an oxidative stress model in RAW264.7 cells. A dramatic decrease in cell viability was observed in the cells exposed to oxidative stress compared to the control. When the cells were treated with SSP in concentrations of 100, 200 or 400 μg/mL post PCV2 infection, an increase in the GSH/GSSG ratio and hydroxyl radical prevention capacity was observed. We also observed decreased ROS and NO production, MPO activity, and iNOS expression in the infected cells. Our results demonstrated that PCV2 infection was able to induce oxidative stress in RAW264.7 cells and that SSP could reduce the negative effects resulting from the PCV2 infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Paraoxonase: The Universal Factor of Antioxidant Defense in Human Body.

PubMed

Borovkova, E I; Antipova, N V; Komeenko, T V; Shakhparonov, M I; Borovkov, I M

The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents.

Role of mitochondrial oxidative stress in hypertension

PubMed Central

Ungvari, Zoltan

2013-01-01

Based on mosaic theory, hypertension is a multifactorial disorder that develops because of genetic, environmental, anatomical, adaptive neural, endocrine, humoral, and hemodynamic factors. It has been recently proposed that oxidative stress may contribute to all of these factors and production of reactive oxygen species (ROS) play an important role in the development of hypertension. Previous studies focusing on the role of vascular NADPH oxidases provided strong support of this concept. Although mitochondria represent one of the most significant sources of cellular ROS generation, the regulation of mitochondrial ROS generation in the cardiovascular system and its pathophysiological role in hypertension are much less understood. In this review, the role of mitochondrial oxidative stress in the pathophysiology of hypertension and cross talk between angiotensin II signaling, pathways involved in mechanotransduction, NADPH oxidases, and mitochondria-derived ROS are considered. The possible benefits of therapeutic strategies that have the potential to attenuate mitochondrial oxidative stress for the prevention/treatment of hypertension are also discussed. PMID:24043248

The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review.

PubMed

Gupta, Sajal; Agarwal, Ashok; Banerjee, Jashoman; Alvarez, Juan G

2007-05-01

Human reproduction is not considered a highly efficient biological process. Before the end of the first trimester, 30%-50% of conceptions end in spontaneous abortion. Most losses occur at the time of implantation. 15%-20% of clinical pregnancies end in spontaneous abortions. Recurrent pregnancy loss is a frustrating clinical problem both for clinicians and patients. Recurrent pregnancy loss affects 0.5%-3% of women in the reproductive age group, and between 50%-60% of recurrent pregnancy losses are idiopathic. Oxidative stress-induced damage has been hypothesized to play a role in spontaneous abortion, idiopathic recurrent pregnancy loss, hydatidiform mole, defective embryogenesis, and drug-induced teratogenicity. Some studies implicate systemic and placental oxidative stress in the pathophysiology of abortion and recurrent pregnancy loss. Oxidant-induced endothelial damage, impaired placental vascularization and immune malfunction have all been proposed to play a role in the pathophysiology of idiopathic recurrent pregnancy loss. Oxidative stress-induced placental dysfunction may be a common cause of the multifactorial and polygenic etiologies of abortion, recurrent pregnancy loss, defective embryogenesis, hydatidiform mole, and drug-induced teratogenic effects. Oxidative stress-induced modification of phospholipids has been linked to the formation of antiphospholipid antibodies in the antiphospholipid syndrome. The objective of this review was to examine the association between oxidative stress, spontaneous abortion and recurrent pregnancy loss, based on the published literature. We conducted an extensive literature search utilizing the databases of Medline, CINAHL, and Cochrane from 1986 to 2005. The following keywords were used: oxidative stress, abortion, recurrent pregnancy loss, reactive oxygen species, antioxidants, fetal development, and embryopathies. We conducted an electronic search, as well as a manual search of cross-references. We have included all studies in the English language found in the literature focusing on oxidative stress and its association with abortions, recurrent pregnancy loss and drug-induced teratogenicity. The role of antioxidant vitamins for primary prevention of oxidative stress-induced pathologies needs to be investigated further. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to state that the causes of spontaneous and recurrent abortion are multifaceted, however, some of the causes may be preventable and also explain that the role of oxidative stress during pregnancy and adverse pregnancy outcomes has a basis in pathophysiology, although the role of oxidative stress and the treatment of oxidative stress during or before pregnancy remains speculative.

Differential Role of Poly(ADP-ribose) polymerase in D. discoideum growth and development

PubMed Central

2011-01-01

Background Poly(ADP-ribose) polymerase is evolutionarily conserved as a responder to various forms of stress. Though PARP's role in cell death is well addressed, its role in development and multicellularity is still an enigma. We have previously reported the role of PARP in oxidative stress induced delayed development of D. discoideum. Results In the current study we highlight the involvement of PARP during D. discoideum development. Oxidative stress affects expression of aca and cAR1 thus affecting aggregation. Although parp expression is not affected during oxidative stress but it is involved during normal development as confirmed by our PARP down-regulation studies. Constitutive PARP down-regulation resulted in blocked development while no effect was observed on D. discoideum growth. Interestingly, stage specific PARP down-regulation arrested development at the slug stage. Conclusion These results emphasize that PARP is essential for complex differentiation and its function may be linked to multicellularity. This is the first report where the involvement of PARP during normal multicellular development in D. discoideum, an ancient eukaryote, is established which could be of evolutionary significance. Thus our study adds one more role to the multitasking function of PARP. PMID:21385463

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

PubMed

Wong, Sing Wan; Yao, Yifei; Hong, Ye; Ma, Zhiyao; Kok, Stanton H L; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T

2017-04-01

High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H 2 O 2 ). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H 2 O 2 . These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

Raman spectroscopy analysis of air grown oxide scale developed on pure zirconium substrate

NASA Astrophysics Data System (ADS)

Kurpaska, L.; Favergeon, J.; Lahoche, L.; El-Marssi, M.; Grosseau Poussard, J.-L.; Moulin, G.; Roelandt, J.-M.

2015-11-01

Using Raman spectroscopy technique, external and internal parts of zirconia oxide films developed at 500 °C and 600 °C on pure zirconium substrate under air at normal atmospheric pressure have been examined. Comparison of Raman peak positions of tetragonal and monoclinic zirconia phases, recorded during the oxide growth at elevated temperature, and after cooling at room temperature have been presented. Subsequently, Raman peak positions (or shifts) were interpreted in relation with the stress evolution in the growing zirconia scale, especially closed to the metal/oxide interface, where the influence of compressive stress in the oxide is the biggest. Reported results, for the first time show the presence of a continuous layer of tetragonal zirconia phase developed in the proximity of pure zirconium substrate. Based on the Raman peak positions we prove that this tetragonal layer is stabilized by the high compressive stress and sub-stoichiometry level. Presence of the tetragonal phase located in the outer part of the scale have been confirmed, yet its Raman characteristics suggest a stress-free tetragonal phase, therefore different type of stabilization mechanism. Presented study suggest that its stabilization could be related to the lattice defects introduced by highstoichiometry of zirconia or presence of heterovalent cations.

Activation of the Nrf2-ARE Pathway in Hepatocytes Protects Against Steatosis in Nutritionally Induced Non-alcoholic Steatohepatitis in Mice

PubMed Central

Lee, Lung-Yi; Köhler, Ulrike A.; Zhang, Li; Roenneburg, Drew; Werner, Sabine; Johnson, Jeffrey A.; Foley, David P.

2014-01-01

Oxidative stress is implicated in the development of non-alcoholic steatohepatitis (NASH). The Nrf2-antioxidant response element pathway protects cells from oxidative stress. Studies have shown that global Nrf2 deficiency hastens the progression of NASH. The purpose of this study was to determine whether long-term hepatocyte-specific activation of Nrf2 mitigates NASH progression. Transgenic mice expressing a constitutively active Nrf2 construct in hepatocytes (AlbCre+/caNrf2+) and littermate controls were generated. These mice were fed standard or methionine-choline-deficient (MCD) diet, a diet used to induce NASH development in rodents. After 28 days of MCD dietary feeding, mice developed significant increases in steatosis, inflammation, oxidative stress, and HSC activation compared with those mice on standard diet. AlbCre+/caNrf2+ animals had significantly decreased serum transaminases and reduced steatosis when compared with the AlbCre+/caNrf2− animals. This significant reduction in steatosis was associated with increased expression of genes involved in triglyceride export (MTTP) and β-oxidation (CPT2). However, there were no differences in the increased oxidative stress, inflammation, and HSC activation from MCD diet administration between the AlbCre+/caNrf2− and AlbCre+/caNrf2+ animals. We conclude that hepatocyte-specific activation of Nrf2-mediated gene expression decreased hepatocellular damage and steatosis in a dietary model of NASH. However, hepatocyte-specific induction of Nrf2-mediated gene expression alone is insufficient to mitigate inflammation, oxidative stress, and HSC activation in this nutritional NASH model. PMID:25294219

Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, Takuma, E-mail: katotaku@doc.medic.mie-u.ac.jp; Tada-Oikawa, Saeko; Wang, Linan

In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen,more » but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases. - Highlights: • Oral exposure to TBT exacerbates airway inflammation. • TBT induces oxidative stress in secondary lymphoid organs, but not in the lung. • TBT preferentially induces regulatory T cell apoptosis over non-Treg cells. • TBT does not enhance pre-existing airway inflammation in sensitized mice. • Chemicals in food contaminants contribute to allergic asthma via oxidative stress.« less

The protective effect of menhaden oil in the oxidative damage and renal necrosis due to dietary choline deficiency.

PubMed

Ossani, Georgina P; Repetto, Marisa G; Boveris, Alberto; Monserrat, Alberto J

2013-02-26

Weanling rats fed a choline-deficient diet develop kidney oxidative damage, tubular and cortical kidney necrosis, renal failure and animal death. The effect of dietary menhaden oil was assayed on the mentioned sequence correlating oxidative stress with renal structure and function. Rats were fed ad libitum 4 different diets: (a) a choline-deficient diet with corn oil and sunflower hydrogenated oil as a source of fatty acids; (b) the same diet supplemented with choline; (c) a choline-deficient diet with menhaden oil as a source of fatty acids; and (d) the previous diet supplemented with choline. Animals were sacrificed at days 0, 2, 4 and 7. The histopathological study of the kidneys showed that renal necrosis was only observed at day 7 in choline-deficient rats receiving the vegetable oil diet, simultaneously with increased creatinine plasma levels. Homogenate chemiluminescence (BOOH-initiated chemiluminescence) and phospholipid oxidation indicate the development of oxidative stress and damage in choline-deficient rats fed vegetable oils as well as the protective effect of menhaden oil. Rats fed with the fish oil diet showed that oxidative stress and damage develop later, as compared with vegetable oil, with no morphological damage during the experimental period.

Role of Magnesium in Oxidative Stress in Individuals with Obesity.

PubMed

Morais, Jennifer Beatriz Silva; Severo, Juliana Soares; Santos, Loanne Rocha Dos; de Sousa Melo, Stéfany Rodrigues; de Oliveira Santos, Raisa; de Oliveira, Ana Raquel Soares; Cruz, Kyria Jayanne Clímaco; do Nascimento Marreiro, Dilina

2017-03-01

Adipose tissue is considered an endocrine organ that promotes excessive production of reactive oxygen species when in excess, thus contributing to lipid peroxidation. Magnesium deficiency contributes to the development of oxidative stress in obese individuals, as this mineral plays a role as an antioxidant, participates as a cofactor of several enzymes, maintains cell membrane stability and mitigates the effects of oxidative stress. The objective of this review is to bring together updated information on the participation of magnesium in the oxidative stress present in obesity. We conducted a search of articles published in the PubMed, SciELO and LILACS databases, using the keywords 'magnesium', 'oxidative stress', 'malondialdehyde', 'superoxide dismutase', 'glutathione peroxidase', 'reactive oxygen species', 'inflammation' and 'obesity'. The studies show that obese subjects have low serum concentrations of magnesium, as well as high concentrations of oxidative stress marker in these individuals. Furthermore, it is evident that the adequate intake of magnesium contributes to its appropriate homeostasis in the body. Thus, this review of current research can help define the need for intervention with supplementation of this mineral for the prevention and treatment of disorders associated with this chronic disease.

Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing of Health and Disease.

PubMed

Tharmalingam, Sujeenthar; Sreetharan, Shayenthiran; Kulesza, Adomas V; Boreham, Douglas R; Tai, T C

2017-10-01

Ionizing radiation exposure from medical diagnostic imaging has greatly increased over the last few decades. Approximately 80% of patients who undergo medical imaging are exposed to low-dose ionizing radiation (LDIR). Although there is widespread consensus regarding the harmful effects of high doses of radiation, the biological effects of low-linear energy transfer (LET) LDIR is not well understood. LDIR is known to promote oxidative stress, however, these levels may not be large enough to result in genomic mutations. There is emerging evidence that oxidative stress causes heritable modifications via epigenetic mechanisms (DNA methylation, histone modification, noncoding RNA regulation). These epigenetic modifications result in permanent cellular transformations without altering the underlying DNA nucleotide sequence. This review summarizes the major concepts in the field of epigenetics with a focus on the effects of low-LET LDIR (<100 mGy) and oxidative stress on epigenetic gene modification. In this review, we show evidence that suggests that LDIR-induced oxidative stress provides a mechanistic link between LDIR and epigenetic gene regulation. We also discuss the potential implication of LDIR exposure during pregnancy where intrauterine fetal development is highly susceptible to oxidative stress-induced epigenetic programing.

Role of Oxidative Stress in Epigenetic Modification in Endometriosis.

PubMed

Ito, Fuminori; Yamada, Yuki; Shigemitsu, Aiko; Akinishi, Mika; Kaniwa, Hiroko; Miyake, Ryuta; Yamanaka, Shoichiro; Kobayashi, Hiroshi

2017-11-01

Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis. Oxidative stress, secondary to the influx of hemoglobin, heme, and iron during retrograde menstruation, is involved in the expression of CpG demethylases, ten-eleven translocation, and jumonji (JMJ). Ten-eleven translocation and JMJ recognize a wide range of endogenous DNA methyltransferases (DNMTs). The increased expression levels of DNMTs may be involved in the subsequent downregulation of the decidualization-related genes. This review supports the hypothesis that there are at least 2 distinct phases of epigenetic modification in endometriosis: the initial wave of iron-induced oxidative stress would be followed by the second big wave of epigenetic modulation of endometriosis susceptibility genes. We summarize the recent advances in our understanding of the underlying epigenetic mechanisms focusing on oxidative stress in endometriosis.

Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Lee, S. M. C.; Martin, D. S.; Smith, S. M.; Zwart, S. R.; Laurie, S. S; Ribeiro, L. C.; Stenger, M. B.

2017-01-01

Current human space travel consists primarily of long-duration missions onboard the International Space Station (ISS), but in the future may include exploration-class missions to nearby asteroids, Mars, or its moons. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative stress and inflammation can accelerate the development of atherosclerosis.

Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma Cells through Intracellular Oxidative Stress

PubMed Central

Lin, Abraham; Truong, Billy; Patel, Sohil; Kaushik, Nagendra; Choi, Eun Ha; Fridman, Gregory; Fridman, Alexander; Miller, Vandana

2017-01-01

A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death. We assessed changes to the intracellular oxidative environment after plasma treatment and correlated it to emission of two danger signals: surface-exposed calreticulin and secreted adenosine triphosphate. Plasma-generated reactive oxygen and charged species were recognized as the major effectors of immunogenic cell death. Chemical attenuators of intracellular reactive oxygen species successfully abrogated oxidative stress following plasma treatment and modulated the emission of surface-exposed calreticulin. Secreted danger signals from cells undergoing immunogenic death enhanced the anti-tumor activity of macrophages. This study demonstrated that plasma triggers immunogenic cell death through oxidative stress pathways and highlights its potential development for cancer immunotherapy. PMID:28467380

Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gan, Xueqi; Huang, Shengbin; Yu, Qing

Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H{sub 2}O{sub 2}-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activitymore » and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H{sub 2}O{sub 2}-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis. - Highlights: • Oxidative stress is an early pathological event in osteoporosis. • Imbalance of mitochondrial dynamics are linked to oxidative stress in osteoporosis. • The role of the Drp1-dependent mitochondrial pathway in osteoporosis.« less

Augmentation of aluminum-induced oxidative stress in rat cerebrum by presence of pro-oxidant (graded doses of ethanol) exposure.

PubMed

Nayak, Prasunpriya; Sharma, Shiv Bhushan; Chowdary, Nadella Vijaya Subbaraya

2010-11-01

Both aluminum and ethanol are pro-oxidants and neurotoxic. Considering the possibilities of co-exposure and sharing mechanisms of producing neurotoxicity, the present study was planned to identify the level of aluminum-induced oxidative stress in altered pro-oxidant (ethanol exposure) status of cerebrum. Male rats were coexposed to aluminum and ethanol for 4 weeks. After the exposure period, cerebral levels of protein, reduced glutathione (GSH), lipid peroxidation (TBARS) were measured. Activities of catalase, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione perioxidase (GPx) of cerebrum were estimated. In most of the cases significant correlations were observed between the alterations and graded ethanol doses, suggesting a dose-dependency in pushing the oxidant equilibrium toward pro-oxidants. Aluminum is found to influence significantly all the studied parameters of oxidative stress. Likewise, ethanol also influenced these parameters significantly, except GR, while the interaction between ethanol and aluminum could significantly influence only the GSH content and GR activity of cerebrum. Present study demonstrate that coexposure of aluminum with pro-oxidant might favor development of aluminum-induced oxidative stress in cerebrum. This observation might be helpful in understanding of mechanism of neurodegenerative disorders and ameliorate them.

Reduction of methylviologen-mediated oxidative stress tolerance in antisense transgenic tobacco seedlings through restricted expression of StAPX.

PubMed

Sun, Wei-Hong; Wang, Yong; He, Hua-Gang; Li, Xue; Song, Wan; Du, Bin; Meng, Qing-Wei

2013-07-01

Ascorbate peroxidases are directly involved in reactive oxygen species (ROS) scavenging by reducing hydrogen peroxide to water. The tomato thylakoid-bound ascorbate peroxidase gene (StAPX) was introduced into tobacco. RNA gel blot analysis confirmed that StAPX in tomato leaves was induced by methylviologen-mediated oxidative stress. The sense transgenic seedlings exhibited higher tAPX activity than that of the wild type (WT) plants under oxidative stress conditions, while the antisense seedlings exhibited lower tAPX activity. Lower APX activities of antisense transgenic seedlings caused higher malondialdehyde contents and relative electrical conductivity. The sense transgenic seedlings with higher tAPX activity maintained higher chlorophyll content and showed the importance of tAPX in maintaining the optimal chloroplast development under methylviologen stress conditions, whereas the antisense lines maintained lower chlorophyll content than WT seedlings. Results indicated that the over-expression of StAPX enhanced tolerance to methylviologen-mediated oxidative stress in sense transgenic tobacco early seedlings, whereas the suppression of StAPX in antisense transgenic seedlings showed high sensitivity to oxidative stress.

Association of the atherogenic index of plasma and oxidative stress status with weight gain during non-complicated pregnancy.

PubMed

Stefanović, Aleksandra; Kotur-Stevuljević, Jelena; Vujović, Ana; Spasić, Slavica; Spasojević-Kalimanovska, Vesna; Jelic-Ivanović, Zorana; Martinović, Jelena; Ardalić, Daniela; Mandić-Marković, Vesna; Miković, Zeljko; Cerović, Nikola

2012-11-01

Pregnancy is a stressful condition linked with altered lipid profile, increased oxidative stress and increased inflammation processes. The purpose of the present study was to determine the associations between those alterations with increased weight gain during pregnancy. The atherogenic index of plasma (AIP) and oxidative stress status parameters were determinated in 50 healthy and 172 pregnant women with non-complicated pregnancy. Pregnant women were divided in four groups according to body mass index (BMI) values (BMI quartiles). Oxidative stress parameters were significantly lower in the control group compared with all the pregnant women quartiles. Unexpectedly, differences in oxidative stress parameters between BMI quartiles groups were not significant. The antioxidant defence parameters remained quite similar in the different BMI quartiles. Weight gain and paraoxonase-1 (PON1) activities were independently associated with increased AIP while weight gain and triglyceride concentration were found to be significant predictors of PON1 activities. The results of our current study indicate the association of maternal weight gain during pregnancy and altered lipid profile, elevated oxidative stress and changed antioxidative capacity of PON1. Taken together all these facts indicate possible increased risk of cardiovascular disease (CVD) development in later life if the weight gain during pregnancy is excessive.

Oxidative stress and antioxidative systems: recipes for successful data collection and interpretation.

PubMed

Noctor, Graham; Mhamdi, Amna; Foyer, Christine H

2016-05-01

Oxidative stress and reactive oxygen species (ROS) are common to many fundamental responses of plants. Enormous and ever-growing interest has focused on this research area, leading to an extensive literature that documents the tremendous progress made in recent years. As in other areas of plant biology, advances have been greatly facilitated by developments in genomics-dependent technologies and the application of interdisciplinary techniques that generate information at multiple levels. At the same time, advances in understanding ROS are fundamentally reliant on the use of biochemical and cell biology techniques that are specific to the study of oxidative stress. It is therefore timely to revisit these approaches with the aim of providing a guide to convenient methods and assisting interested researchers in avoiding potential pitfalls. Our critical overview of currently popular methodologies includes a detailed discussion of approaches used to generate oxidative stress, measurements of ROS themselves, determination of major antioxidant metabolites, assays of antioxidative enzymes and marker transcripts for oxidative stress. We consider the applicability of metabolomics, proteomics and transcriptomics approaches and discuss markers such as damage to DNA and RNA. Our discussion of current methodologies is firmly anchored to future technological developments within this popular research field. © 2016 John Wiley & Sons Ltd.

Identification of Oxidative Stress Related Proteins as Biomarkers for Lung Cancer and Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage

PubMed Central

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L.; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-01-01

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis. PMID:23389041

Identification of oxidative stress related proteins as biomarkers for lung cancer and chronic obstructive pulmonary disease in bronchoalveolar lavage.

PubMed

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-02-06

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.

Ophthalmic acid is a marker of oxidative stress in plants as in animals.

PubMed

Servillo, Luigi; Castaldo, Domenico; Giovane, Alfonso; Casale, Rosario; D'Onofrio, Nunzia; Cautela, Domenico; Balestrieri, Maria Luisa

2018-04-01

Ophthalmic acid (OPH), γ-glutamyl-L-2-aminobutyryl-glycine, a tripeptide analogue of glutathione (GSH), has recently captured considerable attention as a biomarker of oxidative stress in animals. The OPH and GSH biosynthesis, as well as some biochemical behaviors, are very similar. Here, we sought to investigate the presence of OPH in plants and its possible relationship with GSH, known to possess multiple functions in the plant development, growth and response to environmental changes. HPLC-ESI-MS/MS analysis was used to examine the occurrence of OPH in leaves from various plant species, and flours from several plant seeds. Different types of oxidative stress, i.e., water, dark, paraquat, and cadmium stress, were induced in rye, barley, oat, and winter wheat leaves to evaluate the effects on the levels of OPH and its metabolic precursors. OPH and its dipeptide precursor, γ-glutamyl-2-aminobutyric acid, were found to occur in phylogenetically distant plants. Interestingly, the levels of OPH were tightly associated with the oxidative stress tested. Levels of OPH precursors, γ-glutamyl-2-aminobutyric acid and 2-aminobutyric acid, the latter efficiently formed in plants via biosynthetic pathways absent in the animal kingdom, were also found to increase during oxidative stress. OPH occurs in plants and its levels are tightly associated with oxidative stress. OPH behaves as an oxidative stress marker and its biogenesis might occur through a biochemical pathway common to many living organisms. Copyright © 2018 Elsevier B.V. All rights reserved.

The Role of Oxidative Stress in Parkinson’s Disease

PubMed Central

Dias, Vera; Junn, Eunsung; Mouradian, M. Maral

2014-01-01

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD). Disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. Evidence has been developed for oxidative and nitrative damage to key cellular components in the PD substantia nigra. A number of sources and mechanisms for the generation of reactive oxygen species (ROS) are recognized including the metabolism of dopamine itself, mitochondrial dysfunction, iron, neuroinflammatory cells, calcium, and aging. PD causing gene products including DJ-1, PINK1, parkin, alpha-synuclein and LRRK2 also impact in complex ways mitochondrial function leading to exacerbation of ROS generation and susceptibility to oxidative stress. Additionally, cellular homeostatic processes including the ubiquitin-proteasome system and mitophagy are impacted by oxidative stress. It is apparent that the interplay between these various mechanisms contributes to neurodegeneration in PD as a feed forward scenario where primary insults lead to oxidative stress, which damages key cellular pathogenetic proteins that in turn cause more ROS production. Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD. However, therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression. Recent knowledge gained about the specific mechanisms related to PD gene products that modulate ROS production and the response of neurons to stress may provide targeted new approaches towards neuroprotection. PMID:24252804

Nicotine Enhances High-Fat Diet-Induced Oxidative Stress in the Kidney.

PubMed

Arany, Istvan; Hall, Samuel; Reed, Dustin K; Reed, Caitlyn T; Dixit, Mehul

2016-07-01

Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. Both smoking-through nicotine (NIC)-and obesity-by free fatty acid overload-provoke oxidative stress in the kidney, which ultimately results in development of chronic kidney injury. Their combined renal risk, however, is virtually unknown. We tested the hypothesis that chronic NIC exposure worsens renal oxidative stress in mice on high-fat diet (HFD) by altering the balance between expression of pro-oxidant and antioxidant genes. Nine-week-old male C57Bl/6J mice consumed normal diet (ND) or HFD and received either NIC (200 μg/ml) or vehicle (2% saccharine) in their drinking water. Body weight, plasma clinical parameters, renal lipid deposition, markers of renal oxidative stress and injury, as well as renal expression of the pro-oxidant p66shc and the antioxidant MnSOD were determined after 12 weeks. NIC significantly augmented levels of circulating free fatty acid, as well as lipid deposition, oxidative stress and sublethal injury in the kidneys of mice on HFD. In addition, NIC exposure suppressed HFD-mediated induction of MnSOD while increased expression of p66shc in the kidney. Tobacco smoking or the increasingly popular E-cigarettes-via NIC exposure-could worsen obesity-associated lipotoxicity in the kidney. Hence, our findings could help to develop strategies that mitigate adverse effects of NIC on the obese kidney. Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. NIC-the main component of tobacco smoke, E-cigarettes and replacement therapies-links smoking to renal injury via oxidative stress, which could superimpose renal oxidative stress caused by obesity. Our results substantiate this scenario using a mouse model of diet induced obesity and NIC exposure and imply the augmented long-term renal risk in obese smokers. Also, our study may help to develop strategies that mitigate adverse effects of NIC on the obese kidney. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Oxidative stress biomarkers in amniotic fluid of pregnant women with hypothyroidism.

PubMed

Novakovic, Tanja R; Dolicanin, Zana C; Djordjevic, Natasa Z

2017-11-15

Hypothyroidism in pregnancy is the serious state that may lead to fetal morbidity and mortality. Oxidative stress biomarkers in the amniotic fluid can provide important information on the health, development and maturation of the fetus during pregnancy. In this study, we examined whether maternal hypothyroidism contributes to increased oxidative stress biomarkers in the amniotic fluid during the first trimester of pregnancy. The study was conducted on healthy pregnant women and pregnant women with hypothyroidism (gestational age: 16-18 weeks). Oxidative stress biomarkers, such as superoxide anion (O 2 •- ), hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), peroxynitrite (ONOO - ), lipid peroxide (LPO), reduced glutathione (GSH) and oxidized glutathione (GSSG) were assayed in the amniotic fluid. The results of this study indicated that concentrations of O 2 •- and NO are significantly higher, while the concentration of H 2 O 2 is significantly lower in the amniotic fluid of pregnant women with hypothyroidism in comparison to healthy pregnant women. There were no differences in concentrations of LPO, GSH and GSSG among tested groups. Also, we found that amniotic fluid concentration of O 2 •- is negatively correlated with the body weight and Apgar score values of the newborns. These results suggest that pregnancy hypothyroidism is characterized by the amniotic fluid oxidative stress. Incorporation of the oxidative stress biomarkers measurement in the amniotic fluid may be of clinical importance in the management of pregnancy hypothyroidism.

Oxidative stress in Alzheimer disease and mild cognitive impairment: evidence from human data provided by redox proteomics.

PubMed

Swomley, Aaron M; Butterfield, D Allan

2015-10-01

Alzheimer disease (AD) is a neurodegenerative disease with many known pathological features, yet there is still much debate into the exact cause and mechanisms for progression of this degenerative disorder. The amyloid-beta (Aβ)-induced oxidative stress hypothesis postulates that it is the oligomeric Aβ that inserts into membrane systems to initiate much of the oxidative stress observed in brain during the progression of the disease. In order to study the effects of oxidative stress on tissue from patients with AD and amnestic mild cognitive impairment (MCI), we have developed a method called redox proteomics that identifies specific brain proteins found to be selectively oxidized. Here, we discuss experimental findings of oxidatively modified proteins involved in three key cellular processes implicated in the pathogenesis of AD progression: energy metabolism, cell signaling and neurotransmission, as well as the proteasomal degradation pathways and antioxidant response systems. These proteomics studies conducted by our laboratory and others in the field shed light on the molecular changes imposed on the cells of AD and MCI brain, through the deregulated increase in oxidative/nitrosative stress inflicted by Aβ and mitochondrial dysfunction.

Oxidative Stress Associated with Chilling Injury in Immature Fruit: Postharvest Technological and Biotechnological Solutions.

PubMed

Valenzuela, Juan Luis; Manzano, Susana; Palma, Francisco; Carvajal, Fátima; Garrido, Dolores; Jamilena, Manuel

2017-07-08

Immature, vegetable-like fruits are produced by crops of great economic importance, including cucumbers, zucchini, eggplants and bell peppers, among others. Because of their high respiration rates, associated with high rates of dehydration and metabolism, and their susceptibility to chilling injury (CI), vegetable fruits are highly perishable commodities, requiring particular storage conditions to avoid postharvest losses. This review focuses on the oxidative stress that affects the postharvest quality of vegetable fruits under chilling storage. We define the physiological and biochemical factors that are associated with the oxidative stress and the development of CI symptoms in these commodities, and discuss the different physical, chemical and biotechnological approaches that have been proposed to reduce oxidative stress while enhancing the chilling tolerance of vegetable fruits.

Oxidative Stress Associated with Chilling Injury in Immature Fruit: Postharvest Technological and Biotechnological Solutions

PubMed Central

Valenzuela, Juan Luis; Manzano, Susana; Palma, Francisco; Carvajal, Fátima; Jamilena, Manuel

2017-01-01

Immature, vegetable-like fruits are produced by crops of great economic importance, including cucumbers, zucchini, eggplants and bell peppers, among others. Because of their high respiration rates, associated with high rates of dehydration and metabolism, and their susceptibility to chilling injury (CI), vegetable fruits are highly perishable commodities, requiring particular storage conditions to avoid postharvest losses. This review focuses on the oxidative stress that affects the postharvest quality of vegetable fruits under chilling storage. We define the physiological and biochemical factors that are associated with the oxidative stress and the development of CI symptoms in these commodities, and discuss the different physical, chemical and biotechnological approaches that have been proposed to reduce oxidative stress while enhancing the chilling tolerance of vegetable fruits. PMID:28698472

Impacts of oxidative stress on acetylcholinesterase transcription, and activity in embryos of zebrafish (Danio rerio) following Chlorpyrifos exposure.

PubMed

Rodríguez-Fuentes, Gabriela; Rubio-Escalante, Fernando J; Noreña-Barroso, Elsa; Escalante-Herrera, Karla S; Schlenk, Daniel

2015-01-01

Organophosphate pesticides cause irreversible inhibition of AChE which leads to neuronal overstimulation and death. Thus, dogma indicates that the target of OP pesticides is AChE, but many authors postulate that these compounds also disturb cellular redox processes, and change the activities of antioxidant enzymes. Interestingly, it has also been reported that oxidative stress plays also a role in the regulation and activity of AChE. The aims of this study were to determine the effects of the antioxidant, vitamin C (VC), the oxidant, t-butyl hydroperoxide (tBOOH) and the organophosphate Chlorpyrifos (CPF), on AChE gene transcription and activity in zebrafish embryos after 72h exposure. In addition, oxidative stress was evaluated by measuring antioxidant enzymes activities and transcription, and quantification of total glutathione. Apical effects on the development of zebrafish embryos were also measured. With the exception of AChE inhibition and enhanced gene expression, limited effects of CPF on oxidative stress and apical endpoints were found at this developmental stage. Addition of VC had little effect on oxidative stress or AChE, but increased pericardial area and heartbeat rate through an unknown mechanism. TBOOH diminished AChE gene expression and activity, and caused oxidative stress when administered alone. However, in combination with CPF, only reductions in AChE activity were observed with no significant changes in oxidative stress suggesting the adverse apical endpoints in the embryos may have been due to AChE inhibition by CPF rather than oxidative stress. These results give additional evidence to support the role of prooxidants in AChE activity and expression. Copyright © 2015 Elsevier Inc. All rights reserved.

Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

PubMed

Santilli, F; Guagnano, M T; Vazzana, N; La Barba, S; Davi, G

2015-01-01

This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic implications would translate into consistent benefits for effective CV prevention.

Oxidative stress in ventral prostate, ovary, and breast by 2,4-dichlorophenoxyacetic acid in pre- and postnatal exposed rats.

PubMed

Pochettino, Aristides A; Bongiovanni, Bettina; Duffard, Ricardo O; Evangelista de Duffard, Ana María

2013-01-01

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been widely used in agriculture and forestry since the 1940s. 2,4-D has been shown to produce a wide range of adverse effects-from embryotoxicity and teratogenicity to neurotoxicity-on animal and human health. The purpose of this study was to determine the possible effects of pre- and postnatal exposure to 2,4-D on oxidative stress in ventral prostate, ovary and breast. Pregnant rats were daily exposed to oral doses of 70 mg/kg/day of 2,4-D from 16 days of gestation up to 23 days after delivery. Then, the pups were sacrificed by decapitation at postnatal day (PND) 45, 60, or 90. Antioxidant enzyme activities and some parameters of the oxidative stress were assessed in ventral prostate, breast, and ovary. Results show that 2,4-D produced three different effects. First, it increased the concentration of some radical oxygen species and the rates of lipid peroxidation and protein oxidation in ventral prostate, thereby causing oxidative stress at all ages studied. Although an increase in the activity of some antioxidant enzymes was detected, this seemed to have been not enough to counteract the oxidative stress. Second, 2,4-D promoted the oxidative stress in the breasts, mainly during puberty and adulthood, probably because the developing gland is more sensitive to xenobiotics than the adult organ. Third, 2,4-D altered the activity of some antioxidant enzymes and increased lipid peroxide concentration in the ovary. This effect could reflect the variety of ovarian cell types and their different responses to endocrine changes during development. Copyright © 2011 Wiley Periodicals, Inc.

The Protective Effect of Antioxidants Consumption on Diabetes and Vascular Complications

PubMed Central

Dal, Stéphanie; Sigrist, Séverine

2016-01-01

Obesity and diabetes is generally accompanied by a chronic state of oxidative stress, disequilibrium in the redox balance, implicated in the development and progression of complications such as micro- and macro-angiopathies. Disorders in the inner layer of blood vessels, the endothelium, play an early and critical role in the development of these complications. Blunted endothelium-dependent relaxation and/or contractions are quietly associated to oxidative stress. Thus, preserving endothelial function and oxidative stress seems to be an optimization strategy in the prevention of vascular complications associated with diabetes. Diet is a major lifestyle factor that can greatly influence the incidence and the progression of type 2 diabetes and cardiovascular complications. The notion that foods not only provide basic nutrition but can also prevent diseases and ensure good health and longevity is now attained greater prominence. Some dietary and lifestyle modifications associated to antioxidative supply could be an effective prophylactic means to fight against oxidative stress in diabesity and complications. A significant benefit of phytochemicals (polyphenols in wine, grape, teas), vitamins (ascorbate, tocopherol), minerals (selenium, magnesium), and fruits and vegetables in foods is thought to be capable of scavenging free radicals, lowering the incidence of chronic diseases. In this review, we discuss the role of oxidative stress in diabetes and complications, highlight the endothelial dysfunction, and examine the impact of antioxidant foods, plants, fruits, and vegetables, currently used medication with antioxidant properties, in relation to the development and progression of diabetes and cardiovascular complications. PMID:28933404

The Protective Effect of Antioxidants Consumption on Diabetes and Vascular Complications.

PubMed

Dal, Stéphanie; Sigrist, Séverine

2016-07-11

Obesity and diabetes is generally accompanied by a chronic state of oxidative stress, disequilibrium in the redox balance, implicated in the development and progression of complications such as micro- and macro-angiopathies. Disorders in the inner layer of blood vessels, the endothelium, play an early and critical role in the development of these complications. Blunted endothelium-dependent relaxation and/or contractions are quietly associated to oxidative stress. Thus, preserving endothelial function and oxidative stress seems to be an optimization strategy in the prevention of vascular complications associated with diabetes. Diet is a major lifestyle factor that can greatly influence the incidence and the progression of type 2 diabetes and cardiovascular complications. The notion that foods not only provide basic nutrition but can also prevent diseases and ensure good health and longevity is now attained greater prominence. Some dietary and lifestyle modifications associated to antioxidative supply could be an effective prophylactic means to fight against oxidative stress in diabesity and complications. A significant benefit of phytochemicals (polyphenols in wine, grape, teas), vitamins (ascorbate, tocopherol), minerals (selenium, magnesium), and fruits and vegetables in foods is thought to be capable of scavenging free radicals, lowering the incidence of chronic diseases. In this review, we discuss the role of oxidative stress in diabetes and complications, highlight the endothelial dysfunction, and examine the impact of antioxidant foods, plants, fruits, and vegetables, currently used medication with antioxidant properties, in relation to the development and progression of diabetes and cardiovascular complications.

Oxidative stress and mitochondrial adaptive shift during pituitary tumoral growth.

PubMed

Sabatino, Maria Eugenia; Grondona, Ezequiel; Sosa, Liliana D V; Mongi Bragato, Bethania; Carreño, Lucia; Juarez, Virginia; da Silva, Rodrigo A; Remor, Aline; de Bortoli, Lucila; de Paula Martins, Roberta; Pérez, Pablo A; Petiti, Juan Pablo; Gutiérrez, Silvina; Torres, Alicia I; Latini, Alexandra; De Paul, Ana L

2018-05-20

The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellular metabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumour growth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumour development are not well understood. Pituitary tumours present endocrine neoplastic benign growth which, in previous reports, we had shown that in addition to increased proliferation, these tumours were also characterized by cellular senescence signs with no indication of apoptosis. Here, we show clear evidence of oxidative stress in pituitary cells, accompanied by bigger and round mitochondria during tumour development, associated with augmented biogenesis and an increased fusion process. An activation of the Nrf2 stress response pathway together with the attenuation of the oxidative damage signs occurring during tumour development were also observed which will probably provide survival advantages to the pituitary cells. These neoplasms also presented a progressive increase in lactate production, suggesting a metabolic shift towards glycolysis metabolism. These findings might imply an oxidative stress state that could impact on the pathogenesis of pituitary tumours. These data may also reflect that pituitary cells can modulate their metabolism to adapt to different energy requirements and signalling events in a pathophysiological situation to obtain protection from damage and enhance their survival chances. Thus, we suggest that mitochondria function, oxidative stress or damage might play a critical role in pituitary tumour progression. Copyright © 2018 Elsevier Inc. All rights reserved.

Oxidant/Antioxidant Imbalance in Alzheimer's Disease: Therapeutic and Diagnostic Prospects

PubMed Central

2018-01-01

Alzheimer's disease (AD) is the most common cause of dementia and a great socioeconomic burden in the aging society. Compelling evidence demonstrates that molecular change characteristics for AD, such as oxidative stress and amyloid β (Aβ) oligomerization, precede by decades the onset of clinical dementia and that the disease represents a biological and clinical continuum of stages, from asymptomatic to severely impaired. Nevertheless, the sequence of the early molecular alterations and the interplay between them are incompletely understood. This review presents current knowledge about the oxidative stress-induced impairments and compromised oxidative stress defense mechanisms in AD brain and the cross-talk between various pathophysiological insults, with the focus on excessive reactive oxygen species (ROS) generation and Aβ overproduction at the early stages of the disease. Prospects for AD therapies targeting oxidant/antioxidant imbalance are being discussed, as well as for the development of novel oxidative stress-related, blood-based biomarkers for early, noninvasive AD diagnostics. PMID:29636850

Cytoprotective Effects of Pumpkin (Cucurbita Moschata) Fruit Extract against Oxidative Stress and Carbonyl Stress.

PubMed

Shayesteh, Reyhaneh; Kamalinejad, Mohammad; Adiban, Hasan; Kardan, Azin; Keyhanfar, Fariborz; Eskandari, Mohammad Reza

2017-10-01

Background Diabetes mellitus is a chronic endocrine disorder that is associated with significant mortality and morbidity due to microvascular and macrovascular complications. Diabetes complications accompanied with oxidative stress and carbonyl stress in different organs of human body because of the increased generation of free radicals and impaired antioxidant defense systems. In the meantime, reactive oxygen species (ROS) and reactive carbonyl species (RCS) have key mediatory roles in the development and progression of diabetes complications. Therapeutic strategies have recently focused on preventing such diabetes-related abnormalities using different natural and chemical compounds. Pumpkin ( Cucurbita moschata ) is one of the most important vegetables in the world with a broad-range of pharmacological activities such as antihyperglycemic effect. Methods In the present study, the cytoprotective effects of aqueous extract of C. moschata fruit on hepatocyte cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonylation model) were investigated using freshly isolated rat hepatocytes. Results The extract of C. moschata (50 μg/ml) excellently prevented oxidative and carbonyl stress markers, including hepatocyte lysis, ROS production, lipid peroxidation, glutathione depletion, mitochondrial membrane potential collapse, lysosomal damage, and cellular proteolysis. In addition, protein carbonylation was prevented by C. moschata in glyoxal-induced carbonyl stress. Conclusion It can be concluded that C. moschata has cytoprotective effects in oxidative stress and carbonyl stress models and this valuable vegetable can be considered as a suitable herbal product for the prevention of toxic subsequent of oxidative stress and carbonyl stress seen in chronic hyperglycemia. © Georg Thieme Verlag KG Stuttgart · New York.

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF-κB/p65 Activation

PubMed Central

Jiang, Wenkai; Zhou, Lin

2016-01-01

Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2) to induce the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies. PMID:27818721

Internal stresses at the crystalline scale in textured ZrO2 films before lateral cracking

NASA Astrophysics Data System (ADS)

Berdin, Clotilde; Pascal, Serge; Tang, Yan

2015-05-01

Zirconium oxide layers are submitted to internal stresses that play a role in damage of the layer. Lateral cracking is often observed during Zr alloys oxidation. In this paper, we investigated the influence of the microstresses at the crystalline scale on the lateral cracking within a growing oxide on a plane substrate. A parametric study was carried out taking into account the crystallographic texture of the oxide and the presence of a tetragonal zirconia at the metal-oxide interface. Macroscopic computations and polycrystalline aggregate computations were performed. The result indicating the (1 0 6 bar) fiber texture as the most favorable was recovered. It was found that under macroscopic compressive stresses parallel to the plane metal-oxide interface, positive microstresses perpendicular to the interface develops. They can trigger the lateral cracking and the phenomenon is promoted by the presence of tetragonal zirconia at the metal-oxide interface.

Oxidative Stress Induced Inflammation Initiates Functional Decline of Tear Production

PubMed Central

Uchino, Yuichi; Kawakita, Tetsuya; Miyazawa, Masaki; Ishii, Takamasa; Onouchi, Hiromi; Yasuda, Kayo; Ogawa, Yoko; Shimmura, Shigeto; Ishii, Naoaki; Tsubota, Kazuo

2012-01-01

Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1) using a modified tetracycline system (Tet-On/Off system). This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC) in humans). The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease. PMID:23071526

Oxidative stress in normal hematopoietic stem cells and leukemia.

PubMed

Samimi, Azin; Kalantari, Heybatullah; Lorestani, Marzieh Zeinvand; Shirzad, Reza; Saki, Najmaldin

2018-04-01

Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000-2017) of English-language literature using the terms 'oxidative stress,' 'reactive oxygen species,' 'hematopoietic stem cell,' and 'leukemia.' The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long-term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject. © 2018 APMIS. Published by John Wiley & Sons Ltd.

Oxidative stress and NO generation in the rat pancreatitis induced by pancreatic duct ligation.

PubMed

Buchwalow, Igor; Schnekenburger, Jürgen; Atiakshin, Dmitri; Samoilova, Vera; Wolf, Eduard; Boecker, Werner; Tiemann, Katharina

2017-04-01

The interaction between nitric oxide (NO) and superoxides is critical in the development of an acute pancreatitis. Previously, we reported that the expression of superoxides and of the NO-generating enzyme (NO synthase, NOS) was up-regulated in the human pancreatitis, especially within the exocrine compartment indicating an exceptional susceptibility of the exocrine parenchyma to oxidative stress. The aim of the present study was to compare the regulation of NO signalling pathways in the human pancreatitis and in an animal model of an acute pancreatitis induced by pancreatic duct ligation (PDL) in rats. In the PDL-induced rat pancreatitis, we revealed a similar pattern of oxidative stress and NOS up-regulation in acinar and in ductal compartments, like in the human pancreatitis. This demonstrates that the PDL-induced rat pancreatitis is a proper model for further studies of acute pancreatitis development in humans. Copyright © 2017 Elsevier GmbH. All rights reserved.

Systemic inflammatory changes and increased oxidative stress in rural Indian women cooking with biomass fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dutta, Anindita, E-mail: anidu14@gmail.com; Department of Experimental Hematology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata-700 026; Ray, Manas Ranjan

The study was undertaken to investigate whether regular cooking with biomass aggravates systemic inflammation and oxidative stress that might result in increase in the risk of developing cardiovascular disease (CVD) in rural Indian women compared to cooking with a cleaner fuel like liquefied petroleum gas (LPG). A total of 635 women (median age 36 years) who cooked with biomass and 452 age-matched control women who cooked with LPG were enrolled. Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were measured by ELISA. Generation of reactive oxygen species (ROS) by leukocytes was measured by flow cytometry,more » and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Hypertension was diagnosed following the Seventh Report of the Joint Committee. Tachycardia was determined as pulse rate > 100 beats per minute. Particulate matter of diameter less than 10 and 2.5 μm (PM{sub 10} and PM{sub 2.5}, respectively) in cooking areas was measured using real-time aerosol monitor. Compared with control, biomass users had more particulate pollution in indoor air, their serum contained significantly elevated levels of IL-6, IL-8, TNF-α and CRP, and ROS generation was increased by 37% while SOD was depleted by 41.5%, greater prevalence of hypertension and tachycardia compared to their LPG-using neighbors. PM{sub 10} and PM{sub 2.5} levels were positively associated with markers of inflammation, oxidative stress and hypertension. Inflammatory markers correlated with raised blood pressure. Cooking with biomass exacerbates systemic inflammation, oxidative stress, hypertension and tachycardia in poor women cooking with biomass fuel and hence, predisposes them to increased risk of CVD development compared to the controls. Systemic inflammation and oxidative stress may be the mechanistic factors involved in the development of CVD. -- Highlights: ► Effect of chronic biomass smoke exposure on cardiovascular health was investigated. ► Serum markers of systemic inflammation and oxidative stress were studied. ► Biomass using women had increased systemic inflammation and oxidative stress. ► Indoor air pollution and observed changes were positively associated.« less

Parameters of oxidative metabolism in neonates suffering from sepsis and anemia.

PubMed

Sanodze, N; Uberi, N; Uberi, E; Kulumbegov, B

2006-11-01

Neonatal sepsis still remains as one of the actual problems in modern medicine due to its high morbidity and mortality rates determined by diagnostic difficulties and absence of sufficient evidence for effective therapy. Literature data have shown that essential role in pathogenesis of sepsis belongs to the cellular oxidation-reduction misballance and development of the oxidative stress. The aim of our work was to assess indices of pro- and antioxidant systems in term neonates with sepsis on the background of anemia and without it. A total of 41 neonates (17 male, 24 female) with the age range from 3 to 7 days, with early sepsis, and in 2003-2005 years treated at the department of neonates' therapy and intensive care unit of pediatric clinics of the Tbilisi State Medical University were under observation. The control group involved 17 practically healthy neonates of the same age range. In consequence of the analyses there was ascertained, that with anemia increases intensification free-radical oxidation process. At the same time, antioxidant system activity was not change significantly in the sepsis with anemia, than other one. Pathogenesis of anemia may was founded undergo hemolitic anemia results by oxidative stress. According to the results of investigations could be concluded that in case of anemia developed at neonatal sepsis supports intensify of oxidative stress and at the same time anemia is the result of the oxidative stress.

Vermicompost humic acids modulate the accumulation and metabolism of ROS in rice plants.

PubMed

García, Andrés Calderín; Santos, Leandro Azevedo; de Souza, Luiz Gilberto Ambrósio; Tavares, Orlando Carlos Huertas; Zonta, Everaldo; Gomes, Ernane Tarcisio Martins; García-Mina, José Maria; Berbara, Ricardo Luis Louro

2016-03-15

This work aims to determine the reactive oxygen species (ROS) accumulation, gene expression, anti-oxidant enzyme activity, and derived effects on membrane lipid peroxidation and certain stress markers (proline and malondialdehyde-MDA) in the roots of unstressed and PEG-stressed rice plants associated with vermicompost humic acid (VCHA) application. The results show that the application of VCHA to the roots of unstressed rice plants caused a slight but significant increase in root ROS accumulation and the gene expression and activity of the major anti-oxidant enzymes (superoxide dismutase and peroxidase). This action did not have negative effects on root development, and an increase in both root growth and root proliferation occurred. However, the root proline and MDA concentrations and the root permeability results indicate the development of a type of mild stress associated with VCHA application. When VCHA was applied to PEG-stressed plants, a clear alleviation of the inhibition in root development linked to PEG-mediated osmotic stress was observed. This was associated with a reduction in root ROS production and anti-oxidant enzymatic activity caused by osmotic stress. This alleviation of stress caused by VCHA was also reflected as a reduction in the PEG-mediated concentration of MDA in the root as well as root permeability. In summary, the beneficial action of VCHA on the root development of unstressed or PEG-stressed rice plants clearly involves the modulation of ROS accumulation in roots. Copyright © 2016 Elsevier GmbH. All rights reserved.

Biochemical responses and ultrastructural changes in ethylene insensitive mutants of Arabidopsis thialiana subjected to bisphenol A exposure.

PubMed

Ali, Imran; Jan, Mehmood; Wakeel, Abdul; Azizullah, Azizullah; Liu, Bohan; Islam, Faisal; Ali, Abid; Daud, M K; Liu, Yihua; Gan, Yinbo

2017-10-01

Bisphenol A (BPA), an important raw material in plastic industry, has become a serious environmental contaminant due to its wide spread use in different products and increasing release into the environment. BPA is known to cause adverse effects in living organisms including plants. Several studies reported that BPA affects growth and development in plants, mainly through oxidative stress. Plants are known to generally cope with stress mainly through hormonal regulation and adaptation, but little is known about the role of plant hormones in plants under BPA stress. The present study was conducted to investigate the role of ethylene in BPA induced oxidative stress in plants using Arabidopsis thaliana as a test plant. The response of ethylene insensitive mutants of Arabidopsis (ein2-1 and etr1-3) to BPA exposure was studied in comparison to the wild type Arabidopsis (WT). In all three genotypes, exposure to BPA adversely affected cellular structures, stomata and light-harvesting pigments. An increase in reactive oxygen species (ROS) lipid peroxidation and other oxidative stress markers indicated that BPA induced toxicity through oxidative stress. However, the overall results revealed that WT Arabidopsis had more pronounced BPA induced damages while ein2-1 and etr1-3 mutants withstood the BPA induced stress more efficiently. The activity of antioxidant enzymes and expression of antioxidants related genes revealed that the antioxidant defense system in both mutants was more efficiently activated than in WT against BPA induced oxidative stress, which further evidenced the involvement of ethylene in regulating BPA induced oxidative stress. It is concluded that ethylene perception and signaling may be involved in BPA induced oxidative stress responses in plants. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxidative stress, thiols, and redox profiles.

PubMed

Harris, Craig; Hansen, Jason M

2012-01-01

Oxidative stress has been recognized as a contributing factor in the toxicity of a large number of developmental toxicants. Traditional definitions of oxidative stress state that a shift in the balance between reduced and oxidized biomolecules within cells, in favor of the latter, result in changes that are deleterious to vital cell functions and can culminate in malformations and death. The glutathione (GSH)/glutathione disulfide (GSSG) redox couple has been the traditional marker of choice for characterization of oxidative stress because of its high concentrations and direct roles as antioxidant and cellular protectant. Steady state depletion of GSH through conjugation, oxidation, or export has often been reported as the sole criteria for invoking oxidative stress and a myriad of associated deleterious consequences. Numerous other, mostly qualitative, observations have also been reported to suggest oxidative stress has occurred but it is not always clear how well they reflect the state of a cell or its functions. Our emerging understanding of redox signaling and the roles of reactive oxygen species (ROS), thiols, oxidant molecules, and cellular antioxidants, all acting as second messengers, has prompted a redefinition of oxidative stress based on changes in the real posttranslational protein thiol modifications that are central to redox regulation and control. Thiol-based redox couples such as GSH/GSSG, cysteine/cystine (cys/cySS), thioredoxin-reduced/thioredoxin-oxidized (TRX(red)/TRX(ox)) form independent signaling nodes that selectively regulate developmental events and are closely linked to changes in intracellular redox potentials. Accurate assessment of the consequences of increased free radicals in developing conceptuses should best be made using a battery of measurements including the quantitative assessment of intracellular redox potential, ROS, redox status of biomolecules, and induced changes in specific redox signaling nodes. Methods are presented for a determination of ROS production, soluble thiol oxidation, redox potential, and a proteomic approach to evaluate the thiol oxidation state of specific proteins.

Effects of interventions on oxidative stress and inflammation of cardiovascular diseases

PubMed Central

Lee, Sewon; Park, Yoonjung; Zuidema, Mozow Yusof; Hannink, Mark; Zhang, Cuihua

2011-01-01

Excessive oxidative stress and low-grade chronic inflammation are major pathophysiological factors contributing to the development of cardiovascular diseases (CVD) such as hypertension, diabetes and atherosclerosis. Accumulating evidence suggests that a compromised anti-oxidant system can lead to excessive oxidative stress in cardiovascular related organs, resulting in cell damage and death. In addition, increased circulating levels of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-6 and C-reactive protein, are closely related to morbidity and mortality of cardiovascular complications. Emerging evidence suggests that interventions including nutrition, pharmacology and exercise may activate expression of cellular anti-oxidant systems via the nuclear factor erythroid 2-related factor 2-Kelch-like ECH-associated protein 1 signaling pathway and play a role in preventing inflammatory processes in CVD. The focus of the present review is to summarize recent evidence showing the role of these anti-oxidant and anti-inflammatory interventions in cardiovascular disease. We believe that these findings may prompt new effective pathogenesis-oriented interventions, based on the exercise-induced protection from disease in the cardiovascular system, aimed at targeting oxidant stress and inflammation. PMID:21286214

Oxygen Diffusion and Reaction Kinetics in Continuous Fiber Ceramic Matrix Composites

NASA Technical Reports Server (NTRS)

Halbig, Michael C.; Eckel, Andrew J.; Cawley, James D.

1999-01-01

Previous stressed oxidation tests of C/SiC composites at elevated temperatures (350 C to 1500 C) and sustained stresses (69 MPa and 172 MPa) have led to the development of a finite difference cracked matrix model. The times to failure in the samples suggest oxidation occurred in two kinetic regimes defined by the rate controlling mechanisms (i.e. diffusion controlled and reaction controlled kinetics). Microstructural analysis revealed preferential oxidation along as-fabricated, matrix microcracks and also suggested two regimes of oxidation kinetics dependent on the oxidation temperature. Based on experimental results, observation, and theory, a finite difference model was developed. The model simulates the diffusion of oxygen into a matrix crack bridged by carbon fibers. The model facilitates the study of the relative importance of temperature, the reaction rate constant, and the diffusion coefficient on the overall oxidation kinetics.

Significance of Serum Total Oxidant/Antioxidant Status in Patients with Colorectal Cancer

PubMed Central

Yang, Yuwei; Dai, Chunmei; Lu, Anyang; Li, Jie; Liao, Yao; Xiang, Miao; Huang, Qingmei; Wang, Dong

2017-01-01

Oxidative stress is involved in a variety of diseases. Prospective studies investigating the relationship between oxidative stress biomarkers and the status and development of colorectal cancer (CRC) are scarce; previous studies have failed to establish a relationship between the serum total oxidant/antioxidant status and CRC. Therefore, we compared the total serum oxidant/antioxidant levels of CRC patients and healthy subjects, and analyzed their clinical significance in the CRC. Fasting blood samples from 132 CRC patients and 64 healthy subjects were collected. Oxidative stress parameters, including total oxidant status (TOS) and total antioxidant status (TAS), were measured, and the oxidative stress index (OSI) was calculated. The TOS and OSI levels increased significantly (P<0.001) and the TAS level significantly decreased (P<0.001) in the CRC group compared to those in the healthy control group. Oxidative stress parameters differed significantly depending on the patient’s smoking and drinking status (P<0.05). The preoperative and postoperative levels of TOS, TAS, and OSI did not differ significantly between primary sites (colon/rectum) and clinical stages (P>0.05).However, the levels of TOS, TAS, and OSI were significantly different between patients with no metastasis and those with metastases to two organs (P<0.05) Finally, the parameters are affected by smoking and drinking, and subsequent research should be conducted excluding the relevant influencing factors. PMID:28103261

Antioxidant responses to azinphos methyl and carbaryl during the embryonic development of the toad Rhinella (Bufo) arenarum Hensel.

PubMed

Ferrari, Ana; Lascano, Cecilia I; Anguiano, Olga L; D'Angelo, Ana M Pechen de; Venturino, Andrés

2009-06-04

Amphibian embryos are naturally exposed to prooxidant conditions throughout their development. Environmental exposure to contaminants may affect their capacity to respond to challenging conditions, to progress in a normal ontogenesis, and finally to survive and succeed in completing metamorphosis. We studied the effects of the exposure to two anticholinesterase agents, the carbamate carbaryl and the organophosphate azinphos methyl, on the antioxidant defenses of developing embryos of the toad Rhinella (Bufo) arenarum. Reduced glutathione (GSH) levels were increased early by carbaryl, but were decreased by both pesticides at the end of embryonic development. The GSH-dependent enzymes glutathione reductase and glutathione peroxidases showed oscillating activity patterns that could be attributed to an induction of activity in response to oxidative stress and inactivation by excess of reactive oxygen species. Glutathione-S-transferases, which may participate in the conjugation of lipid peroxide products in addition to pesticide detoxification, showed an increase of activity at the beginning and at the end of development. Catalase also showed variations in the activity suggesting, successively, induction and inactivation in response to pesticide exposure-induced oxidative stress. Superoxide dismutase activity was increased by carbaryl and transiently decreased by azinphos methyl exposure. Judging from the depletion in GSH levels and glutathione reductase inhibition at the end of embryonic development, the oxidative stress caused by azinphos methyl seemed to be greater than that caused by carbaryl, which might be in turn related with a higher number of developmental alterations caused by the organophosphate. GSH content is a good biomarker of oxidative stress in the developing embryos exposed to pesticides. The antioxidant enzymes are in turn revealing the balance between their protective capacity and the oxidative damage to the enzyme molecules, decreasing their activity.

Combinatorial stresses kill pathogenic Candida species

PubMed Central

Kaloriti, Despoina; Tillmann, Anna; Cook, Emily; Jacobsen, Mette; You, Tao; Lenardon, Megan; Ames, Lauren; Barahona, Mauricio; Chandrasekaran, Komelapriya; Coghill, George; Goodman, Daniel; Gow, Neil A. R.; Grebogi, Celso; Ho, Hsueh-Lui; Ingram, Piers; McDonagh, Andrew; De Moura, Alessandro P. S.; Pang, Wei; Puttnam, Melanie; Radmaneshfar, Elahe; Romano, Maria Carmen; Silk, Daniel; Stark, Jaroslav; Stumpf, Michael; Thiel, Marco; Thorne, Thomas; Usher, Jane; Yin, Zhikang; Haynes, Ken; Brown, Alistair J. P.

2012-01-01

Pathogenic microbes exist in dynamic niches and have evolved robust adaptive responses to promote survival in their hosts. The major fungal pathogens of humans, Candida albicans and Candida glabrata, are exposed to a range of environmental stresses in their hosts including osmotic, oxidative and nitrosative stresses. Significant efforts have been devoted to the characterization of the adaptive responses to each of these stresses. In the wild, cells are frequently exposed simultaneously to combinations of these stresses and yet the effects of such combinatorial stresses have not been explored. We have developed a common experimental platform to facilitate the comparison of combinatorial stress responses in C. glabrata and C. albicans. This platform is based on the growth of cells in buffered rich medium at 30°C, and was used to define relatively low, medium and high doses of osmotic (NaCl), oxidative (H 2O2) and nitrosative stresses (e.g., dipropylenetriamine (DPTA)-NONOate). The effects of combinatorial stresses were compared with the corresponding individual stresses under these growth conditions. We show for the first time that certain combinations of combinatorial stress are especially potent in terms of their ability to kill C. albicans and C. glabrata and/or inhibit their growth. This was the case for combinations of osmotic plus oxidative stress and for oxidative plus nitrosative stress. We predict that combinatorial stresses may be highly signif cant in host defences against these pathogenic yeasts. PMID:22463109

[Research progress on antioxidation effect of traditional Chinese medicine polysaccharides and sports for diabetes prevention and treatment].

PubMed

Wu, Wei; Zhang, Ling-Li; Zou, Jun

2016-07-01

Researchers found that oxidative stress was closely related to the development of diabetes, and hyperglycemia was a main cause for oxidative stress. Many researchers have proved that oxidative stress, present in diabetes, can aggravate diabetes. Now, traditional Chinese medicines have certain treatment and relief effects for oxidative stress in diabetes, but there are no scientific and systematic conclusions on the efficacy of different Chinese medicines for diabetes and complications. Tomakea scientific and systematic review on the recent years' researches on antioxidation effects of traditional Chinese medication polysaccharides for diabetes, analyze the antioxidation effects of sports in treatment of diabetes, and provide the reference and basis for medications and sports in diabetic patients, as well as prevention and treatments of diabetes and complications from aspects of "internal nursing and external workouts". Databases of CNKI and PubMed were retrieved with key words of "diabetes, oxidative stress, antioxidant, traditional Chinese medication, polysaccharide, sports" in both Chinese and English from Jan 2000 to Apr 2016.Finally 118 papers were included in for analysis and review. Polysaccharides of traditional Chinese medications as well as sports have antioxidation effects for diabetes and its complications, and the combination of these two would produce huge significance for relieving oxidative stress in diabetes, as well as for the prevention and treatment of diabetes and its complications. We need further researches on the levels of oxidative stress markers, doses of Chinese medicines, and the time of taking medications. Copyright© by the Chinese Pharmaceutical Association.

Effect of increasing temperature in the differential activity of oxidative stress biomarkers in various tissues of the Rock goby, Gobius paganellus.

PubMed

Vinagre, Catarina; Madeira, Diana; Mendonça, Vanessa; Dias, Marta; Roma, Joana; Diniz, Mário S

2014-06-01

Oxidative stress biomarkers have been widely used in the development of ecological indices and in the assessment of exposure of aquatic organisms to contaminants from agricultural, industrial and urban pollution. However, temperature is known to also have a significant effect on oxidative stress biomarkers. This way, temperature is a confounding factor that may result in difficulties in the interpretation of oxidative stress biomarkers response patterns. Since climate change is expected to result in more frequent and intense heat wave events it is pertinent to investigate the effect of increasing temperature in the oxidative stress response of common aquatic organisms. It is also important to assess the differential response of different body tissues, given that they are differently exposed to temperature depending on their location and physiological function. This study investigates the effect of increasing temperature (20 °C-34 °C) in the response of multiple biomarkers of oxidative stress: lipid peroxidation, glutathione-S-transferase, superoxide dismutase and catalase activities, in the muscle, liver and gills of a common coastal fish, the Rock goby, Gobius paganellus. The response of the oxidative stress biomarkers analysed were always higher in the gills than in the other tissues. Muscle generally presented the lower levels of any of the biomarkers tested when compared to other tissues. Nevertheless, muscle tissue always responded significantly to temperature, as did the liver, while the gills were unresponsive in terms of lipid peroxidation and glutathione-S-transferase. Unresponsive tissues to temperature may be particularly interesting as indicators of pollution, given that temperature will not be a confounding variable in their oxidative stress response. Copyright © 2014 Elsevier Ltd. All rights reserved.

Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age.

PubMed

Lechuga-Sancho, Alfonso M; Gallego-Andujar, David; Ruiz-Ocaña, Pablo; Visiedo, Francisco M; Saez-Benito, Ana; Schwarz, Mónica; Segundo, Carmen; Mateos, Rosa M

2018-01-01

Oxidative stress and inflammation have been postulated as underlying mechanisms for the development of obesity-related insulin resistance. This association however, remains elusive especially in childhood. We sought to investigate this relation by measuring oxidative stress and antioxidant response biomarkers, before and during an oral glucose tolerance test (OGTT), in different biological samples from obese children. 24 children were recruited for the study, (18 obese and 6 controls). After OGTT, the obese group was subdivided in two, according to whether or not carbohydrate metabolic impairment (Ob.IR+, Ob.IR-; respectively) was found. Different biomarkers were analyzed after fasting (T = 0) and during an OGTT (T = 60 and 120 min). Lipoperoxides were measured in plasma, erythrocytes, and urine; while advanced glycation end products were determined in plasma, and redox status (GSH/GSSG ratio) in erythrocytes. We found marked differences in the characterization of the oxidative status in urine and erythrocytes, and in the dynamics of the antioxidant response during OGTT. Specifically, Ob.IR+ children show increased oxidative stress, deficient antioxidant response and a significant imbalance in redox status, in comparison to controls and Ob.IR- children. Obese children with insulin resistance show increased levels of oxidative stress biomarkers, and a stunted antioxidant response to an OGTT leading to increased oxidative stress after a single glucose load, as detected in erythrocytes, but not in plasma. We propose erythrocytes as sensors of early and acute changes in oxidative stress associated with insulin resistance in childhood obesity. This is a pilot study, performed with a limited sample size, so data should be interpreted with caution until reproduced.

The relation between intensity and complexity of coronary artery lesion and oxidative stress in patients with acute coronary syndrome.

PubMed

Turan, Turhan; Menteşe, Ümit; Ağaç, Mustafa Tarık; Akyüz, Ali Rıza; Kul, Selim; Aykan, Ahmet Çağrı; Bektaş, Hüseyin; Korkmaz, Levent; Öztaş Menteşe, Seda; Dursun, İhsan; Çelik, Şükrü

2015-10-01

Oxidative stress plays a major role in the development of atherosclerosis. However, the relationship between oxidative stress and complexity and intensity of coronary artery disease is less clear. The aim of this study is to assess the relationship between oxidative stress markers and the complexity and intensity of coronary artery disease in patients with acute coronary syndrome (ACS). Sixty-seven consecutive patients with an early phase of ACS (<3 h) were included in this single-centre, cross-sectional, prospective study. Syntax and Gensini scores were calculated based on angiographic findings. Patients were divided into two CAD complexity groups according to their Syntax scores: low SYNTAX score (<22) and moderate to high SYNTAX score (>=22). Likewise patients were divided into two CAD severity groups according to the median Gensini score of 64: less intensive CAD with Gensini score (<64) and intensive CAD with Gensini score >=64. Blood samples were taken in 1 hour within administration in order to measure total oxidative status (TOS) and total antioxidant capacity (TAC) levels determined by Erel method. Oxidative stress index (OSI) was calculated by TOS /TAC. There was no significant difference between the two SYNTAX groups for oxidative stress markers. Median TOS and OSI values were significantly high in the intensive CAD group (p=0.005, p=0.04, respectively). The Gensini score was positively correlated with TOS and OSI (p=0.003, p=0.02, respectively). Oxidative stress markers may be considered supportive laboratory parameters related to CAD intensity but not complexity in ACS patients.

Stabilization of the methyl-CpG binding protein ZBTB38 by the deubiquitinase USP9X limits the occurrence and toxicity of oxidative stress in human cells.

PubMed

Miotto, Benoit; Marchal, Claire; Adelmant, Guillaume; Guinot, Nadège; Xie, Ping; Marto, Jarrod A; Zhang, Lingqiang; Defossez, Pierre-Antoine

2018-05-18

Reactive oxygen species (ROS) are a byproduct of cell metabolism, and can also arise from environmental sources, such as toxins or radiation. Depending on dose and context, ROS have both beneficial and deleterious roles in mammalian development and disease, therefore it is crucial to understand how these molecules are generated, sensed, and detoxified. The question of how oxidative stress connects to the epigenome, in particular, is important yet incompletely understood. Here we show that an epigenetic regulator, the methyl-CpG-binding protein ZBTB38, limits the basal cellular production of ROS, is induced by ROS, and is required to mount a proper response to oxidative stress. Molecularly, these functions depend on a deubiquitinase, USP9X, which interacts with ZBTB38, deubiquitinates it, and stabilizes it. We find that USP9X is itself stabilized by oxidative stress, and is required together with ZBTB38 to limit the basal generation of ROS, as well as the toxicity of an acute oxidative stress. Our data uncover a new nuclear target of USP9X, show that the USP9X/ZBTB38 axis limits, senses and detoxifies ROS, and provide a molecular link between oxidative stress and the epigenome.

Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation

PubMed Central

Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Kauppinen, Anu

2015-01-01

Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD. PMID:26619957

Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress

PubMed Central

Booz, George W.

2011-01-01

Oxidative stress with reactive oxygen species generation is a key weapon in the arsenal of the immune system for fighting invading pathogens and to initiate tissue repair. If excessive or unresolved, however, immune-related oxidative stress can initiate further increasing levels of oxidative stress that cause organ damage and dysfunction. Targeting oxidative stress in these various diseases therapeutically has proven more problematic than first anticipated given the complexities and perversity of both the underlying disease and the immune response. However, growing evidence suggests that the endocannabinoid system, which includes the CB1 and CB2 G protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system, but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development. This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer’s disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain. PMID:21238581

Oxidative Stress Parameters in Saliva and Its Association with Periodontal Disease and Types of Bacteria.

PubMed

Almerich-Silla, Jose Manuel; Montiel-Company, Jose María; Pastor, Sara; Serrano, Felipe; Puig-Silla, Miriam; Dasí, Francisco

2015-01-01

To determine the association between oxidative stress parameters with periodontal disease, bleeding, and the presence of different periodontal bacteria. A cross-sectional study in a sample of eighty-six patients, divided into three groups depending on their periodontal status. Thirty-three with chronic periodontitis, sixteen with gingivitis, and thirty-seven with periodontal healthy as control. Oxidative stress biomarkers (8-OHdG and MDA), total antioxidant capacity (TAOC), and the activity of two antioxidant enzymes (GPx and SOD) were determined in saliva. Subgingival plaque samples were obtained from the deepest periodontal pocket and PCR was used to determine the presence of the 6 fimA genotypes of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, and Treponema denticola. Periodontal disease was found to be associated with increased oxidative stress parameter levels. These levels rose according to the number and type of different periodontal bacteria found in the periodontal pockets. The presence of different types of periodontal bacteria is predictive independent variables in linear regresion models of oxidative stress parameters as dependent variable, above all 8-OHdG. Oxidative stress parameter levels are correlated with the presence of different types of bacteria. Determination of these levels and periodontal bacteria could be a potent tool for controlling periodontal disease development.

Investigations of oxidative stress effects and their mechanisms in rat brain after systemic administration of ceria engineered nanomaterials

NASA Astrophysics Data System (ADS)

Hardas, Sarita S.

Advancing applications of engineered nanomaterials (ENM) in various fields create the opportunity for intended (e.g. drug and gene delivery) or unintended (e.g. occupational and environmental) exposure to ENM. However, the knowledge of ENM-toxicity is lagging behind their application development. Understanding the ENM hazard can help us to avoid potential human health problems associated with ENM applications as well as to increase their public acceptance. Ceria (cerium [Ce] oxide) ENM have many current and potential commercial applications. Beyond the traditional use of ceria as an abrasive, the scope of ceria ENM applications now extends into fuel cell manufacturing, diesel fuel additives and for therapeutic intervention as a putative antioxidant. However, the biological effects of ceria ENM exposure have yet to be fully defined. Both pro-and anti-oxidative effects of ceria ENM exposure are repeatedly reported in literature. EPA, NIEHS and OECD organizations have nominated ceria for its toxicological evaluation. All these together gave us the impetus to examine the oxidative stress effects of ceria ENM after systemic administration. Induction of oxidative stress is one of the primary mechanisms of ENM toxicity. Oxidative stress plays an important role in maintaining the redox homeostasis in the biological system. Increased oxidative stress, due to depletion of antioxidant enzymes or molecules and / or due to increased production of reactive oxygen (ROS) or nitrogen (RNS) species may lead to protein oxidation, lipid peroxidation and/or DNA damage. Increased protein oxidation or lipid peroxidation together with antioxidant protein levels and activity can serve as markers of oxidative stress. To investigate the oxidative stress effects and the mechanisms of ceria-ENM toxicity, fully characterized ceria ENM of different sizes (˜ 5nm, 15nm, 30nm, 55nm and nanorods) were systematically injected into rats intravenously in separate experiments. Three brain regions (hippocampus, cortex and cerebellum) were harvested from control and ceria treated rats after various exposure periods for oxidative stress assessment. The levels of oxidative stress markers viz. protein carbonyl (PC), 3-nitrotyrosine (3NT), and protein bound 4-hydroxy-2-trans-nonenal (HNE) were evaluated for each treatment in each control and treated rat organ. Further, the levels and activities of antioxidant proteins, such as catalase, glutathione peroxidase (GPx), glutathione reductase (GR), super oxide dismutase (SOD), were measured together with levels of heat shock proteins heme oxygenase -1 and 70 (HO-1 and Hsp-70). In addition, the levels of pro-inflammatory cytokines IL-1beta, TNF-alpha, pro-caspase-3, and autophagy marker LC-3A/B were measured by Western blot technique. In agreement with the literature-proposed model of oxidative stress hierarchy mechanism of ENM-toxicity, the statistical analysis of all the results revealed that the ceria ENM-induced oxidative stress mediated biological response strongly depends on the exposure period and to some extent on the size of ceria ENM. More specifically, a single intravenous injection of ceria ENM induced tier-1 (phase-II antioxidant) response after shorter exposure periods (1 h and 20 h) in rat brain. Upon failure of tier-1 response after longer exposure periods (1 d to 30 d), escalated oxidative stress consequently induced tier-2 and tier-3 oxidative stress responses. Based on our observations made at chronic exposure period (90 d) after the single i.v. injection of ceria ENM, we could extend the model of oxidative stress hierarchy mechanisms for ceria-ENM-induced toxicity. Considering the evaluation of all the oxidative stress indices measured in 3-brain regions, oxidative stress effects were more prominent in hippocampus and the least in cerebellum, but no specific pattern or any significant difference was deduced. Keyword: Ceria, cerium oxide, nanomaterial, nanoparticles, nanotoxicity, oxidative stress, phase-II enzymes.

Exercise-Induced Oxidative Stress Responses in the Pediatric Population

PubMed Central

Avloniti, Alexandra; Chatzinikolaou, Athanasios; Deli, Chariklia K.; Vlachopoulos, Dimitris; Gracia-Marco, Luis; Leontsini, Diamanda; Draganidis, Dimitrios; Jamurtas, Athanasios Z.; Mastorakos, George; Fatouros, Ioannis G.

2017-01-01

Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty. PMID:28106721

Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice.

PubMed

Li, Bin; Cui, Wei; Liu, Jia; Li, Ru; Liu, Qian; Xie, Xiao-Hua; Ge, Xiao-Li; Zhang, Jing; Song, Xiu-Juan; Wang, Ying; Guo, Li

2013-12-01

Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases. © 2013.

Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development.

PubMed

Al-Gubory, Kaïs H

2014-07-01

Developmental toxicity caused by exposure to a mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides and heavy metals, as well as unhealthy lifestyle behaviours, mainly tobacco smoking, alcohol consumption and medical drug abuse, are major factors that adversely influence prenatal development and increase susceptibility of offspring to diseases. There is evidence to suggest that the developmental toxicological mechanisms of chemicals and lifestyle factors involve the generation of reactive oxygen species (ROS) and cellular oxidative damage. Overproduction of ROS induces oxidative stress, a state where increased ROS generation overwhelms antioxidant protection and subsequently leads to oxidative damage of cellular macromolecules. Data on the involvement of oxidative stress in the mechanism of developmental toxicity following exposure to environmental pollutants are reviewed in an attempt to provide an updated basis for future studies on the toxic effect of such pollutants, particularly the notion of increased risk for developmental toxicity due to combined and cumulative exposure to various environmental pollutants. The aims of such studies are to better understand the mechanisms by which environmental pollutants adversely affect conceptus development and to elucidate the impact of cumulative exposures to multiple pollutants on post-natal development and health outcomes. Developmental toxicity caused by exposure to mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides and heavy metals, as well as unhealthy lifestyle behaviors, mainly tobacco smoking, alcohol consumption and medical drug abuse, are major factors that adversely influence prenatal development and increase the susceptibility of offspring to development complications and diseases. There is evidence to suggest that the developmental toxicological mechanisms of human-made chemicals and unhealthy lifestyle factors involve the generation of reactive oxygen species (ROS) and cellular oxidative damage. Overproduction of ROS induces oxidative stress, a state where increased generation of ROS overwhelms antioxidant protection and subsequently leads to oxidative damage of cellular macromolecules. Exposure to various environmental pollutants induces synergic and cumulative dose-additive adverse effects on prenatal development, pregnancy outcomes and neonate health. Data from the literature on the involvement of oxidative stress in the mechanism of developmental toxicity following in vivo exposure to environmental pollutants will be reviewed in an attempt to provide an updated basis for future studies on the toxic effect of such pollutants, particularly the notion of increased risk for developmental toxicity due to combined and cumulative exposure to various environmental pollutants. The aims of such studies are to better understand the mechanisms by which environmental pollutants adversely affect conceptus development and to elucidate the impact of cumulative exposures to multiple pollutants on postnatal development and health outcomes. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il; Guillemin, Claire; Neeman-azulay, Meytal

Fetal Growth Restriction (FGR) is a leading cause for long term morbidity. The Cohen diabetic sensitive rats (CDs), originating from Wistar, develop overt diabetes when fed high sucrose low copper diet (HSD) while the original outbred Sabra strain do not. HSD induced FGR and fetal oxidative stress, more prominent in the CDs, that was alleviated more effectively by copper than by the anti-oxidant vitamins C and E. Our aim was to evaluate the impact of copper or the anti-oxidant Tempol on placental size, protein content, oxidative stress, apoptosis and total DNA methylation. Animals were mated following one month of HSDmore » or regular chow diet and supplemented throughout pregnancy with either 0, 1 or 2 ppm of copper sulfate or Tempol in their drinking water. Placental weight on the 21st day of pregnancy decreased in dams fed HSD and improved upon copper supplementation. Placental/fetal weight ratio increased among the CDs. Protein content decreased in Sabra but increased in CDs fed HSD. Oxidative stress biochemical markers improved upon copper supplementation; immunohistochemistry for oxidative stress markers was similar between strains and diets. Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. Placental global DNA methylation was decreased only among the CDs dams fed HSD. We conclude that FGR in this model is associated with smaller placentae, reduced DNA placental methylation, and increased oxidative stress that normalized with copper supplementation. DNA hypomethylation makes our model a unique method for investigating genes associated with growth, oxidative stress, hypoxia and copper. - Highlights: • Sensitive Cohen diabetic rats (CDs) had small placentae and growth restricted fetuses. • CDs dams fed high sucrose low copper diet had placental global DNA hypomethylation. • Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. • Oxidative stress parameters improved by Tempol and resolved by copper supplementation. • Global DNA hypomethylation was resolved both by Tempol and by copper supplementation. • Placental oxidative stress parameters coincides previous findings in the fetal liver.« less

Genetics of Oxidative Stress in Obesity

PubMed Central

Rupérez, Azahara I.; Gil, Angel; Aguilera, Concepción M.

2014-01-01

Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications. PMID:24562334

Genetics of oxidative stress in obesity.

PubMed

Rupérez, Azahara I; Gil, Angel; Aguilera, Concepción M

2014-02-20

Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.

Novel sila-amide derivatives of N-acetylcysteine protects platelets from oxidative stress-induced apoptosis.

PubMed

Paul, Manoj; Thushara, Ram M; Jagadish, Swamy; Zakai, Uzma I; West, Robert; Kemparaju, Kempaiah; Girish, Kesturu S

2017-02-01

Oxidative stress-induced platelet apoptosis is one among the many causes for the development and progression of many disorders like cardiovascular diseases, arthritis, Alzheimer's disease and many chronic inflammatory responses. Many studies have demonstrated the less optimal effect of N-acetyl cysteine (NAC) in oxidative stress-induced cellular damage. This could be due to its less lipophilicity which makes it difficult to enter the cellular membrane. Therefore in the present study, lipophilic sila-amide derivatives (6a and 6b) synthesized through the reaction of NAC with 3-Aminopropyltrimethylsilane and aminomethyltrimethylsilane were used to determine their protective property against oxidative stress-induced platelet apoptosis. At a concentration of 10 µM, compound 6a and 6b were able to significantly inhibit Rotenone/H 2 O 2 induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cytochrome c release from mitochondrial to the cytosol, caspase-9 and -3 activity and phosphatidylserine externalization. Therefore, the compounds can be extrapolated as therapeutic agents to protect platelets from oxidative stress-induced platelet apoptosis and its associated complications.

Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease.

PubMed

Yan, Michael H; Wang, Xinglong; Zhu, Xiongwei

2013-09-01

Alzheimer disease (AD) and Parkinson disease (PD) are the two most common age-related neurodegenerative diseases characterized by prominent neurodegeneration in selective neural systems. Although a small fraction of AD and PD cases exhibit evidence of heritability, among which many genes have been identified, the majority are sporadic without known causes. Molecular mechanisms underlying neurodegeneration and pathogenesis of these diseases remain elusive. Convincing evidence demonstrates oxidative stress as a prominent feature in AD and PD and links oxidative stress to the development of neuronal death and neural dysfunction, which suggests a key pathogenic role for oxidative stress in both AD and PD. Notably, mitochondrial dysfunction is also a prominent feature in these diseases, which is likely to be of critical importance in the genesis and amplification of reactive oxygen species and the pathophysiology of these diseases. In this review, we focus on changes in mitochondrial DNA and mitochondrial dynamics, two aspects critical to the maintenance of mitochondrial homeostasis and function, in relationship with oxidative stress in the pathogenesis of AD and PD. Copyright © 2012 Elsevier Inc. All rights reserved.

Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease

PubMed Central

Yan, Michael H.; Wang, Xinglong; Zhu, Xiongwei

2013-01-01

Alzheimer disease (AD) and Parkinson disease (PD) are the two most common age-related neurodegenerative diseases characterized by prominent neurodegeneration in selective neural systems. Although a small fraction of AD and PD cases exhibit evidence of heritability, among which many genes have been identified, the majority are sporadic without known causes. Molecular mechanisms underlying neurodegeneration and pathogenesis of these diseases remain elusive. Convincing evidence demonstrates oxidative stress as a prominent feature in AD and PD and links oxidative stress to the development of neuronal death and neural dysfunction, which suggests a key pathogenic role for oxidative stress in both AD and PD. Notably, mitochondrial dysfunction is also a prominent feature in these diseases, which is likely to be of critical importance in the genesis and amplification of reactive oxygen species and the pathophysiology of these diseases. In this review, we focus on changes in mitochondrial DNA and mitochondrial dynamics, two aspects critical to the maintenance of mitochondrial homeostasis and function, in relationship with oxidative stress in the pathogenesis of AD and PD. PMID:23200807

Oxidative Stress and Neurodegenerative Disorders

PubMed Central

Li, Jie; O, Wuliji; Li, Wei; Jiang, Zhi-Gang; Ghanbari, Hossein A.

2013-01-01

Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs. PMID:24351827

Uric acid promotes oxidative stress and enhances vascular endothelial cell apoptosis in rats with middle cerebral artery occlusion.

PubMed

Song, Chengfu; Zhao, Xiangdong

2018-05-15

In patients with cerebral infarction (CI), elevated serum uric acid (UA) level may exacerbate the occurrence and development of carotid atherosclerosis (AS). Our study intended to explore the underlying mechanism. We enrolled 86 patients with CI, and divided them into four groups: Non-AS, AS-mild, AS-moderate, and AS-severe groups; the levels of UA and oxidative stress-related factors in serum were detected. The middle cerebral artery occlusion (MCAO) model was used to stimulate CI in rats, and different doses of UA were administrated. The levels of oxidative stress-related factors in serum were detected. Hematoxylin & eosin (H&E) staining was used to observe the morphological alterations, and the apoptotic cell death detection kit was used to detect apoptotic cells. Increased UA concentration and enhanced oxidative stress were found in AS patients. H&E staining results showed that UA treatment exacerbated morphological damage in rats with MCAO, promoted oxidative stress, and enhanced vascular endothelial cell apoptosis in rats with MCAO. © 2017 The Author(s).

The role of stress in self-ordered porous anodic oxide formation and corrosion of aluminum

NASA Astrophysics Data System (ADS)

Capraz, Omer Ozgur

The phenomenon of plastic flow induced by electrochemical reactions near room temperature is significant in porous anodic oxide (PAO) films, charging of lithium batteries and stress-corrosion cracking (SCC). As this phenomenon is poorly understood, fundamental insight into flow from our work may provide useful information for these problems. In-situ monitoring of the stress state allows direct correlation between stress and the current or potential, thus providing fundamental insight into technologically important deformation and failure mechanisms induced by electrochemical reactions. A phase-shifting curvature interferometry was designed to investigate the stress generation mechanisms on different systems. Resolution of our curvature interferometry was found to be ten times more powerful than that obtained by state-of-art multiple deflectometry technique and the curvature interferometry helps to resolve the conflicting reports in the literature. During this work, formation of surface patterns during both aqueous corrosion of aluminum and formation of PAO films were investigated. Interestingly, for both cases, stress induced plastic flow controls the formation of surface patterns. Pore formation mechanisms during anodizing of the porous aluminum oxide films was investigated . PAO films are formed by the electrochemical oxidation of metals such as aluminum and titanium in a solution where oxide is moderately soluble. They have been used extensively to design numerous devices for optical, catalytic, and biological and energy related applications, due to their vertically aligned-geometry, high-specific surface area and tunable geometry by adjusting process variables. These structures have developed empirically, in the absence of understanding the process mechanism. Previous experimental studies of anodizing-induced stress have extensively focused on the measurement of average stress, however the measurement of stress evolution during anodizing does not provide sufficient information to understand the potential stress mechanisms. We developed a new method, which enables us to discriminate the potential stress mechanisms during anodizing and characterize the evolution of the stress profile during film growth. Using stress measurement and characterization techniques, we demonstrated the evolution of the stress profile during the film formation and discussed the role of stress on the PAO film formation. Compressive stress builds up linearly during the anodizing, while barrier oxide film gets thicker until the onset of the pore initiation. Both barrier layer thickness and the integrated oxide stress decreased rapidly to the steady-state period when pore initiation began. The morphology change and stress transients points out the transition from elastic to plastic oxide behavior, similar to those observed in other situations such as lithium intercalation into silicon. The stress profile is consistent with the stress gradient needed to drive plastic flow observed experimentally. We also addressed the dependence of overall stress generation on applied current density. Apparently, stress caused by expansion or contraction of oxide and metal interface depends on the volume change due to overall reactions. In the last chapter, the stress generation during alkaline Al corrosion will be discussed. The enhancement of mechanical degradation by corrosion is the basis for the damage process such as stress-corrosion cracking. Understanding the synergistic effect of stress on stress-corrosion cracking mechanism is necessary to design new materials to improve the safety and viability of existing energy conversion systems. the high-resolution in-situ stress measurements during Al corrosion in alkaline solution was presented, supported by characterization techniques and Fast Fourier Transform analysis. Unprecedented curvature resolution of curvature interferometry permits the monitoring of stress during extended periods of corrosion of thick metal samples. Evolution of concaved-shaped surface patterns is in a great harmony with recorded tensile stress. Furthermore, absolute value of tensile stress onset of the plasticity depends on the dissolution rate of metal and yield stress of metal. The measurements reveal corrosion-induced tensile stress generation, leading to surface plasticity. This finding is evidence that corrosion can directly bring about plasticity, and may be relevant to mechanism of corrosion-induced degradation.

The mitochondrial-targeted antioxidant MitoQ ameliorates metabolic syndrome features in obesogenic diet-fed rats better than Apocynin or Allopurinol.

PubMed

Feillet-Coudray, Christine; Fouret, Gillen; Ebabe Elle, Raymond; Rieusset, Jennifer; Bonafos, Beatrice; Chabi, Beatrice; Crouzier, David; Zarkovic, Kamelija; Zarkovic, Neven; Ramos, Jeanne; Badia, Eric; Murphy, Michael P; Cristol, Jean Paul; Coudray, Charles

2014-10-01

The prevalence of metabolic syndrome (MetS) components including obesity, dyslipidemia, insulin resistance (IR), and hepatic steatosis is rapidly increasing in wealthy societies. It is accepted that inflammation/oxidative stress are involved in the initiation/evolution of the MetS features. The present work was designed to evaluate the effects of three major cellular ROS production systems on obesity, glucose tolerance, and hepatic steatosis development and on oxidative stress onset. To do so, 40 young male Sprague-Dawley rats were divided into 5 groups: 1-control group, 2-high fat (HF) group (60% energy from fat), 3-HF+ MitoQ (mitochondrial ROS scavenger), 4-HF+ Apocynin (NADPH oxidase inhibitor), 5-HF+ Allopurinol (xanthine oxidase inhibitor). After 8 weeks of these treatments, surrogate MetS, mitochondrial function, and oxidative stress markers were measured in blood and liver. As expected, rats that were fed the HF diet exhibited increased body weight, glucose intolerance, overt hepatic steatosis, and increased hepatic oxidative stress. The impacts of the studied ROS inhibitors on these aspects of the MetS were markedly different. MitoQ showed the most clinically relevant effects, attenuating body weight gain and glucose intolerance provoked by the HF diet. Both Apocynin and Allopurinol showed limited effects suggesting secondary roles of xanthine oxidase (XO) or NADPH oxidase-dependent ROS production in the onset of oxidative stress-dependent obesity, glucose intolerance, and hepatic steatosis process. Thus, MitoQ revealed the central role of mitochondrial oxidative stress in the development of MetS and suggested that mitochondria-targeted antioxidants may be worth considering as potentially helpful therapies for MetS features.

Cobalamin Protection against Oxidative Stress in the Acidophilic Iron-oxidizing Bacterium Leptospirillum Group II CF-1

PubMed Central

Ferrer, Alonso; Rivera, Javier; Zapata, Claudia; Norambuena, Javiera; Sandoval, Álvaro; Chávez, Renato; Orellana, Omar; Levicán, Gloria

2016-01-01

Members of the genus Leptospirillum are aerobic iron-oxidizing bacteria belonging to the phylum Nitrospira. They are important members of microbial communities that catalyze the biomining of sulfidic ores, thereby solubilizing metal ions. These microorganisms live under extremely acidic and metal-loaded environments and thus must tolerate high concentrations of reactive oxygen species (ROS). Cobalamin (vitamin B12) is a cobalt-containing tetrapyrrole cofactor involved in intramolecular rearrangement reactions and has recently been suggested to be an intracellular antioxidant. In this work, we investigated the effect of the exogenous addition of cobalamin on oxidative stress parameters in Leptospirillum group II strain CF-1. Our results revealed that the external supplementation of cobalamin reduces the levels of intracellular ROSs and the damage to biomolecules, and also stimulates the growth and survival of cells exposed to oxidative stress exerted by ferric ion, hydrogen peroxide, chromate and diamide. Furthermore, exposure of strain CF-1 to oxidative stress elicitors resulted in the transcriptional activation of the cbiA gene encoding CbiA of the cobalamin biosynthetic pathway. Altogether, these data suggest that cobalamin plays an important role in redox protection of Leptospirillum strain CF-1, supporting survival of this microorganism under extremely oxidative environmental conditions. Understanding the mechanisms underlying the protective effect of cobalamin against oxidative stress may help to develop strategies to make biomining processes more effective. PMID:27242761

Cobalamin Protection against Oxidative Stress in the Acidophilic Iron-oxidizing Bacterium Leptospirillum Group II CF-1.

PubMed

Ferrer, Alonso; Rivera, Javier; Zapata, Claudia; Norambuena, Javiera; Sandoval, Álvaro; Chávez, Renato; Orellana, Omar; Levicán, Gloria

2016-01-01

Members of the genus Leptospirillum are aerobic iron-oxidizing bacteria belonging to the phylum Nitrospira. They are important members of microbial communities that catalyze the biomining of sulfidic ores, thereby solubilizing metal ions. These microorganisms live under extremely acidic and metal-loaded environments and thus must tolerate high concentrations of reactive oxygen species (ROS). Cobalamin (vitamin B12) is a cobalt-containing tetrapyrrole cofactor involved in intramolecular rearrangement reactions and has recently been suggested to be an intracellular antioxidant. In this work, we investigated the effect of the exogenous addition of cobalamin on oxidative stress parameters in Leptospirillum group II strain CF-1. Our results revealed that the external supplementation of cobalamin reduces the levels of intracellular ROSs and the damage to biomolecules, and also stimulates the growth and survival of cells exposed to oxidative stress exerted by ferric ion, hydrogen peroxide, chromate and diamide. Furthermore, exposure of strain CF-1 to oxidative stress elicitors resulted in the transcriptional activation of the cbiA gene encoding CbiA of the cobalamin biosynthetic pathway. Altogether, these data suggest that cobalamin plays an important role in redox protection of Leptospirillum strain CF-1, supporting survival of this microorganism under extremely oxidative environmental conditions. Understanding the mechanisms underlying the protective effect of cobalamin against oxidative stress may help to develop strategies to make biomining processes more effective.

Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain.

PubMed

Shrivastava, Rupal; Raza, Saimah; Yadav, Abhishek; Kushwaha, Pramod; Flora, Swaran J S

2014-07-01

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.

Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

PubMed

Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

2017-01-01

Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

Pathogenesis of Chronic Cardiorenal Syndrome: Is There a Role for Oxidative Stress?

PubMed Central

Rubattu, Speranza; Mennuni, Silvia; Testa, Marco; Mennuni, Mara; Pierelli, Giorgia; Pagliaro, Beniamino; Gabriele, Erica; Coluccia, Roberta; Autore, Camillo; Volpe, Massimo

2013-01-01

Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-β1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome. PMID:24264044

Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury

PubMed Central

Endesfelder, Stefanie; Weichelt, Ulrike; Strauß, Evelyn; Schlör, Anja; Sifringer, Marco; Scheuer, Till; Bührer, Christoph; Schmitz, Thomas

2017-01-01

Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. PMID:28106777

Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury.

PubMed

Endesfelder, Stefanie; Weichelt, Ulrike; Strauß, Evelyn; Schlör, Anja; Sifringer, Marco; Scheuer, Till; Bührer, Christoph; Schmitz, Thomas

2017-01-18

Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28-32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

Chronic social stress increases nitric oxide-dependent vasorelaxation in normotensive rats

PubMed Central

Puzserova, Angelika; Bernatova, Iveta

2010-01-01

The aim of this study was to examine oxidative load and endothelium-dependent vasorelaxation in the serotonin pre-constricted femoral artery (FA) of Wistar-Kyoto (WKY) rats exposed to chronic social stress produced by crowding in the presence or absence of ascorbic acid (AsA) in working solution. Adult male rats were randomly divided into control (living space: 480 cm2/rat) or stressed (living space: 200 cm2/rat) groups for 8 weeks. Blood pressure and heart rate, determined using tail-cuff plethysmography, were not influenced by stress vs. control. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured in the left ventricle and liver (for assessment of oxidative load) and were found unchanged by chronic crowding. The nitric oxide (NO)-dependent component of endothelium-dependent relaxation was investigated in the FA using a wire myograph. In both the presence and absence of AsA, acetylcholine-induced relaxation of the FA of stressed rats significantly exceeded that of the controls, which was associated with an increase of the NO-dependent component. In conclusion, the data showed that chronic crowding did not produce oxidative stress in the organs investigated and indicate that elevation of NO production during chronic stress is an important way of adaptation, which may prevent normotensive rats from the development of stress-induced hypertension. PMID:21331175

Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

PubMed

Hecker, Louise

2018-04-01

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

Finite element analysis of the tetragonal to monoclinic phase transformation during oxidation of zirconium alloys

NASA Astrophysics Data System (ADS)

Platt, P.; Frankel, P.; Gass, M.; Howells, R.; Preuss, M.

2014-11-01

Corrosion is a key limiting factor in the degradation of zirconium alloys in light water reactors. Developing a mechanistic understanding of the corrosion process offers a route towards improving safety and efficiency as demand increases for higher burn-up of fuel. Oxides formed on zirconium alloys are composed of both monoclinic and meta-stable tetragonal phases, and are subject to a number of potential mechanical degradation mechanisms. The work presented investigates the link between the tetragonal to monoclinic oxide phase transformation and degradation of the protective character of the oxide layer. To achieve this, Abaqus finite element analysis of the oxide phase transformation has been carried out. Study of the change in transformation strain energy shows how relaxation of oxidation induced stress and fast fracture at the metal-oxide interface could destabilise the tetragonal phase. Central to this is the identification of the transformation variant most likely to form, and understanding why twinning of the transformed grain is likely to occur. Development of transformation strain tensors and analysis of the strain components allows some separation of dilatation and shear effects. Maximum principal stress is used as an indication of fracture in the surrounding oxide layer. Study of the stress distributions shows the way oxide fracture is likely to occur and the differing effects of dilatation and shape change. Comparison with literature provides qualitative validation of the finite element simulations.

PPAR{alpha} agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Xiaoyang; Division of Cardiothoracic Surgery, The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, BCM 390, One Baylor Plaza, Houston, TX 77030; Shen, Ying H.

2010-04-09

Oxidative stress has been shown to play an important role in the development of hypertensive renal injury. Peroxisome proliferator-activated receptors {alpha} (PPAR{alpha}) has antioxidant effect. In this study, we demonstrated that fenofibrate significantly reduced proteinuria, inflammatory cell recruitment and extracellular matrix (ECM) proteins deposition in the kidney of SHRs without apparent effect on blood pressure. To investigate the mechanisms involved, we found that fenofibrate treatment markedly reduced oxidative stress accompanied by reduced activity of renal NAD(P)H oxidase, increased activity of Cu/Zn SOD, and decreased phosphorylation of p38MAPK and JNK in the kidney of SHRs. Taken together, fenofibrate treatment can protectmore » against hypertensive renal injury without affecting blood pressure by inhibiting inflammation and fibrosis via suppression of oxidative stress and MAPK activity.« less

Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism.

PubMed

Al-Amin, Md Mamun; Rahman, Md Mahbubur; Khan, Fazlur Rahman; Zaman, Fahmida; Mahmud Reza, Hasan

2015-06-01

Prenatal exposure to valproic acid on gestational day 12.5 may lead to the impaired behavior in the offspring, which is similar to the human autistic symptoms. To the contrary, astaxanthin shows neuroprotective effect by its antioxidant mechanism. We aimed to (i) develop mice model of autism and (ii) investigate the effect of astaxanthin on such model animals. Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12.5. Prenatal valproic acid-exposed mice were divided into 2 groups on postnatal day 25 and astaxanthin (2mg/kg) was given to the experimental group (VPA_AST, n=10) while saline was given to the control group (VPA, n=10) for 4 weeks. Behavioral test including social interaction, open field and hot-plate were conducted on postnatal day 25 and oxidative stress markers such as lipid peroxidation, advanced protein oxidation product, nitric oxide, glutathione, and activity of superoxide dismutase and catalase were estimated on postnatal day 26 to confirm mice model of autism and on postnatal day 56 to assess the effect of astaxanthin. On postnatal day 25, prenatal valproic acid-exposed mice exhibited (i) delayed eye opening (ii) longer latency to respond painful stimuli, (iii) poor sociability and social novelty and (iv) high level of anxiety. In addition, an increased level of oxidative stress was found by determining different oxidative stress markers. Treatment with astaxanthin significantly (p<0.05) improved the behavioral disorder and reduced the oxidative stress in brain and liver. In conclusion, prenatal exposure to valproic day in pregnant mice leads to the development of autism-like features. Astaxanthin improves the impaired behavior in animal model of autism presumably by its antioxidant activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential role of oxidative stress in mediating the effect of altered gravity on the developing rat cerebellum

NASA Astrophysics Data System (ADS)

Sajdel-Sulkowska, Elizabeth M.; Nguon, Kosal; Sulkowski, Zachary L.; Lipinski, Boguslaw

We have previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that exposure to hypergravity results in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. To test this hypothesis we compared cerebellar oxidative stress markers 3-nitrotyrosine (3-NT; an index of oxidative protein modification) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an index of oxidative DNA damage) between stationary control (SC) and rat neonates exposed to 1.65 G (HG) on a 24-ft centrifuge from gestational day (G) 8 to postnatal day (P) 21. The levels of 3-NT and 8-OH-dG were determined by specific ELISAs. We also compared the Purkinje cell number (stereorologically) and rotarod performance between the two groups. The levels of 3-NT were increased only in HG females on P6 and on P12 in the cerebellum, and only in HG females on P12 in the extracellabellar tissue. Limited cerebellar data suggests an increase in the levels of 8-OH-dG on P12 only in HG females. In extracerebellar tissue the increase in 8-OH-dG levels was observed in both HG males and HG females except on P6 when it was only observed in HG males. While preliminary, these data suggest that the effect of hypergravity on the developing brain is sex-dependent and may involve oxidative stress. Oxidative stress may, in turn, contribute to the decrease Purkinje cell number and impaired motor behavior observed in hypergravity-exposed rats.

Brain-targeted ACE2 overexpression attenuates neurogenic hypertension by inhibiting COX mediated inflammation

PubMed Central

Sriramula, Srinivas; Xia, Huijing; Xu, Ping; Lazartigues, Eric

2014-01-01

Overactivity of the renin angiotensin system (RAS), oxidative stress, and cyclooxygenases (COX) in the brain are implicated in the pathogenesis of hypertension. We previously reported that Angiotensin-Converting Enzyme 2 (ACE2) overexpression in the brain attenuates the development of DOCA-salt hypertension, a neurogenic hypertension model with enhanced brain RAS and sympathetic activity. To elucidate the mechanisms involved, we investigated whether oxidative stress, mitogen activated protein kinase signaling and cyclooxygenase (COX) activation in the brain are modulated by ACE2 in neurogenic hypertension. DOCA-salt hypertension significantly increased expression of Nox-2 (+61 ±5 %), Nox-4 (+50 ±13 %) and nitrotyrosine (+89 ±32 %) and reduced activity of the antioxidant enzymes, catalase (−29 ±4 %) and SOD (−31 ±7 %), indicating increased oxidative stress in the brain of non-transgenic mice. This increased oxidative stress was attenuated in transgenic mice overexpressing ACE2 in the brain. DOCA-salt-induced reduction of nNOS expression (−26 ±7 %) and phosphorylated eNOS/total eNOS (−30 ±3 %), and enhanced phosphorylation of Akt and ERK1/2 in the paraventricular nucleus (PVN), were reversed by ACE2 overexpression. In addition, ACE2 overexpression blunted the hypertension-mediated increase in gene and protein expression of COX-1 and COX-2 in the PVN. Furthermore, gene silencing of either COX-1 or COX-2 in the brain, reduced microglial activation and accompanied neuro-inflammation, ultimately attenuating DOCA-salt hypertension. Together, these data provide evidence that brain ACE2 overexpression reduces oxidative stress and COX-mediated neuro-inflammation, improves anti-oxidant and nitric oxide signaling, and thereby attenuates the development of neurogenic hypertension. PMID:25489058

Oxidative stress and kidney injury in trans-radial catheterization.

PubMed

Tsarouhas, Konstantinos; Tsitsimpikou, Christina; Papantoni, Xrisoula; Lazaridou, Dimitra; Koutouzis, Michael; Mazzaris, Savvas; Rezaee, Ramin; Mamoulakis, Charalambos; Georgoulias, Panagiotis; Nepka, Charitini; Rentoukas, Elias; Kyriakides, Zenon; Tsatsakis, Aristidis; Spandidos, Demetrios A; Kouretas, Demetrios

2018-05-01

Oxidative stress is linked to coronary artery disease and is a major mechanism in contrast-induced nephropathy. Trans-radial approach in coronary angiography (CA) with minimized peri-procedural bleeding is expected to reduce acute kidney injury incidence. In the present study, oxidative stress patterns observed in radial CA and their associations with early manifestations of kidney injury are described. A total of 20 stable coronary disease patients submitted to CA and 17 sex-matched patients undergoing computed tomography for myoskeletal reasons were enrolled. Reduced glutathione, catalase, thiobarbituric acid reactive species (TBARS) levels and total anti-oxidant status were measured at various time points postangiography. In ischemic patients baseline TBARS levels were 2-fold lower compared to controls, while carbonyls levels were 35% higher. Glutathione was almost 4-fold lower than the control group. Glutathione and lipid peroxidation in ischemic patients gradually increased after contrast medium administration and reached 180% (P<0.001) and 20% (P=0.021) after 4-6 h, respectively. Four patients presented early evidence of contrast-induced nephropathy postangiography, while no control patient developed acute kidney injury. In the multiple logistic regression analysis, only the creatinine levels at baseline influenced the frequency of early contrast-induced nephropathy development (β =0.36, 95% CI: 0.285-0.438, P=0.01). Glutathione low levels were dominant in the baseline values of ischemic patients who developed contrast-induced nephropathy. Glutathione levels rapidly increased while protein oxidation decreased at the expense of lipid peroxidation. In conclusion, early oxidative stress changes occur in trans-radial CA patients with a mild profile, sufficient to mobilize patient antioxidant defenses.

Interplay between Oxidative Stress and Nutrient Sensing Signaling in the Developmental Origins of Cardiovascular Disease

PubMed Central

Tain, You-Lin; Hsu, Chien-Ning

2017-01-01

Cardiovascular disease (CVD) presents a global health burden, despite recent advances in management. CVD can originate from early life by so-called “developmental origins of health and disease” (DOHaD). Epidemiological and experimental evidence supports that early-life insults can induce programming of later CVD. Underlying the DOHaD concept, early intervention may offset programming process to prevent the development of CVD, namely reprogramming. Oxidative stress and nutrient sensing signals have been considered to be major mechanisms of cardiovascular programming, while the interplay between these two mechanisms have not been examined in detail. This review summarizes current evidence that supports the link between oxidative stress and nutrient sensing signaling to cardiovascular programming, with an emphasis on the l-arginine–asymmetric dimethylarginine (ADMA)–nitric oxide (NO) pathway. This review provides an overview of evidence from human studies supporting fetal programming of CVD, insight from animal models of cardiovascular programming and oxidative stress, impact of the l-arginine–ADMA–NO pathway in cardiovascular programming, the crosstalk between l-arginine metabolism and nutrient sensing signals, and application of reprogramming interventions to prevent the programming of CVD. A greater understanding of the mechanisms underlying cardiovascular programming is essential to developing early reprogramming interventions to combat the globally growing epidemic of CVD. PMID:28420139

Obesity induced alterations in redox homeostasis and oxidative stress are present from an early age

PubMed Central

Lechuga-Sancho, Alfonso M.; Gallego-Andujar, David; Ruiz-Ocaña, Pablo; Visiedo, Francisco M.; Saez-Benito, Ana; Schwarz, Mónica; Segundo, Carmen

2018-01-01

Objectives Oxidative stress and inflammation have been postulated as underlying mechanisms for the development of obesity-related insulin resistance. This association however, remains elusive especially in childhood. We sought to investigate this relation by measuring oxidative stress and antioxidant response biomarkers, before and during an oral glucose tolerance test (OGTT), in different biological samples from obese children. Subjects 24 children were recruited for the study, (18 obese and 6 controls). After OGTT, the obese group was subdivided in two, according to whether or not carbohydrate metabolic impairment (Ob.IR+, Ob.IR-; respectively) was found. Different biomarkers were analyzed after fasting (T = 0) and during an OGTT (T = 60 and 120 min). Lipoperoxides were measured in plasma, erythrocytes, and urine; while advanced glycation end products were determined in plasma, and redox status (GSH/GSSG ratio) in erythrocytes. Results We found marked differences in the characterization of the oxidative status in urine and erythrocytes, and in the dynamics of the antioxidant response during OGTT. Specifically, Ob.IR+ children show increased oxidative stress, deficient antioxidant response and a significant imbalance in redox status, in comparison to controls and Ob.IR- children. Conclusion Obese children with insulin resistance show increased levels of oxidative stress biomarkers, and a stunted antioxidant response to an OGTT leading to increased oxidative stress after a single glucose load, as detected in erythrocytes, but not in plasma. We propose erythrocytes as sensors of early and acute changes in oxidative stress associated with insulin resistance in childhood obesity. This is a pilot study, performed with a limited sample size, so data should be interpreted with caution until reproduced. PMID:29370267

Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades

PubMed Central

Peng, Zhao Feng; Chen, Minghui Jessica; Manikandan, Jayapal; Melendez, Alirio J; Shui, Guanghou; Russo-Marie, Françoise; Whiteman, Matthew; Beart, Philip M; Moore, Philip K; Cheung, Nam Sang

2012-01-01

Abstract Nitric oxide is implicated in the pathogenesis of various neuropathologies characterized by oxidative stress. Although nitric oxide has been reported to be involved in the exacerbation of oxidative stress observed in several neuropathologies, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to nitric oxide induced neuronal injury by global transcriptomic profiling. Microarray analyses were undertaken on RNA from murine primary cortical neurons treated with the nitric oxide generator DETA-NONOate (NOC-18, 0.5 mM) for 8–24 hrs. Biological pathway analysis focused upon 3672 gene probes which demonstrated at least a ±1.5-fold expression in a minimum of one out of three time-points and passed statistical analysis (one-way anova, P < 0.05). Numerous enriched processes potentially determining nitric oxide mediated neuronal injury were identified from the transcriptomic profile: cell death, developmental growth and survival, cell cycle, calcium ion homeostasis, endoplasmic reticulum stress, oxidative stress, mitochondrial homeostasis, ubiquitin-mediated proteolysis, and GSH and nitric oxide metabolism. Our detailed time-course study of nitric oxide induced neuronal injury allowed us to provide the first time a holistic description of the temporal sequence of cellular events contributing to nitrergic injury. These data form a foundation for the development of screening platforms and define targets for intervention in nitric oxide neuropathologies where nitric oxide mediated injury is causative. PMID:21352476

Astrocyte Resilience to Oxidative Stress Induced by Insulin-like Growth Factor I (IGF-I) Involves Preserved AKT (Protein Kinase B) Activity*

PubMed Central

Dávila, David; Fernández, Silvia; Torres-Alemán, Ignacio

2016-01-01

Disruption of insulin-like growth factor I (IGF-I) signaling is a key step in the development of cancer or neurodegeneration. For example, interference of the prosurvival IGF-I/AKT/FOXO3 pathway by redox activation of the stress kinases p38 and JNK is instrumental in neuronal death by oxidative stress. However, in astrocytes, IGF-I retains its protective action against oxidative stress. The molecular mechanisms underlying this cell-specific protection remain obscure but may be relevant to unveil new ways to combat IGF-I/insulin resistance. Here, we describe that, in astrocytes exposed to oxidative stress by hydrogen peroxide (H2O2), p38 activation did not inhibit AKT (protein kinase B) activation by IGF-I, which is in contrast to our previous observations in neurons. Rather, stimulation of AKT by IGF-I was significantly higher and more sustained in astrocytes than in neurons either under normal or oxidative conditions. This may be explained by phosphorylation of the phosphatase PTEN at the plasma membrane in response to IGF-I, inducing its cytosolic translocation and preserving in this way AKT activity. Stimulation of AKT by IGF-I, mimicked also by a constitutively active AKT mutant, reduced oxidative stress levels and cell death in H2O2-exposed astrocytes, boosting their neuroprotective action in co-cultured neurons. These results indicate that armoring of AKT activation by IGF-I is crucial to preserve its cytoprotective effect in astrocytes and may form part of the brain defense mechanism against oxidative stress injury. PMID:26631726

Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome.

PubMed

Zhou, Li; Chen, Ping; Peng, Yating; Ouyang, Ruoyun

2016-01-01

Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP), antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field.

Label-free imaging of metabolism and oxidative stress in human induced pluripotent stem cell-derived cardiomyocytes

PubMed Central

Datta, Rupsa; Heylman, Christopher; George, Steven C.; Gratton, Enrico

2016-01-01

In this work we demonstrate a label-free optical imaging technique to assess metabolic status and oxidative stress in human induced pluripotent stem cell-derived cardiomyocytes by two-photon fluorescence lifetime imaging of endogenous fluorophores. Our results show the sensitivity of this method to detect shifts in metabolism and oxidative stress in the cardiomyocytes upon pathological stimuli of hypoxia and cardiotoxic drugs. This non-invasive imaging technique could prove beneficial for drug development and screening, especially for in vitro cardiac models created from stem cell-derived cardiomyocytes and to study the pathogenesis of cardiac diseases and therapy. PMID:27231614

Effects of repeated restraint stress and WiFi signal exposure on behavior and oxidative stress in rats.

PubMed

Othman, Haifa; Ammari, Mohamed; Sakly, Mohsen; Abdelmelek, Hafedh

2017-10-01

Today, due to technology development and aversive events of daily life, Human exposure to both radiofrequency and stress is unavoidable. This study investigated the co-exposure to repeated restraint stress and WiFi signal on cognitive function and oxidative stress in brain of male rats. Animals were divided into four groups: Control, WiFi-exposed, restrained and both WiFi-exposed and restrained groups. Each of WiFi exposure and restraint stress occurred 2 h (h)/day during 20 days. Subsequently, various tests were carried out for each group, such as anxiety in elevated plus maze, spatial learning abilities in the water maze, cerebral oxidative stress response and cholinesterase activity in brain and serum. Results showed that WiFi exposure and restraint stress, alone and especially if combined, induced an anxiety-like behavior without impairing spatial learning and memory abilities in rats. At cerebral level, we found an oxidative stress response triggered by WiFi and restraint, per se and especially when combined as well as WiFi-induced increase in acetylcholinesterase activity. Our results reveal that there is an impact of WiFi signal and restraint stress on the brain and cognitive processes especially in elevated plus maze task. In contrast, there are no synergistic effects between WiFi signal and restraint stress on the brain.

Understanding of the development of in-plane residual stress in sol-gel-derived metal oxide thin films

NASA Astrophysics Data System (ADS)

Ohno, Kentaro; Uchiyama, Hiroaki; Kozuka, Hiromitsu

2012-01-01

The in-plane residual stress in thin films greatly affects their properties and functionality as well as the substrate bending, and hence is an important factor to be controlled. In order to obtain general knowledge on the development of residual stress in sol-gel-derived oxide thin films, the in-plane residual stress was measured for yttria stabilized zirconia gel films on Si(100) wafers as a function of firing temperature by measuring the substrate curvature. The films showed a rather complex variation in residual stress, and the mechanism of the residual stress evolution was discussed, referencing the intrinsic stress and the x-ray diffraction data. At low annealing temperatures of 100-200 °C, the residual tensile stress decreased and became compressive partially due to the structural relaxation occurring during cooling. When the firing temperature was increased over 200 °C, the residual stress turned tensile, and increased with increasing annealing temperature, which was attributed to the increase in intrinsic stress due to film densification as well as to the reduced structural relaxation due to the progress of densification. The residual tensile stress slightly decreased at firing temperatures of 500-600 °C, which was attributed to the reduction in intrinsic stress due to thermally activated atomic diffusion as well as to emergence of thermal stress. At firing temperature over 600 °C, the residual tensile stress increased again, which was attributed to the increase in thermal stress generated during cooling due to the increased Young's modulus of the film. Although appearing to be complicated, the whole variation of residual stress with firing temperature could be understood in terms of film densification, structural relaxation, atomic diffusion, progress of crystallization and thermal strain. The illustration presented in the work may provide a clear insight on how the residual stress could be developed in a variety of functional sol-gel-derived, crystalline oxide thin films.

Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of secoisolariciresinol diglucoside (SDG).

PubMed

Prasad, K

2000-06-01

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant activity and has been shown to prevent hypercholesterolemic atherosclerosis. An investigation was made of the effects of SDG on the development of diabetes in diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes [insulin dependent diabetes mellitus (IDDM)] to determine if this type of diabetes is due to oxidative stress and if SDG can prevent the incidence of diabetes. The rats were divided into three groups: Group I, BioBreeding normal rats (BBn rats) (n = 10); group II, BBdp untreated (n = 11); and group III, BBdp treated with SDG 22 mg/kg body wt, orally) (n = 14). Oxidative stress was determined by measuring lipid peroxidation product malondialdehyde (MDA) an index of level of reactive oxygen species in blood and pancreas; and pancreatic chemiluminescence (Pancreatic-CL), a measure of antioxidant reserve. Incidence of diabetes was 72.7% in untreated and 21.4% in SDG-treated group as determined by glycosuria and hyperglycemia. SDG prevented the development of diabetes by approximately 71%. Development of diabetes was associated with an increase in serum and pancreatic MDA and a decrease in antioxidant reserve. Prevention in development of diabetes by SDG was associated with a decrease in serum and pancreatic-MDA and an increase in antioxidant reserve. These results suggest that IDDM is mediated through oxidative stress and that SDG prevents the development of diabetes.

Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt.

PubMed

Nagasaka, Hironori; Okano, Yoshiyuki; Aizawa, Madoka; Miida, Takashi; Yorifuji, Tohru; Tajima, Go; Sakura, Nobuo; Takatani, Tomozumi; Sanayama, Yoshitami; Sugamoto, Kenji; Mayumi, Mitsufumi; Kobayashi, Kunihiko; Hirano, Kenichi; Takayanagi, Masaki; Tsukahara, Hirokazu

2010-01-01

Children with congenital portosystemic venous shunt (PSVS) are at risk for developing pulmonary hypertension, irrespective of the severity of portal hypertension or liver damage. Altered metabolisms of nitric oxide (NO) and endothelin-1 (ET-1), which are linked with oxidative stress and control vascular tone, might contribute to the vascular disturbance. This study examined 14 children (aged 1-5 years) with congenital PSVS lacking major liver damage and portal hypertension. Serum levels of nitrite/nitrate (NOx) as stable metabolites of NO, and of asymmetric dimethylarginine (ADMA) as an endogenous NO synthase inhibitor were determined, along with the plasma level of ET-1. Oxidative stress, which might affect the production of such mediators, was also examined using specific urinary and blood markers. The NOx levels were significantly lower in affected children than in the age-matched control group, although ET-1 levels were significantly higher than the control levels. In the affected children, the ADMA levels and ADMA/NOx ratios were higher, respectively, by 30% and 130% and showed significant positive correlations with the shunt ratios. Oxidative stress markers, including plasma thiobarbiturate reactive substances and urinary acrolein-lysine and 8-hydroxy-2'-deoxyguanosine, were significantly higher in affected children than in the control group, consistent with them being subjected to enhanced oxidative stress. These results suggest the presence of altered metabolisms of vascular mediators and enhanced oxidative stress in asymptomatic preschool children with congenital PSVS.

Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

PubMed Central

Di Pietro, Marisa; Filardo, Simone; De Santis, Fiorenzo; Sessa, Rosa

2013-01-01

Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development. PMID:23877837

Açaí (Euterpe oleracea Mart.) Modulates Oxidative Stress Resistance in Caenorhabditis elegans by Direct and Indirect Mechanisms

PubMed Central

Bonomo, Larissa de Freitas; Silva, David Nunes; Boasquivis, Patrícia Ferreira; Paiva, Franciny Aparecida; Guerra, Joyce Ferreira da Costa; Martins, Talita Alves Faria; de Jesus Torres, Álvaro Gustavo; de Paula, Igor Thadeu Borges Raposo; Caneschi, Washington Luiz; Jacolot, Philippe; Grossin, Nicolas; Tessier, Frederic J.; Boulanger, Eric; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; de Paula Oliveira, Riva

2014-01-01

Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms. PMID:24594796

Açaí (Euterpe oleracea Mart.) modulates oxidative stress resistance in Caenorhabditis elegans by direct and indirect mechanisms.

PubMed

Bonomo, Larissa de Freitas; Silva, David Nunes; Boasquivis, Patrícia Ferreira; Paiva, Franciny Aparecida; Guerra, Joyce Ferreira da Costa; Martins, Talita Alves Faria; de Jesus Torres, Álvaro Gustavo; de Paula, Igor Thadeu Borges Raposo; Caneschi, Washington Luiz; Jacolot, Philippe; Grossin, Nicolas; Tessier, Frederic J; Boulanger, Eric; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Oliveira, Riva de Paula

2014-01-01

Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms.

Oxidative stress-induced protein damage inhibits DNA repair and determines mutation risk and anticancer drug effectiveness

PubMed Central

McAdam, Elizabeth; Brem, Reto; Karran, Peter

2016-01-01

The relationship between sun exposure and non-melanoma skin cancer risk is well established. Solar ultraviolet radiation (UV; wavelengths 280-400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280-320 nm). How the 20-fold more abundant UVA (320-400 mn) component of solar UV radiation increases skin cancer risk is not understood. We demonstrate here that the contribution of UVA to the effects of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the cells’ susceptibility to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin. Statement of implication: Since NER is both a defence against cancer a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative-stress has implications for both cancer risk and for the effectiveness of anticancer therapy. PMID:27106867

Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.

PubMed

Yamamoto, Hiroya; Kanno, Keishi; Ikuta, Takuya; Arihiro, Koji; Sugiyama, Akiko; Kishikawa, Nobusuke; Tazuma, Susumu

2016-05-01

We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Role of oxidative stress in a rat model of radiation-induced erectile dysfunction.

PubMed

Kimura, Masaki; Rabbani, Zahid N; Zodda, Andrew R; Yan, Hui; Jackson, Isabel L; Polascik, Thomas J; Donatucci, Craig F; Moul, Judd W; Vujaskovic, Zeljko; Koontz, Bridget F

2012-06-01

Chronic oxidative stress is one of the major factors playing an important role in radiation-induced normal tissue injury. However, the role of oxidative stress in radiation-induced erectile dysfunction (ED) has not been fully investigated. Aims.  To investigate role of oxidative stress after prostate-confined irradiation in a rat model of radiation-induced ED. Fifty-four young adult male rats (10-12 weeks of age) were divided into age-matched sham radiotherapy (RT) and RT groups. Irradiated animals received prostate-confined radiation in a single 20 Gy fraction. Intracavernous pressure (ICP) measurements with cavernous nerve electrical stimulation were conducted at 2, 4, and 9 weeks following RT. The protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (Nox4 and gp91(phox)), markers of oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), lipid peroxidation (4-hydroxynonenal [4HNE]), and inflammatory response including inducible nitric oxide synthase, macrophage activation (ED-1), and nitrotyrosine, and endogenous antioxidant defense by nuclear factor erythroid 2-related factor (Nrf2) were evaluated in irradiated prostate tissue and corpora cavernosa (CC). In addition, we investigated the relationships between results of ICP/mean arterial pressure (MAP) ratios and expression level of oxidative stress markers. In the RT group, hemodynamic functional studies demonstrated a significant time-dependent decrease in ICP. Increased expression of Nox4, gp91(phox), 8-OHdG, and 4HNE were observed in the prostate and CC after RT. Similarly, expressions of inflammatory markers were significantly increased. There was a trend for increased Nrf2 after 4 weeks. ICP/MAP ratio negatively correlated with higher expression level of oxidative markers. NADPH oxidase activation and chronic oxidative stress were observed in irradiated prostate tissue and CC, which correlated with lower ICP/MAP ratio. Persistent inflammatory responses were also found in both tissues after RT. These findings suggest that oxidative stress plays a crucial role in the development of radiation-induced ED. © 2012 International Society for Sexual Medicine.

Evaluation of free radical-scavenging and anti-oxidant properties of black berry against fluoride toxicity in rats.

PubMed

Hassan, H A; Abdel-Aziz, A F

2010-01-01

Oxidative damage to cellular components such as lipids and cell membranes by free radicals and other reactive oxygen species is believed to be associated with the development of degenerative diseases. Fluoride intoxication is associated with oxidative stress and altered anti-oxidant defense mechanism. So the present study was extended to investigate black berry anti-oxidant capacity towards superoxide anion radicals, hydroxyl radicals and nitrite in different organs of fluoride-intoxicated rats. The data indicated that sodium fluoride (10.3mg/kg bw) administration induced oxidative stress as evidenced by elevated levels of lipid peroxidation and nitric oxide in red blood cells, kidney, testis and brain tissues. Moreover, significantly decreased glutathione level, total anti-oxidant capacity and superoxide dismutase activity were observed in the examined tissues. On the other hand, the induced oxidative stress and the alterations in anti-oxidant system were normalized by the oral administration of black berry juice (1.6g/kg bw). Therefore it can be concluded that black berry administration could minimize the toxic effects of fluoride indicating its free radical-scavenging and potent anti-oxidant activities. Published by Elsevier Ltd.

Vegetables’ juice influences polyol pathway by multiple mechanisms in favour of reducing development of oxidative stress and resultant diabetic complications

PubMed Central

Tiwari, Ashok K.; Kumar, D. Anand; Sweeya, Pisupati S.; Chauhan, H. Anusha; Lavanya, V.; Sireesha, K.; Pavithra, K.; Zehra, Amtul

2014-01-01

Objective: Hyperglycemia induced generation of free radicals and consequent development of oxidative stress by polyol pathway is one of the crucial mechanisms stirring up development of diabetic complications. We evaluated influence of ten vegetables’ juice on polyol pathway along with their antioxidant and antioxidative stress potentials. Materials and Methods: Aldose reductase activity was determined utilising goat lens and human erythrocytes. In goat lens, utilization of nicotinamine adenine dinucleotide phosphate (NADPH) and aldose reductase inhibition was assayed. In human erythrocytes, sorbitol formation was measured as an index of aldose reductase activity under normoglycemic and hyperglycemic conditions. Ability of juices in inhibiting oxidative damage to deoxyribose sugar and calf thymus DNA and inhibitory activity against hydrogen peroxide induced hemolysis of erythrocytes was also analysed. Phytochemical contents like total polyphenol, total flavonoid and total protein were measured to find their influence on biological activities. Results: Vegetables’ juice displayed varying degrees of inhibitory potentials in mitigating NADPH dependent catalytic activity of aldose reductase in goat lens, accumulation of sorbitol in human erythrocytes under different glucose concentrations; Fenton-reaction induced oxidative damage to deoxyribose sugar, and calf thymus DNA. Substantial variations in vegetables phytochemicals content were also noticed in this study. Conclusions: Vegetables’ juice possesses potent activities in influencing polyol pathway by various mechanisms in favour of reducing development of oxidative stress independent of their inherent antioxidative properties. Juice of ivy gourd followed by green cucumber and ridge gourd were among the most potent for they displayed strong activities on various parameters analysed in this study. These vegetables’ juice may become part of mechanism-based complementary antioxidant therapy to prevent development of diabetic complications. PMID:24991118

The placental pursuit for an adequate oxidant balance between the mother and the fetus

PubMed Central

Herrera, Emilio A.; Krause, Bernardo; Ebensperger, German; Reyes, Roberto V.; Casanello, Paola; Parra-Cordero, Mauro; Llanos, Anibal J.

2014-01-01

The placenta is the exchange organ that regulates metabolic processes between the mother and her developing fetus. The adequate function of this organ is clearly vital for a physiologic gestational process and a healthy baby as final outcome. The umbilico-placental vasculature has the capacity to respond to variations in the materno-fetal milieu. Depending on the intensity and the extensity of the insult, these responses may be immediate-, mediate-, and long-lasting, deriving in potential morphostructural and functional changes later in life. These adjustments usually compensate the initial insults, but occasionally may switch to long-lasting remodeling and dysfunctional processes, arising maladaptation. One of the most challenging conditions in modern perinatology is hypoxia and oxidative stress during development, both disorders occurring in high-altitude and in low-altitude placental insufficiency. Hypoxia and oxidative stress may induce endothelial dysfunction and thus, reduction in the perfusion of the placenta and restriction in the fetal growth and development. This Review will focus on placental responses to hypoxic conditions, usually related with high-altitude and placental insufficiency, deriving in oxidative stress and vascular disorders, altering fetal and maternal health. Although day-to-day clinical practice, basic and clinical research are clearly providing evidence of the severe impact of oxygen deficiency and oxidative stress establishment during pregnancy, further research on umbilical and placental vascular function under these conditions is badly needed to clarify the myriad of questions still unsettled. PMID:25009498

N-Acetylcysteine Amide Protects Against Oxidative Stress–Induced Microparticle Release From Human Retinal Pigment Epithelial Cells

PubMed Central

Carver, Kyle A.; Yang, Dongli

2016-01-01

Purpose Oxidative stress is a major factor involved in retinal pigment epithelium (RPE) apoptosis that underlies AMD. Drusen, extracellular lipid- and protein-containing deposits, are strongly associated with the development of AMD. Cell-derived microparticles (MPs) are small membrane-bound vesicles shed from cells. The purpose of this study was to determine if oxidative stress drives MP release from RPE cells, to assess whether these MPs carry membrane complement regulatory proteins (mCRPs: CD46, CD55, and CD59), and to evaluate the effects of a thiol antioxidant on oxidative stress–induced MP release. Methods Retinal pigment epithelium cells isolated from human donor eyes were cultured and treated with hydrogen peroxide (H2O2) to induce oxidative stress. Isolated MPs were fixed for transmission electron microscopy or processed for component analysis by flow cytometry, Western blot analysis, and confocal microscopy. Results Transmission electron microscopy showed that MPs ranged in diameter from 100 to 1000 nm. H2O2 treatment led to time- and dose-dependent elevations in MPs with externalized phosphatidylserine and phosphatidylethanolamine, known markers of MPs. These increases were strongly correlated to RPE apoptosis. Oxidative stress significantly increased the release of mCRP-positive MPs, which were prevented by a thiol antioxidant, N-acetylcysteine amide (NACA). Conclusions This is the first evidence that oxidative stress induces cultured human RPE cells to release MPs that carry mCRPs on their surface. The levels of released MPs are strongly correlated with RPE apoptosis. N-acetylcysteine amide prevents oxidative stress–induced effects. Our findings indicate that oxidative stress reduces mCRPs on the RPE surface through releasing MPs. PMID:26842754

Redox metabolites signal polymicrobial biofilm development via the NapA oxidative stress cascade in Aspergillus

PubMed Central

Zheng, He; Kim, Jaekuk; Liew, Mathew; Yan, John K.; Herrera, Oscar; Bok, JinWoo; Kelleher, Neil L.; Keller, Nancy P.; Wang, Yun

2014-01-01

Summary Background Filamentous fungi and bacteria form mixed-species biofilms in nature and diverse clinical contexts. They secrete a wealth of redox-active small molecule secondary metabolites, which are traditionally viewed as toxins that inhibit growth of competing microbes. Results Here we report that these “toxins” can act as interspecies signals, affecting filamentous fungal development via oxidative stress regulation. Specifically, in co-culture biofilms, Pseudomonas aeruginosa phenazine-derived metabolites differentially modulated Aspergillus fumigatus development, shifting from weak vegetative growth to induced asexual sporulation (conidiation) along a decreasing phenazine gradient. The A. fumigatus morphological shift correlated with the production of phenazine radicals and concomitant reactive oxygen species (ROS) production generated by phenazine redox cycling. Phenazine conidiation signaling was conserved in the genetic model A. nidulans, and mediated by NapA, a homolog of AP-1-like bZIP transcription factor, which is essential for the response to oxidative stress in humans, yeast, and filamentous fungi. Expression profiling showed phenazine treatment induced a NapA-dependent response of the global oxidative stress metabolome including the thioredoxin, glutathione and NADPH-oxidase systems. Conidiation induction in A. nidulans by another microbial redox-active secondary metabolite, gliotoxin, also required NapA. Conclusions This work highlights that microbial redox metabolites are key signals for sporulation in filamentous fungi, which are communicated through an evolutionarily conserved eukaryotic stress response pathway. It provides a foundation for interspecies signaling in environmental and clinical biofilms involving bacteria and filamentous fungi. PMID:25532893

Thioredoxin: a key regulator of cardiovascular homeostasis.

PubMed

Yamawaki, Hideyuki; Haendeler, Judith; Berk, Bradford C

2003-11-28

The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. The oxidation mechanism for disease pathogenesis states that an imbalance in cell redox state alters function of multiple cell pathways. In this study, we review the essential role for TRX to limit oxidative stress directly via antioxidant effects and indirectly by protein-protein interaction with key signaling molecules, such as apoptosis signal-regulating kinase 1. We propose that TRX and its endogenous regulators are important future targets to develop clinical therapies for cardiovascular disorders associated with oxidative stress.

A Topical Mitochondria-Targeted Redox Cycling Nitroxide Mitigates Oxidative Stress Induced Skin Damage

PubMed Central

Brand, Rhonda M.; Epperly, Michael W.; Stottlemyer, J. Mark; Skoda, Erin M.; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E.; Greenberger, Joel S.; Falo, Louis D.

2017-01-01

Skin is the largest human organ and provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation induced skin damage ranges from photoaging and cutaneous carcinogenesis from UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species (ROS). Mitochondria are particularly susceptible to oxidative stress, and mitochondrial dependent apoptosis plays a major role in radiation induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent ROS accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrial targeted antioxidant prevents and mitigates radiation induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin’s antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. PMID:27794421

Analysis of Oxidative Stress Status, Catalase and Catechol-O-Methyltransferase Polymorphisms in Egyptian Vitiligo Patients

PubMed Central

Mehaney, Dina A.; Darwish, Hebatallah A.; Hegazy, Rehab A.; Nooh, Mohammed M.; Tawdy, Amira M.; Gawdat, Heba I.; El-Sawalhi, Maha M.

2014-01-01

Vitiligo is the most common depigmentation disorder of the skin. Oxidative stress is implicated as one of the probable events involved in vitiligo pathogenesis possibly contributing to melanocyte destruction. Evidence indicates that certain genes including those involved in oxidative stress and melanin synthesis are crucial for development of vitiligo. This study evaluates the oxidative stress status, the role of catalase (CAT) and catechol-O-Methyltransferase (COMT) gene polymorphisms in the etiology of generalized vitiligo in Egyptians. Total antioxidant capacity (TAC) and malondialdehyde (MDA) levels as well as CAT exon 9 T/C and COMT 158 G/A polymorphisms were determined in 89 patients and 90 age and sex-matched controls. Our results showed significantly lower TAC along with higher MDA levels in vitiligo patients compared with controls. Meanwhile, genotype and allele distributions of CAT and COMT polymorphisms in cases were not significantly different from those of controls. Moreover, we found no association between both polymorphisms and vitiligo susceptibility. In conclusion, the enhanced oxidative stress with the lack of association between CAT and COMT polymorphisms and susceptibility to vitiligo in our patients suggest that mutations in other genes related to the oxidative pathway might contribute to the etiology of generalized vitiligo in Egyptian population. PMID:24915010

Effect of interface reaction and diffusion on stress-oxidation coupling at high temperature

NASA Astrophysics Data System (ADS)

Yue, Mengkun; Dong, Xuelin; Fang, Xufei; Feng, Xue

2018-04-01

High-temperature structural materials undergo oxidation during the service, and stress would generate in the oxide film. Understanding the coupling effect between stress and oxidation contributes to the understanding of material degradation and failure during the oxidation process. Here, we propose a model to investigative the coupling effect of stress and oxidation at high temperature by considering the three-stage oxidation process, where both the interface reaction and the diffusion process are present. The governing equations including the oxidation kinetics and stress equilibrium for isothermal oxidation under stress-oxidation coupling effect have been derived. The theory is validated by comparing with the experimental results of SiO2 grown on Si substrate. Results show that the coupling of stress and oxidation influences the growth of the oxide film by affecting all three stages of the oxidation process.

Effect of acetochlor on transcription of genes associated with oxidative stress, apoptosis, immunotoxicity and endocrine disruption in the early life stage of zebrafish.

PubMed

Jiang, Jinhua; Wu, Shenggan; Liu, Xinju; Wang, Yanhua; An, Xuehua; Cai, Leiming; Zhao, Xueping

2015-09-01

The study presented here aimed to characterize the effects of acetochlor on expression of genes related to endocrine disruption, oxidative stress, apoptosis and immune system in zebrafish during its embryo development. Different trends in gene expression were observed after exposure to 50, 100, 200μg/L acetochlor for 96h. Results demonstrated that the transcription patterns of many key genes involved in the hypothalamic-pituitary-gonadal/thyroid (HPG/HPT) axis (e.g., VTG1, ERβ1, CYP19a and TRα), cell apoptosis pathway (e.g., Bcl2, Bax, P53 and Cas8), as well as innate immunity (e.g., CXCL-C1C, IL-1β and TNFα) were affected in newly hatched zebrafish after exposure to acetochlor. In addition, the up-regulation of CAT, GPX, GPX1a, Cu/Zn-SOD and Ogg1 suggested acetochlor might trigger oxidative stress in zebrafish. These finding indicated that acetochlor could simultaneously induce multiple responses during zebrafish embryonic development, and bidirectional interactions among oxidative stress, apoptosis pathway, immune and endocrine systems might be present. Copyright © 2015 Elsevier B.V. All rights reserved.

Gankyrin has an antioxidative role through the feedback regulation of Nrf2 in hepatocellular carcinoma

PubMed Central

Yang, Chun; Tan, Ye-xiong; Yang, Guang-zhen; Zhang, Jian; Pan, Yu-fei; Liu, Chen; Fu, Jing; Chen, Yao; Ding, Zhi-wen

2016-01-01

Oxidative stress status has a key role in hepatocellular carcinoma (HCC) development and progression. Normally, reactive oxygen species (ROS) levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors. How HCC cells respond to excessive oxidative stress remains elusive. Here, we identified a feedback loop between gankyrin, an oncoprotein overexpressed in human HCC, and Nrf2 maintaining the homeostasis in HCC cells. Mechanistically, gankyrin was found to interact with the Kelch domain of Keap1 and effectively competed with Nrf2 for Keap1 binding. Increased expression of gankyrin in HCC cells blocked the binding between Nrf2 and Keap1, inhibiting the degradation of Nrf2 by proteasome. Interestingly, accumulation and translocation of Nrf2 increased the transcription of gankyrin through binding to the ARE elements in the promoter of gankyrin. The positive feedback regulation involving gankyrin and Nrf2 modulates a series of antioxidant enzymes, thereby lowering intracellular ROS and conferring a steadier intracellular environment, which prevents mitochondrial damage and cell death induced by excessive oxidative stress. Our results indicate that gankyrin is a regulator of cellular redox homeostasis and provide a link between oxidative stress and the development of HCC. PMID:27091842

Activation of endogenous antioxidants as a common therapeutic strategy against cancer, neurodegeneration and cardiovascular diseases: A lesson learnt from DJ-1.

PubMed

Chan, Julie Y H; Chan, Samuel H H

2015-12-01

This review aims at presenting a new concept pertaining to the development of antioxidants, namely, to evolve from disease-oriented therapy to mechanism-oriented therapy. Using as our illustrative example is DJ-1, a homodimeric protein that is ubiquitously expressed in a variety of mammalian tissues, including the brain, and is found in the matrix and the intermembrane space of the mitochondria. DJ-1 is known to be an endogenous antioxidant against cancer, neurodegeneration and cardiovascular diseases, of which oxidative stress plays a causal role. Interestingly, the mechanistic targets of DJ-1 as an antioxidant, including Daxx, Nrf2, thioredoxin, glutathione, α-synuclein, PTEN/PI3K/Akt, and Pink/Parkin are also associated with those oxidative stress-related diseases. Furthermore, activators of DJ-1 are available in the form of mortalin, phenylbutyrate and quinone oxidoreductase 1. It follows that activation of DJ-1 as a common endogenous antioxidant provides a new strategy against cancer, neurodegeneration and cardiovascular diseases. Since clinical trials on exogenous application of the known antioxidants have basically failed, an alternative approach would logically be to activate the endogenous antioxidants that are already present in the appropriate cellular locale where elevated oxidative stress is the culprit for the disease. At the same time, since oxidative stress is a common denominator among cancer, neurodegeneration and cardiovascular diseases, development of antioxidant therapy should target the reduction in reactive oxygen species. Instead of focusing on disease-oriented therapy, pharmaceutical companies should concentrate on developing agents and dosing schemes for effective activation of the endogenous antioxidants that are associated with a multitude of oxidative stress-related diseases (mechanism-oriented therapy). Copyright © 2015 Elsevier Inc. All rights reserved.

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats.

PubMed

Capellini, Verena Kise; Baldo, Caroline Floreoto; Celotto, Andréa Carla; Batalhão, Marcelo Eduardo; Cárnio, Evelin Capellari; Rodrigues, Alfredo José; Evora, Paulo Roberto Barbosa

2010-08-01

To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters. Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats. MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups. NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress.

Development of an in vitro cell culture model to investigate the induction and quantification of oxidative stress and its inhibition by alpha-tocopherol.

PubMed

Lawlor, S M; O'Brien, N M

1994-02-01

The ability of the natural antioxidant alpha-tocopherol to protect against oxidative stress in vitro was assessed. Primary cultures of chicken embryo fibroblasts (CEF) were oxidatively stressed by exposure to paraquat (PQ). Activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured as indices of oxidative stress. CEF incubated with 0.125-1.0 mm PQ for 18 hr exhibited increased SOD activity (P < 0.05). CAT activity increased with 0.25 mm PQ (P < 0.05). GSH-Px activity decreased significantly in the presence of PQ. No cytotoxicity, as indicated by lactate dehydrogenase release, was observed at PQ concentrations below 2 mm. Incorporation of added alpha-tocopherol (100 nm) into 0.25 mm PQ-treated CEF resulted in SOD activity not significantly different from that observed in control cells not treated with PQ. Lower levels of added alpha-tocopherol (16 nm) returned CAT to its control value. However, even at 1000 nm alpha-tocopherol, GSH-Px activity was not protected in PQ-treated cells. CEF represent a useful model to study both inducers and inhibitors of oxidative stress.

An effective method for preparation of high-purity pelargonidin-3-O-glucoside from strawberry and its protective effect on cellular oxidative stress.

PubMed

Xu, Yang; Hu, Dongwen; Li, Yuting; Sun, Chongde; Chen, Wei

2018-01-01

Accumulating evidence indicates that consumption of berries may exert beneficial effects against oxidative stress mediated diseases. Pelargonidin-3-O-glucoside (Pg3G), a bioactive ingredient in strawberry, has been reported to possess a potent antioxidant capacity. This study was therefore designed to develop an effective method to prepare pure Pg3G from strawberry and investigate its protective effect against H 2 O 2 -induced oxidative stress. According to our results, Pg3G occupied 85.55% of total anthocyanin content in strawberry. 240mg of Pg3G with the purity of 97.26% was finally isolated from 320g of strawberry lyophilized powder (SLP) by combination of AB-8 macroporous resin and high-speed counter-current chromatography (HSCCC) technologies. Further study unveiled that Pg3G significantly inhibited H 2 O 2 -induced ROS generation, GSH depletion and mitochondrial dysfunction, thereby ameliorating H 2 O 2 -induced oxidative stress. Overall, this study suggests that pelargonidin-3-O-glucoside can be used as a natural bioactive agent to prevent cellular oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Pulmonary dysfunctions, oxidative stress and DNA damage in brick kiln workers.

PubMed

Kaushik, R; Khaliq, F; Subramaneyaan, M; Ahmed, R S

2012-11-01

Brick kilns in the suburban areas in developing countries pose a big threat to the environment and hence the health of their workers and people residing around them. The present study was planned to assess the lung functions, oxidative stress parameters and DNA damage in brick kiln workers. A total of 31 male subjects working in brick kiln, and 32 age, sex and socioeconomic status matched controls were included in the study. The lung volumes, capacities and flow rates, namely, forced expiratory volume in first second (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC, expiratory reserve volume, inspiratory capacity (IC), maximal expiratory flow when 50% of FVC is remaining to be expired, maximum voluntary ventilation, peak expiratory flow rate and vital capacity were significantly decreased in the brick kiln workers. Increased oxidative stress as evidenced by increased malonedialdehyde levels and reduced glutathione content, glutathione S-transferase activity and ferric reducing ability of plasma were observed in the study group when compared with controls. Our results indicate a significant correlation between oxidative stress parameters and pulmonary dysfunction, which may be due to silica-induced oxidative stress and resulting lung damage.

A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni.

PubMed

Dai, Lei; Sahin, Orhan; Tang, Yizhi; Zhang, Qijing

2017-12-15

Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress-resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX R ) in C. jejuni We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR , which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX R phenotype and facilitating Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, the same mechanism may operate in multiple bacterial species. Additionally, we developed a novel method that allows for rapid quantification of spontaneous OX R mutants in a bacterial population. This method represents a technical innovation and may also be applied to other bacterial species. These findings significantly advance our understanding of bacterial mechanisms for survival under oxidative stress. Copyright © 2017 American Society for Microbiology.

Effect of Regular Exercise on the Histochemical Changes of d-Galactose-Induced Oxidative Renal Injury in High-Fat Diet-Fed Rats

PubMed Central

Park, Sok; Kim, Chan-Sik; Lee, Jin; Suk Kim, Jung; Kim, Junghyun

2013-01-01

Renal lipid accumulation exhibits slowly developing chronic kidney disease and is associated with increased oxidative stress. The impact of exercise on the obese- and oxidative stress-related renal disease is not well understood. The purpose of this study was to investigate whether a high-fat diet (HFD) would accelerate d-galactose-induced aging process in rat kidney and to examine the preventive effect of regular exercise on the obese- and oxidative stress-related renal disease. Oxidative stress was induced by an administration of d-galactose (100 mg/kg intraperitoneally injected) for 9 weeks, and d-galactose-treated rats were also fed with a high-fat diet (60% kcal as fat) for 9 weeks to induce obesity. We investigated the efficacy of regular exercise in reducing renal injury by analyzing Nε-carboxymethyllysine (CML), 8-hydroxygluanine (8-OHdG) and apoptosis. When rats were fed with a HFD for 9 weeks in d-galactose-treated rats, an increased CML accumulation, oxidative DNA damage and renal podocyte loss were observed in renal glomerular cells and tubular epithelial cells. However, the regular exercise restored all these renal changes in HFD plus d-galactose-treated rats. Our data suggested that long-term HFD may accelerate the deposition of lipoxidation adducts and oxidative renal injury in d-galactose-treated rats. The regular exercise protects against obese- and oxidative stress-related renal injury by inhibiting this lipoxidation burden. PMID:24023395

Psychological stress-induced cerebrovascular dysfunction: the role of metabolic syndrome and exercise.

PubMed

Brooks, Steven; Brnayan, Kayla W; DeVallance, Evan; Skinner, Roy; Lemaster, Kent; Sheets, J Whitney; Pitzer, Christopher R; Asano, Shinichi; Bryner, Randall W; Olfert, I Mark; Frisbee, Jefferson C; Chantler, Paul D

2018-05-01

What is the central question of this study? How does chronic stress impact cerebrovascular function and does metabolic syndrome accelerate the cerebrovascular adaptations to stress? What role does exercise training have in preventing cerebrovascular changes to stress and metabolic syndrome? What is the main finding and its importance? Stressful conditions lead to pathological adaptations of the cerebrovasculature via an oxidative nitric oxide pathway, and the presence of metabolic syndrome produces a greater susceptibility to stress-induced cerebrovascular dysfunction. The results also provide insight into the mechanisms that may contribute to the influence of stress and the role of exercise in preventing the negative actions of stress on cerebrovascular function and structure. Chronic unresolvable stress leads to the development of depression and cardiovascular disease. There is a high prevalence of depression with the metabolic syndrome (MetS), but to what extent the MetS concurrent with psychological stress affects cerebrovascular function is unknown. We investigated the differential effect of MetS on cerebrovascular structure/function in rats (16-17 weeks old) following 8 weeks of unpredictable chronic mild stress (UCMS) and whether exercise training could limit any cerebrovascular dysfunction. In healthy lean Zucker rats (LZR), UCMS decreased (28%, P < 0.05) ex vivo middle cerebral artery (MCA) endothelium-dependent dilatation (EDD), but changes in MCA remodelling and stiffness were not evident, though cerebral microvessel density (MVD) decreased (30%, P < 0.05). The presence of UCMS and MetS (obese Zucker rats; OZR) decreased MCA EDD (35%, P < 0.05) and dilatation to sodium nitroprusside (20%, P < 0.05), while MCA stiffness increased and cerebral MVD decreased (31%, P < 0.05), which were linked to reduced nitric oxide and increased oxidative levels. Aerobic exercise prevented UCMS impairments in MCA function and MVD in LZR, and partly restored MCA function, stiffness and MVD in OZR. Our data suggest that the benefits of exercise with UCMS were due to a reduction in oxidative stress and increased production of nitric oxide in the cerebral vessels. In conclusion, UCMS significantly impaired MCA structure and function, but the effects of UCMS were more substantial in OZR vs. LZR. Importantly, aerobic exercise when combined with UCMS prevented the MCA dysfunction through subtle shifts in nitric oxide and oxidative stress in the cerebral microvasculature. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

Establishment of chronic hepatitis C virus infection: Translational evasion of oxidative defence

PubMed Central

Chan, Shiu-Wan

2014-01-01

Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the world population. HCV is a single-stranded, positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family. The virus establishes a chronic infection in the face of an active host oxidative defence, thus adaptation to oxidative stress is key to virus survival. Being a small RNA virus with a limited genomic capacity, we speculate that HCV deploys a different strategy to evade host oxidative defence. Instead of counteracting oxidative stress, it utilizes oxidative stress to facilitate its own survival. Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step. This is particularly true when HCV utilizes an internal ribosome entry site element in translation, which is distinctive from that of cap-dependent translation of the vast majority of cellular genes, thus allowing selective translation of genes under conditions when global protein synthesis is compromised. Indeed, we were the first to show that HCV translation was stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes, suggesting that HCV is able to adapt to and utilize the host anti-viral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity. Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity. As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity, which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants. PMID:24659872

Topical nutraceutical Optixcare EH ameliorates experimental ocular oxidative stress in rats.

PubMed

Kador, Peter F; Guo, Changmei; Kawada, Hiroyoshi; Randazzo, James; Blessing, Karen

2014-09-01

Based on the hypothesis that oral nutraceuticals do not adequately reach all ocular tissues in the anterior segment, we evaluated the ability of a 3% concentration of the ingredients in a topical nutraceutical antioxidant formulation called Optixcare Eye Health (Optixcare EH) to ameliorate oxidative stress in rat models of age-related ocular diseases. Diabetes was induced by tail-vein injection of streptozotocin, and the development of cataracts was monitored by slit lamp. Young rats were exposed to ultraviolet (UV) light, and the reduction in lens glutathione (GSH) levels and increase in 4-hydroxynonenol (4-HNE) were measured. Oxidative stress in the neural retina was generated by exposure of dark-adapted rats to 1,000 lx of light, and oxidative stress markers were measured. Dry eye was induced in rats by twice daily (b.i.d.) subcutaneous scopolamine injections. Topical Optixcare EH was administered b.i.d. and compared in select experiments to the multifunctional antioxidant JHX-4, the topical aldose reductase inhibitor (ARI) Kinostat™, oral Ocu-GLO™, and the topical ocular comfort agents Optixcare Eye Lube, Optixcare Eye Lube + Hyaluron, and Idrop Vet Plus hyaluronic acid. In diabetic rats, topical ARI treatment prevented cataract formation while the nutraceuticals delayed their development with Optixcare EH>Ocu-GLO. In UV-exposed rats, the reduction of GSH and increase in 4-HNE in the lens were normalized in order JHX-4>Optixcare EH>Ocu-GLO. In the retina, oxidative stress markers were reduced better by oral JHX-4 compared with topical Optixcare EH. In the scopolamine-induced dry-eye rats, tear flow was maintained by Optixcare EH treatment, while none of the comfort agents examined altered tear flow. Topical administration of a 3% concentration of the ingredients in Optixcare EH reduces experimentally induced reactive oxygen species in rats exposed to several sources of ocular oxidative stress. In addition, Optixcare EH maintains tear volume in scopolamine-induced dry eye. This suggests that in the anterior segment, the ingredients in Optixcare EH may have clinical potential against ocular oxidative stress.

Development and characterization of a hydrogen peroxide-resistant cholangiocyte cell line: A novel model of oxidative stress-related cholangiocarcinoma genesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanan, Raynoo; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002; Techasen, Anchalee

Oxidative stress is a cause of inflammation–related diseases, including cancers. Cholangiocarcinoma is a liver cancer with bile duct epithelial cell phenotypes. Our previous studies in animal and human models indicated that oxidative stress is a major cause of cholangiocarcinoma development. Hydrogen peroxide (H{sub 2}O{sub 2}) can generate hydroxyl radicals, which damage lipids, proteins, and nucleic acids, leading to cell death. However, some cells can survive by adapting to oxidative stress conditions, and selective clonal expansion of these resistant cells would be involved in oxidative stress-related carcinogenesis. The present study aimed to establish H{sub 2}O{sub 2}-resistant cell line from an immortal cholangiocytemore » cell line (MMNK1) by chronic treatment with low-concentration H{sub 2}O{sub 2} (25 μM). After 72 days of induction, H{sub 2}O{sub 2}-resistant cell lines (ox-MMNK1-L) were obtained. The ox-MMNK1-L cell line showed H{sub 2}O{sub 2}-resistant properties, increasing the expression of the anti-oxidant genes catalase (CAT), superoxide dismutase-1 (SOD1), superoxide dismutase-2 (SOD2), and superoxide dismutase-3 (SOD3) and the enzyme activities of CAT and intracellular SODs. Furthermore, the resistant cells showed increased expression levels of an epigenetics-related gene, DNA methyltransferase-1 (DNMT1), when compared to the parental cells. Interestingly, the ox-MMNK1-L cell line had a significantly higher cell proliferation rate than the MMNK1 normal cell line. Moreover, ox-MMNK1-L cells showed pseudopodia formation and the loss of cell-to-cell adhesion (multi-layers) under additional oxidative stress (100 μM H{sub 2}O{sub 2}). These findings suggest that H{sub 2}O{sub 2}-resistant cells can be used as a model of oxidative stress-related cholangiocarcinoma genesis through molecular changes such as alteration of gene expression and epigenetic changes. - Highlights: • An H{sub 2}O{sub 2}-resistant ox-MMNK1-L cells was established from immortalized cholangiocytes. • The resistance was acquired by daily treatment of low H{sub 2}O{sub 2} (25 μM) for 15 passages. • The cells highly expressed catalase, SODs and DNMT1 with rapid cell proliferation. • Pseudopodia and the loss of cell-to-cell adhesion appeared by 100 μM H{sub 2}O{sub 2} treatment. • The resistant cells can be used as a model of oxidative stress-related carcinogenesis.« less

Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution: Part 3 of a 3-Part Series.

PubMed

Niemann, Bernd; Rohrbach, Susanne; Miller, Mark R; Newby, David E; Fuster, Valentin; Kovacic, Jason C

2017-07-11

Oxidative stress occurs whenever the release of reactive oxygen species (ROS) exceeds endogenous antioxidant capacity. In this paper, we review the specific role of several cardiovascular risk factors in promoting oxidative stress: diabetes, obesity, smoking, and excessive pollution. Specifically, the risk of developing heart failure is higher in patients with diabetes or obesity, even with optimal medical treatment, and the increased release of ROS from cardiac mitochondria and other sources likely contributes to the development of cardiac dysfunction in this setting. Here, we explore the role of different ROS sources arising in obesity and diabetes, and the effect of excessive ROS production on the development of cardiac lipotoxicity. In parallel, contaminants in the air that we breathe pose a significant threat to human health. This paper provides an overview of cigarette smoke and urban air pollution, considering how their composition and biological effects have detrimental effects on cardiovascular health. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress

PubMed Central

Zhong, Peng; Wang, Jingying; Weng, Qiaoyou; Qian, Yuanyuan; Han, Jibo; Zou, Chunpeng; Liang, Guang

2017-01-01

Diabetic nephropathy (DN) is a progressive kidney disease due to glomerular capillary damage in diabetic patients. Endoplasmic reticulum (ER) stress caused by reactive oxygen species (ROS) is associated with DN progression. Epidermal growth factor receptor (EGFR) mediates oxidative stress and damage of cardiomyocytes in diabetic mice. Here we demonstrated that AG1478, a specific inhibitor of EGFR, blocked EGFR and AKT phosphorylation in diabetic mice. Oxidative stress and ER stress markers were eliminated after AG1478 administration. AG1478 decreased pro-fibrotic genes TGF-β and collagen IV. Furthermore, we found that high glucose (HG) induced oxidative stress and ER stress, and subsequently increased ATF4 and CHOP. These changes were eliminated by either AG1478 or ROS scavenger N-acetyl-L-cysteine (NAC) administration. These results were confirmed by knock-down approaches in renal mesangial SV40 cells. However, AG1478, not NAC, reversed HG induced EGFR and AKT phosphorylation. These results suggest that EGFR/AKT/ROS/ER stress signaling plays an essential role in DN development and inhibiting EGFR may serve as a potential therapeutic strategy in diabetic kidney diseases. PMID:28427241

The Response to Heat Shock and Oxidative Stress in Saccharomyces cerevisiae

PubMed Central

Morano, Kevin A.; Grant, Chris M.; Moye-Rowley, W. Scott

2012-01-01

A common need for microbial cells is the ability to respond to potentially toxic environmental insults. Here we review the progress in understanding the response of the yeast Saccharomyces cerevisiae to two important environmental stresses: heat shock and oxidative stress. Both of these stresses are fundamental challenges that microbes of all types will experience. The study of these environmental stress responses in S. cerevisiae has illuminated many of the features now viewed as central to our understanding of eukaryotic cell biology. Transcriptional activation plays an important role in driving the multifaceted reaction to elevated temperature and levels of reactive oxygen species. Advances provided by the development of whole genome analyses have led to an appreciation of the global reorganization of gene expression and its integration between different stress regimens. While the precise nature of the signal eliciting the heat shock response remains elusive, recent progress in the understanding of induction of the oxidative stress response is summarized here. Although these stress conditions represent ancient challenges to S. cerevisiae and other microbes, much remains to be learned about the mechanisms dedicated to dealing with these environmental parameters. PMID:22209905

The Role of Ca2+ Imbalance in the Induction of Acute Oxidative Stress and Cytotoxicity in Cultured Rat Cerebellar Granule Cells Challenged with Tetrabromobisphenol A.

PubMed

Zieminska, Elzbieta; Lenart, Jacek; Diamandakis, Dominik; Lazarewicz, Jerzy W

2017-03-01

Using primary cultures of rat cerebellar granule cells (CGC) we examined the role of calcium transients induced by tetrabromobisphenol A (TBBPA) in triggering oxidative stress and cytotoxicity. CGC were exposed for 30 min to 10 or 25 µM TBBPA. Changes in intracellular calcium concentration ([Ca 2+ ] i ), in the production of reactive oxygen species (ROS), and in the potential of mitochondria (∆Ψm) were measured fluorometrically during the exposure. The intracellular glutathione (GSH) and catalase activity were determined after the incubation; cell viability was evaluated 24 h later. TBBPA concentration-dependently increased [Ca 2+ ] i and ROS production, and reduced GSH content, catalase activity, ∆Ψm and neuronal viability. The combination of NMDA and ryanodine receptor antagonists, MK-801 and bastadin 12 with ryanodine, respectively, prevented Ca 2+ transients and partially reduced cytotoxicity induced by TBBPA at both concentrations. The antagonists also completely inhibited oxidative stress and depolarization of mitochondria evoked by 10 µM TBBPA, whereas these effects were only partially reduced in the 25 µM TBBPA treatment. Free radical scavengers prevented TBBPA-induced development of oxidative stress and improved CGC viability without having any effect on the rises in Ca 2+ and drop in ∆Ψm. The co-administration of scavengers with NMDA and ryanodine receptor antagonists provided almost complete neuroprotection. These results indicate that Ca 2+ imbalance and oxidative stress both mediate acute toxicity of TBBPA in CGC. At 10 µM TBBPA Ca 2+ imbalance is a primary event, inducing oxidative stress, depolarization of mitochondria and cytotoxicity, whilst at a concentration of 25 µM TBBPA an additional Ca 2+ -independent portion of oxidative stress and cytotoxicity emerges.

Mitoprotective antioxidant EUK-134 stimulates fatty acid oxidation and prevents hypertrophy in H9C2 cells.

PubMed

Purushothaman, Sreeja; Nair, R Renuka

2016-09-01

Oxidative stress is an important contributory factor for the development of cardiovascular diseases like hypertension-induced hypertrophy. Mitochondrion is the major source of reactive oxygen species. Hence, protecting mitochondria from oxidative damage can be an effective therapeutic strategy for the prevention of hypertensive heart disease. Conventional antioxidants are not likely to be cardioprotective, as they cannot protect mitochondria from oxidative damage. EUK-134 is a salen-manganese complex with superoxide dismutase and catalase activity. The possible role of EUK-134, a mitoprotective antioxidant, in the prevention of hypertrophy of H9C2 cells was examined. The cells were stimulated with phenylephrine (50 μM), and hypertrophy was assessed based on cell volume and expression of brain natriuretic peptide and calcineurin. Enhanced myocardial lipid peroxidation and protein carbonyl content, accompanied by nuclear factor-kappa B gene expression, confirmed the presence of oxidative stress in hypertrophic cells. Metabolic shift was evident from reduction in the expression of medium-chain acyl-CoA dehydrogenase. Mitochondrial oxidative stress was confirmed by the reduced expression of mitochondria-specific antioxidant peroxiredoxin-3 and enhanced mitochondrial superoxide production. Compromised mitochondrial function was apparent from reduced mitochondrial membrane potential. Pretreatment with EUK-134 (10 μM) was effective in the prevention of hypertrophic changes in H9C2 cells, reduction of oxidative stress, and prevention of metabolic shift. EUK-134 treatment improved the oxidative status of mitochondria and reversed hypertrophy-induced reduction of mitochondrial membrane potential. Supplementation with EUK-134 is therefore identified as a novel approach to attenuate cardiac hypertrophy and lends scope for the development of EUK-134 as a therapeutic agent in the management of human cardiovascular disease.

The high-fat diet induces myocardial fibrosis in the metabolically healthy obese minipigs-The role of ER stress and oxidative stress.

PubMed

Li, Sin-Jin; Liu, Chia-Hsin; Chu, Hsien-Pin; Mersmann, Harry J; Ding, Shih-Torng; Chu, Chun-Han; Wang, Chia-Yu; Chen, Ching-Yi

2017-06-01

The cellular mechanisms of obesity-induced cardiomyopathy are multiple and not completely elucidated. The objective of this study was to differentiate two obesity-associated cardiomyopathy miniature pig models: one with the metabolic syndrome (MetS), and one with a metabolically healthy obesity (MHO). The cellular responses during the development of obesity-induced cardiomyopathy were investigated. Five-month-old Lee-Sung (MetS) and Lanyu (MHO) minipigs were made obese by feeding a high-fat diet (HFD) for 6 months. Obese pigs exhibited a greater heart weight than control pigs. Interstitial and perivascular fibrosis developed in the myocardium of obese pigs. The HFD induced cardiac lipid accumulation and oxidative stress and also decreased the antioxidant defense in MetS pigs. This diet activated oxidative stress without changing cardiac antioxidant defense and lipid content in MHO pigs. The HFD upregulated the expression of Grp94, CHOP, caspase 12, p62, and LC3II, and increased the ratio of LC3II to LC3I in the left ventricle (LV) of MetS pigs. Compared to obese MetS pigs, less Grp94 and elevated CHOP expression was found in the obese MHO heart. The HFD did not change the ratio of LC3II to LC3I and p62 expression in obese MHO pigs. The obese MetS pigs had an extensive and greater inflammatory response in the plasma than the obese MHO pigs, which had a lesser and milder inflammation. Oxidative stress and ER stress were involved in the progression of MHO-related cardiomyopathy. Inflammation, autophagy, ER stress, oxidative stress, and lipotoxicity participated in the pathological mechanism of MetS-related cardiomyopathy. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Effect of endurance exercise training on oxidative stress in spontaneously hypertensive rats (SHR) after emergence of hypertension.

PubMed

Kimura, Hiroko; Kon, Nobuko; Furukawa, Satoshi; Mukaida, Masahiro; Yamakura, Fumiyuki; Matsumoto, Kazuko; Sone, Hirohito; Murakami-Murofushi, Kimiko

2010-01-01

The purpose of this study is to elucidate the effect of wheel training on oxidative stress maker levels in spontaneous hypertensive rats (SHR). 4-hydroxynonenal and 3-nitrotyrosine levels in the aorta of SHRs were allowed to run for 10 weeks from the age of 15 weeks were measured and compared with those of nonexercised SHRs. The 4-hydroxynonenal and 3-nitrotyrosine levels in the exercised group were significantly lower than those in the nonexercised group. The exercised group showed a significant increase of manganese-containing superoxide dismutase. Endurance exercise showed a possible suppressing effect on the arteriosclerosis development by reducing oxidative stress, even after emergence of hypertension.

Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation.

PubMed

Kato, Takuma; Tada-Oikawa, Saeko; Wang, Linan; Murata, Mariko; Kuribayashi, Kagemasa

2013-11-15

In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen, but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases. © 2013.

Aminoethyl nitrate – the novel super nitrate?

PubMed Central

Bauersachs, Johann

2009-01-01

Long-term use of most organic nitrates is limited by development of tolerance, induction of oxidative stress and endothelial dysfunction. In this issue of the BJP, Schuhmacher et al. characterized a novel class of organic nitrates with amino moieties (aminoalkyl nitrates). Aminoethyl nitrate was identified as a novel organic mononitrate with high potency but devoid of induction of mitochondrial oxidative stress. Cross-tolerance to nitroglycerin or the endothelium-dependent agonist acetylcholine after in vivo treatment was not observed. Like all nitrates, aminoethyl nitrate induced vasorelaxation by activation of soluble guanylate cyclase. Thus, in contrast to the prevailing view, high potency in an organic nitrate is not necessarily accompanied by induction of oxidative stress or endothelial dysfunction. This work from Daiber's group is an important step forward in the understanding of nitrate bioactivation, tolerance phenomena and towards the development of better organic nitrates for clinical use. PMID:19732062

Testing of resveratrol microemulsion photostability and protective effect against UV induced oxidative stress.

PubMed

Juškaitė, Vaida; Ramanauskienė, Kristina; Briedis, Vitalis

2017-06-27

Resveratrol is well known for its antioxidant activity and susceptibility to ultraviolet radiation. Development of formulations providing improved stability and relevant drug delivery of resveratrol is still a challenging task. The aim of this study was to determine protective characteristics of formulated microemulsions by evaluating photoisomerization of resveratrol and to investigate the effects of resveratrol on human keratinocyte cells under oxidative stress caused by ultraviolet radiation. Incorporation of resveratrol into microemulsions resulted in increased photostability of active compounds and the results demonstrated that photodegradation of resveratrol was significantly delayed. Results of biopharmaceutical evaluation in vitro demonstrated that up to 60 % of resveratrol was released from microemulsions within 6 hours under a constant release rate profile. In vivo biological testing confirmed the ability of resveratrol to protect cells from oxidative stress and to increase cell viability. It was concluded that microemulsions might be considered in the development of UV light sensitive compounds.

Tolerance of pentose utilising yeast to hydrogen peroxide-induced oxidative stress.

PubMed

Spencer, Jennifer; Phister, Trevor G; Smart, Katherine A; Greetham, Darren

2014-03-17

Bioethanol fermentations follow traditional beverage fermentations where the yeast is exposed to adverse conditions such as oxidative stress. Lignocellulosic bioethanol fermentations involve the conversion of pentose and hexose sugars into ethanol. Environmental stress conditions such as osmotic stress and ethanol stress may affect the fermentation performance; however, oxidative stress as a consequence of metabolic output can also occur. However, the effect of oxidative stress on yeast with pentose utilising capabilities has yet to be investigated. Assaying for the effect of hydrogen peroxide-induced oxidative stress on Candida, Pichia and Scheffersomyces spp. has demonstrated that these yeast tolerate hydrogen peroxide-induced oxidative stress in a manner consistent with that demonstrated by Saccharomyces cerevisiae. Pichia guillermondii appears to be more tolerant to hydrogen peroxide-induced oxidative stress when compared to Candida shehatae, Candida succiphila or Scheffersomyces stipitis. Sensitivity to hydrogen peroxide-induced oxidative stress increased in the presence of minimal media; however, addition of amino acids and nucleobases was observed to increase tolerance. In particular adenine increased tolerance and methionine reduced tolerance to hydrogen peroxide-induced oxidative stress.

Tolerance of pentose utilising yeast to hydrogen peroxide-induced oxidative stress

PubMed Central

2014-01-01

Background Bioethanol fermentations follow traditional beverage fermentations where the yeast is exposed to adverse conditions such as oxidative stress. Lignocellulosic bioethanol fermentations involve the conversion of pentose and hexose sugars into ethanol. Environmental stress conditions such as osmotic stress and ethanol stress may affect the fermentation performance; however, oxidative stress as a consequence of metabolic output can also occur. However, the effect of oxidative stress on yeast with pentose utilising capabilities has yet to be investigated. Results Assaying for the effect of hydrogen peroxide-induced oxidative stress on Candida, Pichia and Scheffersomyces spp. has demonstrated that these yeast tolerate hydrogen peroxide-induced oxidative stress in a manner consistent with that demonstrated by Saccharomyces cerevisiae. Pichia guillermondii appears to be more tolerant to hydrogen peroxide-induced oxidative stress when compared to Candida shehatae, Candida succiphila or Scheffersomyces stipitis. Conclusions Sensitivity to hydrogen peroxide-induced oxidative stress increased in the presence of minimal media; however, addition of amino acids and nucleobases was observed to increase tolerance. In particular adenine increased tolerance and methionine reduced tolerance to hydrogen peroxide-induced oxidative stress. PMID:24636079

Resveratrol protects primary rat hepatocytes against oxidative stress damage: activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes.

PubMed

Rubiolo, Juan Andrés; Mithieux, Gilles; Vega, Félix Victor

2008-09-04

Oxidative stress is recognized as an important factor in the development of liver pathologies. The reactive oxygen species endogenously generated or as a consequence of xenobiotic metabolism are eliminated by enzymatic and nonenzymatic cellular systems. Besides endogen defences, the antioxidant consumption in the diet has an important role in the protection against the development of diseases product of oxidative damage. Resveratrol is a naturally occurring compound which is part of the human diet. This molecule has been shown to have many biological properties, including antioxidant activity. We decided to test if resveratrol could protect primary hepatocytes in culture from oxidative stress damage and if so, to determine if this compound affects the cellular detoxifying systems and their regulation through the Nrf2 transcription factor that regulates the expression of antioxidant and phase II detoxifying enzymes. Cell death by necrosis was detected by measuring the activity of lactate dehydrogenase liberated to the medium. The activities of antioxidant and phase II enzymes were measured using previously described methods. Activation of the Nrf2 transcription factor was studied by confocal microscopy and the Nrf2 and its coding mRNA levels were determined by western blot and quantitative PCR respectively. Resveratrol pre-treatment effectively protected hepatocytes in culture exposed to oxidative stress, increasing the activities of catalase, superoxide dismutase, glutathione peroxidase, NADPH quinone oxidoreductase and glutathione-S-transferase. Resveratrol increases the level of Nrf2 and induces its translocation to the nucleus. Also, it increases the concentration of the coding mRNA for Nrf2. In this work we show that resveratrol could be a useful drug for the protection of liver cells from oxidative stress induced damage.

AT1 receptor blocker losartan protects against mechanical ventilation-induced diaphragmatic dysfunction

PubMed Central

Kwon, Oh Sung; Smuder, Ashley J.; Wiggs, Michael P.; Hall, Stephanie E.; Sollanek, Kurt J.; Morton, Aaron B.; Talbert, Erin E.; Toklu, Hale Z.; Tumer, Nihal

2015-01-01

Mechanical ventilation is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged ventilator support results in diaphragmatic atrophy and contractile dysfunction leading to diaphragm weakness, which is predicted to contribute to problems in weaning patients from the ventilator. While it is established that ventilator-induced oxidative stress is required for the development of ventilator-induced diaphragm weakness, the signaling pathway(s) that trigger oxidant production remain unknown. However, recent evidence reveals that increased plasma levels of angiotensin II (ANG II) result in oxidative stress and atrophy in limb skeletal muscles. Using a well-established animal model of mechanical ventilation, we tested the hypothesis that increased circulating levels of ANG II are required for both ventilator-induced diaphragmatic oxidative stress and diaphragm weakness. Cause and effect was determined by administering an angiotensin-converting enzyme inhibitor (enalapril) to prevent ventilator-induced increases in plasma ANG II levels, and the ANG II type 1 receptor antagonist (losartan) was provided to prevent the activation of ANG II type 1 receptors. Enalapril prevented the increase in plasma ANG II levels but did not protect against ventilator-induced diaphragmatic oxidative stress or diaphragm weakness. In contrast, losartan attenuated both ventilator-induced oxidative stress and diaphragm weakness. These findings indicate that circulating ANG II is not essential for the development of ventilator-induced diaphragm weakness but that activation of ANG II type 1 receptors appears to be a requirement for ventilator-induced diaphragm weakness. Importantly, these experiments provide the first evidence that the Food and Drug Administration-approved drug losartan may have clinical benefits to protect against ventilator-induced diaphragm weakness in humans. PMID:26359481

Cytotoxicity of citral against melanoma cells: The involvement of oxidative stress generation and cell growth protein reduction.

PubMed

Sanches, Larissa Juliani; Marinello, Poliana Camila; Panis, Carolina; Fagundes, Tatiane Renata; Morgado-Díaz, José Andrés; de-Freitas-Junior, Julio Cesar Madureira; Cecchini, Rubens; Cecchini, Alessandra Lourenço; Luiz, Rodrigo Cabral

2017-03-01

Citral is a natural compound that has shown cytotoxic and antiproliferative effects on breast and hematopoietic cancer cells; however, there are few studies on melanoma cells. Oxidative stress is known to be involved in all stages of melanoma development and is able to modulate intracellular pathways related to cellular proliferation and death. In this study, we hypothesize that citral exerts its cytotoxic effect on melanoma cells by the modulation of cellular oxidative status and/or intracellular signaling. To test this hypothesis, we investigated the antiproliferative and cytotoxic effects of citral on B16F10 murine melanoma cells evaluating its effects on cellular oxidative stress, DNA damage, cell death, and important signaling pathways, as these pathways, namely, extracellular signal-regulated kinases 1/2 (ERK1/2), AKT, and phosphatidylinositol-3 kinase, are involved in cell proliferation and differentiation. The p53 and nuclear factor kappa B were also investigated due to their ability to respond to intracellular stress. We observed that citral exerted antiproliferative and cytotoxic effects in B16F10; induced oxidative stress, DNA lesions, and p53 nuclear translocation; and reduced nitric oxide levels and nuclear factor kappa B, ERK1/2, and AKT. To investigate citral specificity, we used non-neoplastic human and murine cells, HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts), and observed that although citral effects were not specific for cancer cells, non-neoplastic cells were more resistant to citral than B16F10. These findings highlight the potential clinical utility of citral in melanoma, with a mechanism of action involving the oxidative stress generation, nitric oxide depletion, and interference in signaling pathways related to cell proliferation.

Water-soluble fractions from defatted sesame seeds protect human neuroblast cells against peroxyl radicals and hydrogen peroxide-induced oxidative stress.

PubMed

Ben Othman, Sana; Katsuno, Nakako; Kitayama, Akemi; Fujimura, Makoto; Kitaguchi, Kohji; Yabe, Tomio

2016-09-01

Oxidative stress is involved in the development of aging-related diseases, such as neurodegenerative diseases. Dietary antioxidants that can protect neuronal cells from oxidative damage play an important role in preventing such diseases. Previously, we reported that water-soluble fractions purified from defatted sesame seed flour exhibit good antioxidant activity in vitro. In the present study, we investigated the protective effects of white and gold sesame seed water-soluble fractions (WS-wsf and GS-wsf, respectively) against 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and hydrogen peroxide (H2O2) induced oxidative stress in human neuroblast SH-SY5Y cells. Pretreatment with WS-wsf and GS-wsf did not protect cells against AAPH-induced cytotoxicity, while simultaneous co-treatment with AAPH significantly improved cell viability and inhibited membrane lipid peroxidation. These results suggest that WS-wsf and GS-wsf protect cells from AAPH-induced extracellular oxidative damage via direct scavenging of peroxyl radicals. When oxidative stress was induced by H2O2, pretreatment WS-wsf and GS-wsf significantly enhanced cell viability. These results suggest that in addition to radical scavenging, WS-wsf and GS-wsf enhance cellular resistance to intracellular oxidative stress by activation of the Nrf-2/ARE pathway as confirmed by the increased Nrf2 protein level in the nucleus and increased heme oxygenase 1 (HO-1) mRNA expression. The roles of ferulic and vanillic acids as bioactive antioxidants in these fractions were also confirmed. In conclusion, our results indicated that WS-wsf and GS-wsf, which showed antioxidant activity in vitro, are also efficient antioxidants in a cell system protecting SH-SY5Y cells against both extracellular and intracellular oxidative stress.

Redox signaling is an early event in the pathogenesis of renovascular hypertension.

PubMed

Hartono, Stella P; Knudsen, Bruce E; Zubair, Adeel S; Nath, Karl A; Textor, Stephen J; Lerman, Lilach O; Grande, Joseph P

2013-09-10

Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3⁺ T cells and F4/80⁺ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.

Dimethylarginine Dimethylaminohydrolase 1 Protects Against High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice.

PubMed

Li, Tianhe; Feng, Run; Zhao, Chenyang; Wang, Yue; Wang, Jian; Liu, Shasha; Cao, Jianwei; Wang, Hongyun; Wang, Ting; Guo, Yuting; Lu, Zhongbing

2017-04-10

High plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are associated with hepatic dysfunction in patients with nonalcoholic fatty liver disease (NAFLD). However, it is unknown whether ADMA is involved in the pathogenesis of NAFLD. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an enzyme that degrades ADMA. In this study, we used Ddah1 -/- mice to investigate the effects of the ADMA/DDAH1 pathway on high-fat diet (HFD)-induced hepatic steatosis. After HFD feeding for 20 weeks, Ddah1 -/- mice were more obese and had developed more severe hepatic steatosis and worse insulin resistance compared with wild-type (WT) mice. In the livers of HFD-fed mice, loss of DDAH1 resulted in higher levels of lipogenic genes, lower expression of β-oxidation genes, and greater induction of oxidative stress, endoplasmic reticulum stress, and inflammation than in the WT livers. Furthermore, ADMA treatment in HepG2 cells led to oxidative stress and steatosis, whereas overexpression of DDAH1 attenuated palmitic acid-induced steatosis, oxidative stress, and inflammation. Innovation and Conclusion: Our results provide the first direct evidence that the ADMA/DDAH1 pathway has a marked effect on hepatic lipogenesis and steatosis induced by HFD feeding. Our findings suggest that strategies to increase DDAH1 activity in hepatocytes may provide a novel approach to attenuate NAFLD development. Antioxid. Redox Signal. 26, 598-609.

Naturally high plasma glucose levels in mourning doves (Zenaida macroura) do not lead to high levels of reactive oxygen species in the vasculature.

PubMed

Smith, Christina L; Toomey, Matthew; Walker, Benjimen R; Braun, Eldon J; Wolf, Blair O; McGraw, Kevin; Sweazea, Karen L

2011-06-01

Plasma glucose (P(Glu)) concentrations in birds are 1.5-2 times higher than those of mammals of similar body mass. In mammals, sustained elevations of P(Glu) lead to oxidative stress and free radical-mediated scavenging of endogenous vasodilators (e.g., nitric oxide), contributing to elevated blood pressure. Despite the relatively high P(Glu) levels in birds, they appear resistant to the development of oxidative stress in tissues such as the heart, brain and kidneys. To our knowledge no information exists on oxidative stress susceptibility in the resistance vasculature of birds. Therefore, we compared endogenous antioxidant mechanisms in the resistance vasculature of mourning doves (MODO; Zenaida macroura) and rats (Rattus norvegicus). Reactive oxygen species (ROS) were assessed with the fluorescent indicator 7'-dichlorodihydrofluorescein diacetate, acetyl ester in mesenteric arteries from rats and wild-caught MODO. Despite having significantly higher P(Glu) than rats, there were no significant differences in ROS levels between mesenteric arteries from rats or doves. Although superoxide dismutase and catalase activities were lower in the plasma, total antioxidant capacity, uric acid, vitamin E (α-tocopherol), and carotenoids (lutein and zeaxanthin) were significantly higher in MODO than in rats. Thus, compared to rats, MODO have multiple circulating antioxidants that may prevent the development of oxidative stress in the vasculature. Copyright © 2011 Elsevier GmbH. All rights reserved.

Expression Patterns of Glutathione Transferase Gene (GstI) in Maize Seedlings Under Juglone-Induced Oxidative Stress

PubMed Central

Sytykiewicz, Hubert

2011-01-01

Juglone (5-hydroxy-1,4-naphthoquinone) has been identified in organs of many plant species within Juglandaceae family. This secondary metabolite is considered as a highly bioactive substance that functions as direct oxidant stimulating the production of reactive oxygen species (ROS) in acceptor plants. Glutathione transferases (GSTs, E.C.2.5.1.18) represent an important group of cytoprotective enzymes participating in detoxification of xenobiotics and limiting oxidative damages of cellular macromolecules. The purpose of this study was to investigate the impact of tested allelochemical on growth and development of maize (Zea mays L.) seedlings. Furthermore, the effect of juglone-induced oxidative stress on glutathione transferase (GstI) gene expression patterns in maize seedlings was recorded. It was revealed that 4-day juglone treatment significantly stimulated the transcriptional activity of GstI in maize seedlings compared to control plants. By contrast, at the 6th and 8th day of experiments the expression gene responses were slightly lower as compared with non-stressed seedlings. Additionally, the specific gene expression profiles, as well as the inhibition of primary roots and coleoptile elongation were proportional to juglone concentrations. In conclusion, the results provide strong molecular evidence that allelopathic influence of juglone on growth and development of maize seedlings may be relevant with an induction of oxidative stress in acceptor plants. PMID:22174645

Antioxidant functionalized polymer capsules to prevent oxidative stress.

PubMed

Larrañaga, Aitor; Isa, Isma Liza Mohd; Patil, Vaibhav; Thamboo, Sagana; Lomora, Mihai; Fernández-Yague, Marc A; Sarasua, Jose-Ramon; Palivan, Cornelia G; Pandit, Abhay

2018-02-01

Polymeric capsules exhibit significant potential for therapeutic applications as microreactors, where the bio-chemical reactions of interest are efficiently performed in a spatial and time defined manner due to the encapsulation of an active biomolecule (e.g., enzyme) and control over the transfer of reagents and products through the capsular membrane. In this work, catalase loaded polymer capsules functionalized with an external layer of tannic acid (TA) are fabricated via a layer-by-layer approach using calcium carbonate as a sacrificial template. The capsules functionalised with TA exhibit a higher scavenging capacity for hydrogen peroxide and hydroxyl radicals, suggesting that the external layer of TA shows intrinsic antioxidant properties, and represents a valid strategy to increase the overall antioxidant potential of the developed capsules. Additionally, the hydrogen peroxide scavenging capacity of the capsules is enhanced in the presence of the encapsulated catalase. The capsules prevent oxidative stress in an in vitro inflammation model of degenerative disc disease. Moreover, the expression of matrix metalloproteinase-3 (MMP-3), and disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5), which represents the major proteolytic enzymes in intervertebral disc, are attenuated in the presence of the polymer capsules. This platform technology exhibits potential to reduce oxidative stress, a key modulator in the pathology of a broad range of inflammatory diseases. Oxidative stress damages important cell structures leading to cellular apoptosis and senescence, for numerous disease pathologies including cancer, neurodegeneration or osteoarthritis. Thus, the development of biomaterials-based systems to control oxidative stress has gained an increasing interest. Herein, polymer capsules loaded with catalase and functionalized with an external layer of tannic acid are fabricated, which can efficiently scavenge important reactive oxygen species (i.e., hydroxyl radicals and hydrogen peroxide) and modulate extracellular matrix activity in an in vitro inflammation model of nucleus pulposus. The present work represents accordingly, an important advance in the development and application of polymer capsules with antioxidant properties for the treatment of oxidative stress, which is applicable for multiple inflammatory disease targets. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome

PubMed Central

Chen, Ping

2016-01-01

Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP), antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field. PMID:27774119

Oxidative stress status in patients with melasma.

PubMed

Seçkin, Havva Yıldız; Kalkan, Göknur; Baş, Yalçın; Akbaş, Ali; Önder, Yalçın; Özyurt, Hüseyin; Sahin, Mehmet

2014-09-01

Melasma is an acquired skin disease characterized clinically by development of gray-brown macules or patches. The lesions have geographic borders and most often seen on face and less frequently on the neck and forearms. Pathogenesis has not been completely understood yet. Although the disease constitutes a very disturbing cosmetic problem, it has not obtained an efficient treatment. There were not any studies in the literature that evaluates the role of oxidative stress in melasma. The evaluation of the role of oxidative stress in melasma. Fifty melasma patients and 50 healthy volunteers were included in the study. The diagnosis was made clinically and the patients were evaluated by Melasma Area Severity Index. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzyme activities and malondialdehyde, nitric oxide, protein carbonyl levels were measured both in the melasma group and the control group. SOD and GSH-Px enzyme activities were significantly higher in the patient group in comparison with the control group (p < 0.001). Protein carbonyl levels were significantly lower in the patient group (p < 0.001). The results show that the balance between oxidant and anti-oxidants was disrupted and the oxidative stress increased in melasma. These results improve the understanding of etiology-pathogenesis of the disease and its treatment.

[Effect of a hypocaloric diet in the oxidative stress in obese subjects without prescription of exercise and antioxidants].

PubMed

Gutiérrez, Liliana; García, José R; Rincón, María de Jesús; Ceballos, Guillermo M; Olivares, Ivonne M

2015-07-06

Obesity is characterized by a generalized increase of adipose tissue, high production of adipocytokines and presence of oxidative systemic stress. The objective of this study was to evaluate the changes generated in the oxidative stress and anthropometric parameters in obese subjects by the prescription of a hypocaloric diet in combination with moderate aerobic exercise and supplementation with antioxidants. Oxidative damage was determined in the plasma from 30 normal weight and 30 obese subjects. Three groups of treatment were established: Hypocaloric diet (HD), HD plus moderate aerobic exercise (HDE) and HDE plus antioxidants (DHEA). Biomarkers of oxidative stress (thiobarbituric acid reactive substances [TBARS], carbonyl groups, dityrosine) and anthropometric parameters were determined. Higher values of biomarkers of oxidative damage were observed in obese (TBARS 13.74 ± 1.2 μM; carbonyl groups 0.89 ± 0.04 nmol of osazone/mg of protein; dityrosine 478.9 ± 27.4 RFU/mg of protein) in comparison to normal weight subjects (TBARS 7.08 ± 0.8 μM; carbonyl groups 0.65 ± 0.04 nmol of osazone/mg of protein; dityrosine 126.3 ± 12.6 RFU/mg of protein), thus showing the presence of an oxidative damage. The prescription of HD decreased the oxidative damage and anthropometric parameters in the obese subjects. We did not observe additional benefit effects on these determinations with HDE or HDEA treatments. We demonstrated that an HD decreases the oxidative damage in obese subjects. Oxidative stress is an important factor in the development of comorbidity in obesity. Therefore, the prescription of a HD could be a key issue in the treatment of the disease. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

High-salt in addition to high-fat diet may enhance inflammation and fibrosis in liver steatosis induced by oxidative stress and dyslipidemia in mice.

PubMed

Uetake, Yuzaburo; Ikeda, Hitoshi; Irie, Rie; Tejima, Kazuaki; Matsui, Hiromitsu; Ogura, Sayoko; Wang, Hong; Mu, ShengYu; Hirohama, Daigoro; Ando, Katsuyuki; Sawamura, Tatsuya; Yatomi, Yutaka; Fujita, Toshiro; Shimosawa, Tatsuo

2015-02-13

It is widely known that salt is an accelerating factor for the progression of metabolic syndrome and causes cardiovascular diseases, most likely due to its pro-oxidant properties. We hypothesized that excessive salt intake also facilitates the development of nonalcoholic steatohepatitis (NASH), which is frequently associated with metabolic syndrome. We examined the exacerbating effect of high-salt diet on high-fat diet-induced liver injury in a susceptible model to oxidative stress, apoE knockout and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transgenic mice. High-salt diet led to NASH in high-fat diet-fed LOX-1 transgenic/apoE knockout mice without affecting high-fat diet-induced dyslipidemia or hepatic triglyceride accumulation. Additionally, a high-salt and high-fat diet stimulated oxidative stress production and inflammatory reaction to a greater extent than did a high-fat diet in the liver of LOX-1 transgenic/apoE knockout mice. We demonstrated that high-salt diet exacerbated NASH in high-fat diet-fed LOX-1 transgenic /apoE knockout mice and that this effect was associated with the stimulation of oxidative and inflammatory processes; this is the first study to suggest the important role of excessive salt intake in the development of NASH.

The Role of Thyroid Hormones as Inductors of Oxidative Stress and Neurodegeneration

PubMed Central

Villanueva, I.; Alva-Sánchez, C.; Pacheco-Rosado, J.

2013-01-01

Reactive oxygen species (ROS) are oxidizing agents amply implicated in tissue damage. ROS production is inevitably linked to ATP synthesis in most cells, and the rate of production is related to the rate of cell respiration. Multiple antioxidant mechanisms limit ROS dispersion and interaction with cell components, but, when the balance between ROS production and scavenging is lost, oxidative damage develops. Many traits of aging are related to oxidative damage by ROS, including neurodegenerative diseases. Thyroid hormones (THs) are a major factor controlling metabolic and respiratory rates in virtually all cell types in mammals. The general metabolic effect of THs is a relative acceleration of the basal metabolism that includes an increase of the rate of both catabolic and anabolic reactions. THs are related to oxidative stress not only by their stimulation of metabolism but also by their effects on antioxidant mechanisms. Thyroid dysfunction increases with age, so changes in THs levels in the elderly could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear. In this review, we analyze the participation of thyroid hormones on ROS production and oxidative stress, and the way the changes in thyroid status in aging are involved in neurodegenerative diseases. PMID:24386502

Attenuation of oxidative and nitrosative stress in cortical area associates with antidepressant-like effects of tropisetron in male mice following social isolation stress.

PubMed

Haj-Mirzaian, Arya; Amiri, Shayan; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Kordjazy, Nastaran; Olson, Carl O; Rastegar, Mojgan; Naserzadeh, Parvaneh; Marzban, Hassan; Dehpour, Ahmad Reza; Hosseini, Mir-Jamal; Samiei, Elika; Mehr, Shahram Ejtemaei

2016-06-01

Tropisetron, a 5-HT3 receptor antagonist widely used as an antiemetic, has been reported to have positive effects on mood disorders. Adolescence is a critical period during the development of brain, where exposure to chronic stress during this time is highly associated with the development of depression. In this study, we showed that 4 weeks of juvenile social isolation stress (SIS) provoked depressive-like behaviors in male mice, which was associated with disruption of mitochondrial function and nitric oxide overproduction in the cortical areas. In this study, tropisetron (5mg/kg) reversed the negative behavioral effects of SIS in male mice. We found that the effects of tropisetron were mediated through mitigating the negative activity of inducible nitric oxide synthase (iNOS) on mitochondrial activity. Administration of aminoguanidine (specific iNOS inhibitor, 20mg/kg) augmented the protective effects of tropisetron (1mg/kg) on SIS. Furthermore, l-arginine (nitric oxide precursor, 100mg/kg) abolished the positive effects of tropisetron. These results have increased our knowledge on the pivotal role of mitochondrial function in the pathophysiology of depression, and highlighted the role of 5-HT3 receptors in psychosocial stress response during adolescence. Finally, we observed that tropisetron alleviated the mitochondrial dysfunction through decreased nitrergic system activity in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeting the Transcription Factor Nrf2 to Ameliorate Oxidative Stress and Inflammation in Chronic Kidney Disease

PubMed Central

Ruiz, Stacey; Pergola, Pablo E.; Zager, Richard A.; Vaziri, Nosratola D.

2012-01-01

Oxidative stress and inflammation are mediators in the development and progression of chronic kidney disease (CKD) and its complications, and they are inseparably linked as each begets and amplifies the other. CKD-associated oxidative stress is due to increased production of reactive oxygen species (ROS) and diminished antioxidant capacity. The latter is largely caused by impaired activation of Nrf2, the transcription factor that regulates genes encoding antioxidant and detoxifying molecules. Protective effects of Nrf2 are evidenced by amelioration of oxidative stress, inflammation, and kidney disease in response to natural Nrf2 activators in animal models, while Nrf2 deletion amplifies these pathogenic pathways and leads to autoimmune nephritis. Given the role of impaired Nrf2 activity in CKD-induced oxidative stress and inflammation, interventions aimed at restoring Nrf2 may be effective in retarding CKD progression. Clinical trials of the potent Nrf2 activator bardoxolone methyl showed significant improvement in renal function in CKD patients with type 2 diabetes. Results of the ongoing BEACON trial investigating the effect of this drug on time to end-stage renal disease or cardiovascular death will help further characterize the efficacy of Nrf2 pharmacological modulation in CKD. This article provides an overview of the role of impaired Nrf2 activity in the pathogenesis of CKD-associated oxidative stress and inflammation and the potential utility of targeting Nrf2 in the treatment of CKD. PMID:23325084

Oxidative stress markers and genetic polymorphisms of glutathione S-transferase T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos, Nigeria.

PubMed

Oshodi, Y; Ojewunmi, O; Oshodi, T A; Ijarogbe, G T; Ogun, O C; Aina, O F; Lesi, Fea

2017-09-01

The role of oxidative stress has been identified in the development of autism spectrum disorder (ASD), and polymorphisms of glutathione S-transferase have been associated with some diseases linked to oxidative stress. Hence, we evaluated the serum levels of oxidative stress markers and investigated genetic polymorphisms of glutathione S-transferase associated with autism. Forty-two children clinically diagnosed with ASD using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and a clinical interview were included in the study. Twenty-three age-matched controls without any known genetic/developmental disorder were also recruited. Oxidative stress markers along with the genetic polymorphisms of glutathione S-transferase were determined. Reduced glutathione in ASD patients was significantly lower than the control (P = 0.008), whereas other oxidative stress markers measured were not significantly different in both the control and case populations. The frequencies of GSTT1 and GSTM1 null genotypes were lower among the controls compared with the cases, however, no association risk was observed. The observed risk of carrying Val/Val genotype among the cases was approximately six times that of the controls. Individuals with ASD showed a significant diminished level of reduced glutathione, however, the distribution of GSTT1, GSTM1, and GSTP1 polymorphisms was not found to be associated with autism in this study population.

[Fructose as a factor of Carbonyl and oxidative stress development and accelerated aging in the yeast Saccharomyces].

PubMed

Lozins'ka, L M; Semchyshyn, G M

2011-01-01

Excessive and prolonged consumption of fructose may lead to the development of metabolic disorders. However, the mechanisms of disturbances are still discussed. In the present work, the budding yeast Saccharomyces cerevisiae has been used as a model to compare the effects of prolonged consumption of different concentrations of glucose and fructose on certain physiology-biochemical parameters of eukaryotes. It has been shown that the yeast growth, their metabolic activity, intracellular level of glycogen and oxidized proteins were higher in cells grown on fructose. The observation is consistent with the data on a higher in vitro ability of fructose than glucose to initiate glycation which products of which are highly reactive a-dicarbonyl compounds and activated oxygen forms. Thus the intensity of carbonyl and oxidative stress is higher in cells grown on fructose. This can explain a higher rate of aging of yeast consuming fructose as a source of carbon and energy as compared to cells growing on glucose. However, carbohydrate restriction used in this study ham- pered the accumulation of glycogen and oxidized proteins and did not reveal any difference between markers of aging and carbonyl and oxidative stress in yeast grown on glucose and fructose.

Postprandial effects of wine consumption on lipids and oxidative stress biomarkers.

PubMed

Covas, M I; Konstantinidou, V; Mysytaki, E; Fitó, M; Weinbrenner, T; De La Torre, R; Farré-Albadalejo, M; Lamuela-Raventós, R

2003-01-01

Postprandial lipemia has been recognized as a risk factor for atherosclerosis development. Consuming meals with suitable sources of antioxidants such as red wine reduces postprandial oxidative stress. However, information about the postprandial effects of wine ingestion outside meals on lipids and on in vivo low-density lipoprotein (LDL) oxidation in humans is scarce. The aim of this study was to investigate postprandial changes in lipids and in vivo LDL oxidation after moderate (250 ml) red wine ingestion, before and after sustained wine consumption of 250 ml/day for 4 days. After 4 days of sustained wine consumption a decrease in the LDL/high-density lipoprotein cholesterol ratio was observed after wine ingestion (p = 0.026). On day 4, a decrease in oxidized LDL levels and an increase in the antioxidant enzyme glutathione peroxidase activity (p = 0.025) were observed after wine ingestion. Our results show that consumption of red wine at moderate doses outside meals does not promote oxidative stress. Daily consumption of moderate doses of red wine can improve postprandial lipid profile and oxidative status when wine is ingested outside meals.

Structure and function of large arteries in hypertension in relation to oxidative stress markers.

PubMed

Klima, Łukasz; Kawecka-Jaszcz, Kalina; Stolarz-Skrzypek, Katarzyna; Menne, Jan; Fijorek, Kamil; Olszanecka, Agnieszka; Wojciechowska, Wiktoria; Bilo, Grzegorz; Czarnecka, Danuta

2013-01-01

The relationship between hypertension and oxidative stress remains unexplained. Nevertheless, it is well established that reactive oxygen species have an influence on the arterial wall, endothelial function and therefore determine blood pressure. The evaluation of selected oxidative stress markers in hypertensive patients and an assessment of the relationship between oxidative stress markers and the arterial structure and function. We also aimed to investigate whether the influence of oxidative stress on remodelling of arteries, their structural and functional changes is independent of hypertension or is related to hypertension. Altogether 217 subjects (114 female, 103 male) were enrolled from hypertensive families. The mean age was 45.5 ± 16 years, and the group included 155 hypertensives. In every subject, the pulse wave velocity and intima-media thickness (IMT) in carotid arteries were measured as well as selected oxidative stress markers such as asymmetric dimethylarginin (ADMA), symmetric dimethylarginin (SDMA), advanced oxidation protein products (AOPP) and oxidised low density lipoproteins (ox-LDL). The results of multivariate analysis show that in hypertensive patients: the ADMA level increased with increasing peripheral pulse pressure (b = 0.003; p < 0.001), and AOPP was related to higher carotid IMT (b = 0.91; p = 0.036). In normotensive subjects, the following associations were found: between ADMA and central pulse pressure (b = 0.006; p = 0.008), between SDMA and the peripheral augmentation index (b = -0.03; p = 0.014), between AOPP and the peripheral augmentation index (b = 0.011; p = 0.04), and between ox-LDL/LDL ratio and the peripheral augmentation index (b = -0.025; p = 0.004). The SDMA/ADMA ratio was associated with estimated glomerular filtration rate in both groups (b = -0.0061; p < 0.0001 and b = -0.005; p < 0.017, respectively). In hypertensives, we observed a relation with peripheral pulse pressure (b = -0.0067; p = 0.0143). Moreover, in normotensives there was an association between the SDMA/ADMA ratio and uric acid (b = 1.3629; p = 0.046). We found that the influence of oxidative stress on the structure and function of large arteries was independent of hypertension. Therefore oxidative stress may play a significant role in the development of arterial stiffness. Higher oxidative stress is associated with more advanced arterial remodelling in hypertension.

Oxidative Stressors Modify the Response of Streptococcus mutans to Its Competence Signal Peptides

PubMed Central

De Furio, Matthew; Ahn, Sang Joon

2017-01-01

ABSTRACT The dental caries pathogen Streptococcus mutans is continually exposed to several types of stress in the oral biofilm environment. Oxidative stress generated by reactive oxygen species has a major impact on the establishment, persistence, and virulence of S. mutans. Here, we combined fluorescent reporter-promoter fusions with single-cell imaging to study the effects of reactive oxygen species on activation of genetic competence in S. mutans. Exposure to paraquat, which generates superoxide anion, produced a qualitatively different effect on activation of expression of the gene for the master competence regulator, ComX, than did treatment with hydrogen peroxide (H2O2), which can yield hydroxyl radical. Paraquat suppressed peptide-mediated induction of comX in a progressive and cumulative fashion, whereas the response to H2O2 displayed a strong threshold behavior. Low concentrations of H2O2 had little effect on induction of comX or the bacteriocin gene cipB, but expression of these genes declined sharply if extracellular H2O2 exceeded a threshold concentration. These effects were not due to decreased reporter gene fluorescence. Two different threshold concentrations were observed in the response to H2O2, depending on the gene promoter that was analyzed and the pathway by which the competence regulon was stimulated. The results show that paraquat and H2O2 affect the S. mutans competence signaling pathway differently, and that some portions of the competence signaling pathway are more sensitive to oxidative stress than others. IMPORTANCE Streptococcus mutans inhabits the oral biofilm, where it plays an important role in the development of dental caries. Environmental stresses such as oxidative stress influence the growth of S. mutans and its important virulence-associated behaviors, such as genetic competence. S. mutans competence development is a complex behavior that involves two different signaling peptides and can exhibit cell-to-cell heterogeneity. Although oxidative stress is known to influence S. mutans competence, it is not understood how oxidative stress interacts with the peptide signaling or affects heterogeneity. In this study, we used fluorescent reporters to probe the effect of reactive oxygen species on competence signaling at the single-cell level. Our data show that different reactive oxygen species have different effects on S. mutans competence, and that some portions of the signaling pathway are more acutely sensitive to oxidative stress than others. PMID:28887419

Action of 6-amino-3-pyridinols as novel antioxidants against free radicals and oxidative stress in solution, plasma, and cultured cells.

PubMed

Omata, Yo; Saito, Yoshiro; Yoshida, Yasukazu; Jeong, Byeong-Seon; Serwa, Remigiusz; Nam, Tae-gyu; Porter, Ned A; Niki, Etsuo

2010-05-15

Free radical-mediated lipid peroxidation has been implicated in the pathogenesis of various diseases. Lipid peroxidation products are cytotoxic and they modify proteins and DNA bases, leading eventually to degenerative disorders. Various synthetic antioxidants have been developed and assessed for their capacity to inhibit lipid peroxidation and oxidative stress induced by free radicals. In this study, the capacity of novel 6-amino-2,4,5-trimethyl-3-pyridinols for scavenging peroxyl radicals, inhibiting plasma lipid peroxidation in vitro, and preventing cytotoxicity induced by glutamate, 6-hydroxydopamine, 1-methyl-4-phenylpyridium (MPP(+) ), and hydroperoxyoctadecadienoic acid was assessed. It was found that they exerted higher reactivity toward peroxyl radicals and more potent activity for inhibiting the above oxidative stress than alpha-tocopherol, the most potent natural antioxidant, except against the cytotoxicity induced by MPP(+). These results suggest that the novel 6-amino-3-pyridinols may be potent antioxidants against oxidative stress. Copyright 2010 Elsevier Inc. All rights reserved.

Hydrogen Sulfide Regulates Salt Tolerance in Rice by Maintaining Na+/K+ Balance, Mineral Homeostasis and Oxidative Metabolism Under Excessive Salt Stress

PubMed Central

Mostofa, Mohammad G.; Saegusa, Daisuke; Fujita, Masayuki; Tran, Lam-Son Phan

2015-01-01

Being a salt sensitive crop, rice growth and development are frequently affected by soil salinity. Hydrogen sulfide (H2S) has been recently explored as an important priming agent regulating diverse physiological processes of plant growth and development. Despite its enormous prospects in plant systems, the role of H2S in plant stress tolerance is still elusive. Here, a combined pharmacological, physiological and biochemical approach was executed aiming to examine the possible mechanism of H2S in enhancement of rice salt stress tolerance. We showed that pretreating rice plants with H2S donor sodium bisulfide (NaHS) clearly improved, but application of H2S scavenger hypotaurine with NaHS decreased growth and biomass-related parameters under salt stress. NaHS-pretreated salt-stressed plants exhibited increased chlorophyll, carotenoid and soluble protein contents, as well as suppressed accumulation of reactive oxygen species (ROS), contributing to oxidative damage protection. The protective mechanism of H2S against oxidative stress was correlated with the elevated levels of ascorbic acid, glutathione, redox states, and the enhanced activities of ROS- and methylglyoxal-detoxifying enzymes. Notably, the ability to decrease the uptake of Na+ and the Na+/K+ ratio, as well as to balance mineral contents indicated a role of H2S in ion homeostasis under salt stress. Altogether, our results highlight that modulation of the level of endogenous H2S genetically or exogenously could be employed to attain better growth and development of rice, and perhaps other crops, under salt stress. Furthermore, our study reveals the importance of the implication of gasotransmitters like H2S for the management of salt stress, thus assisting rice plants to adapt to adverse environmental changes. PMID:26734015

The role of the RB tumour suppressor pathway in oxidative stress responses in the haematopoietic system

PubMed Central

Macleod, Kay F.

2010-01-01

Exposure to pro-oxidants and defects in the repair of oxidative base damage are associated with disease and ageing and also contribute to the development of anaemia, bone marrow failure and haematopoietic malignancies. This Review assesses emerging data indicative of a specific role for the RB tumour suppressor pathway in the response of the haematopoietic system to oxidative stress. This is mediated through signalling pathways that involve DNA damage sensors, forkhead box O (Foxo) transcription factors and p38 mitogen-activated protein kinases and has downstream consequences for cell cycle progression, antioxidant capacity, mitochondrial mass and cellular metabolism. PMID:18800074

Defining the Relationship Between Biomarkers of Oxidation and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Lee, Stuart M. C.; Stenger, Michael B.; Smith, Scott M.; Zwart, Sara R.

2016-01-01

Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative damage and inflammation can accelerate the development of atherosclerosis.

Long-chain omega 3 fatty acids: molecular bases of potential antioxidant actions.

PubMed

Giordano, Elena; Visioli, Francesco

2014-01-01

Several lines of investigation are being developed to assess the impact of polyunsaturated fatty acids, namely those of the omega 3 series, intake on oxidative stress. Keeping in mind that there might be a dose-response relation, in vivo and in vitro data strongly suggest that omega 3 fatty acids might act as anti- rather than pro-oxidant in several cells such as vascular cells, hence diminishing inflammation, oxidative stress, and, in turn, the risk of atherosclerosis and degenerative disorders such as cardiovascular disease. © 2013 Published by Elsevier Ltd.

Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage.

PubMed

Padín-Irizarry, Vivian; Colón-Lorenzo, Emilee E; Vega-Rodríguez, Joel; Castro, María Del R; González-Méndez, Ricardo; Ayala-Peña, Sylvette; Serrano, Adelfa E

2016-06-01

Plasmodium parasites are exposed to endogenous and exogenous oxidative stress during their complex life cycle. To minimize oxidative damage, the parasites use glutathione (GSH) and thioredoxin (Trx) as primary antioxidants. We previously showed that disruption of the Plasmodium berghei gamma-glutamylcysteine synthetase (pbggcs-ko) or the glutathione reductase (pbgr-ko) genes resulted in a significant reduction of GSH in intraerythrocytic stages, and a defect in growth in the pbggcs-ko parasites. In this report, time course experiments of parasite intraerythrocytic development and morphological studies showed a growth delay during the ring to schizont progression. Morphological analysis shows a significant reduction in size (diameter) of trophozoites and schizonts with increased number of cytoplasmic vacuoles in the pbggcs-ko parasites in comparison to the wild type (WT). Furthermore, the pbggcs-ko mutants exhibited an impaired response to oxidative stress and increased levels of nuclear DNA (nDNA) damage. Reduced GSH levels did not result in mitochondrial DNA (mtDNA) damage or protein carbonylations in neither pbggcs-ko nor pbgr-ko parasites. In addition, the pbggcs-ko mutant parasites showed an increase in mRNA expression of genes involved in oxidative stress detoxification and DNA synthesis, suggesting a potential compensatory mechanism to allow for parasite proliferation. These results reveal that low GSH levels affect parasite development through the impairment of oxidative stress reduction systems and damage to the nDNA. Our studies provide new insights into the role of the GSH antioxidant system in the intraerythrocytic development of Plasmodium parasites, with potential translation into novel pharmacological interventions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

VeA is associated with the response to oxidative stress in the aflatoxin producer Aspergillus flavus

USDA-ARS?s Scientific Manuscript database

Survival of fungal species depends on the ability of these organisms to respond to environmental stresses. Osmotic stress or high levels of reactive oxygen species (ROS) can cause stress in fungi resulting in growth inhibition. Both eukaryotic and prokaryotic cells have developed numerous mechanisms...

Oxidative stress and production of bioactive monoterpene indole alkaloids: biotechnological implications.

PubMed

Matsuura, Hélio Nitta; Rau, Mariana Ritter; Fett-Neto, Arthur Germano

2014-02-01

Monoterpene indole alkaloids (MIAs) encompass plant natural products with important pharmacological relevance. They include the anti-tumoral MIAs found in Catharanthus roseus and Camptotheca acuminata. The often low yields of bioactive alkaloids in plants has prompted research to identify the factors regulating MIA production. Oxidative stress is a general response associated with biotic and abiotic stresses leading to several secondary responses, including elicitation of MIA production. These changes in secondary metabolism may take place directly or via second messengers, such as Ca(2+) and reactive oxygen species (ROS). H2O2 is the main ROS that participates in MIA biosynthesis. This review analyzes the links between oxidative stress, elicitation of bioactive MIA production and their potential roles in antioxidant defense, as well as exploring the implications to developing biotechnological strategies relevant for alkaloid supply.

Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats.

PubMed

Salim, Samina; Sarraj, Nada; Taneja, Manish; Saha, Kaustuv; Tejada-Simon, Maria Victoria; Chugh, Gaurav

2010-04-02

Recent work has suggested correlation of oxidative stress with anxiety-like behavior. There also is evidence for anxiolytic effects of physical exercise. However, a direct role of oxidative stress in anxiety is not clear and a protective role of physical exercise in oxidative stress-mediated anxiety has never been addressed. In this study, we have utilized rats to test direct involvement of oxidative stress with anxiety-like behavior and have identified oxidative stress mechanisms likely involved in anxiolytic effects of physical exercise. Intraperitoneal injections at non-toxic dose of l-buthionine-(S,R)-sulfoximine (BSO), an agent that increases oxidative stress markers, increased anxiety-like behavior of rats compared to vehicle-treated control rats. Prior 2 weeks treatment with the antioxidant, tempol attenuated BSO-induced anxiety-like behavior of rats suggesting a role of oxidative stress in this phenomenon. Moreover, moderate treadmill exercise prevented BSO-induced anxiety-like behavior of rats and also prevented BSO-mediated increase in oxidative stress markers in serum, urine and brain tissue homogenates from hippocampus, amygdala and locus coeruleus. Thus increasing oxidative stress increases anxiety-like behavior of rats. Moreover, antioxidant or treadmill exercise training both reduce oxidative stress in the rat brain regions implicated in anxiety response and prevent anxiety-like behavior of rats. Published by Elsevier B.V.

Resveratrol Prevents the Development of Hypertension Programmed by Maternal Plus Post-Weaning High-Fructose Consumption Through Modulation of Oxidative Stress, Nutrient-Sensing Signals, and Gut Microbiota.

PubMed

Tain, You-Lin; Lee, Wei-Chia; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

2018-04-30

High-fructose (HF) intake, oxidative stress, nutrient-sensing signals, and gut microbiota dysbiosis are closely related to the development of hypertension. We investigated whether resveratrol can prevent hypertension induced by maternal plus post-weaning HF diets in adult offspring via the above-mentioned mechanisms. Female Sprague-Dawley rats received either a normal (ND) or 60% high-fructose (HF) diet during gestation and lactation. Male offspring were assigned to five groups (maternal diet/post-weaning diet; n = 8/group): ND/ND, ND/HF, HF/ND, HF/HF, and HF/HF+ Resveratrol. Resveratrol (50 mg/L) was administered in drinking water from weaning to three months of age. We found that HF/HF induced hypertension in adult offspring. Maternal HF diet altered gut microbiota composition in adult offspring, including decreasing the abundance of genera Bacteroides, Dysgonomonas, and Turicibacter, while increasing phylum Verrucomicrobia and Akkermansia muciniphila. Additionally, HF/HF diets increased oxidative stress and decreased renal mRNA expression of Prkaa2, Prkag2, Ppara, Pparb, Ppargc1a, and Sirt4. Resveratrol reduced renal oxidative stress, activated nutrient-sensing signals, modulated gut microbiota, and prevented associated HF/HF-induced programmed hypertension. Targeting oxidative stress, nutrient-sensing signals, and gut microbiota by resveratrol might be a useful therapeutic strategy for treatment of hypertension induced by excessive consumption of fructose in the adult rat offspring. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features.

PubMed

Ghezzo, Alessandro; Visconti, Paola; Abruzzo, Provvidenza M; Bolotta, Alessandra; Ferreri, Carla; Gobbi, Giuseppe; Malisardi, Gemma; Manfredini, Stefano; Marini, Marina; Nanetti, Laura; Pipitone, Emanuela; Raffaelli, Francesca; Resca, Federica; Vignini, Arianna; Mazzanti, Laura

2013-01-01

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na(+)/K(+)-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD.

Opposite effects of catalase and MnSOD ectopic expression on stress induced defects and mortality in the desmin deficient cardiomyopathy model.

PubMed

Rapti, Kleopatra; Diokmetzidou, Antigoni; Kloukina, Ismini; Milner, Derek J; Varela, Aimilia; Davos, Constantinos H; Capetanaki, Yassemi

2017-09-01

Oxidative stress has been linked strongly to cell death and cardiac remodeling processes, all hallmarks of heart failure. Mice deficient for desmin (des-/-), the major muscle specific intermediate filament protein, develop dilated cardiomyopathy and heart failure characterized by mitochondrial defects and cardiomyocyte death. The cellular and biochemical alterations in the hearts of these mice strongly suggest that oxidative stress is one of the mechanisms contributing to the pathogenesis of the phenotype. Recently, we showed that indeed the desmin deficient cardiomyocytes are under increased oxidative stress. In order to verify these findings in vivo, we generated transgenic animals overexpressing SOD2 (MnSOD) and/or catalase in the heart and crossed them with des-/- mice, thus allowing us to evaluate the contribution of oxidative injury in inherited cardiomyopathies, as well as the therapeutic potential of antioxidant strategies. Moderate MnSOD and/or catalase overexpression in des-/- hearts leads to a marked decrease in intracellular reactive oxygen species (ROS), ameliorates mitochondrial and other ultrastructural defects, minimizes myocardial degeneration and leads to a significant improvement of cardiac function. Importantly, catalase overexpression increased the 50% survival rate of des-/- mice in an obligatory exercise to 100%. In contrast, MnSOD overexpression enhanced the lethality of des-/- mice, underscoring the importance of a fine balanced cellular redox status. Overall, the present study supports the contribution of oxidative stress in the development of des-/- cardiomyopathy and points to a well-considered antioxidant treatment as therapeutic for cardiomyopathies. Copyright © 2017 Elsevier Inc. All rights reserved.

A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn.

PubMed

Ramírez-Vélez, Robinson; Romero, Miryam; Echeverri, Isabella; Ortega, José Guillermo; Mosquera, Mildrey; Salazar, Blanca; Girón, Sandra Lorena; Saldarriaga, Wilmar; Aguilar de Plata, Ana Cecilia; Mateus, Julio Cesar

2011-02-28

Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn. 320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions. Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population. NCT00872365.

Development of the NBT assay as a marker of sperm oxidative stress.

PubMed

Tunc, Ozlem; Thompson, Jeremy; Tremellen, Kelton

2010-02-01

Oxidative stress is a well-established cause of male infertility, with reactive oxygen species (ROS) causing infertility principally by impairing sperm motility and DNA integrity. Currently, most clinics do not test their infertile patients for the presence of oxidative stress because the available tests are expensive or difficult to perform. As antioxidant therapy may improve sperm DNA integrity and pregnancy outcomes, it has become apparent that there is an unmet clinical need for an inexpensive and easy-to-perform assay to identify sperm oxidative stress. The aim of this study was to develop a standardized protocol for performing a photometric nitro blue tetrazolium (NBT) assay for the measurement of seminal ROS production via production of coloured formazan, whilst correlating these results with impaired sperm function (motility and DNA integrity). Semen samples from 21 fertile and 36 male aetiology infertile men were assessed for ROS production (NBT assay), sperm DNA integrity (TUNEL), apoptosis (Annexin V) and sperm motility. Infertile men's semen contained on average fourfold higher levels of ROS than fertile men. The production of ROS by sperm was positively correlated with sperm DNA fragmentation and apoptosis, whilst being negatively correlated with sperm motility. Receiver-operating characteristic plot analysis established a cut-off point of 24 microg formazan/10(7) sperm having a sensitivity of 91.7% and a specificity of 81% for determining the fertility status of an individual. This study has been successful in establishing a standardized protocol for performing a photometric seminal NBT assay that has significant clinical utility in identifying men with impaired fertility because of oxidative stress.

Glucose fluctuation increased hepatocyte apoptosis under lipotoxicity and the involvement of mitochondrial permeability transition opening.

PubMed

Yin, Xueyao; Zheng, Fenping; Pan, Qianqian; Zhang, Saifei; Yu, Dan; Xu, Zhiye; Li, Hong

2015-12-01

Oxidative stress is considered to be an important factor in producing lethal hepatocyte injury associated with nonalcoholic fatty liver disease (NAFLD). Glucose fluctuation, more pronounced in patients with diabetes, has been recognized as an even stronger oxidative stress inducer than the sustained hyperglycemia. Here, we investigated the role of glucose variability in the development of the NAFLD based on hepatocyte apoptosis and possible mechanisms. To achieve this goal we studied C57BL/6J mice that were maintained on a high fat diet (HFD) and injected with glucose (3 g/kg) twice daily to induce intermittent high glucose (IHG). We also studied hepatic L02 cells incubated with palmitic acid (PA) to induce steatosis. The following experimental groups were compared: normal glucose (NG), sustained high glucose (SHG) and IHG with or without PA. We found that, although hepatic enzyme levels and liver lipid deposition were comparable between HFD mice injected with glucose or saline, the glucose injected mice displayed marked hepatocyte apoptosis and inflammation, accompanied by increased lipid peroxide in liver. In vitro, in the presence of PA, IHG increased L02 cell apoptosis and oxidative stress and produced pronounced mitochondrial dysfunction relative to the NG and SHG groups. Furthermore, treatment with the mitochondrial permeability transition (MPT) inhibitor, cyclosporin A (1.5 μmol/l), prevented mitochondrial dysfunction, oxidative stress and hepatocyte apoptosis. Our data suggests that IHG under lipotoxicity might contribute to the development of NAFLD by increasing oxidative stress and hepatocyte apoptosis via MPT and its related mitochondrial dysfunction. © 2015 Society for Endocrinology.

Plasma oxidative stress biomarkers and progesterone profiles in a dairy cow diagnosed with an ovarian follicular cyst.

PubMed

Talukder, S; Ingenhoff, L; Kerrisk, K L; Celi, P

2014-01-01

This study was conducted to examine the oxidative stress biomarkers in a cow diagnosed with a follicular cyst in her left ovary. Progesterone (P4) and plasma oxidative stress status was measured in 13 Holstein cows after synchronization of oestrus with controlled internal drug release (CIDR) and prostaglandinF2α (PGF2α) protocol. The presence and size of ovarian structures were monitored by transrectal ultrasound at 4 hourly intervals. Of the 13 cows, 12 were monitored until ovulation was detected and recorded, whereas one cow failed to ovulate and developed a follicular cyst. Oxidative stress biomarkers; reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP), oxidative stress index (OSI), glutathione (GSH), ceruloplasmin and advanced oxidation protein products (AOPP) were measured in the cystic cow and compared to those of the 12 ovulated cows and are referred to as higher or lower if they are outside the mean ± standard error of mean of those of ovulated cows. The cystic cow had lower ROMs and OSI between 36 and 84 h after PGF2α injection and at 9 h, from 36 to 60 h after PGF2α injection respectively. On the other hand, antioxidant (BAP and GSH) was higher in the cystic cow compared to her ovulated herd mates. The observed imbalance between oxidant and antioxidant might have disrupted the physiological events for ovulation to occur, leading to cystic ovarian disease.

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

PubMed Central

Peterson, Tina M.L.; Luckhart, Shirley

2008-01-01

Malaria parasite infection in anopheline mosquitoes induces nitrosative and oxidative stresses that limit parasite development, but also damage mosquito tissues in proximity to the response. Based on these observations, we proposed that cellular defenses in the mosquito may be induced to minimize self-damage. Specifically, we hypothesized that peroxiredoxins (Prxs), enzymes known to detoxify reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), protect mosquito cells. We identified an Anopheles stephensi 2-Cys Prx ortholog of Drosophila melanogaster Prx-4783, which protects fly cells against oxidative stresses. To assess function, AsPrx-4783 was overexpressed in D. melanogaster (S2) and in A. stephensi (MSQ43) cells and silenced in MSQ43 cells with RNA interference before treatment with various ROS and RNOS. Our data revealed that AsPrx-4783 and DmPrx-4783 differ in host cell protection and that AsPrx-4783 protects A. stephensi cells against stresses that are relevant to malaria parasite infection in vivo, namely nitric oxide (NO), hydrogen peroxide, nitroxyl, and peroxynitrite. Further, AsPrx-4783 expression is induced in the mosquito midgut by parasite infection at times associated with peak nitrosative and oxidative stresses. Hence, whereas the NO-mediated defense response is toxic to both host and parasite, AsPrx-4783 may shift the balance in favor of the mosquito. PMID:16540402

Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

PubMed

Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

2015-01-01

We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

Predicting disease onset in clinically healthy people

PubMed Central

2016-01-01

Virtually all human disease is induced by oxidative stress. Oxidative stress, which is caused by toxic environmental exposure, the presence of disease, lifestyle choices, stress, chronic inflammation or combinations of these, is responsible for most disease. Oxidative stress from all sources is additive and it is the total oxidative stress from all sources that induces the onset of most disease. Oxidative stress leads to lipid peroxidation, which in turn produces Malondialdehyde. Serum malondialdehyde level is an additive parameter resulting from all sources of oxidative stress and, therefore, is a reliable indicator of total oxidative stress which can be used to predict the onset of disease in clinically asymptomatic individuals and to suggest the need for treatment that can prevent much human disease. PMID:28652846

How Does the Macula Protect Itself from Oxidative Stress?

PubMed Central

Handa, James T.

2012-01-01

Oxidative stress has been hypothesized to contribute to the development of age-related macular degeneration (AMD), the most common cause of blindness in the United States. At present, there is no treatment for early disease. Reactive oxygen species (ROS) play a physiological role in the retinal pigment epithelium (RPE), a key cell type in this disease, but with excessive ROS, oxidative damage or excessive innate immune system activation can result. The RPE has developed a robust antioxidant system driven by the transcription factor Nrf2. Impaired Nrf2 signaling can lead to oxidative damage or activate the innate immune response, both of which can lead to RPE apoptosis, a defining change in AMD. Several mouse models simulating environmental stressors or targeting specific antioxidant enzymes such as superoxide dismutase or Nrf2, have simulated some of the features of AMD. While ROS are short-lived, oxidatively damaged molecules termed oxidation specific epitopes (OSEs), can be long-lived and a source of chronic stress that activates the innate immune system through pattern recognition receptors (PRRs). The macula accumulates a number of OSEs including carboxyethylpyrrole, malondialdehyde, 4-hydroxynonenal, and advanced glycation endproducts, as well as their respective neutralizing PRRs. Excessive accumulation of OSEs results in pathologic immune activation. For example, mice immunized with the carboxyethylpyrrole develop cardinal features of AMD. Regulating ROS in the RPE by modulating antioxidant systems or neutralizing OSEs through an appropriate innate immune response are potential modalities to treat or prevent early AMD. PMID:22503691

How does the macula protect itself from oxidative stress?

PubMed

Handa, James T

2012-08-01

Oxidative stress has been hypothesized to contribute to the development of age-related macular degeneration (AMD), the most common cause of blindness in the United States. At present, there is no treatment for early disease. Reactive oxygen species (ROS) play a physiological role in the retinal pigment epithelium (RPE), a key cell type in this disease, but with excessive ROS, oxidative damage or excessive innate immune system activation can result. The RPE has developed a robust antioxidant system driven by the transcription factor Nrf2. Impaired Nrf2 signaling can lead to oxidative damage or activate the innate immune response, both of which can lead to RPE apoptosis, a defining change in AMD. Several mouse models simulating environmental stressors or targeting specific antioxidant enzymes such as superoxide dismutase or Nrf2, have simulated some of the features of AMD. While ROS are short-lived, oxidatively damaged molecules termed oxidation specific epitopes (OSEs), can be long-lived and a source of chronic stress that activates the innate immune system through pattern recognition receptors (PRRs). The macula accumulates a number of OSEs including carboxyethylpyrrole, malondialdehyde, 4-hydroxynonenal, and advanced glycation endproducts, as well as their respective neutralizing PRRs. Excessive accumulation of OSEs results in pathologic immune activation. For example, mice immunized with the carboxyethylpyrrole develop cardinal features of AMD. Regulating ROS in the RPE by modulating antioxidant systems or neutralizing OSEs through an appropriate innate immune response are potential modalities to treat or prevent early AMD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Overexpression of a Medicago truncatula stress-associated protein gene (MtSAP1) leads to nitric oxide accumulation and confers osmotic and salt stress tolerance in transgenic tobacco.

PubMed

Charrier, Aurélie; Planchet, Elisabeth; Cerveau, Delphine; Gimeno-Gilles, Christine; Verdu, Isabelle; Limami, Anis M; Lelièvre, Eric

2012-08-01

The impact of Medicago truncatula stress-associated protein gene (MtSAP1) overexpression has been investigated in Nicotiana tabacum transgenic seedlings. Under optimal conditions, transgenic lines overexpressing MtSAP1 revealed better plant development and higher chlorophyll content as compared to wild type seedlings. Interestingly, transgenic lines showed a stronger accumulation of nitric oxide (NO), a signaling molecule involved in growth and development processes. This NO production seemed to be partially nitrate reductase dependent. Due to the fact that NO has been also reported to play a role in tolerance acquisition of plants to abiotic stresses, the responses of MtSAP1 overexpressors to osmotic and salt stress have been studied. Compared to the wild type, transgenic lines were less affected in their growth and development. Moreover, NO content in MtSAP1 overexpressors was always higher than that detected in wild seedlings under stress conditions. It seems that this better tolerance induced by MtSAP1 overexpression could be associated with this higher NO production that would enable seedlings to reach a high protection level to prepare them to cope with abiotic stresses.

Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.

PubMed

Plaisance, Valérie; Brajkovic, Saška; Tenenbaum, Mathie; Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

2016-01-01

Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment.

Protective Role of Intracellular Melatonin Against Oxidative Stress and UV Radiation in Saccharomyces cerevisiae.

PubMed

Bisquert, Ricardo; Muñiz-Calvo, Sara; Guillamón, José M

2018-01-01

Melatonin (Mel) is considered a potent natural antioxidant molecule given its free-radical scavenging ability. Its origin is traced back to the origin of aerobic life as early defense against oxidative stress and radiation. More complex signaling functions have been attributed to Mel as a result of evolution in different biological kingdoms, which comprise gene expression modulation, enzyme activity, and mitochondrial homeostasis regulation processes, among others. Since Mel production has been recently reported in wine yeast, we tested the protective effect of Mel on Saccharomyces cerevisiae against oxidative stress and UV light. As the optimal conditions for S. cerevisiae to synthesize Mel are still unknown, we developed an intracellular Mel-charging method to test its effect against stresses. To assess Mel's ability to protect S. cerevisiae from both stresses, we ran growth tests in liquid media and viability assays by colony count after Mel treatment, followed by stress. We also analyzed gene expression by qPCR on a selection of genes involved in stress protection in response to Mel treatment under oxidative stress and UV radiation. The viability in the Mel-treated cells after H 2 O 2 stress was up to 35% greater than for the untreated controls, while stress amelioration reached 40% for UVC light (254 nm). Mel-treated cells showed a significant shortened lag phase compared to the control cells under the stress and normal growth conditions. The gene expression analysis showed that Mel significantly modulated gene expression in the unstressed cells in the exponential growth phase, and also during various stress treatments.

The impact of levothyroxine sodium treatment on oxidative stress in Hashimoto's thyroiditis.

PubMed

Ates, Ihsan; Altay, Mustafa; Yilmaz, Fatma Meric; Topcuoglu, Canan; Yilmaz, Nisbet; Berker, Dilek; Guler, Serdar

2016-06-01

Although several studies reported increased oxidative stress in Hashimoto's thyroiditis (HT), the effect of levothyroxine treatment on oxidative status is not studied extensively. Therefore, we conducted this study to investigate the effects of levothyroxine replacement on oxidative stress in HT. Thirty-six patients recently diagnosed with HT-related hypothyroidism and 36 healthy controls were included in the study. Levothyroxine replacement was started to patients with hypothyroidism, and had been followed-up for 6 months. Mean basal serum total antioxidant status (TAS), total thiol, arylesterase, and paraoxonase 1 (PON1) levels were significantly lower, and serum total oxidant status (TOS) and oxidative stress index (OSI) were significantly higher in the patients with hypothyroid than the controls. In the hypothyroid group serum TAS, total thiol, arylesterase, and PON1 levels increased and serum TOS and OSI levels decreased significantly after levothyroxine treatment. Pretreatment serum TAS, total thiol, PON1, and arylesterase levels were positively correlated with free levothyroxine (fT4) and negatively correlated with thyroid-stimulating hormone (TSH), antithyroid peroxidase (anti-TPO), and antithyroglobulin (anti-TG) levels. Also, pretreatment serum TOS and OSI levels were negatively correlated with fT4 levels and positively correlated with TSH, anti-TPO, and anti-TG. We have also found that the fT4 and anti-TPO levels are independent predictors of the oxidative stress parameters in stepwise multivariable linear regression analysis. This study suggests that levothyroxine replacement decreases oxidant status and increases antioxidant status following the 6 months of levothyroxine replacement in hypothyroidism that develops in accordance with the HT. © 2016 European Society of Endocrinology.

Local stress determination in chromia-former thanks to micro-Raman spectroscopy: A way to investigate spontaneous delamination processes

NASA Astrophysics Data System (ADS)

Guerain, M.; Goudeau, P.; Panicaud, B.; Grosseau-Poussard, J. L.

2013-02-01

Spontaneous delamination process for α-Cr2O3 thermal oxide films growing on NiCr-30 alloys is studied thanks to micro Raman spectroscopy. In particular, stress maps are performed through and around buckles developed on chromia films. Depending on the cooling rate at the end of the oxidation process, different buckle types appear which are investigated. Associated residual stress distribution clearly evidences the stress release field. In addition, geometrical features are determined for the different buckle types, and from comparison with modelling describing buckle formation and propagation, it is possible to get the interface toughness distribution.

Characteristic of the Oxidative Stress in Blood of Patients in Dependence of Community-Acquired Pneumonia Severity.

PubMed

Muravlyova, Larissa; Molotov-Luchankiy, Vilen; Bakirova, Ryszhan; Klyuyev, Dmitriy; Demidchik, Ludmila; Lee, Valentina

2016-03-15

At the present time the alternation of the oxidative metabolism is considered as one of the leading pathogenic mechanisms in the development and progression of community-acquired pneumonia (CAP). However the nature and direction of the oxidative protein changes in CAP patient's blood had been almost unexplored. To define oxidative and modified proteins in erythrocytes and blood plasma of CAP patients. Blood plasma and erythrocytes obtained from: 42 patients with moderate severity pneumonia, 12 patients with grave severity pneumonia and 32 healthy volunteers. Content of advanced oxidation protein products, malondialdehyde and reactive carbonyl derivatives were estimated as indicators of the oxidative stress and oxidative damage of proteins. In patients with grave severity the level of oxidative proteins and MDA in erythrocytes exceeded both: control values and similar meanings in CAP patients with moderate severity. The further growth of MDA in this group patients' blood plasma was observed, but the level of oxidative proteins decreased in comparison with those in CAP patients with moderate severity. To sum up, our derived data show, that injury of erythrocytes' redox-status and blood plasma components plays an essential role in development and progression CAP.

Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy.

PubMed

Akolkar, Gauri; da Silva Dias, Danielle; Ayyappan, Prathapan; Bagchi, Ashim K; Jassal, Davinder S; Salemi, Vera Maria Cury; Irigoyen, Maria Claudia; De Angelis, Katia; Singal, Pawan K

2017-10-01

Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins. Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and caused structural damage. These changes were associated with a myocardial increase in reactive oxygen species, reduction in antioxidant enzyme activities, increased expression of apoptotic proteins, and inflammation. Dox also caused an increase in the expression of proapoptotic proteins Bax, Bnip-3, Bak, and caspase-3. An increase in oxidative/nitrosative stress attributable to Dox was indicated by an increase in superoxide, protein carbonyl formation, lipid peroxidation, nitric oxide (NO), NO synthase (NOS) activity, protein nitrosylation, and inducible NOS protein expression. Dox increased the levels of cardiac proinflammatory cytokines TNF-α, IL-1β, and IL-6, whereas the expression of Vit C transporter proteins (sodium-ascorbate cotransporter 2 and glucose transporter 4) was reduced. Prophylactic and concurrent treatment with Vit C prevented all these changes and improved survival in the Vit C + Dox group. Vit C also improved Dox-mediated systolic and diastolic dysfunctions and structural damage. These results suggest a cardioprotective role of Vit C in Dox-induced cardiomyopathy by reducing oxidative/nitrosative stress, inflammation, and apoptosis, as well as improving Vit C transporter proteins. NEW & NOTEWORTHY This in vivo study provides novel data that vitamin C improves cardiac structure and function in doxorubicin-induced cardiomyopathy by reducing oxidative/nitrosative stress, apoptosis, and inflammation along with upregulation of cardiac vitamin C transporter proteins. The latter may have a crucial role in improving antioxidant status in this cardiomyopathy. Copyright © 2017 the American Physiological Society.

Characterization of sakA gene from pathogenic dimorphic fungus Penicillium marneffei.

PubMed

Nimmanee, Panjaphorn; Woo, Patrick C Y; Kummasook, Aksarakorn; Vanittanakom, Nongnuch

2015-01-01

Eukaryotes utilize stress activated protein kinase (SAPK) pathways to adapt to environmental stress, including heat, osmotic, oxidative or nutrient stresses. Penicillium marneffei (Talaromyces marneffei), the dimorphic pathogenic fungus that can cause disseminated mycosis in HIV-infected patients, has to encounter various types of stresses both outside and inside host cells. However, the strategies used by this fungus in response to these stresses are still unclear. In this report, the stress-activated kinase (sakA) gene of P. marneffei was characterized and the roles of this gene on various stress conditions were studied. The sakA gene deletion mutant was constructed using the split marker method. The phenotypes and sensitivities to varieties of stresses, including osmotic, oxidative, heat and cell wall stresses of the deletion mutant were compared with the wild type and the sakA complemented strains. Results demonstrated that the P. marneffei sakA gene encoded a putative protein containing TXY phosphorylation lip found in the stress high osmolarity glycerol 1 (Hog1)/Spc1/p38 MAPK family, and that this gene was involved not only in tolerance against oxidative and heat stresses, but also played a role in asexual development, chitin deposition, yeast cell generation in vitro and survival inside mouse and human macrophages. Copyright © 2014 Elsevier GmbH. All rights reserved.

Exhaustive submaximal endurance and resistance exercises induce temporary immunosuppression via physical and oxidative stress

PubMed Central

Jin, Chan-Ho; Paik, Il-Young; Kwak, Yi-Sub; Jee, Yong-Seok; Kim, Joo-Young

2015-01-01

Regular running and strength training are the best ways to improve aerobic capacity and develop the size of skeletal muscles. However, uncontrolled physical activities can often lead to an undertraining or over-training syndrome. In particular, overtraining causes persistent fatigue and reduces physical performance due to changes in the various physiological and immunological factors. In this study, we gave an exhaustive submaximal endurance or resistance exercise to participants and investigated the relationship between physical stress (cortisol level in blood), oxidative stress (intracellular ROS accumulation), and adaptive immune response (CD4:CD8 ratio). Materials and Methods Ten male volunteers were recruited, and performed a submaximal endurance or resistance exercise with 85% of VO2max or 1-repetition maximum until exhaustion. Blood samples were collected at rest, and at 0 and 30 min after the exercise. Cortisol levels, oxidative stress, and immune cell phenotypes in peripheral blood were evaluated. Cortisol levels in the sera increased after the exhaustive endurance and resistance exercises and such increments were maintained through the recovery. Intra-cellular ROS levels also increased after the exhaustive endurance and resistance exercises. The ratio of CD4+ T cells to CD8+ T cells after each type of submaximal exercise decreased compared with that at the resting stage, and returned to the resting level at 30 min after the exercise. In this study, an exhaustive endurance or a resistance exercise with submaximal intensity caused excessive physical stress, intra-cellular oxidative stress, and post-exercise immunosuppression. This result suggests that excessive physical stress induced temporary immune dysfunction via physical and oxidative stress. PMID:26331134

Hydrophilic CeO2 nanocubes protect pancreatic β-cell line INS-1 from H2O2-induced oxidative stress

NASA Astrophysics Data System (ADS)

Lyu, Guang-Ming; Wang, Yan-Jie; Huang, Xue; Zhang, Huai-Yuan; Sun, Ling-Dong; Liu, Yan-Jun; Yan, Chun-Hua

2016-04-01

Oxidative stress plays a key role in the occurrence and development of diabetes. With their unique redox properties, CeO2 nanoparticles (nanoceria) exhibit promising potential for the treatment of diabetes resulting from oxidative stress. Here, we develop a novel preparation of hydrophilic CeO2 nanocubes (NCs) with two different sizes (5 nm and 25 nm) via an acetate assisted hydrothermal method. Dynamic light scattering, zeta potential measurements and thermogravimetric analyses were utilized to investigate the changes in the physico-chemical characteristics of CeO2 NCs when exposed to in vitro cell culture conditions. CCK-8 assays revealed that the CeO2 NCs did not impair cell proliferation in the pancreatic β-cell line INS-1 at the highest dose of 200 μg mL-1 over the time scale of 72 h, while being able to protect INS-1 cells from H2O2-induced cytotoxicity even after protein adsorption. It is also noteworthy that nanoceria with a smaller hydrodynamic radius exhibit stronger antioxidant and anti-apoptotic effects, which is consistent with their H2O2 quenching capability in biological systems. These findings suggest that nanoceria can be used as an excellent antioxidant for controlling oxidative stress-induced pancreatic β-cell damage.Oxidative stress plays a key role in the occurrence and development of diabetes. With their unique redox properties, CeO2 nanoparticles (nanoceria) exhibit promising potential for the treatment of diabetes resulting from oxidative stress. Here, we develop a novel preparation of hydrophilic CeO2 nanocubes (NCs) with two different sizes (5 nm and 25 nm) via an acetate assisted hydrothermal method. Dynamic light scattering, zeta potential measurements and thermogravimetric analyses were utilized to investigate the changes in the physico-chemical characteristics of CeO2 NCs when exposed to in vitro cell culture conditions. CCK-8 assays revealed that the CeO2 NCs did not impair cell proliferation in the pancreatic β-cell line INS-1 at the highest dose of 200 μg mL-1 over the time scale of 72 h, while being able to protect INS-1 cells from H2O2-induced cytotoxicity even after protein adsorption. It is also noteworthy that nanoceria with a smaller hydrodynamic radius exhibit stronger antioxidant and anti-apoptotic effects, which is consistent with their H2O2 quenching capability in biological systems. These findings suggest that nanoceria can be used as an excellent antioxidant for controlling oxidative stress-induced pancreatic β-cell damage. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00826g

Maternal one carbon metabolism through increased oxidative stress and disturbed angiogenesis can influence placental apoptosis in preeclampsia.

PubMed

Kasture, Vaishali V; Sundrani, Deepali P; Joshi, Sadhana R

2018-05-14

Adequate maternal nutrition is critical for a healthy pregnancy outcome and poor maternal nutrition is known to be associated with pregnancy complications like preeclampsia. We have earlier demonstrated that there is an imbalance in the levels of micronutrients (folate and vitamin B 12 ) along with low levels of long chain polyunsaturated fatty acids (LCPUFA) and high homocysteine levels in women with preeclampsia. Homocysteine is known to be involved in the formation of free radicals leading to increased oxidative stress. Higher oxidative stress has been shown to be associated with increased apoptotic markers in the placenta. Preeclampsia is of placental origin and is associated with increased oxidative stress, disturbed angiogenesis and placental apoptosis. The process of angiogenesis is important for placental and fetal development and various angiogenic growth factors inhibit apoptosis by inactivation of proapoptotic proteins through a series of cellular signalling pathways. We propose that an altered one carbon cycle resulting in increased oxidative stress and impaired angiogenesis will contribute to increased placental apoptosis leading to preeclampsia. Understanding the association of one carbon cycle components and the possible mechanisms through which they regulate apoptosis will provide clues for reducing risk of pregnancy complications. Copyright © 2017. Published by Elsevier Inc.

Oxidative Stress in the Local and Systemic Events of Apical Periodontitis

PubMed Central

Hernández-Ríos, Patricia; Pussinen, Pirkko J.; Vernal, Rolando; Hernández, Marcela

2017-01-01

Oxidative stress is involved in the pathogenesis of a variety of inflammatory disorders. Apical periodontitis (AP) usually results in the formation of an osteolytic apical lesion (AL) caused by the immune response to endodontic infection. Reactive oxygen species (ROS) produced by phagocytic cells in response to bacterial challenge represent an important host defense mechanism, but disturbed redox balance results in tissue injury. This mini review focuses on the role of oxidative stress in the local and associated systemic events in chronic apical periodontitis. During endodontic infection, ligation of Toll-like receptors (TLRs) on phagocytes' surface triggers activation, phagocytosis, synthesis of ROS, activation of humoral and cellular responses, and production of inflammatory mediators, such as, cytokines and matrix metalloproteinases (MMPs). The increment in ROS perturbs the normal redox balance and shifts cells into a state of oxidative stress. ROS induce molecular damage and disturbed redox signaling, that result in the loss of bone homeostasis, increased pro-inflammatory mediators, and MMP overexpression and activation, leading to apical tissue breakdown. On the other hand, oxidative stress has been strongly involved in the pathogenesis of atherosclerosis, where a chronic inflammatory process develops in the arterial wall. Chronic AP is associated with an increased risk of cardiovascular diseases (CVD) and especially atherogenesis. The potential mechanisms linking these diseases are also discussed. PMID:29163211

Characterization of Mediators of Cardiac And Renal Development in Response to Increased Prenatal Testosterone

DTIC Science & Technology

2008-08-01

II diabetes, dyslipidemia , and obesity, the combination of which is more commonly referred to as the metabolic syndrome, and various reproductive...insulin resistance, cardiovascular disease, hypertension, and dyslipidemia (Sir-Petermann et al. 2002a; Sir-Petermann et al. 2005; Orio et al. 2006). Up...resulting in dyslipidemia and oxidative stress (Bansilal et al. 2007). The combination of dyslipidemia and oxidative stress then leads to

Developing Treatment, Treatment Validation, and Treatment Scope in the Setting of an Autism Clinical Trial

DTIC Science & Technology

2012-10-01

clinical phenotype. In addition polymorphic variants of genes of certain enzymes that synthesize and metabolize docosahexaenoic acid ( DHA ) may contribute...This project is to test to see if DHA treatment can beneficially affect excretion of urinary biomarkers of oxidative stress and the autism...excretion of the polyunsaturated fatty acid (PUFA) derived biomarkers of oxidative stress (isoprostanes and neuroprostanes) together with the changes in

Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

PubMed Central

Daiber, Andreas; Oelze, Matthias; Wenzel, Philip; Bollmann, Franziska; Pautz, Andrea; Kleinert, Hartmut

2012-01-01

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/– mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy. PMID:22506100

Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses.

PubMed

Banse, Heidi E; Frank, Nicholas; Kwong, Grace P S; McFarlane, Dianne

2015-10-01

In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are associated with the development of laminitis. Although obesity is associated with insulin dysregulation, the mechanism of obesity-associated insulin dysregulation remains to be established. We hypothesized that oxidative stress in skeletal muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty-five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 μIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Markers of oxidative stress (oxidative damage, mitochondrial function, and antioxidant capacity) were evaluated in skeletal muscle biopsies. A Spearman's rank correlation coefficient was used to determine relationships between markers of oxidative stress and BCS. Furthermore, to assess the role of oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Increasing BCS was associated with an increase in gene expression of a mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related receptor alpha, ERRα) and with increased antioxidant enzyme total superoxide dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared, TotSOD activity was increased and protein carbonyls, a marker of oxidative damage, decreased in the O-HI compared to the L-NI horses. These findings suggest that a protective antioxidant response occurred in the muscle of obese animals and that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia.

Growth Stresses in Thermally Grown Oxides on Nickel-Based Single-Crystal Alloys

NASA Astrophysics Data System (ADS)

Rettberg, Luke H.; Laux, Britta; He, Ming Y.; Hovis, David; Heuer, Arthur H.; Pollock, Tresa M.

2016-03-01

Growth stresses that develop in α-Al2O3 scale that form during isothermal oxidation of three Ni-based single crystal alloys have been studied to elucidate their role in coating and substrate degradation at elevated temperatures. Piezospectroscopy measurements at room temperature indicate large room temperature compressive stresses in the oxides formed at 1255 K or 1366 K (982 °C or 1093 °C) on the alloys, ranging from a high of 4.8 GPa for René N4 at 1366 K (1093 °C) to a low of 3.8 GPa for René N5 at 1255 K (982 °C). Finite element modeling of each of these systems to account for differences in coefficients of thermal expansion of the oxide and substrate indicates growth strains in the range from 0.21 to 0.44 pct at the oxidation temperature, which is an order of magnitude higher than the growth strains measured in the oxides on intermetallic coatings that are typically applied to these superalloys. The magnitudes of the growth strains do not scale with the parabolic oxidation rate constants measured for the alloys. Significant spatial inhomogeneities in the growth stresses were observed, due to (i) the presence of dendritic segregation and (ii) large carbides in the material that locally disrupts the structure of the oxide scale. The implications of these observations for failure during cyclic oxidation, fatigue cycling, and alloy design are considered.

Resuscitation With 100% Oxygen Causes Intestinal Glutathione Oxidation and Reoxygenation Injury in Asphyxiated Newborn Piglets

PubMed Central

Haase, Erika; Bigam, David L.; Nakonechny, Quentin B.; Jewell, Laurence D.; Korbutt, Gregory; Cheung, Po-Yin

2004-01-01

Objective: To compare mesenteric blood flow, oxidative stress, and mucosal injury in piglet small intestine during hypoxemia and reoxygenation with 21%, 50%, or 100% oxygen. Summary Background Data: Necrotizing enterocolitis is a disease whose pathogenesis likely involves hypoxia-reoxygenation and the generation of oxygen-free radicals, which are known to cause intestinal injury. Resuscitation of asphyxiated newborns with 100% oxygen has been shown to increase oxidative stress, as measured by the glutathione redox ratio, and thus may predispose to free radical-mediated tissue injury. Methods: Newborn piglets subjected to severe hypoxemia for 2 hours were resuscitated with 21%, 50%, or 100% oxygen while superior mesenteric artery (SMA) flow and hemodynamic parameters were continuously measured. Small intestinal tissue samples were analyzed for histologic injury and levels of oxidized and reduced glutathione. Results: SMA blood flow decreased to 34% and mesenteric oxygen delivery decreased to 9% in hypoxemic piglets compared with sham-operated controls. With reoxygenation, SMA blood flow increased to 177%, 157%, and 145% of baseline values in piglets resuscitated with 21%, 50%, and 100% oxygen, respectively. Mesenteric oxygen delivery increased to more than 150% of baseline values in piglets resuscitated with 50% or 100% oxygen, and this correlated significantly with the degree of oxidative stress, as measured by the oxidized-to-reduced glutathione ratio. Two of eight piglets resuscitated with 100% oxygen developed gross and microscopic evidence of pneumatosis intestinalis and severe mucosal injury, while all other piglets were grossly normal. Conclusions: Resuscitation of hypoxemic newborn piglets with 100% oxygen is associated with an increase in oxygen delivery and oxidative stress, and may be associated with the development of small intestinal hypoxia-reoxygenation injury. Resuscitation of asphyxiated newborns with lower oxygen concentrations may help to decrease the risk of necrotizing enterocolitis. PMID:15273563

[Influence of dietary intake on plasma biomarkers of oxidative stress in humans].

PubMed

Barbosa, K B F; Bressan, J; Zulet, M A; Martínez Hernández, J A

2008-01-01

Oxidative stress is related to an imbalance between the production of reactive species and the antioxidant defenses. In essence, oxidative stress has been defined as a disturbance in the pro-oxidant/antioxidant balance, leading to potential damage. It has been suggested that oxidative stress is involved in the etiology of several chronic diseases including cardiovascular disease, diabetes, cancer and neurodegenerative processes. The antioxidant defenses include nonenzymatic (especially dietary antioxidants) and antioxidant enzymes. Vitamins, minerals and phytochemicals (polyphenols and carotenoids) are among the major dietary antioxidants. The assessment of oxidative stress status though specific biomarkers has acquired great importance. The major biomarkers include the products of the attack of free radicals and reactive species to various substrates: lipids, proteins and nucleic acids. Measurement of antioxidant capacity may also involve the assessment of specific oxidative stress biomarkers. Most of the studies that have examined the association between diet and oxidative stress consider the effects of antioxidant supplements (vitamins and minerals), drinks and foods with bioactive compounds or dietary patterns on oxidative stress biomarkers. Some of these studies have demonstrated beneficial results on oxidative stress markers. However, the role of diet on oxidative stress biomarkers remains unclear and represents a potentially fruitful area for further research in the health area.

Cyanidin-3-glucoside attenuates angiotensin II-induced oxidative stress and inflammation in vascular endothelial cells.

PubMed

Sivasinprasasn, Sivanan; Pantan, Rungusa; Thummayot, Sarinthorn; Tocharus, Jiraporn; Suksamrarn, Apichart; Tocharus, Chainarong

2016-10-28

Angiotensin II (Ang II) causes oxidative stress and vascular inflammation, leading to vascular endothelial cell dysfunction, and is associated with the development of inflammatory cardiovascular diseases such as atherosclerosis. Therefore, interventions of oxidative stress and inflammation may contribute to the reduction of cardiovascular diseases. Cyanidin-3-glucoside (C3G) plays a role in the prevention of oxidative damage in several diseases. Here, we investigated the effect of C3G on Ang II-induced oxidative stress and vascular inflammation in human endothelial cells (EA.hy926). C3G dose-dependently suppressed the free radicals and inhibited the nuclear factor-kappa B (NF-κB) signaling pathway by protecting the degradation of inhibitor of kappa B-alpha (IκB-α), inhibiting the expression and translocation of NF-κB into the nucleus through the down-regulation of NF-κB p65 and reducing the expression of inducible nitric oxide synthase (iNOS). Pretreatment with C3G not only prohibited the NF-κB signaling pathway but also promoted the activity of the nuclear erythroid-related factor 2 (Nrf2) signaling pathway through the upregulation of endogenous antioxidant enzymes. Particularly, we observed that C3G significantly enhanced the production of superoxide dismutase (SOD) and induced the expression of heme oxygenase (HO-1). Our findings confirm that C3G can protect against vascular endothelial cell inflammation induced by AngII. C3G may represent a promising dietary supplement for the prevention of inflammation, thereby decreasing the risk for the development of atherosclerosis. Copyright © 2016. Published by Elsevier Ireland Ltd.

Rational synthetic combination genetic devices boosting high temperature ethanol fermentation.

PubMed

Sun, Huan; Jia, Haiyang; Li, Jun; Feng, Xudong; Liu, Yueqin; Zhou, Xiaohong; Li, Chun

2017-06-01

The growth and production of yeast in the industrial fermentation are seriously restrained by heat stress and exacerbated by heat induced oxidative stress. In this study, a novel synthetic biology approach was developed to globally boost the viability and production ability of S. cerevisiae at high temperature through rationally designing and combing heat shock protein (HSP) and superoxide dismutase (SOD) genetic devices to ultimately synergistically alleviate both heat stress and oxidative stress. HSP and SOD from extremophiles were constructed to be different genetic devices and they were preliminary screened by heat resistant experiments and anti-oxidative experiments, respectively. Then in order to customize and further improve thermotolerance of S. cerevisiae , the HSP genetic device and SOD genetic device were rationally combined. The results show the simply assemble of the same function genetic devices to solve heat stress or oxidative stress could not enhance the thermotolerance considerably. Only S. cerevisiae with the combination genetic device (FBA1p- sod-MB4 -FBA1p- shsp-HB8 ) solving both stress showed 250% better thermotolerance than the control and displayed further 55% enhanced cell density compared with the strains with single FBA1p- sod-MB4 or FBA1p- shsp-HB8 at 42 °C. Then the most excellent combination genetic device was introduced into lab S. cerevisiae and industrial S. cerevisiae for ethanol fermentation. The ethanol yields of the two strains were increased by 20.6% and 26.3% compared with the control under high temperature, respectively. These results indicate synergistically defensing both heat stress and oxidative stress is absolutely necessary to enhance the thermotolerance and production of S. cerevisiae .

Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway.

PubMed

Wang, Qin; Chuikov, Sergei; Taitano, Sophina; Wu, Qi; Rastogi, Arjun; Tuck, Samuel J; Corey, Joseph M; Lundy, Steven K; Mao-Draayer, Yang

2015-06-17

Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric acid esters (FAE), containing the active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF) on mouse and rat neural stem/progenitor cells (NPCs) and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H2O2) treatment. In addition, utilizing the reactive oxygen species (ROS) assay, we showed that DMF reduced ROS production induced by H2O2. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1). Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS).

The effect of day and night shifts on oxidative stress and anxiety symptoms of the nurses.

PubMed

Ulas, T; Buyukhatipoglu, H; Kirhan, I; Dal, M S; Eren, M A; Hazar, A; Demir, M E; Aydogan, T; Karababa, F; Uyanikoglu, A; Kurkcuoglu, I C

2012-05-01

Oxidative stress is believed to have a role in the development of chronic diseases. It is also known that long-term night and shift work in nurses might be associated with many health-related problems like fatigue, sleep problems, anxiety and difficulties in maintaining regular lifestyles. In this study, we aimed to evaluate the changes of oxidative stress parameters and anxiety indexes of the nurses on day and night shifts. One hundred and twenty nurses in ordinary service and intensive care unit (ICU) were enrolled to the study. Subjects were divided into 2 groups; group 1 (n = 60) consisted of nurses working in a day shift and group 2 (n = 60) as working in the night shift. Further, both groups were divided in to 2 groups again; group la and 2a (both n = 30) who working in the ICU, group 1b and 2b (both n = 30) in the ordinary service. Just before and the end of the shifts, blood samples were obtained to measure total antioxidant status (TAS) and total oxidant status (TOS). Oxidative stress index (OSI) was calculated. Anxiety index were determined at the end of the shift using State-Trait Anxiety Inventory index. Oxidative stress parameters were increased in all nurses at the end of the day and night shifts (p < 0.05). However, both in service and ICU nurses TAS, TOS, and OSI levels were not significantly different at the beginning and the end of the shifts (p > 0.05). Anxiety indexes of each ordinary service and ICU nurses were found to be similar (p > 0.05). Ordinary service and ICU nurses' oxidative stress parameters and anxiety indexes were not different and all nurses suffer the similar effects of the shifts both in day and night.

Silibinin Attenuates Sulfur Mustard Analog-Induced Skin Injury by Targeting Multiple Pathways Connecting Oxidative Stress and Inflammation

PubMed Central

Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

2012-01-01

Chemical warfare agent sulfur mustard (HD) inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES)-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM) treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p<0.05) reversal in CEES-induced decrease in cell viability, apoptotic and necrotic cell death, DNA damage, and an increase in oxidative stress. Silibinin (1 mg) applied topically to mouse skin 30 min post-CEES exposure (2 mg), was effective in reversing CEES-induced increases in skin bi-fold (62%) and epidermal thickness (85%), apoptotic cell death (70%), myeloperoxidase activity (complete reversal), induction of iNOS, COX-2, and MMP-9 protein levels (>90%), and activation of transcription factors NF-κB and AP-1 (complete reversal). Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants. PMID:23029417

Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway

PubMed Central

Wang, Qin; Chuikov, Sergei; Taitano, Sophina; Wu, Qi; Rastogi, Arjun; Tuck, Samuel J.; Corey, Joseph M.; Lundy, Steven K.; Mao-Draayer, Yang

2015-01-01

Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric acid esters (FAE), containing the active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF) on mouse and rat neural stem/progenitor cells (NPCs) and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H2O2) treatment. In addition, utilizing the reactive oxygen species (ROS) assay, we showed that DMF reduced ROS production induced by H2O2. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1). Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS). PMID:26090715

Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

PubMed

Tewari-Singh, Neera; Jain, Anil K; Inturi, Swetha; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

2012-01-01

Chemical warfare agent sulfur mustard (HD) inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES)-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM) treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p<0.05) reversal in CEES-induced decrease in cell viability, apoptotic and necrotic cell death, DNA damage, and an increase in oxidative stress. Silibinin (1 mg) applied topically to mouse skin 30 min post-CEES exposure (2 mg), was effective in reversing CEES-induced increases in skin bi-fold (62%) and epidermal thickness (85%), apoptotic cell death (70%), myeloperoxidase activity (complete reversal), induction of iNOS, COX-2, and MMP-9 protein levels (>90%), and activation of transcription factors NF-κB and AP-1 (complete reversal). Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

Vitamin E Supplementation Ameliorates Newcastle Disease Virus-Induced Oxidative Stress and Alleviates Tissue Damage in the Brains of Chickens

PubMed Central

Rehman, Zaib Ur; Qiu, Xusheng; Sun, Yingjie; Liao, Ying; Tan, Lei; Song, Cuiping; Yu, Shengqing; Ding, Zhuang; Nair, Venugopal; Meng, Chunchun; Ding, Chan

2018-01-01

Newcastle disease (ND), characterized by visceral, respiratory, and neurological pathologies, causes heavy economic loss in the poultry industry around the globe. While significant advances have been made in effective diagnosis and vaccine development, molecular mechanisms of ND virus (NDV)-induced neuropathologies remain elusive. In this study, we report the magnitude of oxidative stress and histopathological changes induced by the virulent NDV (ZJ1 strain) and assess the impact of vitamin E in alleviating these pathologies. Comparative profiling of plasma and brains from mock and NDV-infected chicken demonstrated alterations in several oxidative stress makers such as nitric oxide, glutathione, malondialdehyde, total antioxidant capacity, glutathione S-transferase, superoxide dismutase, and catalases. While decreased levels of glutathione and total antioxidant capacity and increased concentrations of malondialdehyde and nitric oxide were observed in NDV-challenged birds at all time points, these alterations were eminent at latter time points (5 days post infection). Additionally, significant decreases in the activities of glutathione S-transferase, superoxide dismutase, and catalase were observed in the plasma and brains collected from NDV-infected chickens. Intriguingly, we observed that supplementation of vitamin E can significantly reduce the alteration of oxidative stress parameters. Under NDV infection, extensive histopathological alterations were observed in chicken brain including neural inflammation, capillary hyperemia, necrosis, and loss of prominent axons, which were reduced with the treatment of vitamin E. Taken together, our findings highlight that neurotropic NDV induces extensive tissue damage in the brain and alters plasma oxidative stress profiles. These findings also demonstrate that supplementing vitamin E ameliorates these pathologies in chickens and proposes its supplementation for NDV-induced stresses. PMID:29614025

Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture.

PubMed

Han, Zhenying; Li, Li; Wang, Liang; Degos, Vincent; Maze, Mervyn; Su, Hua

2014-11-01

Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle cerebral artery occlusion (pMCAO) was performed in C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0.8 mg/kg PHA 568487 (PHA, α-7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (α-7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Behavior was tested 3 days after pMCAO. Neuronal injury, CD68(+) , M1 (pro-inflammatory) and M2 (anti-inflammatory) microglia/macrophages, phosphorylated p65 component of nuclear factor kappa b in microglia/macrophages, oxidative and anti-oxidant gene expression were quantified. Compared to saline-treated mice, PHA-treated mice performed better in behavioral tests, had fewer apoptotic neurons (NeuN(+) TUNEL(+) ), fewer CD68(+) and M1 macrophages, and more M2 macrophages. PHA increased anti-oxidant gene expression and decreased oxidative stress and phosphorylation of nuclear factor kappa b p65. Methyllycaconitine had the opposite effects. Our data indicate that α-7 nAchR agonist treatment reduces neuroinflammation and oxidative stress, which are associated with reduced brain injury in mice with ischemic stroke plus tibia fracture. Bone fracture at the acute stage of stroke exacerbates neuroinflammation, oxidative stress, and brain injury, and our study has shown that the α-7 nAchR agonist, PHA (PHA 568487), attenuates neuroinflammation, oxidative stress, and brain injury in mice with stroke and bone fracture. Hence, PHA could provide an opportunity to develop a new strategy to reduce brain injury in patients suffering from stroke and bone fracture. © 2014 International Society for Neurochemistry.

Systemic Treatment with a 5HT1a Agonist Induces Anti-oxidant Protection and Preserves the Retina from Mitochondrial Oxidative Stress

PubMed Central

Biswal, Manas R.; Ahmed, Chulbul M.; Ildefonso, Cristhian J.; Han, Pingyang; Li, Hong; Jivanji, Hiral; Mao, Haoyu

2015-01-01

Chronic oxidative stress contributes to age related diseases including age related macular degeneration (AMD). Earlier work showed that the 5-hydroxy-tryptophan 1a (5HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) protects retinal pigment epithelium (RPE) cells from hydrogen peroxide treatment and mouse retinas from oxidative insults including light injury. In our current experiments, RPE derived cells subjected to mitochondrial oxidative stress were protected from cell death by the up-regulation of anti-oxidant enzymes and of the metal ion chaperon metallothionein. Differentiated RPE cells were resistant to oxidative stress, and the expression of genes for protective proteins was highly increased by oxidative stress plus drug treatment. In mice treated with 8-OH-DPAT, the same genes (MT1, HO1, NqO1, Cat, Sod1) were induced in the neural retina, but the drug did not affect the expression of Sod2, the gene for manganese superoxide dismutase. We used a mouse strain deleted for Sod2 in the RPE to accelerate age-related oxidative stress in the retina and to test the impact of 8-OH-DPAT on the photoreceptor and RPE degeneration developed in these mice. Treatment of mice with daily injections of the drug led to increased electroretinogram (ERG) amplitudes in dark-adapted mice and to a slight improvement in visual acuity. Most strikingly, in mice treated with a high dose of the drug (5 mg/kg) the structure of the RPE and Bruch's membrane and the normal architecture of photoreceptor outer segments were preserved. These results suggest that systemic treatment with this class of drugs may be useful in preventing geographic atrophy, the advanced form of dry AMD, which is characterized by RPE degeneration. PMID:26315784

[Evaluation of the treatment with D-chiro-inositol on levels of oxidative stress in PCOS patients].

PubMed

De Leo, V; La Marca, A; Cappelli, V; Stendardi, A; Focarelli, R; Musacchio, M C; Piomboni, P

2012-12-01

Recent studies on the pathophysiology of infertility have shown that oxidative stress (OS) can be one of the causal factors. The OS is, by definition, an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems. It seems that oxidative stress plays an important role in almost all phases of human reproduction. In fact, ROS are involved in the modulation of a large spectrum of reproductive functions such as oocyte maturation, ovarian steroidogenesis, corpus luteum functions and are involved in the processes of fertilization, embryo development and pregnancy, but also in some diseases that cause infertility. Polycystic ovary syndrome (PCOS) has recently been associated with increased oxidative stress, often put in relation to the syndrome's typical metabolic disorder. Inositol is an intracellular mediator of insulin, currently much used as a therapeutic agent in PCOS. While its main action takes place via insulin sensitization, little is known about the possible effects of other disorders, such as oxidative stress, associated with PCOS. The purpose of this study was therefore to assess the effect of D-chiro-inositol on the state of oxidative stress in the follicular fluid of women with PCOS. Follicular fluids were obtained from women who have turned to the Center for Diagnosis and Treatment of Sterility of Obstetrics and Gynecology of the University Hospital of Siena and Modena diagnosed with PCOS. The women were treated with D-chiro-inositol (500 mg x 2 per day) for 3 months before being subjected to cycles of in vitro fertilization (IVF). The state of oxidative stress was measured by marking of free thiol groups of proteins in the follicular fluid with 3-(N-Maleimidopropionyl)-biocytin. In our study we obtained a lesser presence of free thiol protein groups equal to 77.8% in the follicular fluid of women with PCOS not treated with D-chiro-inositolo, compared to patients who instead have carried out such treatment. These results suggest that in PCOS women there is an increase of the oxidation of thiol groups of proteins follicular, correlated to a progressive increase of the oxidative stress and that the administration of D-chiro-inositol in patients with this disease seems to reduce the oxidation of thiol groups.

Structure-activity relationship study of vitamin k derivatives yields highly potent neuroprotective agents.

PubMed

Josey, Benjamin J; Inks, Elizabeth S; Wen, Xuejun; Chou, C James

2013-02-14

Historically known for its role in blood coagulation and bone formation, vitamin K (VK) has begun to emerge as an important nutrient for brain function. While VK involvement in the brain has not been fully explored, it is well-known that oxidative stress plays a critical role in neurodegenerative diseases. It was recently reported that VK protects neurons and oligodendrocytes from oxidative injury and rescues Drosophila from mitochondrial defects associated with Parkinson's disease. In this study, we take a chemical approach to define the optimal and minimum pharmacophore responsible for the neuroprotective effects of VK. In doing so, we have developed a series of potent VK analogues with favorable drug characteristics that provide full protection at nanomolar concentrations in a well-defined model of neuronal oxidative stress. Additionally, we have characterized key cellular responses and biomarkers consistent with the compounds' ability to rescue cells from oxidative stress induced cell death.

Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

PubMed

Kaushik, Manish Singh; Srivastava, Meenakshi; Srivastava, Alka; Singh, Anumeha; Mishra, Arun Kumar

2016-11-01

In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

Analytical performances of d-ROMs test and BAP test in canine plasma. Definition of the normal range in healthy Labrador dogs.

PubMed

Pasquini, A; Luchetti, E; Marchetti, V; Cardini, G; Iorio, E L

2008-02-01

An high level of ROS (Reactive Oxygen Species), due to an increased production of oxidant species and/or a decreased efficacy of antioxidant system, can lead to oxidative stress, an emerging health risk factor involved in the aging and in many diseases, including inflammatory, infectious and degenerative disorders, either in humans or in animals. In the last years some assays panels have been developed to globally evaluate the oxidative balance by means of the concomitant assessment of ROS production and antioxidant system capability. In this report, the validation trials of d-ROMs (Reactive Oxygen Metabolites- derived compounds) and BAP (Biological Antioxidant Potential) tests in canine specie are described and also the specific referral ranges are calculated in a Labrador population. The results of linearity, precision and accuracy trials show that both tests exhibit good to excellent analytical performances. The possibility of measuring oxidative stress in vivo with simple, cheap and accurate tests, d-ROMs test and BAP test, provides for the veterinarians a very suitable tool to monitor oxidative stress and to correctly choice of eventual antioxidant supplementations in diseases proven related to oxidative stress in animals and particularly in dogs. Further studies will be useful to confirm this possibility.

N-acetylcysteine protects melanocytes against oxidative stress/damage and delays onset of UV-induced melanoma in mice

PubMed Central

Cotter, Murray A.; Thomas, Joshua; Cassidy, Pamela; Robinette, Kyle; Jenkins, Noah; Scott, R. Florell; Leachman, Sancy; Samlowski, Wolfram E.; Grossman, Douglas

2008-01-01

UV radiation is the major environmental risk factor for melanoma and a potent inducer of oxidative stress, which is implicated in the pathogenesis of several malignancies. We evaluated whether the thiol antioxidant N-acetylcysteine (NAC) could protect melanocytes from UV-induced oxidative stress/damage in vitro and from UV-induced melanoma in vivo. In melan-a cells, a mouse melanocyte line, NAC (1–10 mM) conferred protection from several UV-induced oxidative sequelae including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine (8-OG), and depletion of free reduced thiols (primarily glutathione). Mice transgenic for hepatocyte growth factor and Survivin, previously shown to develop melanoma following a single neonatal dose of UV irradiation, were administered NAC (7 mg/ml, mother’s drinking water) transplacentally and through nursing until two weeks after birth. Delivery of NAC in this manner reduced thiol depletion and blocked formation of 8-OG in skin following neonatal UV treatment. Mean onset of UV-induced melanocytic tumors was significantly delayed in NAC-treated compared to control mice (21 vs. 14 weeks, p=0.0003). Our data highlight the potential importance of oxidative stress in the pathogenesis of melanoma, and suggest that NAC may be useful as a chemopreventive agent. PMID:17908992

Davallialactone reduces inflammation and repairs dentinogenesis on glucose oxidase-induced stress in dental pulp cells.

PubMed

Lee, Young-Hee; Kim, Go-Eun; Song, Yong-Beom; Paudel, Usha; Lee, Nan-Hee; Yun, Bong-Sik; Yu, Mi-Kyung; Yi, Ho-Keun

2013-11-01

The chronic nature of diabetes mellitus (DM) raises the risk of oral complication diseases. In general, DM causes oxidative stress to organs. This study aimed to evaluate the cellular change of dental pulp cells against glucose oxidative stress by glucose oxidase with a high glucose state. The purpose of this study was to test the antioxidant character of davallialactone and to reduce the pathogenesis of dental pulp cells against glucose oxidative stress. The glucose oxidase with a high glucose concentration was tested for hydroxy peroxide (H2O2) production, cellular toxicity, reactive oxygen species (ROS) formation, induction of inflammatory molecules and disturbance of dentin mineralization in human dental pulp cells. The anti-oxidant effect of Davallilactone was investigated to restore dental pulp cells' vitality and dentin mineralization via reduction of H2O2 production, cellular toxicity, ROS formation and inflammatory molecules. The treatment of glucose oxidase with a high glucose concentration increased H2O2 production, cellular toxicity, and inflammatory molecules and disturbed dentin mineralization by reducing pulp cell activity. However, davallialactone reduced H2O2 production, cellular toxicity, ROS formation, inflammatory molecules, and dentin mineralization disturbances even with a long-term glucose oxidative stress state. The results of this study imply that the development of oral complications is related to the irreversible damage of dental pulp cells by DM-induced oxidative stress. Davallialactone, a natural antioxidant, may be useful to treat complicated oral disease, representing an improvement for pulp vital therapy. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Leukocyte Telomere Length in the Neonatal Offspring of Mothers with Gestational and Pre-Gestational Diabetes.

PubMed

Gilfillan, Christopher; Naidu, Pratyusha; Gunawan, Florence; Hassan, Fadwa; Tian, Pei; Elwood, Ngaire

2016-01-01

Telomeres undergo shortening with cell division, accelerated by increased oxidative stress. We aimed to demonstrate shortened telomeres in the offspring of mothers who have diabetes as a consequence of exposure to increased oxidative stress during intrauterine development. We examined the level of glycaemia (glucose, HbA1c, fructosamine), oxidative stress (lipid peroxidation) and the levels of antioxidant enzymes (Superoxide dismutase (SOD) and Selenium dependent glutathione peroxidase) and correlate these findings with mean telomere length (TL) in maternal and foetal blood in groups of pregnant women with pre-gestational diabetes (PGD), gestational diabetes (GD) and a euglycaemic control group. Foetal and maternal glucose, maternal HbA1c, and foetal insulin and C-peptide were higher in the PGD group with the GD group being intermediate. Markers of oxidative stress did not vary between groups with the exception of foetal SOD activity that was highest in the GD group. There were no detectable differences in maternal or foetal TL between study groups. An exploratory analysis looking at correlations between glycaemic and oxidative stress parameters and TL revealed a negative correlation between maternal and foetal glucose and TL across the whole study population. This relationship held for the short-term marker of glycaemic control, fructosamine. We were unable to show significant telomere shortening in the offspring of mothers with PGD or GD. Exploratory analysis revealed a relationship between foetal TL and short-term glycaemia particularly in PGD. It is possible that increased telomerase activity can compensate for long-term increased oxidative stress but not for short-term dysglycaemia.

Oxidative airway inflammation leads to systemic and vascular oxidative stress in a murine model of allergic asthma.

PubMed

Al-Harbi, Naif O; Nadeem, A; Al-Harbi, Mohamed M; Imam, F; Al-Shabanah, Othman A; Ahmad, Sheikh F; Sayed-Ahmed, Mohamed M; Bahashwan, Saleh A

2015-05-01

Oxidant-antioxidant imbalance plays an important role in repeated cycles of airway inflammation observed in asthma. It is when reactive oxygen species (ROS) overwhelm antioxidant defenses that a severe inflammatory state becomes apparent and may impact vasculature. Several studies have shown an association between airway inflammation and cardiovascular complications; however so far none has investigated the link between airway oxidative stress and systemic/vascular oxidative stress in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of vascular/systemic oxidant-antioxidant balance. Rats were sensitized intraperitoneally with ovalbumin (OVA) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with OVA. Rats were then assessed for airway and vascular inflammation, oxidative stress (ROS, lipid peroxides) and antioxidants measured as total antioxidant capacity (TAC) and thiol content. Challenge with OVA led to increased airway inflammation and oxidative stress with a concomitant increase in vascular inflammation and oxidative stress. Oxidative stress in the vasculature was significantly inhibited by antioxidant treatment, N-acetyl cysteine; whereas hydrogen peroxide (H2O2) inhalation worsened it. Therefore, our study shows that oxidative airway inflammation is associated with vascular/systemic oxidative stress which might predispose these patients to increased cardiovascular risk. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer.

PubMed

Belotte, Jimmy; Fletcher, Nicole M; Awonuga, Awoniyi O; Alexis, Mitchell; Abu-Soud, Husam M; Saed, Mohammed G; Diamond, Michael P; Saed, Ghassan M

2014-04-01

To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 µmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P < .05 for statistical significance. Both cisplatin resistant cell lines displayed a significant decrease in GSR messenger RNA (mRNA) levels and activity (P < .01). As compared to sensitive controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.

Preventive effect of α-lipoic acid on prepulse inhibition deficits in a juvenile two-hit model of schizophrenia.

PubMed

Deslauriers, J; Racine, W; Sarret, P; Grignon, S

2014-07-11

Some pathophysiological models of schizophrenia posit that prenatal inflammation sensitizes the developing brain to second insults in early life and enhances brain vulnerability, thereby increasing the risk of developing the disorder during adulthood. We previously developed a two-hit animal model, based on the well-established prenatal immune challenge with poly-inosinic/cytidylic acid (polyI:C), followed by juvenile restraint stress (RS). We observed an additive disruption of prepulse inhibition (PPI) of acoustic startle in juvenile mice submitted to both insults. Previous studies have also reported that oxidative stress is associated with pathophysiological mechanisms of psychiatric disorders, including schizophrenia. We report here that PPI disruption in our two-hit animal model of schizophrenia is associated with an increase in oxidative stress. These findings led us to assess whether α-lipoic acid, an antioxidant, can prevent both increase in oxidative status and PPI deficits in our juvenile in vivo model of schizophrenia. In the offspring submitted to prenatal injection of polyI:C and to RS, treatment with α-lipoic acid prevented the development of PPI deficits 24h after the last period of RS. α-Lipoic acid also improved PPI performance in control mice. The reversal effect of α-lipoic acid pretreatment on these behavioral alterations was further accompanied by a normalization of the associated oxidative status and dopaminergic and GABAergic abnormalities in the prefrontal cortex. Based on our double insult paradigm, these results support the hypothesis that oxidative stress plays an important role in the development of PPI deficits, a well-known behavior associated with schizophrenia. These findings form the basis of future studies aiming to unravel mechanistic insights of the putative role of antioxidants in the treatment of schizophrenia, especially during the prodromal stage. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Buffer Modulation of Menadione-Induced Oxidative Stress in Saccharomyces cerevisiae

PubMed Central

Lushchak, Oleh V.; Bayliak, Maria M.; Korobova, Olha V.; Levine, Rodney L.; Lushchak, Volodymyr I.

2012-01-01

The objective of this study was to compare in vivo the effects of bicarbonate and phosphate buffers on surviving and menadione-induced oxidative stress in yeast cells. The latter were treated with different concentrations of menadione in the presence of these two buffers. If at 25 mM concentration of buffers menadione only slightly reduced yeast surviving, at 50 mM concentration cell killing by menadione was much more pronounced in bicarbonate than in phosphate buffer. Although the content of protein carbonyl groups did not show development of oxidative stress under menadione-induced stress, inactivation of aconitase and decrease in glutathione level mirrored its induction. However, cellular glutathione and aconitase activity decrease did not correlate with yeast survival. In vitro, aconitase was more quickly inactivated in 50 mM carbonate, than in 50 mM phosphate buffer. The possible involvement of the carbonate radical in these processes is discussed. PMID:19843376

Buffer modulation of menadione-induced oxidative stress in Saccharomyces cerevisiae.

PubMed

Lushchak, Oleh V; Bayliak, Maria M; Korobova, Olha V; Levine, Rodney L; Lushchak, Volodymyr I

2009-01-01

The objective of this study was to compare, in vivo, the effects of bicarbonate and phosphate buffers on survival and menadione-induced oxidative stress in yeast cells. The latter were treated with different concentrations of menadione in the presence of these two buffers. At 25 mM concentration of buffers, menadione only slightly reduced yeast surviving; at 50 mM concentration, cell killing by menadione was much more pronounced in bicarbonate than in phosphate buffer. Although the content of protein carbonyl groups did not show development of oxidative stress under menadione-induced stress, inactivation of aconitase and decrease in glutathione level mirrored its induction. However, cellular glutathione and aconitase activity decrease did not correlate with yeast survival. In vitro, aconitase was more quickly inactivated in 50 mM carbonate, than in 50 mM phosphate buffer. The possible involvement of the carbonate radical in these processes is discussed.

Developmental Ethanol Exposure Leads to Dysregulation of Lipid Metabolism and Oxidative Stress in Drosophila

PubMed Central

Logan-Garbisch, Theresa; Bortolazzo, Anthony; Luu, Peter; Ford, Audrey; Do, David; Khodabakhshi, Payam; French, Rachael L.

2014-01-01

Ethanol exposure during development causes an array of developmental abnormalities, both physiological and behavioral. In mammals, these abnormalities are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum disorder (FASD). We have established a Drosophila melanogaster model of FASD and have previously shown that developmental ethanol exposure in flies leads to reduced expression of insulin-like peptides (dILPs) and their receptor. In this work, we link that observation to dysregulation of fatty acid metabolism and lipid accumulation. Further, we show that developmental ethanol exposure in Drosophila causes oxidative stress, that this stress is a primary cause of the developmental lethality and delay associated with ethanol exposure, and, finally, that one of the mechanisms by which ethanol increases oxidative stress is through abnormal fatty acid metabolism. These data suggest a previously uncharacterized mechanism by which ethanol causes the symptoms associated with FASD. PMID:25387828

Sex differences in complex regional pain syndrome type I (CRPS-I) in mice.

PubMed

Tang, Chaoliang; Li, Juan; Tai, Wai Lydia; Yao, Weifeng; Zhao, Bo; Hong, Junmou; Shi, Si; Wang, Song; Xia, Zhongyuan

2017-01-01

Sex differences have been increasingly highlighted in complex regional pain syndrome (CRPS) in clinical practice. In CRPS type I (CRPS-I), although inflammation and oxidative stress have been implicated in its pathogenesis, whether pain behavior and the underlying mechanism are sex-specific is unclear. In the present study, we sought to explore whether sex differences have an impact on inflammation, oxidative stress, and pain sensitivity in CRPS-I. Chronic post-ischemia pain (CPIP) was established in both male and female mice as an animal model of CRPS-I. Edema and mechanical allodynia of bilateral hind paws were assessed after reperfusion. Blood samples were analyzed for serum levels of oxidative stress markers and inflammatory cytokines. Both male and female mice developed edema. Male mice developed CPIP at day 3 after reperfusion; female mice developed CPIP at day 2 after reperfusion. Female mice displayed significantly earlier and higher mechanical allodynia in the ischemic hind paw, which was associated with higher serum levels of IL-2, TNF-α, isoprostanes, 8 OhdG, and malondialdehyde at day 2 after reperfusion. Moreover, female mice showed significantly lower SOD and IL-4 compared to male mice at day 2 after reperfusion. Our results indicate that sex differences in inflammatory and oxidative stress states may play a central role in the sex-specific nociceptive hypersensitivity in CRPS-I, and offer a new insight into pharmacology treatments to improve pain management with CRPS.

Increased proton leak and SOD2 expression in myotubes from obese non-diabetic subjects with a family history of type 2 diabetes.

PubMed

Aguer, Céline; Pasqua, Melissa; Thrush, A Brianne; Moffat, Cynthia; McBurney, Michael; Jardine, Karen; Zhang, Rui; Beauchamp, Brittany; Dent, Robert; McPherson, Ruth; Harper, Mary-Ellen

2013-10-01

Muscle insulin resistance is linked to oxidative stress and decreased mitochondrial function. However, the exact cause of muscle insulin resistance is still unknown. Since offspring of patients with type 2 diabetes mellitus (T2DM) are susceptible to developing insulin resistance, they are ideal for studying the early development of insulin resistance. By using primary muscle cells derived from obese non-diabetic subjects with (FH+) or without (FH-) a family history of T2DM, we aimed to better understand the link between mitochondrial function, oxidative stress, and muscle insulin resistance. Insulin-stimulated glucose uptake and glycogen synthesis were normal in FH+ myotubes. Resting oxygen consumption rate was not different between groups. However, proton leak was higher in FH+ myotubes. This was associated with lower ATP content and decreased mitochondrial membrane potential in FH+ myotubes. Surprisingly, mtDNA content was higher in FH+ myotubes. Oxidative stress level was not different between FH+ and FH- groups. Reactive oxygen species content was lower in FH+ myotubes when differentiated in high glucose/insulin (25mM/150pM), which could be due to higher oxidative stress defenses (SOD2 expression and uncoupled respiration). The increased antioxidant defenses and mtDNA content in FH+ myotubes suggest the existence of compensatory mechanisms, which may provisionally prevent the development of insulin resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

Elevated Risk of Type 2 Diabetes for Development of Alzheimer Disease: a Key Role for Oxidative Stress in Brain

PubMed Central

Butterfield, D. Allan; Di Domenico, Fabio; Barone, Eugenio

2014-01-01

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggest that oxidative stress play a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data and interpreted from the point of view of oxidative stress with the aim to highlight progresses in this field. PMID:24949886

Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage

USDA-ARS?s Scientific Manuscript database

Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

Hydrogen peroxide priming modulates abiotic oxidative stress tolerance: insights from ROS detoxification and scavenging

PubMed Central

Hossain, Mohammad A.; Bhattacharjee, Soumen; Armin, Saed-Moucheshi; Qian, Pingping; Xin, Wang; Li, Hong-Yu; Burritt, David J.; Fujita, Masayuki; Tran, Lam-Son P.

2015-01-01

Plants are constantly challenged by various abiotic stresses that negatively affect growth and productivity worldwide. During the course of their evolution, plants have developed sophisticated mechanisms to recognize external signals allowing them to respond appropriately to environmental conditions, although the degree of adjustability or tolerance to specific stresses differs from species to species. Overproduction of reactive oxygen species (ROS; hydrogen peroxide, H2O2; superoxide, O2⋅-; hydroxyl radical, OH⋅ and singlet oxygen, 1O2) is enhanced under abiotic and/or biotic stresses, which can cause oxidative damage to plant macromolecules and cell structures, leading to inhibition of plant growth and development, or to death. Among the various ROS, freely diffusible and relatively long-lived H2O2 acts as a central player in stress signal transduction pathways. These pathways can then activate multiple acclamatory responses that reinforce resistance to various abiotic and biotic stressors. To utilize H2O2 as a signaling molecule, non-toxic levels must be maintained in a delicate balancing act between H2O2 production and scavenging. Several recent studies have demonstrated that the H2O2-priming can enhance abiotic stress tolerance by modulating ROS detoxification and by regulating multiple stress-responsive pathways and gene expression. Despite the importance of the H2O2-priming, little is known about how this process improves the tolerance of plants to stress. Understanding the mechanisms of H2O2-priming-induced abiotic stress tolerance will be valuable for identifying biotechnological strategies to improve abiotic stress tolerance in crop plants. This review is an overview of our current knowledge of the possible mechanisms associated with H2O2-induced abiotic oxidative stress tolerance in plants, with special reference to antioxidant metabolism. PMID:26136756

Role of Nitric Oxide in Stress-Induced Anxiety: From Pathophysiology to Therapeutic Target.

PubMed

Kumar, A; Chanana, P

2017-01-01

Stress is often marked by a state of hyperarousal to aid the initiation of necessary stress response for the successful management of stressful stimuli. It can be manifested as a challenge (stimulus) that requires behavioral, psychological, and physiological adaptations for the maintenance of a state of homeostasis in response to stressful stimuli. In an organism, miscellaneous stressors trigger a wide spectrum of alterations in hormonal and neuronal physiologies, resulting in behavioral (anxiety and depression disorders, diminished food intake and gastrointestinal dysfunctions, decline in sexual behavior, diabetes, and loss of cognitive function) and other physiological responses. Stress serves as a potent etiological link to development of several neuropsychiatric diseases such as depression, anxiety, and cognitive impairments. Exposure to stressful stimuli has been found to be associated with activation of nitric oxide synthase and generation of NO which reacts with spontaneous oxygen species to aid formation of active nitrogen radicals. High concentrations of reactive nitrogen radicals may cause damage to intracellular proteins, in addition to causing impairment to components of the mitochondrial transport chain, leading to cellular energy deficiency. This may further serve as an etiological link to the development of secondary neurological diseases associated with chronic stress. Also, during stress exposure, pharmacological inhibition of nitric oxide production displays reduction in indicators of anxiety- and depressive-like behavior in animal models. Therefore, the purpose of this chapter is to present an overview on the role of NO in stress-evoked emergence of secondary neurological disorders like anxiety as well as citing examples where NO has been used as a therapeutic target for the management of stress-induced anxiety-like behavior. © 2017 Elsevier Inc. All rights reserved.

[Occupational hazards, DNA damage, and oxidative stress on exposure to waste anesthetic gases].

PubMed

Lucio, Lorena M C; Braz, Mariana G; do Nascimento Junior, Paulo; Braz, José Reinaldo C; Braz, Leandro G

The waste anesthetic gases (WAGs) present in the ambient air of operating rooms (OR), are associated with various occupational hazards. This paper intends to discuss occupational exposure to WAGs and its impact on exposed professionals, with emphasis on genetic damage and oxidative stress. Despite the emergence of safer inhaled anesthetics, occupational exposure to WAGs remains a current concern. Factors related to anesthetic techniques and anesthesia workstations, in addition to the absence of a scavenging system in the OR, contribute to anesthetic pollution. In order to minimize the health risks of exposed professionals, several countries have recommended legislation with maximum exposure limits. However, developing countries still require measurement of WAGs and regulation for occupational exposure to WAGs. WAGs are capable of inducing damage to the genetic material, such as DNA damage assessed using the comet assay and increased frequency of micronucleus in professionals with long-term exposure. Oxidative stress is also associated with WAGs exposure, as it induces lipid peroxidation, oxidative damage in DNA, and impairment of the antioxidant defense system in exposed professionals. The occupational hazards related to WAGs including genotoxicity, mutagenicity and oxidative stress, stand as a public health issue and must be acknowledged by exposed personnel and responsible authorities, especially in developing countries. Thus, it is urgent to stablish maximum safe limits of concentration of WAGs in ORs and educational practices and protocols for exposed professionals. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Acylcarnitines: potential implications for skeletal muscle insulin resistance.

PubMed

Aguer, Céline; McCoin, Colin S; Knotts, Trina A; Thrush, A Brianne; Ono-Moore, Kikumi; McPherson, Ruth; Dent, Robert; Hwang, Daniel H; Adams, Sean H; Harper, Mary-Ellen

2015-01-01

Insulin resistance may be linked to incomplete fatty acid β-oxidation and the subsequent increase in acylcarnitine species in different tissues including skeletal muscle. It is not known if acylcarnitines participate in muscle insulin resistance or simply reflect dysregulated metabolism. The aims of this study were to determine whether acylcarnitines can elicit muscle insulin resistance and to better understand the link between incomplete muscle fatty acid β-oxidation, oxidative stress, inflammation, and insulin-resistance development. Differentiated C2C12, primary mouse, and human myotubes were treated with acylcarnitines (C4:0, C14:0, C16:0) or with palmitate with or without carnitine acyltransferase inhibition by mildronate. Treatment with C4:0, C14:0, and C16:0 acylcarnitines resulted in 20-30% decrease in insulin response at the level of Akt phosphorylation and/or glucose uptake. Mildronate reversed palmitate-induced insulin resistance concomitant with an ∼25% decrease in short-chain acylcarnitine and acetylcarnitine secretion. Although proinflammatory cytokines were not affected under these conditions, oxidative stress was increased by 2-3 times by short- or long-chain acylcarnitines. Acylcarnitine-induced oxidative stress and insulin resistance were reversed by treatment with antioxidants. Results are consistent with the conclusion that incomplete muscle fatty acid β-oxidation causes acylcarnitine accumulation and associated oxidative stress, raising the possibility that these metabolites play a role in muscle insulin resistance. © FASEB.

Does oxidative stress shorten telomeres?

PubMed

Boonekamp, Jelle J; Bauch, Christina; Mulder, Ellis; Verhulst, Simon

2017-05-01

Oxidative stress shortens telomeres in cell culture, but whether oxidative stress explains variation in telomere shortening in vivo at physiological oxidative stress levels is not well known. We therefore tested for correlations between six oxidative stress markers and telomere attrition in nestling birds (jackdaws Corvus monedula ) that show a high rate of telomere attrition in early life. Telomere attrition was measured between ages 5 and 30 days, and was highly variable (average telomere loss: 323 bp, CV = 45%). Oxidative stress markers were measured in blood at age 20 days and included markers of oxidative damage (TBARS, dROMs and GSSG) and markers of antioxidant protection (GSH, redox state, uric acid). Variation in telomere attrition was not significantly related to these oxidative stress markers (| r | ≤ 0.08, n = 87). This finding raises the question whether oxidative stress accelerates telomere attrition in vivo The accumulation of telomere attrition over time depends both on the number of cell divisions and on the number of base pairs lost per DNA replication and, based on our findings, we suggest that in a growing animal cell proliferation, dynamics may be more important for explaining variation in telomere attrition than oxidative stress. © 2017 The Author(s).

Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model.

PubMed

Escribano, Begoña M; Medina-Fernández, Francisco J; Aguilar-Luque, Macarena; Agüera, Eduardo; Feijoo, Montserrat; Garcia-Maceira, Fe I; Lillo, Rafael; Vieyra-Reyes, Patricia; Giraldo, Ana I; Luque, Evelio; Drucker-Colín, René; Túnez, Isaac

2017-01-01

Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord. For this purpose, samples obtained from EAE rats and relapsing-remitting (RRMS) MS patients were used. In addition, EAE rats were treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab was also employed in RRMS. The results of this study revealed an improvement in the clinical symptoms of the EAE and MS with the treatments, as well as a reduction in the oxidative stress parameters and in LBP. Correlations between the clinical variables of the disease, i.e. oxidative damage and LBP, were established. Although the conclusions of this research are indeed relevant, further investigation would be necessary to establish the intrinsic mechanisms of the MS-oxidative stress-microbiota relationship.

Oxidative stress following traumatic brain injury: enhancement of endogenous antioxidant defense systems and the promise of improved outcome.

PubMed

Eghwrudjakpor, P O; Allison, A B

2010-01-01

Management of brain injury can pose enormous challenges to the health team. There are many studies aimed at discovering or developing pharmacotherapeutic agents targeted at improving outcome of head-injured patients. This paper reviews the role of oxidative stress in neuronal loss following traumatic brain injury and presents experimental and clinical evidence of the role of exogenous antioxidants as neuroprotectants. We reviewed published literature on reactive oxygen species and their role in experimental and clinical brain injuries in journals and the Internet using Yahoo and Google search engines. Traumatic brain injury causes massive production of reactive oxygen species with resultant oxidative stress. In experimental brain injury, exogenous antioxidants are useful in limiting oxidative damage. Results with clinical brain injury are however more varied. Oxidative stress due to excessive generation of reactive oxygen species with consequent impairment of endogenous antioxidant defence mechanisms plays a significant role in the secondary events leading to neuronal death. Enhancement of the defence mechanisms through the use of exogenous antioxidants may be neuroprotective, especially if the agents can penetrate cell membranes, are able to cross the blood-brain barrier and if they are administered within the neuroprotective time window.

Changes in the antioxidant metabolism in the embryonic development of the common South American toad Bufo arenarum: differential responses to pesticide in early embryos and autonomous-feeding larvae.

PubMed

Ferrari, Ana; Anguiano, Liliana; Lascano, Cecilia; Sotomayor, Verónica; Rosenbaum, Enrique; Venturino, Andrés

2008-01-01

Amphibians may be critically challenged by aquatic contaminants during their embryonic development. Many classes of compounds, including organophosphorus pesticides, are able to cause oxidative stress that affects the delicate cellular redox balance regulating tissue modeling. We determined the progression of antioxidant defenses during the embryonic development of the South American common toad, Bufo arenarum. Superoxide dismutase (SOD) and catalase (CAT) activities were high in the unfertilized eggs, and remained constant during the first stages of development. SOD showed a significant increase when the gills were completely active and opercular folds began to form. Reductase (GR) activity was low in the oocytes and increased significantly when gills and mouth were entirely developed and the embryos presented a higher exposure to pro-oxidant conditions suggesting an environmental control. Reduced glutathione (GSH) content was also initially low, and rose continuously pointing out an increasing participation of GSH-related enzymes in the control of oxidative stress. GSH peroxidases and GSH-S-transferases showed relatively high and constant activities, probably related to lipid peroxide control. B. arenarum embryos have plenty of yolk platelets containing lipids, which provide the energy and are actively transferred to the newly synthesized membranes during the early embryonic development. Exposure to the pro-oxidant pesticide malathion during 48 h did not significantly affect the activity of antioxidant enzymes in early embryos, but decreased the activities of CAT, GR, and the pool of GSH in larvae. Previous work indicated that lipid peroxide levels were kept low in malathion-exposed larvae, thus we conclude that oxidative stress is overcome by the antioxidant defenses. The increase in the antioxidant metabolism observed in the posthatching phase of development of B. arenarum embryo, thus constitutes a defense against natural and human-generated pro-oxidants present in the aquatic environment.

[The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].

PubMed

Shormanov, I S; Mozhaev, I I; Sokolova, Kh A; Solovev, A S

2017-12-01

This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.

Implication of Oxidative Stress in Fetal Programming of Cardiovascular Disease

PubMed Central

Rodríguez-Rodríguez, Pilar; Ramiro-Cortijo, David; Reyes-Hernández, Cynthia G.; López de Pablo, Angel L.; González, M. Carmen; Arribas, Silvia M.

2018-01-01

Lifestyle and genetic background are well known risk factors of cardiovascular disease (CVD). A third contributing factor is suboptimal fetal development, due to nutrient or oxygen deprivation, placental insufficiency, or exposure to toxic substances. The fetus adapts to adverse intrauterine conditions to ensure survival; the immediate consequence is low birth weight (LBW) and the long-term effect is an increased susceptibility to develop CVD in adult life. This process is known as Developmental Origins of Health and Disease (DOHaD) or fetal programming of CVD. The influence of fetal life for the future cardiovascular health of the individual has been evidenced by numerous epidemiologic studies in populations suffering from starvation during intrauterine life. Furthermore, experimental animal models have provided support and enabled exploring the underlying mechanisms. Oxidative stress seems to play a central role in fetal programming of CVD, both in the response of the feto-placental unit to the suboptimal intrauterine environment and in the alterations of physiologic systems of cardiovascular control, ultimately leading to disease. This review aims to summarize current knowledge on the alterations in oxidative balance in response to fetal stress factors covering two aspects. Firstly, the evidence from human studies of the implication of oxidative stress in LBW induced by suboptimal conditions during intrauterine life, emphasizing the role of the placenta. In the second part we summarize data on specific redox alterations in key cardiovascular control organs induced by exposure to known stress factors in experimental animals and discuss the emerging role of the mitochondria. PMID:29875698

Oxidation of a Commercial Nickel-Based Superalloy under Static Loading

NASA Astrophysics Data System (ADS)

Foss, B. J.; Hardy, M. C.; Child, D. J.; McPhail, D. S.; Shollock, B. A.

2014-12-01

The current demands of the aviation industry for increased gas-turbine efficiency necessitate higher turbine entry temperatures, requiring that alloys exhibit superior oxidation resistance. The synergistic effects of oxidation and mechanical stresses pose a complex issue. The purpose of the current research was to examine the effects of stress on the oxidation and oxygen transport in a commercial nickel-based superalloy. Fine grain RR1000 in both polished and shot-peened conditions was studied for classic (zero load) and statically loaded conditions using integrated two-stage isotopic tracing combined with focused-ion-beam secondary ion mass spectrometry (FIB-SIMS). Cr2O3 external oxide formed with semicontinuous TiO2 above and below. Preferential grain boundary Al2O3 internal oxide formation, γ'-dissolution, and recrystallization occurred subsurface. Oxidation mechanisms were dominated by anionic/cationic growth in the external oxide with inward oxygen transport, initially through the partially unprotective external oxide, then along internal oxide/alloy interfaces. Loading did not influence the oxidation products formed but did bring about expedited oxidation kinetics and changes to the oxide morphology. The oxygen diffusivity D {O/ * } (×10-13 cm2s-1) ranged from 0.39 for the polished alloy to 3.7 for the shot-peened condition under compressive stress. Arguably, the most significant effects took place in the subsurface regions. Increased oxidation kinetics were attributed to the development of fast cation diffusion paths as the alloy deformed by creep.

NADPH oxidase mediates depressive behavior induced by chronic stress in mice.

PubMed

Seo, Ji-Seon; Park, Jin-Young; Choi, Juli; Kim, Tae-Kyung; Shin, Joo-Hyun; Lee, Ja-Kyeong; Han, Pyung-Lim

2012-07-11

Stress is a potent risk factor for depression, yet the underlying mechanism is not clearly understood. In the present study, we explored the mechanism of development and maintenance of depression in a stress-induced animal model. Mice restrained for 2 h daily for 14 d showed distinct depressive behavior, and the altered behavior persisted for >3 months in the absence of intervention. Acute restraint induced a surge of oxidative stress in the brain, and stress-induced oxidative stress progressively increased with repetition of stress. In vitro, the stress hormone glucocorticoid generated superoxide via upregulation of NADPH oxidase. Consistently, repeated restraints increased the expression of the key subunits of NADPH oxidase, p47phox and p67phox, in the brain. Moreover, stressed brains markedly upregulated the expression of p47phox to weak restress evoked in the poststress period, and this molecular response was reminiscent of amplified ROS surge to restress. Pharmacological inhibition of NADPH oxidase by the NADPH oxidase inhibitor apocynin during the stress or poststress period completely blocked depressive behavior. Consistently, heterozygous p47phox knock-out mice (p47phox(+/-)) or molecular inhibition of p47phox with Lenti shRNA-p47phox in the hippocampus suppressed depressive behavior. These results suggest that repeated stress promotes depressive behavior through the upregulation of NADPH oxidase and the resultant metabolic oxidative stress, and that the inhibition of NADPH oxidase provides beneficial antidepression effects.

A redox proteomics approach to investigate the mode of action of nanomaterials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riebeling, Christian; Wiemann, Martin; Schnekenburger, Jürgen

2016-05-15

Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive research efforts are targeted to understanding modes of action of ENMs, which may also support the development of new predictive assays. Oxidative stress is a widely accepted paradigm associated with different adverse outcomes of ENMs. It has frequently been identified in in vitro and in vivo studies and different assays have been developed for this purpose. Fluorescent dye basedmore » read-outs are most frequently used for cell testing in vitro but may be limited due to possible interference of the ENMs. Recently, other assays have been put forward such as acellular determination of ROS production potential using methods like electron spin resonance, antioxidant quantification or the use of specific sensors. In addition, Omics based approaches have gained increasing attention. In particular, redox proteomics can combine the assessment of oxidative stress with the advantage of getting more detailed mechanistic information. Here we propose a comprehensive testing strategy for assessing the oxidative stress potential of ENMs, which combines acellular methods and fast in vitro screening approaches, as well as a more involved detailed redox proteomics approach. This allows for screening and prioritization in a first tier and, if required, also for unraveling mechanistic details down to compromised signaling pathways. - Highlights: • Oxidative stress is a general paradigm for nanomaterial hazard mechanism of action. • Reactive oxygen species generation can be predicted using acellular assays. • Cellular assays based on fluorescence suffer from interference by nanomaterials. • Protein carbonylation is an irreversible and predictive mark of oxidative stress. • Proteomics of carbonylation indicates affected pathways and mechanism of action.« less

Systemic inflammatory changes and increased oxidative stress in rural Indian women cooking with biomass fuels.

PubMed

Dutta, Anindita; Ray, Manas Ranjan; Banerjee, Anirban

2012-06-15

The study was undertaken to investigate whether regular cooking with biomass aggravates systemic inflammation and oxidative stress that might result in increase in the risk of developing cardiovascular disease (CVD) in rural Indian women compared to cooking with a cleaner fuel like liquefied petroleum gas (LPG). A total of 635 women (median age 36 years) who cooked with biomass and 452 age-matched control women who cooked with LPG were enrolled. Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were measured by ELISA. Generation of reactive oxygen species (ROS) by leukocytes was measured by flow cytometry, and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Hypertension was diagnosed following the Seventh Report of the Joint Committee. Tachycardia was determined as pulse rate >100 beats per minute. Particulate matter of diameter less than 10 and 2.5 μm (PM₁₀ and PM₂.₅, respectively) in cooking areas was measured using real-time aerosol monitor. Compared with control, biomass users had more particulate pollution in indoor air, their serum contained significantly elevated levels of IL-6, IL-8, TNF-α and CRP, and ROS generation was increased by 37% while SOD was depleted by 41.5%, greater prevalence of hypertension and tachycardia compared to their LPG-using neighbors. PM₁₀ and PM₂.₅ levels were positively associated with markers of inflammation, oxidative stress and hypertension. Inflammatory markers correlated with raised blood pressure. Cooking with biomass exacerbates systemic inflammation, oxidative stress, hypertension and tachycardia in poor women cooking with biomass fuel and hence, predisposes them to increased risk of CVD development compared to the controls. Systemic inflammation and oxidative stress may be the mechanistic factors involved in the development of CVD. Copyright © 2012 Elsevier Inc. All rights reserved.

Activation of PPAR-γ by pioglitazone attenuates oxidative stress in aging rat cerebral arteries through upregulating UCP2.

PubMed

Wang, Peijian; Li, Binghu; Cai, Guocai; Huang, Mingqing; Jiang, Licheng; Pu, Jing; Li, Lu; Wu, Qi; Zuo, Li; Wang, Qiulin; Zhou, Peng

2014-12-01

Increasing amounts of evidence implicate oxidative stress as having a pivotal role in age-related cerebrovascular dysfunction, which is an important risk factor for the development of cerebrovascular disease. Previous studies have shown that the activation of the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) in vascular endothelial cells results in an improvement of vascular function. Pioglitazone, a well-known PPAR-γ agonist, protects against oxidative stress in the rostral ventrolateral medulla by the upregulation of mitochondrial uncoupling protein 2 (UCP2). In this study, we sought to explore the effects and the underlying mechanisms of pioglitazone on age-related oxidative stress elevation and cerebrovascular dysfunction in aging rat cerebral arteries. A natural aging model was constructed and used in these experiments. One-month oral administration of pioglitazone (20 mg·kg·d) ameliorated the production of reactive oxygen species, promoted endothelial nitric oxide synthase phosphorylation and increased the nitric oxide available, thus improving endothelium-dependent relaxation in aging rat cerebral arteries. One-month pioglitazone administration also restored PPAR-γ expression and increased the levels of UCP2 in aging rat cerebral arteries. Using in vitro studies, we demonstrated that pioglitazone attenuated reactive oxygen species levels in aging human umbilical vein endothelial cells through PPAR-γ activation. Furthermore, we found that this occurs in an UCP2-dependent manner. Our study demonstrated that the activation of PPAR-γ by pioglitazone protected against oxidative stress damage in aging cerebral arteries by upregulating UCP2. PPAR-γ may be a new target in treating age-related cerebrovascular dysfunction.

Wine and oxidative stress: up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans.

PubMed

Covas, María Isabel; Gambert, Philippe; Fitó, Montserrat; de la Torre, Rafael

2010-02-01

Wine and alcohol consumption has been considered to be protective against coronary heart disease development, an oxidative stress associated disease. Wine contains polyphenols displaying antioxidant properties tested in in vitro and in vivo studies. Due to this, a general consensus exists, both among the general public and the scientific community, that wine, particularly red wine, is an antioxidant beverage. Alcohol consumption, however, is associated with oxidative damage. Several studies have been carried out on the antioxidant health benefits of wine and wine polyphenols. However, adequate scientific evidence (Level I or II) is required to be provided before recommendations or statements which can reach the general public can be formulated. Here, we summarize the state of the art of the up-to-date body of knowledge, and the extent to which there exists evidence of the benefits of moderate wine consumption on oxidative damage in humans. From the available data, there is no evidence, at present, that sustained wine consumption provides antioxidant benefits in healthy volunteers other than to counteract a possible pro-oxidative effect of the alcohol. On the contrary, data on the antioxidant protective effect of red wine in oxidative stress situations are promising. In this way, the postprandial oxidative stress after a meal, despite the diversity of biomarkers used for its evaluation, is counteracted by the ingestion of wine. Further studies are warranted. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Influence of oxidative stress on the development of collateral circulation in total coronary occlusions.

PubMed

Demirbag, Recep; Gur, Mustafa; Yilmaz, Remzi; Kunt, Alper Sami; Erel, Ozcan; Andac, M Halit

2007-03-02

The purpose of this study was to investigate whether the levels of total antioxidant capacity (TAC), total peroxide and oxidative stress index (OSI) are associated with the development of collaterals in total coronary occlusions. Our study group contained 176 consecutive men patients with single-vessel TCO, 94 of whom had poorly developed coronary collateral, while 82 had well-developed coronary collateral. TAC and total peroxide concentration were measured of plasma. The ratio of TAC to total peroxide was accepted as an indicator of oxidative stress. The values of total peroxide and OSI in the Group I were significantly lower than that in Group II (p<0.001, for both). TAC levels were significantly higher in patients with poorly developed collaterals than in well-developed collateral group (p<0.001). OSI values were also significantly different among the Rentrop class-0, -1, -2 and -3 (ANOVA p<0.001). We found significant correlations between collaterals score and TAC, total peroxide and OSI levels (p<0.001 for all). In multiple linear regression analysis, total peroxide and OSI were independent predictors of collaterals score (p=0.006 and p<0.001 respectively). This study clearly demonstrates that the level of OSI is independently and positively associated with the presence of collateral circulation in total coronary occlusion patients.

Stress in Obesity and Associated Metabolic and Cardiovascular Disorders

PubMed Central

Holvoet, Paul

2012-01-01

Obesity has significant implications for healthcare, since it is a major risk factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is associated with high atherosclerotic cardiovascular risk, which can only partially be explained by its components. Therefore, to explain how obesity contributes to the development of metabolic and cardiovascular disorders, more and better insight is required into the effects of personal and environmental stress on disease processes. In this paper, we show that obesity is a chronic inflammatory disease, which has many molecular mechanisms in common with atherosclerosis. Furthermore, we focus on the role of oxidative stress associated with obesity in the development of the metabolic syndrome. We discuss how several stress conditions are related to inflammation and oxidative stress in association with obesity and its complications. We also emphasize the relation between stress conditions and the deregulation of epigenetic control mechanisms by means of microRNAs and show how this impairment further contributes to the development of obesity, closing the vicious circle. Finally, we discuss the limitations of current anti-inflammation and antioxidant therapy to treat obesity. PMID:24278677

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

PubMed

Stevanovic, Ana; Coburn, Mark; Menon, Ares; Rossaint, Rolf; Heyland, Daren; Schälte, Gereon; Werker, Thilo; Wonisch, Willibald; Kiehntopf, Michael; Goetzenich, Andreas; Rex, Steffen; Stoppe, Christian

2014-01-01

Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. ClinicalTrials.gov NCT01409057.

Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

PubMed

Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2013-07-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features

PubMed Central

Visconti, Paola; Bolotta, Alessandra; Ferreri, Carla; Gobbi, Giuseppe; Malisardi, Gemma; Manfredini, Stefano; Marini, Marina; Nanetti, Laura; Pipitone, Emanuela; Raffaelli, Francesca; Resca, Federica; Mazzanti, Laura

2013-01-01

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (−66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD. PMID:23840462

The role of oxidative stress in the development of alcoholic liver disease.

PubMed

Galicia-Moreno, M; Gutiérrez-Reyes, G

2014-01-01

Alcohol is the most accepted addictive substance worldwide and its consumption is related to multiple health, economic, and social problems. The liver is the organ in charge of ethanol metabolism and it is susceptible to alcohol's toxic effects. To provide a detailed review of the role of oxidative stress in alcoholic liver disease and the mechanisms of damage involved, along with current information on the hepatoprotective effectiveness of the molecules that have been studied. A search of the PubMed database was conducted using the following keywords oxidative stress, alcoholic liver damage, alcoholic cirrhosis, and antioxidants. There was no time limit for gathering all available information on the subject at hand. According to the literature reviewed, oxidative stress plays an important role in the pathogenesis of alcoholic liver damage. Molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), formed during ethanol metabolism, structurally and functionally modify organic molecules. Consequently, biologic processes are altered and hepatocytes are sensitized to the action of cytokines like tumor necrosis factor-α, as well as to the action of endotoxins, activating signaling pathways such as those controlled by nuclear factor kappa B, extracellular signal regulated kinases, and mitogen activated protein kinase. Oxidative stress plays an important role in the development of liver damage resulting from alcohol consumption. The molecules that have currently displayed a hepatoprotective effect in preclinical and clinical trials must be studied further so that their effectiveness can be confirmed and they can possibly be used as adjuvant treatments for this disease. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Resistance exercise attenuates skeletal muscle oxidative stress, systemic pro-inflammatory state, and cachexia in Walker-256 tumor-bearing rats.

PubMed

Padilha, Camila Souza; Borges, Fernando Henrique; Costa Mendes da Silva, Lilian Eslaine; Frajacomo, Fernando Tadeu Trevisan; Jordao, Alceu Afonso; Duarte, José Alberto; Cecchini, Rubens; Guarnier, Flávia Alessandra; Deminice, Rafael

2017-09-01

The aim of this study was to investigate the effects of resistance exercise training (RET) on oxidative stress, systemic inflammatory markers, and muscle wasting in Walker-256 tumor-bearing rats. Male (Wistar) rats were divided into 4 groups: sedentary controls (n = 9), tumor-bearing (n = 9), exercised (n = 9), and tumor-bearing exercised (n = 10). Exercised and tumor-bearing exercised rats were exposed to resistance exercise of climbing a ladder apparatus with weights tied to their tails for 6 weeks. The physical activity of control and tumor-bearing rats was confined to the space of the cage. After this period, tumor-bearing and tumor-bearing exercised animals were inoculated subcutaneously with Walker-256 tumor cells (11.0 × 10 7 cells in 0.5 mL of phosphate-buffered saline) while control and exercised rats were injected with vehicle. Following inoculation, rats maintained resistance exercise training (exercised and tumor-bearing exercised) or sedentary behavior (control and tumor-bearing) for 12 more days, after which they were euthanized. Results showed muscle wasting in the tumor-bearing group, with body weight loss, increased systemic leukocytes, and inflammatory interleukins as well as muscular oxidative stress and reduced mTOR signaling. In contrast, RET in the tumor-bearing exercised group was able to mitigate the reduced body weight and muscle wasting with the attenuation of muscle oxidative stress and systemic inflammatory markers. RET also prevented loss of muscle strength associated with tumor development. RET, however, did not prevent the muscle proteolysis signaling via FBXO32 gene messenger RNA expression in the tumor-bearing group. In conclusion, RET performed prior tumor implantation prevents cachexia development by attenuating tumor-induced systemic pro-inflammatory condition with muscle oxidative stress and muscle damage.

Aging Exacerbates Obesity-Induced Oxidative Stress and Inflammation in Perivascular Adipose Tissue in Mice: A Paracrine Mechanism Contributing to Vascular Redox Dysregulation and Inflammation

PubMed Central

Bailey-Downs, Lora C.; Tucsek, Zsuzsanna; Toth, Peter

2013-01-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet–fed obese C57BL/6 mice. High-fat diet–induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet–induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals. PMID:23213032

Oxidant stress regulatory genetic variation in recipients and donors contributes to risk of primary graft dysfunction after lung transplantation

PubMed Central

Cantu, Edward; Shah, Rupal J.; Lin, Wei; Daye, Zhongyin J.; Diamond, Joshua M.; Suzuki, Yoshikazu; Ellis, John H.; Borders, Catherine F.; Andah, Gerald A.; Beduhn, Ben; Meyer, Nuala J.; Ruschefski, Melanie; Aplenc, Richard; Feng, Rui; Christie, Jason D.

2014-01-01

Objective Oxidant stress pathway activation during ischemia reperfusion injury may contribute to the development of primary graft dysfunction (PGD) after lung transplantation. We hypothesized oxidant stress gene variation in recipients and donors is associated with PGD. Methods Donors and recipients from the Lung Transplant Outcomes Group (LTOG) cohort were genotyped using the Illumina IBC chip filtered for oxidant stress pathway genes. Single nucleotide polymorphisms (SNPs) grouped into SNP-sets based on haplotype blocks within 49 oxidant stress genes selected from gene ontology pathways and literature review were tested for PGD association using a sequencing kernel association test. Analyses were adjusted for clinical confounding variables and population stratification. Results 392 donors and 1038 recipients met genetic quality control standards. 30% of subjects developed grade 3 PGD within 72 hours. Donor NADPH Oxidase 3 (NOX3) was associated with PGD (p=0.01) with 5 individual significant loci (p-values between 0.006 and 0.03). In recipients, variation in glutathione peroxidase (GPX1) and NRF-2 (NFE2L2) was significantly associated with PGD (p=0.01 for both). The GPX1 association included 3 individual loci (p-values between 0.006 and 0.049) and the NFE2L2 association included 2 loci (p=0.03 and 0.05). Significant epistatic effects influencing PGD susceptibility were evident between three different donor blocks of NOX3 and recipient NFE2L2 (p=0.026, p=0.017 and p=0.031). Conclusions Our study prioritizes GPX1, NOX3, and NFE2L2 genes for future research in PGD pathogenesis, and highlights a donor-recipient interaction of NOX3 and NFE2L2 that increases PGD risk. PMID:25439478

Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: a double-blind, randomized clinical trial.

PubMed

Alfonso, Helman; Franklin, Peter; Ching, Simon; Croft, Kevin; Burcham, Phil; Olsen, Nola; Reid, Alison; Joyce, David; de Klerk, Nick; Musk, Aw Bill

2015-10-01

Many of the pathological consequences in the lung following inhalation of asbestos fibres arise as a consequence of persistent oxidative stress and inflammation. Inflammatory responses can be observed in asymptomatic asbestos-exposed individuals. There are currently no interventions to reduce inflammatory or oxidative responses to asbestos before disease develops. We investigated the effects of oral N-acetylcysteine (NAC) on indicators of inflammation or oxidative stress in asymptomatic people previously exposed to asbestos. A double-blind, randomized, placebo-controlled study was conducted to assess the effectiveness and safety of 1800 mg of NAC given orally over a period of 4 months. This was a proof of principle study. Effectiveness was assessed using indicators of inflammation or oxidation as primary end-points. Serum levels of total combined thiols (cysteine, cysteinylglycine, glutathione and homocysteine) were used to monitor the NAC supplementation. Thirty-four subjects were randomly allocated to NAC and 32 to placebo. Serum levels of total combined thiols were similar between the groups after intervention. There were no differences in levels of inflammatory or oxidative stress end-points between the groups. No adverse effects were identified. No evidence was found that NAC supplementation replenishes total combined thiols in the blood of healthy subjects with a history of asbestos exposure. There was also no evidence of reduced indicators of inflammation or oxidative stress. Further studies should determine the conditions required to increase levels of total anti-oxidant capacity in the blood and in the lungs of subjects with either asbestos-related diseases or subclinical lung inflammation. © 2015 Asian Pacific Society of Respirology.

Oxidative stress is associated with increased pulmonary artery systolic pressure in humans.

PubMed

Ghasemzadeh, Nima; Patel, Riyaz S; Eapen, Danny J; Veledar, Emir; Al Kassem, Hatem; Manocha, Pankaj; Khayata, Mohamed; Zafari, A Maziar; Sperling, Laurence; Jones, Dean P; Quyyumi, Arshed A

2014-06-01

Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine, glutathione, and its oxidized disulphide were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/oxidized glutathione couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (P<0.001), sex (P=0.002), mitral regurgitation (P<0.001), left ventricular ejection fraction (P<0.001), left atrial size (P<0.001), diabetes mellitus (P=0.03), plasma Ln cystine (β=9.53; P<0.001), Ln glutathione (β=-5.4; P=0.002), and Eh glutathione (β=0.21; P=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (β=6.56; P=0.007), mitral regurgitation (β=4.52; P<0.001), statin use (β=-3.39; P=0.03), left ventricular ejection fraction (β=-0.26; P=0.003), and age (β=0.17; P=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study.

Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

PubMed Central

Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

2010-01-01

Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells.

PubMed

Kátai, Emese; Pál, József; Poór, Viktor Soma; Purewal, Rupeena; Miseta, Attila; Nagy, Tamás

2016-12-01

O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H 2 O 2 for 30 min. to induce oxidative stress. We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. In conclusion, our results show that temporary elevation in O-GlcNAc modification after H 2 O 2 -induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Assessing Human Health Risk to Endocrine Disrupting Chemicals: a Focus on Prenatal Exposures and Oxidative Stress

PubMed Central

Neier, Kari; Marchlewicz, Elizabeth H.; Dolinoy, Dana C.; Padmanabhan, Vasantha

2016-01-01

Understanding the health risk posed by endocrine disrupting chemicals (EDCs) is a challenge that is receiving intense attention. The following study criteria should be considered to facilitate risk assessment for exposure to EDCs: 1) characterization of target health outcomes and their mediators, 2) study of exposures in the context of critical periods of development, 3) accurate estimates of human exposures and use of human-relevant exposures in animal studies, and 4) cross-species comparisons. In this commentary, we discuss the importance and relevance of each of these criteria in studying the effects of prenatal exposure to EDCs. Our discussion focuses on oxidative stress as a mediator of EDC-related health effects due to its association with both EDC exposure and health outcomes. Our recent study (Veiga-Lopez et al. 2015)1 addressed each of the four outlined criteria and demonstrated that prenatal bisphenol-A exposure is associated with oxidative stress, a risk factor for developing diabetes and cardiovascular diseases in adulthood. PMID:27231701

Oxidant induced alteration of carbohydrate production and allocation in plants

Treesearch

Robert L. Heath

1998-01-01

Urban air basin produced oxidants, notably ozone, induce a decline in productivity in plants. This loss of productivity is manifested by slower growth, hindered development, lower reproduction rates, impaired ability to resist disease, and other stresses. While many metabolic events have been linked to oxidant exposure, three major shifts have been well-studied:...

The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

PubMed

Oliver, Shüné V; Brooke, Basil D

2016-01-01

Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and insecticide resistance phenotype in malaria vectors.

Mitochondria inheritance is a key factor for tolerance to dehydration in wine yeast production.

PubMed

Picazo, C; Gamero-Sandemetrio, E; Orozco, H; Albertin, W; Marullo, P; Matallana, E; Aranda, A

2015-03-01

Mitochondria are the cell's powerhouse when organisms are grown in the presence of oxygen. They are also the source of reactive oxygen species that cause damage to the biochemical components of the cell and lead to cellular ageing and death. Under winemaking conditions, Saccharomyces yeasts exclusively have a fermentative metabolism due to the high sugar content of grape must. However, their production as an active dry yeast (ADY) form required aerobic propagation and a dehydration process. In these industrial steps, oxidative stress is particularly harmful for the cell. In this work, we analysed the impact of the mitochondrial genome on oxidative stress response, longevity and dehydration tolerance using the synthetic interspecific hybrids obtained between two S. cerevisiae and S. uvarum strains. The isogenic nature of nuclear DNA of such hybrids allowed us to analyse the impact of mitochondrial DNA for fermentative and oxidative stress conditions. Under grape must conditions, the inheritance of mitochondrial DNA poorly impacted the fermentative performance of interspecific hybrids, unlike the hybrids with S. cerevisiae mitochondrial inheritance, which displayed increased tolerance to oxidative stress and dehydration, and showed an extended chronological longevity when cells were grown with aeration. In modern oenology, yeast starters are employed to inoculate grape juice, usually in the form of active dry yeast (ADY). The dehydration process implies stressful conditions that lead to oxidative damage. Other yeast species and interspecific hybrids other than Saccharomyces cerevisiae may be used to confer novel properties to the final product. However, these yeasts are usually more sensitive to drying. Understanding the causes of oxidative stress tolerance is therefore necessary for developing the use of these organisms in industry. This study indicates the impact of mitochondrial DNA inheritance for oxidative stress resistance in an interspecific context using isogenic Saccharomyces cerevisiae × Saccharomyces uvarum hybrids. © 2014 The Society for Applied Microbiology.

Establishment of pancreatic microenvironment model of ER stress: Quercetin attenuates β-cell apoptosis by invoking nitric oxide-cGMP signaling in endothelial cells.

PubMed

Suganya, Natarajan; Mani, Krishna Priya; Sireesh, Dornadula; Rajaguru, Palanisamy; Vairamani, Mariappanadar; Suresh, Thiruppathi; Suzuki, Takayoshi; Chatterjee, Suvro; Ramkumar, Kunka Mohanram

2018-05-01

The involvement of endoplasmic reticulum (ER) stress in endothelial dysfunction and diabetes-associated complications has been well documented. Inhibition of ER stress represents a promising therapeutic strategy to attenuate endothelial dysfunction in diabetes. Recent attention has focused on the development of small molecule inhibitors of ER stress to maintain endothelial homeostasis in diabetes. Here we have developed a reliable, robust co-culture system that allows a study on the endothelial cells and pancreatic β-cells crosstalk under ER stress and validated using a known ER stress modulator, quercetin. Furthermore, sensitizing of endothelial cells by quercetin (25 μM) confers protection of pancreatic β-cells against ER stress through nitric oxide (NO ∙ ) signaling. In addition, increased intracellular insulin and NO ∙ -mediated cyclic 3',5'-guanosine monophosphate (cGMP) levels in pancreatic β-cells further confirmed the mechanism of protection under co-culture system. In addition, the potential protein targets of quercetin against ER stress in the endothelial cells were investigated through proteomic profiling and its phosphoprotein targets through Bioplex analysis. On the whole, the developed in vitro co-culture set up can serve as a platform to study the signaling network between the endothelial and pancreatic β-cells as well as provides a mechanistic insight for the validation of novel ER stress modulators. Copyright © 2018 Elsevier Inc. All rights reserved.

Oxidation- and Creep-Enhanced Fatigue of Haynes 188 Alloy-Oxide Scale System Under Simulated Pulse Detonation Engine Conditions

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Fox, Dennis S.; Miller, Robert A.

2002-01-01

The development of the pulse detonation engine (PDE) requires robust design of the engine components that are capable of enduring harsh detonation environments. In this study, a high cycle thermal fatigue test rig was developed for evaluating candidate PDE combustor materials using a CO2 laser. The high cycle thermal fatigue behavior of Haynes 188 alloy was investigated under an enhanced pulsed laser test condition of 30 Hz cycle frequency (33 ms pulse period, and 10 ms pulse width including 0.2 ms pulse spike). The temperature swings generated by the laser pulses near the specimen surface were characterized by using one-dimensional finite difference modeling combined with experimental measurements. The temperature swings resulted in significant thermal cyclic stresses in the oxide scale/alloy system, and induced extensive surface cracking. Striations of various sizes were observed at the cracked surfaces and oxide/alloy interfaces under the cyclic stresses. The test results indicated that oxidation and creep-enhanced fatigue at the oxide scale/alloy interface was an important mechanism for the surface crack initiation and propagation under the simulated PDE condition.

Oxidative stress, redox stress or redox success?

PubMed

Gutteridge, John M C; Halliwell, Barry

2018-05-09

The first life forms evolved in a highly reducing environment. This reduced state is still carried by cells today, which makes the concept of "reductive stress" somewhat redundant. When oxygen became abundant on the Earth, due to the evolution of photosynthesis, life forms had to adapt or become extinct. Living organisms did adapt, proliferated and an explosion of new life forms resulted, using reactive oxygen species (ROS) to drive their evolution. Adaptation to oxygen and its reduction intermediates necessitated the simultaneous evolution of select antioxidant defences, carefully regulated to allow ROS to perform their major roles. Clearly this "oxidative stress" did not cause a major problem to the evolution of complex life forms. Why not? Iron and oxygen share a close relationship in aerobic evolution. Iron is used in proteins to transport oxygen, promote electron transfers, and catalyse chemical reactions. In all of these functions, iron is carefully sequestered within proteins and restricted from reacting with ROS, this sequestration being one of our major antioxidant defences. Iron was abundant to life forms before the appearance of oxygen. However, oxygen caused its oxidative precipitation from solution and thereby decreased its bioavailability and thus the risk of iron-dependent oxidative damage. Micro-organisms had to adapt and develop strategies involving siderophores to acquire iron from the environment and eventually their host. This battle for iron between bacteria and animal hosts continues today, and is a much greater daily threat to our survival than "oxidative stress" and "redox stress". Copyright © 2018. Published by Elsevier Inc.

Transgenic Alfalfa Plants Expressing the Sweetpotato Orange Gene Exhibit Enhanced Abiotic Stress Tolerance

PubMed Central

Wang, Zhi; Ke, Qingbo; Kim, Myoung Duck; Kim, Sun Ha; Ji, Chang Yoon; Jeong, Jae Cheol; Lee, Haeng-Soon; Park, Woo Sung; Ahn, Mi-Jeong; Li, Hongbing; Xu, Bingcheng; Deng, Xiping; Lee, Sang-Hoon; Lim, Yong Pyo; Kwak, Sang-Soo

2015-01-01

Alfalfa (Medicago sativa L.), a perennial forage crop with high nutritional content, is widely distributed in various environments worldwide. We recently demonstrated that the sweetpotato Orange gene (IbOr) is involved in increasing carotenoid accumulation and enhancing resistance to multiple abiotic stresses. In this study, in an effort to improve the nutritional quality and environmental stress tolerance of alfalfa, we transferred the IbOr gene into alfalfa (cv. Xinjiang Daye) under the control of an oxidative stress-inducible peroxidase (SWPA2) promoter through Agrobacterium tumefaciens-mediated transformation. Among the 11 transgenic alfalfa lines (referred to as SOR plants), three lines (SOR2, SOR3, and SOR8) selected based on their IbOr transcript levels were examined for their tolerance to methyl viologen (MV)-induced oxidative stress in a leaf disc assay. The SOR plants exhibited less damage in response to MV-mediated oxidative stress and salt stress than non-transgenic plants. The SOR plants also exhibited enhanced tolerance to drought stress, along with higher total carotenoid levels. The results suggest that SOR alfalfa plants would be useful as forage crops with improved nutritional value and increased tolerance to multiple abiotic stresses, which would enhance the development of sustainable agriculture on marginal lands. PMID:25946429

Transgenic alfalfa plants expressing the sweetpotato Orange gene exhibit enhanced abiotic stress tolerance.

PubMed

Wang, Zhi; Ke, Qingbo; Kim, Myoung Duck; Kim, Sun Ha; Ji, Chang Yoon; Jeong, Jae Cheol; Lee, Haeng-Soon; Park, Woo Sung; Ahn, Mi-Jeong; Li, Hongbing; Xu, Bingcheng; Deng, Xiping; Lee, Sang-Hoon; Lim, Yong Pyo; Kwak, Sang-Soo

2015-01-01

Alfalfa (Medicago sativa L.), a perennial forage crop with high nutritional content, is widely distributed in various environments worldwide. We recently demonstrated that the sweetpotato Orange gene (IbOr) is involved in increasing carotenoid accumulation and enhancing resistance to multiple abiotic stresses. In this study, in an effort to improve the nutritional quality and environmental stress tolerance of alfalfa, we transferred the IbOr gene into alfalfa (cv. Xinjiang Daye) under the control of an oxidative stress-inducible peroxidase (SWPA2) promoter through Agrobacterium tumefaciens-mediated transformation. Among the 11 transgenic alfalfa lines (referred to as SOR plants), three lines (SOR2, SOR3, and SOR8) selected based on their IbOr transcript levels were examined for their tolerance to methyl viologen (MV)-induced oxidative stress in a leaf disc assay. The SOR plants exhibited less damage in response to MV-mediated oxidative stress and salt stress than non-transgenic plants. The SOR plants also exhibited enhanced tolerance to drought stress, along with higher total carotenoid levels. The results suggest that SOR alfalfa plants would be useful as forage crops with improved nutritional value and increased tolerance to multiple abiotic stresses, which would enhance the development of sustainable agriculture on marginal lands.

Parameters for measurement of oxidative stress in diabetes mellitus: applicability of enzyme-linked immunosorbent assay for clinical evaluation.

PubMed

Noiri, Eisei; Tsukahara, Hirokazu

2005-05-01

Investigations of the mechanisms involved in the onset and progression of diabetes have recently confronted the role of reactive oxygen species (ROS) and oxidative stress. Prolonged exposure to hyperglycemic conditions induces nonenzymatic glycation of protein via the so-called Maillard reaction, resulting in Schiff-base products and Amadori products that engender ROS production. These processes initiate and exacerbate micro- and macrovascular complications in diabetes. Increased oxidative stress is induced by excessive ROS production and inadequate antioxidant defenses. Recently, oxidative stress status markers have been associated directly with the severity and prognosis of diabetes. To examine oxidative stress, reliable and high-throughput methods are needed to examine large numbers of clinical samples. The emerging availability of enzyme-linked immunosorbent assay (ELISA) for oxidative stress status markers allows its application to assessment of various pathophysiologic conditions, including diabetes. This review outlines the recent achievements of ELISA application for clinical studies elucidating oxidative stress. It introduces the potential applicability of ELISA for investigating oxidative stress in diabetes.

Towards an Integrated View of Early Molecular Changes Underlying Vulnerability to Social Stress in Psychosis.

PubMed

Barron, Henry; Hafizi, Sina; Mizrahi, Romina

2017-01-01

Psychotic disorders are heterogeneous and complex, involving many putative causal factors interacting along the course of disease development. Many of the factors implicated in the pathogenesis of psychosis also appear to be involved in disease onset and subsequent neuroprogression. Herein, we highlight the pertinent literature implicating inflammation and oxidative stress in the pathogenesis of psychosis, and the potential contribution of N-methyl-D-aspartate receptors (NMDARs). We also emphasize the role of peripubertal social stress in psychosis, and the ways in which hippocampal dysfunction can mediate dysregulation of the hypothalamic-pituitary-adrenal axis and cortisol release. Finally, we propose a model wherein inflammation and oxidative stress act as a first hit, producing altered parvalbumin interneuron development, NMDAR hypofunction, microglial priming, and sensitivity to a second hit of peripubertal social stress. With a greater understanding of how these factors interact, it may be possible to detect, prevent, and treat psychosis more effectively. © 2017 S. Karger AG, Basel.

Staphylococcus aureus CymR Is a New Thiol-based Oxidation-sensing Regulator of Stress Resistance and Oxidative Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ji, Quanjiang; Zhang, Liang; Sun, Fei

As a human pathogen, Staphylococcus aureus must cope with oxidative stress generated by the human immune system. Here, we report that CymR utilizes its sole Cys-25 to sense oxidative stress. Oxidation followed by thiolation of this cysteine residue leads to dissociation of CymR from its cognate promoter DNA. In contrast, the DNA binding of the CymRC25S mutant was insensitive to oxidation and thiolation, suggesting that CymR senses oxidative stress through oxidation of its sole cysteine to form a mixed disulfide with low molecular weight thiols. The determined crystal structures of the reduced and oxidized forms of CymR revealed that Cys-25more » is oxidized to Cys-25-SOH in the presence of H{sub 2}O{sub 2}. Deletion of cymR reduced the resistance of S. aureus to oxidative stresses, and the resistance was restored by expressing a C25S mutant copy of cymR. In a C25S substitution mutant, the expression of two genes, tcyP and mccB, was constitutively repressed and did not respond to hydrogen peroxide stress, whereas the expression of the genes were highly induced under oxidative stress in a wild-type strain, indicating the critical role of Cys-25 in redox signaling in vivo. Thus, CymR is another master regulator that senses oxidative stress and connects stress responses to virulence regulation in S. aureus.« less

The mechanisms associated with the development of hypertension after exposure to lead, mercury species or their mixtures differs with the metal and the mixture ratio.

PubMed

Wildemann, Tanja M; Siciliano, Steven D; Weber, Lynn P

2016-01-02

Hypertension is considered to be the most important risk factor for the development of cardiovascular diseases. Beside life-style risk factors, exposure to lead and mercury species are increasingly discussed as potential risk factors. Although there are a few previous studies, the underlying mechanism by which exposure to lead and mercury disturb blood pressure regulation is not currently understood. Potential mechanisms are oxidative stress production, kidney damage and activation of the renin-angiotensin system (RAS), all of which can interact to cause dysregulation of blood pressure. Male rats (Wistar) were exposed to lead, inorganic mercury, methylmercury or two mixtures of all three metals for four weeks through the drinking water. The two mixture ratios were based on ratios of known reference values or environmental exposure from the literature. To investigate the potential mechanism of actions, blood pressure was measured after four weeks and compared to plasma nitrotyrosine or reduced/oxidized glutathione levels in liver as markers for oxidative stress. Plasma renin and angiotensin II levels were used as markers for RAS activation. Finally, kidney function and injury were assessed via urinary and plasma creatinine levels, creatinine clearance and urinary kidney-injury molecule (KIM-1). While exposure to lead by itself increased oxidative stress and kidney damage along with blood pressure, inorganic mercury did not affect blood pressure or any end-point examined. Conversely, methylmercury instead increased RAS activation along with blood pressure. Surprisingly, when administered as mixtures, lead no longer increased oxidative stress or altered kidney function. Moreover, the mixture based on an environmental ratio no longer had an effect on blood pressure, while the reference value ratio still retained an increase in blood pressure. Based on our results, the prominent mechanism of action associated with the development of hypertension seems to be oxidative stress and kidney damage for lead, while increased RAS activation links methylmercury to hypertension, but these mechanisms along with hypertension disappear when metals are present in some mixtures. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis.

PubMed

Forsyth, Christopher B; Farhadi, Ashkan; Jakate, Shriram M; Tang, Yueming; Shaikh, Maliha; Keshavarzian, Ali

2009-03-01

Because only 30% of alcoholics develop alcoholic liver disease (ALD), a factor other than heavy alcohol consumption must be involved in the development of alcohol-induced liver injury. Animal and human studies suggest that bacterial products, such as endotoxins, are the second key co-factors, and oxidant-mediated gut leakiness is one of the sources of endotoxemia. Probiotics have been used to prevent and treat diseases associated with gut-derived bacterial products and disorders associated with gut leakiness. Indeed, "probiotic"Lactobacillus rhamnosus has been successfully used to treat alcohol-induced liver injury in rats. However, the mechanism of action involved in the potential beneficial effects of L. rhamnosus in alcohol liver injury is not known. We hypothesized that probiotics could preserve normal barrier function in an animal model of ALD by preventing alcohol-induced oxidative stress and thus prevent the development of hyperpermeability and subsequent alcoholic steatohepatitis (ASH). Male Sprague-Dawley rats were gavaged with alcohol twice daily (8 gm/kg) for 10 weeks. In addition, alcoholic rats were also treated with once daily gavage of either 2.5 x 10(7) live L. rhamnosus Gorbach-Goldin (LGG) or vehicle (V). Intestinal permeability (baseline and at 10 weeks) was determined using a sugar bolus and GC analysis of urinary sugars. Intestinal and liver tissues were analyzed for markers of oxidative stress and inflammation. In addition, livers were assessed histologically for severity of ASH and total fat (steatosis). Alcohol+LGG (ALC+LGG)-fed rats had significantly (P< or =.05) less severe ASH than ALC+V-fed rats. L. rhamnosus Gorbach-Goldin also reduced alcohol-induced gut leakiness and significantly blunted alcohol-induced oxidative stress and inflammation in both intestine and the liver. L. rhamnosus Gorbach-Goldin probiotic gavage significantly ameliorated ASH in rats. This improvement was associated with reduced markers of intestinal and liver oxidative stress and inflammation and preserved gut barrier function. Our study provides a scientific rationale to test probiotics for treatment and/or prevention of alcoholic liver disease in man.

Environmental protection to 922K (1200 F) for titanium alloys

NASA Technical Reports Server (NTRS)

Groves, M. T.

1973-01-01

Evaluations are presented of potential coating systems for protection of titanium alloys from hot-salt stress-corrosion up to temperatures of 755 K (900 F) and from oxidation embrittlement up to temperature of 922 K (1200 F). Diffusion type coatings containing Si, Al, Cr, Ni or Fe as single coating elements or in various combinations were evaluated for oxidation protection, hot-salt stress-corrosion (HSSC) resistance, effects on tensile properties, fatigue properties, erosion resistance and ballistic impact resistance on an alpha and beta phase titanium alloy (Ti-6Al-2Sn-4Zr-2Mo). All of the coatings investigated demonstrated excellent oxidation protectiveness, but none of the coatings provided protection from hot-salt stress-corrosion. Experimental results indicated that both the aluminide and silicide types of coatings actually decreased the HSSC resistance of the substrate alloy. The types of coatings which have typically been used for oxidation protection of refractory metals and nickel base superalloys are not suitable for titanium alloys because they increase the susceptibility to hot-salt stress-corrosion, and that entirely new coating concepts must be developed for titanium alloy protection in advanced turbine engines.

Optical cryoimaging of rat kidney and the effective role of chromosome 13 in salt-induced hypertension

NASA Astrophysics Data System (ADS)

Salehpour, F.; Yang, C.; Kurth, T.; Cowley, A. W.; Ranji, M.

2015-03-01

The objective of this work is to assess oxidative stress levels in salt-sensitive hypertension animal model using 3D optical cryoimager to image mitochondrial redox ratio. We studied Dahl salt-induced (SS) rats, and compared the results with a consomic SS rat strain (SSBN13). The SSBN13 strain was developed by the introgression of chromosome from the Brown Norway (BN) rat into the salt-sensitive (SS) genetic background and exhibits significant protection from salt induced hypertension1 . These two groups were fed on a high salt diet of 8.0% NaCl for one week. Mitochondrial redox ratio (NADH/FAD=NADH RR), was used as a quantitative marker of the oxidative stress in kidney tissue. Maximum intensity projected images and their corresponding histograms in each group were acquired from each kidney group. The result showed a 49% decrease in mitochondrial redox ratio of SS compared to SSBN13 translated to an increase in the level of oxidative stress of the tissue. Therefore, the results quantify oxidative stress levels and its effect on mitochondrial redox in salt sensitive hypertension.

Thermosensitive hydrogel made of ferulic acid-gelatin and chitosan glycerophosphate.

PubMed

Cheng, Yung-Hsin; Yang, Shu-Hua; Liu, Chia-Ching; Gefen, Amit; Lin, Feng-Huei

2013-02-15

Reactive oxygen species-induced oxidative stress is involved in apoptosis of nucleus pulposus (NP) cells that can alter cellular phenotype and accelerate disc degeneration. Ferulic acid (FA) possesses an excellent antioxidant and anti-inflammatory properties. In the study, we developed the thermosensitive FA-gelatin/chitosan/glycerol phosphate (FA-G/C/GP) hydrogel which was applied as a sustained release system of FA to treat NP cells from the damage caused by oxidative stress. The gelation temperature of the FA-G/C/GP hydrogel was 32.17 °C. NP cells submitted to oxidative stress promoted by H(2)O(2), and post-treated with FA-G/C/GP exhibited down-regulation of MMP-3 and up-regulation aggrecan and type II collagen in mRNA level. The sulfated-glycosaminoglycan production was increased and the apoptosis was inhibited in the post-treatment group. The results suggest that the thermosensitive FA-G/C/GP hydrogel can treat NP cells from the damage caused by oxidative stress and may apply in minimally invasive surgery for NP regeneration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cerebral Small Vessel Disease: Targeting Oxidative Stress as a Novel Therapeutic Strategy?

PubMed Central

De Silva, T. Michael; Miller, Alyson A.

2016-01-01

Cerebral small vessel disease (SVD) is a major contributor to stroke, and a leading cause of cognitive impairment and dementia. Despite the devastating effects of cerebral SVD, the pathogenesis of cerebral SVD is still not completely understood. Moreover, there are no specific pharmacological strategies for its prevention or treatment. Cerebral SVD is characterized by marked functional and structural abnormalities of the cerebral microcirculation. The clinical manifestations of these pathological changes include lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. The main purpose of this review is to discuss evidence implicating oxidative stress in the arteriopathy of both non-amyloid and amyloid (cerebral amyloid angiopathy) forms of cerebral SVD and its most important risk factors (hypertension and aging), as well as its contribution to cerebral SVD-related brain injury and cognitive impairment. We also highlight current evidence of the involvement of the NADPH oxidases in the development of oxidative stress, enzymes that are a major source of reactive oxygen species in the cerebral vasculature. Lastly, we discuss potential pharmacological strategies for oxidative stress in cerebral SVD, including some of the historical and emerging NADPH oxidase inhibitors. PMID:27014073

Calcium and Calmodulin Are Involved in Nitric Oxide-Induced Adventitious Rooting of Cucumber under Simulated Osmotic Stress

PubMed Central

Niu, Lijuan; Yu, Jian; Liao, Weibiao; Yu, Jihua; Zhang, Meiling; Dawuda, Mohammed M.

2017-01-01

Osmotic stress is a major form of abiotic stress that adversely affects growth and development of plants and subsequently reduces yield and quality of crops. In this study, the effect of nitric oxide (NO) and calcium (Ca2+) on the process of adventitious rooting in cucumber (Cucumis sativus L.) under simulated osmotic stress was investigated. The results revealed that the effect of exogenous NO and Ca2+ in promoting the development of adventitious roots in cucumber seedlings under simulated osmotic stress was dose-dependent, with a maximal biological response at 10 μM NO donor nitroprusside (SNP) or 200 μM Ca2+. The application of Ca2+ chelators or channel inhibitors and calmodulin (CaM) antagonists significantly reversed NO-induced adventitious rooting, implying that endogenous Ca2+/CaM might be involved in NO-induced adventitious rooting under osmotic stress. Moreover, intracellular Ca amount was also increased by NO in cucumber hypocotyls during the development of adventitious roots under osmotic stress. This increase of endogenous Ca2+ was inhibited by NO specific scavenger 2-(4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO), nitrate reductase inhibitors tungstate (Na2WO4) and sodium azide (NaN3). This gives an indication that Ca2+ might be a downstream signaling molecule in the adventitious root development by NO under osmotic condition. The results also show that NO or Ca2+ play a positive role in improving plant water status and photosynthetic system by increasing chlorophyll content and photochemical activity in leaves. Furthermore, NO and Ca2+ treatment might alleviate the negative effects of osmotic stress by decreasing membrane damage and reactive oxygen species (ROS) production by enhancing the activities of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX). Therefore, Ca2+/CaM may act as a downstream signaling molecule in NO-induced development of adventitious root under simulated osmotic stress through improving the photosynthetic performance of leaves and activating antioxidative system in plants. PMID:29021804

Calcium and Calmodulin Are Involved in Nitric Oxide-Induced Adventitious Rooting of Cucumber under Simulated Osmotic Stress.

PubMed

Niu, Lijuan; Yu, Jian; Liao, Weibiao; Yu, Jihua; Zhang, Meiling; Dawuda, Mohammed M

2017-01-01

Osmotic stress is a major form of abiotic stress that adversely affects growth and development of plants and subsequently reduces yield and quality of crops. In this study, the effect of nitric oxide (NO) and calcium (Ca 2+ ) on the process of adventitious rooting in cucumber ( Cucumis sativus L.) under simulated osmotic stress was investigated. The results revealed that the effect of exogenous NO and Ca 2+ in promoting the development of adventitious roots in cucumber seedlings under simulated osmotic stress was dose-dependent, with a maximal biological response at 10 μM NO donor nitroprusside (SNP) or 200 μM Ca 2+ . The application of Ca 2+ chelators or channel inhibitors and calmodulin (CaM) antagonists significantly reversed NO-induced adventitious rooting, implying that endogenous Ca 2+ /CaM might be involved in NO-induced adventitious rooting under osmotic stress. Moreover, intracellular Ca amount was also increased by NO in cucumber hypocotyls during the development of adventitious roots under osmotic stress. This increase of endogenous Ca 2+ was inhibited by NO specific scavenger 2-(4-carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO), nitrate reductase inhibitors tungstate (Na 2 WO 4 ) and sodium azide (NaN 3 ) . This gives an indication that Ca 2+ might be a downstream signaling molecule in the adventitious root development by NO under osmotic condition. The results also show that NO or Ca 2+ play a positive role in improving plant water status and photosynthetic system by increasing chlorophyll content and photochemical activity in leaves. Furthermore, NO and Ca 2+ treatment might alleviate the negative effects of osmotic stress by decreasing membrane damage and reactive oxygen species (ROS) production by enhancing the activities of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX). Therefore, Ca 2+ /CaM may act as a downstream signaling molecule in NO-induced development of adventitious root under simulated osmotic stress through improving the photosynthetic performance of leaves and activating antioxidative system in plants.

Interdependence of tetrapyrrole metabolism, the generation of oxidative stress and the mitigative oxidative stress response

PubMed Central

Busch, Andrea W.U.; Montgomery, Beronda L.

2015-01-01

Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms. PMID:25618582

Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight.

PubMed

Schoenfeld, Michael P; Ansari, Rafat R; Zakrajsek, June F; Billiar, Timothy R; Toyoda, Yoshiya; Wink, David A; Nakao, Atsunori

2011-01-01

Cosmic radiation is known to induce DNA and lipid damage associated with increased oxidative stress and remains a major concern in space travel. Hydrogen, recently discovered as a novel therapeutic medical gas in a variety of biomedical fields, has potent antioxidant and anti-inflammatory activities. It is expected that space mission activities will increase in coming years both in numbers and duration. It is therefore important to estimate and prevent the risks encountered by astronauts due to oxidative stress prior to developing clinical symptoms of disease. We hypothesize that hydrogen administration to the astronauts by either inhalation or drinking hydrogen-rich water may potentially yield a novel and feasible preventative/therapeutic strategy to prevent radiation-induced adverse events. Copyright © 2010 Elsevier Ltd. All rights reserved.

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism.

PubMed

Parker, William; Hornik, Chi Dang; Bilbo, Staci; Holzknecht, Zoie E; Gentry, Lauren; Rao, Rasika; Lin, Shu S; Herbert, Martha R; Nevison, Cynthia D

2017-04-01

The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic breakdown of pharmaceuticals during early development. Thus, one explanation for the increased prevalence of autism is that increased exposure to acetaminophen, exacerbated by inflammation and oxidative stress, is neurotoxic in babies and small children. This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth.

Oxidative Stressors Modify the Response of Streptococcus mutans to Its Competence Signal Peptides.

PubMed

De Furio, Matthew; Ahn, Sang Joon; Burne, Robert A; Hagen, Stephen J

2017-11-15

The dental caries pathogen Streptococcus mutans is continually exposed to several types of stress in the oral biofilm environment. Oxidative stress generated by reactive oxygen species has a major impact on the establishment, persistence, and virulence of S. mutans Here, we combined fluorescent reporter-promoter fusions with single-cell imaging to study the effects of reactive oxygen species on activation of genetic competence in S. mutans Exposure to paraquat, which generates superoxide anion, produced a qualitatively different effect on activation of expression of the gene for the master competence regulator, ComX, than did treatment with hydrogen peroxide (H 2 O 2 ), which can yield hydroxyl radical. Paraquat suppressed peptide-mediated induction of comX in a progressive and cumulative fashion, whereas the response to H 2 O 2 displayed a strong threshold behavior. Low concentrations of H 2 O 2 had little effect on induction of comX or the bacteriocin gene cipB , but expression of these genes declined sharply if extracellular H 2 O 2 exceeded a threshold concentration. These effects were not due to decreased reporter gene fluorescence. Two different threshold concentrations were observed in the response to H 2 O 2 , depending on the gene promoter that was analyzed and the pathway by which the competence regulon was stimulated. The results show that paraquat and H 2 O 2 affect the S. mutans competence signaling pathway differently, and that some portions of the competence signaling pathway are more sensitive to oxidative stress than others. IMPORTANCE Streptococcus mutans inhabits the oral biofilm, where it plays an important role in the development of dental caries. Environmental stresses such as oxidative stress influence the growth of S. mutans and its important virulence-associated behaviors, such as genetic competence. S. mutans competence development is a complex behavior that involves two different signaling peptides and can exhibit cell-to-cell heterogeneity. Although oxidative stress is known to influence S. mutans competence, it is not understood how oxidative stress interacts with the peptide signaling or affects heterogeneity. In this study, we used fluorescent reporters to probe the effect of reactive oxygen species on competence signaling at the single-cell level. Our data show that different reactive oxygen species have different effects on S. mutans competence, and that some portions of the signaling pathway are more acutely sensitive to oxidative stress than others. Copyright © 2017 American Society for Microbiology.

The glutathione mimic ebselen inhibits oxidative stress but not endoplasmic reticulum stress in endothelial cells.

PubMed

Ahwach, Salma Makhoul; Thomas, Melanie; Onstead-Haas, Luisa; Mooradian, Arshag D; Haas, Michael J

2015-08-01

Reactive oxygen species are associated with cardiovascular disease, diabetes, and atherosclerosis, yet the use of antioxidants in clinical trials has been ineffective at improving outcomes. In endothelial cells, high-dextrose-induced oxidative stress and endoplasmic reticulum stress promote endothelial dysfunction leading to the recruitment and activation of peripheral blood lymphocytes and the breakdown of barrier function. Ebselen, a glutathione peroxidase 1 (GPX1) mimic, has been shown to improve β-cell function in diabetes and prevent atherosclerosis. To determine if ebselen inhibits both oxidative stress and endoplasmic reticulum (ER) stress in endothelial cells, we examined its effects in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC) with and without high-dextrose. Oxidative stress and ER stress were measured by 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride chemiluminescence and ER stress alkaline phosphatase assays, respectively. GPX1 over-expression and knockdown were performed by transfecting cells with a GPX1 expression construct or a GPX1-specific siRNA, respectively. Ebselen inhibited dextrose-induced oxidative stress but not ER stress in both HUVEC and HCAEC. Ebselen also had no effect on tunicamycin-induced ER stress in HCAEC. Furthermore, augmentation of GPX1 activity directly by sodium selenite supplementation or transfection of a GPX1 expression plasmid decreased dextrose-induced oxidative stress but not ER stress, while GPX1 knockout enhanced oxidative stress but had no effect on ER stress. These results suggest that ebselen targets only oxidative stress but not ER stress. Copyright © 2015. Published by Elsevier Inc.

Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney.

PubMed

Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh; Samini, Fariborz

2017-03-01

Restraint stress has been indicated to induce oxidative damage in tissues. Several investigations have reported that curcumin (CUR) may have a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CUR on restraint stress induced oxidative stress damage in the brain, liver and kidneys. For chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days. The animals received systemic administrations of CUR daily for 21days. In order to evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), as well as antioxidant enzyme activities superoxide dismutase (SOD) glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were measured in the brain, liver and kidney of rats after the end of restraint stress. The restraint stress significantly increased MDA level, but decreased the level of GSH and activists of SOD, GPx, GR, and CAT the brain, liver and kidney of rats in comparison to the normal rats (P<0.001). Intraperitoneal administration of CUR significantly attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in the tissues versus the control group (P<0.05). This study shows that CUR can prevent restraint stress-induced oxidative damage in the brain, liver and kidney of rats and propose that CUR may be useful agents against oxidative stress in the tissues. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Monitoring Intracellular Redox Changes in Ozone-exposed airway epithelial cells

EPA Science Inventory

Background: The toxicity of many compounds involves oxidative injury to cells. Direct assessment of mechanistic events involved in xenobiotic-induced oxidative stress is not easily achievable. Development of genetically-encoded probes designed for monitoring intracellular redox s...

A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress.

PubMed

Chaudhari, Namrata; Talwar, Priti; Parimisetty, Avinash; Lefebvre d'Hellencourt, Christian; Ravanan, Palaniyandi

2014-01-01

Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded-protein response (UPR) through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS). Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress.

Oxidative status and serum PON1 activity in beta-thalassemia minor.

PubMed

Selek, Sahbettin; Aslan, Mehmet; Horoz, Mehmet; Gur, Mustafa; Erel, Ozcan

2007-03-01

Paraoxonase-1 (PON1) deficiency is related to increased susceptibility to low density lipoprotein oxidation and development of atherosclerosis. The aim of this study was to investigate paraoxonase and arylesterase activities along with oxidative status parameters, and to find out if there is any increased susceptibility to atherogenesis, which might be reflected with increased oxidative stress and decreased serum PON1 activity in beta-thalassemia minor (BTM) subjects. Thirty-two subjects with BTM and 28 healthy subjects as control were enrolled in the study. Serum paraoxonase and arylesterase activities, lipid hydroperoxide (LOOH) levels, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined. Serum TAC, paraoxonase and arylesterase activities were significantly lower in BTM subjects than controls (for all p<0.001), while TOS, LOOH levels and OSI were significantly higher (p<0.001, p<0.05 and p<0.001; respectively). In BTM subjects, OSI, TOS, LOOH levels and TAC were significantly correlated with serum paraoxonase (r=-0.245, p<0.05; r=-0.231, p<0.05; r=-0.264, p<0.05 and, r=0.342, p<0.05, respectively) and arylesterase activities (r=-0.332, p<0.05, r=-0.308, p<0.05; r=-0.320, p<0.05 and r=0.443, p<0.05). Additionally, hemoglobin level was also correlated with serum paraoxonase (r=0.501, p<0.001) and arylesterase activities (r=0.501, p<0.001), TAC (r=0.402, p<0.05), TOS (r=-0.274, p<0.05) and OSI (r=-0.352, p<0.05). Oxidative stress is increased, while serum PON1 activity is decreased in BTM subjects. Decrease in PON1 activity seems to be associated with both the degree of oxidative stress and anemia. BTM subjects may be more prone to development of atherogenesis due to low serum PON1 activity.

Mechanism-based genotoxicity screening of metal oxide nanoparticles using the ToxTracker panel of reporter cell lines.

PubMed

Karlsson, Hanna L; Gliga, Anda R; Calléja, Fabienne M G R; Gonçalves, Cátia S A G; Wallinder, Inger Odnevall; Vrieling, Harry; Fadeel, Bengt; Hendriks, Giel

2014-09-02

The rapid expansion of manufacturing and use of nano-sized materials fuels the demand for fast and reliable assays to identify their potential hazardous properties and underlying mechanisms. The ToxTracker assay is a recently developed mechanism-based reporter assay based on mouse embryonic stem (mES) cells that uses GFP-tagged biomarkers for detection of DNA damage, oxidative stress and general cellular stress upon exposure. Here, we evaluated the ability of the ToxTracker assay to identify the hazardous properties and underlying mechanisms of a panel of metal oxide- and silver nanoparticles (NPs) as well as additional non-metallic materials (diesel, carbon nanotubes and quartz). The metal oxide- and silver nanoparticles were characterized in terms of agglomeration and ion release in cell medium (using photon cross correlation spectroscopy and inductively coupled plasma with optical emission spectroscopy, respectively) as well as acellular ROS production (DCFH-DA assay). Cellular uptake was investigated by means of transmission electron microscopy. GFP reporter induction and cytotoxicity of the NPs was simultaneously determined using flow cytometry, and genotoxicity was further tested using conventional assays (comet assay, γ-H2AX and RAD51 foci formation). We show that the reporter cells were able to take up nanoparticles and, furthermore, that exposure to CuO, NiO and ZnO nanoparticles as well as to quartz resulted in activation of the oxidative stress reporter, although only at high cytotoxicity for ZnO. NiO NPs activated additionally a p53-associated cellular stress response, indicating additional reactive properties. Conventional assays for genotoxicity assessment confirmed the response observed in the ToxTracker assay. We show for CuO NPs that the induction of oxidative stress is likely the consequence of released Cu ions whereas the effect by NiO was related to the particles per se. The DNA replication stress-induced reporter, which is most strongly associated with carcinogenicity, was not activated by any of the tested nanoparticles. We conclude that the ToxTracker reporter system can be used as a rapid mechanism-based tool for the identification of hazardous properties of metal oxide NPs. Furthermore, genotoxicity of metal oxide NPs seems to occur mainly via oxidative stress rather than direct DNA binding with subsequent replication stress.

Endogenous ROS levels in C. elegans under exogenous stress support revision of oxidative stress theory of life-history tradeoffs.

PubMed

Smith, Samson W; Latta, Leigh C; Denver, Dee R; Estes, Suzanne

2014-07-24

The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals. Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments--consistent with the oxidative stress theory of aging. Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory.

Endogenous ROS levels in C. elegans under exogenous stress support revision of oxidative stress theory of life-history tradeoffs

PubMed Central

2014-01-01

Background The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals. Results Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments--consistent with the oxidative stress theory of aging. Conclusions Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory. PMID:25056725

Oxidative Stress in Dilated Cardiomyopathy Caused by MYBPC3 Mutation

PubMed Central

Lynch, Thomas L.; Sivaguru, Mayandi; Velayutham, Murugesan; Cardounel, Arturo J.; Michels, Michelle; Barefield, David; Govindan, Suresh; dos Remedios, Cristobal; van der Velden, Jolanda; Sadayappan, Sakthivel

2015-01-01

Cardiomyopathies can result from mutations in genes encoding sarcomere proteins including MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). However, whether oxidative stress is augmented due to contractile dysfunction and cardiomyocyte damage in MYBPC3-mutated cardiomyopathies has not been elucidated. To determine whether oxidative stress markers were elevated in MYBPC3-mutated cardiomyopathies, a previously characterized 3-month-old mouse model of dilated cardiomyopathy (DCM) expressing a homozygous MYBPC3 mutation (cMyBP-C(t/t)) was used, compared to wild-type (WT) mice. Echocardiography confirmed decreased percentage of fractional shortening in DCM versus WT hearts. Histopathological analysis indicated a significant increase in myocardial disarray and fibrosis while the second harmonic generation imaging revealed disorganized sarcomeric structure and myocyte damage in DCM hearts when compared to WT hearts. Intriguingly, DCM mouse heart homogenates had decreased glutathione (GSH/GSSG) ratio and increased protein carbonyl and lipid malondialdehyde content compared to WT heart homogenates, consistent with elevated oxidative stress. Importantly, a similar result was observed in human cardiomyopathy heart homogenate samples. These results were further supported by reduced signals for mitochondrial semiquinone radicals and Fe-S clusters in DCM mouse hearts measured using electron paramagnetic resonance spectroscopy. In conclusion, we demonstrate elevated oxidative stress in MYPBC3-mutated DCM mice, which may exacerbate the development of heart failure. PMID:26508994

Ameliorative Effects of Acacia Honey against Sodium Arsenite-Induced Oxidative Stress in Some Viscera of Male Wistar Albino Rats.

PubMed

Aliyu, Muhammad; Ibrahim, Sani; Inuwa, Hajiya M; Sallau, Abdullahi B; Abbas, Olagunju; Aimola, Idowu A; Habila, Nathan; Uche, Ndidi S

2013-01-01

Cancer is a leading cause of death worldwide and its development is frequently associated with oxidative stress-induced by carcinogens such as arsenicals. Most foods are basically health-promoting or disease-preventing and a typical example of such type is honey. This study was undertaken to investigate the ameliorative effects of Acacia honey on sodium arsenite-induced oxidative stress in the heart, lung and kidney tissues of male Wistar rats. Male Wistar albino rats divided into four groups of five rats each were administered distilled water, Acacia honey (20%), sodium arsenite (5 mg/kg body weight), Acacia honey, and sodium arsenite daily for one week. They were sacrificed anesthetically using 60 mg/kg sodium pentothal. The tissues were used for the assessment of glutathione peroxidase, catalase, and superoxide dismutase activities, protein content and lipid peroxidation. Sodium arsenite significantly (P < 0.05) suppressed the glutathione peroxidase, catalase, superoxide dismutase activities with simultaneous induction of lipid peroxidation. Administration of Acacia honey significantly increased (P < 0.05) glutathione peroxidase, catalase, and superoxide dismutase activities with concomitant suppression of lipid peroxidation as evident by the decrease in malondialdehyde level. From the results obtained, Acacia honey mitigates sodium arsenite induced-oxidative stress in male Wistar albino rats, which suggest that it may attenuate oxidative stress implicated in chemical carcinogenesis.

Redox Regulation of Plant Development

PubMed Central

Considine, Michael J.

2014-01-01

Abstract Significance: We provide a conceptual framework for the interactions between the cellular redox signaling hub and the phytohormone signaling network that controls plant growth and development to maximize plant productivity under stress-free situations, while limiting growth and altering development on exposure to stress. Recent Advances: Enhanced cellular oxidation plays a key role in the regulation of plant growth and stress responses. Oxidative signals or cycles of oxidation and reduction are crucial for the alleviation of dormancy and quiescence, activating the cell cycle and triggering genetic and epigenetic control that underpin growth and differentiation responses to changing environmental conditions. Critical Issues: The redox signaling hub interfaces directly with the phytohormone network in the synergistic control of growth and its modulation in response to environmental stress, but a few components have been identified. Accumulating evidence points to a complex interplay of phytohormone and redox controls that operate at multiple levels. For simplicity, we focus here on redox-dependent processes that control root growth and development and bud burst. Future Directions: The multiple roles of reactive oxygen species in the control of plant growth and development have been identified, but increasing emphasis should now be placed on the functions of redox-regulated proteins, along with the central roles of reductants such as NAD(P)H, thioredoxins, glutathione, glutaredoxins, peroxiredoxins, ascorbate, and reduced ferredoxin in the regulation of the genetic and epigenetic factors that modulate the growth and vigor of crop plants, particularly within an agricultural context. Antioxid. Redox Signal. 21, 1305–1326. PMID:24180689

Good Stress, Bad Stress and Oxidative Stress: Insights from Anticipatory Cortisol Reactivity

PubMed Central

Aschbacher, Kirstin; O'Donovan, Aoife; Wolkowitz, Owen M.; Dhabhar, Firdaus S.; Su, Yali; Epel, Elissa

2014-01-01

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F2α (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-OxoG) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as “peak” cortisol reactivity, while the increase from 0 to 15 min was defined as “anticipatory” cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-OxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01.) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the Hypothalamic-Pituitary-Adrenal axis. It also supports the less studied model of ‘eustress’ - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage. PMID:23490070

Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity.

PubMed

Aschbacher, Kirstin; O'Donovan, Aoife; Wolkowitz, Owen M; Dhabhar, Firdaus S; Su, Yali; Epel, Elissa

2013-09-01

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less studied model of 'eustress' - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage. Copyright © 2013 Elsevier Ltd. All rights reserved.

Implantation of Neural Probes in the Brain Elicits Oxidative Stress

PubMed Central

Ereifej, Evon S.; Rial, Griffin M.; Hermann, John K.; Smith, Cara S.; Meade, Seth M.; Rayyan, Jacob M.; Chen, Keying; Feng, He; Capadona, Jeffrey R.

2018-01-01

Clinical implantation of intracortical microelectrodes has been hindered, at least in part, by the perpetual inflammatory response occurring after device implantation. The neuroinflammatory response observed after device implantation has been correlated to oxidative stress that occurs due to neurological injury and disease. However, there has yet to be a definitive link of oxidative stress to intracortical microelectrode implantation. Thus, the objective of this study is to give direct evidence of oxidative stress following intracortical microelectrode implantation. This study also aims to identify potential molecular targets to attenuate oxidative stress observed postimplantation. Here, we implanted adult rats with silicon non-functional microelectrode probes for 4 weeks and compared the oxidative stress response to no surgery controls through postmortem gene expression analysis and qualitative histological observation of oxidative stress markers. Gene expression analysis results at 4 weeks postimplantation indicated that EH domain-containing 2, prion protein gene (Prnp), and Stearoyl-Coenzyme A desaturase 1 (Scd1) were all significantly higher for animals implanted with intracortical microelectrode probes compared to no surgery control animals. To the contrary, NADPH oxidase activator 1 (Noxa1) relative gene expression was significantly lower for implanted animals compared to no surgery control animals. Histological observation of oxidative stress showed an increased expression of oxidized proteins, lipids, and nucleic acids concentrated around the implant site. Collectively, our results reveal there is a presence of oxidative stress following intracortical microelectrode implantation compared to no surgery controls. Further investigation targeting these specific oxidative stress linked genes could be beneficial to understanding potential mechanisms and downstream therapeutics that can be utilized to reduce oxidative stress-mediated damage following microelectrode implantation. PMID:29487848

Oxidative stress and decreased thiol level in patients with migraine: cross-sectional study.

PubMed

Eren, Yasemin; Dirik, Ebru; Neşelioğlu, Salim; Erel, Özcan

2015-12-01

Although migraine is a neurological disorder known since long, its physiopathology remains unclear. Recent studies suggest that migraine is associated with oxidative stress; however, they report divergent results. The aim of the present study was to evaluate total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and serum thiol level in migraine patients with or without aura. The study group consisted of 141 migraine patients. The control group included 70 healthy subjects. TAS, TOS, OSI were evaluated using a method developed by Erel. Serum thiol level was measured using the Hu method. No difference was found in TAS, TOS, OSI between the patients and controls. The level of thiol was significantly lower in patients than in controls. Negative correlations were detected between thiol level and Migraine Disability Assessment score in patients. Although TAS, TOS, and OSI were similar to those of the control group, serum thiol level, an important marker of antioxidant capacity, was significantly lower in migraines compared with controls, and caused more serious disability. Novel treatment approaches may be developed based on these data, and compounds containing thiol, such as alpha lipoic acid and N-acetyl cysteine, may be used in prophylaxis.

Clinical Perspective of Oxidative Stress in Sporadic ALS

PubMed Central

D’Amico, Emanuele; Factor-Litvak, Pam; Santella, Regina M.; Mitsumoto, Hiroshi

2013-01-01

Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis. PMID:23797033

Protection by dimethyl fumarate against diabetic cardiomyopathy in type 1 diabetic mice likely via activation of nuclear factor erythroid-2 related factor 2.

PubMed

Hu, Xinyue; Rajesh, Mohanraj; Zhang, Jian; Zhou, Shanshan; Wang, Shudong; Sun, Jian; Tan, Yi; Zheng, Yang; Cai, Lu

2018-05-01

Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months. Cardiac functions were determined using echocardiography. Oxidative stress, pro-inflammatory cytokines and pro-fibrotic markers were determined with commercially available kits, real-time quantitative PCR or western blot techniques. DCM was characterized by diminished cardiac function, accompanied by oxidative stress and enhanced expression of pro-inflammatory cytokines. Diabetic cardiac tissue exhibited marked fibrosis, revealed by extracellular matrix deposition as determined by Sirius red staining of the myocardial tissues. Furthermore, Nrf2 and its downstream effectors were repressed in diabetic myocardium. On the contrary, diabetic animals treated with DMF exhibited blunted oxidative stress, inflammation, fibrosis and this correlated with Nrf2 activation. Our findings suggest that DMF could potentially thwart diabetes-induced myocardial tissue injury, likely via activation of Nrf2 function, providing firm impetus for future repurposing of DMF in the management of DCM. Copyright © 2018 Elsevier B.V. All rights reserved.

Environmentally persistent free radicals induce airway hyperresponsiveness in neonatal rat lungs

PubMed Central

2011-01-01

Background Increased asthma risk/exacerbation in children and infants is associated with exposure to elevated levels of ultrafine particulate matter (PM). The presence of a newly realized class of pollutants, environmentally persistent free radicals (EPFRs), in PM from combustion sources suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma. Methods Neonatal rats (7-days of age) were exposed to EPFR-containing combustion generated ultrafine particles (CGUFP), non-EPFR containing CGUFP, or air for 20 minutes per day for one week. Pulmonary function was assessed in exposed rats and age matched controls. Lavage fluid was isolated and assayed for cellularity and cytokines and in vivo indicators of oxidative stress. Pulmonary histopathology and characterization of differential protein expression in lung homogenates was also performed. Results Neonates exposed to EPFR-containing CGUFP developed significant pulmonary inflammation, and airway hyperreactivity. This correlated with increased levels of oxidative stress in the lungs. Using differential two-dimensional electrophoresis, we identified 16 differentially expressed proteins between control and CGUFP exposed groups. In the rats exposed to EPFR-containing CGUFP; peroxiredoxin-6, cofilin1, and annexin A8 were upregulated. Conclusions Exposure of neonates to EPFR-containing CGUFP induced pulmonary oxidative stress and lung dysfunction. This correlated with alterations in the expression of various proteins associated with the response to oxidative stress and the regulation of glucocorticoid receptor translocation in T lymphocytes. PMID:21388553

Gender-dimorphic effects of adipose-derived stromal vascular fractions on HUVECs exposed to oxidative stress.

PubMed

Lim, Soyeon; Kim, Il-Kwon; Choi, Jung-Won; Seo, Hyang-Hee; Lim, Kyu Hee; Lee, Seahyoung; Lee, Hoon-Bum; Kim, Sang Woo; Hwang, Ki-Chul

2017-01-01

Stromal vascular fractions (SVFs) are a heterogeneous collection of cells within adipose tissue that are being studied for various clinical indications. In this study, we aimed to determine whether SVF transplantation into impaired tissues has differential effects on inflammatory and angiogenetic properties with regard to gender. As reactive oxygen species have been implicated in cardiovascular disease development, we investigated differences in gene and protein expression related to inflammation and angiogenesis in HUVECs co-cultured with adipose-derived SVFs from male (M group) and female (F group) individuals under oxidative stress conditions. The expression of several inflammatory (interleukin (IL)-33) and angiogenetic (platelet-derived growth factor (PDGF)) factors differed dramatically between male and female donors. Anti-inflammatory and pro-angiogenetic responses were observed in HUVECs co-cultured with SVFs under oxidative stress conditions, and these characteristics may exhibit partially differential effects according to gender. Using network analysis, we showed that co-culturing HUVECs with SVFs ameliorated pyroptosis/apoptosis via an increase in oxidative stress. Activation of caspase-1 and IL-1B was significantly altered in HUVECs co-cultured with SVFs from female donors. These findings regarding gender-dimorphic regulation of adipose-derived SVFs provide valuable information that can be used for evidence-based gender-specific clinical treatment of SVF transplantation for understanding of cardiovascular disease, allowing for the development of additional treatment.

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats.

PubMed

Chen, Siyao; Zheng, Saijun; Liu, Zhiwei; Tang, Chaoshu; Zhao, Bin; Du, Junbao; Jin, Hongfang

2015-02-01

The role of endogenous sulfur dioxide (SO2), an efficient gasotransmitter maintaining homeostasis, in the development of acute lung injury (ALI) remains unidentified. We aimed to investigate the role of endogenous SO2 in the pathogenesis of ALI. An oleic acid (OA)-induced ALI rat model was established. Endogenous SO2 levels, lung injury, oxidative stress markers and apoptosis were examined. OA-induced ALI rats showed a markedly downregulated endogenous SO2/aspartate aminotransferase 1 (AAT1)/AAT2 pathway and severe lung injury. Chemical colorimetry assays demonstrated upregulated reactive oxygen species generation and downregulated antioxidant capacity in OA-induced ALI rats. However, SO2 increased endogenous SO2 levels, protected against oxidative stress and alleviated ALI. Moreover, compared with OA-treated cells, in human alveolar epithelial cells SO2 downregulated O2(-) and OH(-) generation. In contrast, L-aspartic acid-β-hydroxamate (HDX, Sigma-Aldrich Corporation), an inhibitor of endogenous SO2 generating enzyme, promoted free radical generation, upregulated poly (ADP-ribose) polymerase expression, activated caspase-3, as well as promoted cell apoptosis. Importantly, apoptosis could be inhibited by the free radical scavengers glutathione (GSH) and N-acetyl-L-cysteine (NAC). The results suggest that SO2/AAT1/AAT2 pathway might protect against the development of OA-induced ALI by inhibiting oxidative stress.

Fructose and glucose differentially affect aging and carbonyl/oxidative stress parameters in Saccharomyces cerevisiae cells.

PubMed

Semchyshyn, Halyna M; Lozinska, Liudmyla M; Miedzobrodzki, Jacek; Lushchak, Volodymyr I

2011-05-15

Fructose is commonly used as an industrial sweetener and has been excessively consumed in human diets in the last decades. High fructose intake is causative in the development of metabolic disorders, but the mechanisms underlying fructose-induced disturbances are under debate. Fructose compared to glucose has been found to be a more potent initiator of the glycation reaction. Therefore, we supposed that glucose and fructose might have different vital effects. Here we compare the effects of glucose and fructose on yeast cell viability and markers of carbonyl/oxidative stress. Analysis of the parameters in cells growing on glucose and fructose clearly reveals that yeast growing on fructose has higher levels of carbonyl groups in proteins, α-dicarbonyl compounds and reactive oxygen species. This may explain the observation that fructose-supplemented growth as compared with growth on glucose resulted in more pronounced age-related decline in yeast reproductive ability and higher cell mortality. The results are discussed from the point of view that fructose rather than glucose is more extensively involved in glycation and ROS generation in vivo, yeast aging and development of carbonyl/oxidative stress. It should be noted that carbohydrate restriction used in this study does not reveal a significant difference between markers of aging and carbonyl/oxidative stress in yeasts cultivated on glucose and fructose. Copyright © 2011 Elsevier Ltd. All rights reserved.

Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease

PubMed Central

Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej R.; Evans, Michele K.

2013-01-01

Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. PMID:23428415

The association of plasma oxidative status and inflammation with the development of atrial fibrillation in patients presenting with ST elevation myocardial infarction.

PubMed

Bas, Hasan Aydin; Aksoy, Fatih; Icli, Atilla; Varol, Ercan; Dogan, Abdullah; Erdogan, Dogan; Ersoy, Ibrahim; Arslan, Akif; Ari, Hatem; Bas, Nihal; Sutcu, Recep; Ozaydin, Mehmet

2017-04-01

Atrial fibrillation (AF) is the most common supraventricular arrhythmia following ST elevation myocardial infarction (STEMI). Oxidative stress and inflammation may cause structural and electrical remodeling in the atria making these critical processes in the pathology of AF. In this study, we aimed to evaluate the association between total oxidative status (TOS), total antioxidative capacity (TAC) and high-sensitivity C-reactive protein (hs-CRP) in the development of AF in patients presenting with STEMI. This prospective cohort study consisted of 346 patients with STEMI. Serum TAC and TOS were assessed by Erel's method. Patients were divided into two groups: those with and those without AF. Predictors of AF were determined by multivariate regression analysis. In the present study, 9.5% of patients developed AF. In the patients with AF, plasma TOS and oxidative stress index (OSI) values were significantly higher and plasma TAC levels were significantly lower compared to those without AF (p = .003, p = .002, p < .0001, respectively). Multivariate regression analysis results showed that, female gender (Odds ratio [OR] = 3.07; 95% Confidence Interval [CI] = 1.26-7.47; p = .01), left atrial diameter (OR =1.28; 95% CI =1.12-1.47; p < .0001), hs-CRP (OR =1.02; 95% CI =1.00-1.03; p = .001) and OSI (OR =1.10; 95% CI =1.04-1.18; p = .001) were associated with the development of AF in patients presenting with STEMI. The main finding of this study is that oxidative stress and inflammation parameters were associated with the development of AF in patients presenting with STEMI. Other independent predictors of AF were female gender, left atrial diameter and hs-CRP.

Ferulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in mice.

PubMed

Zeni, Ana Lúcia Bertarello; Camargo, Anderson; Dalmagro, Ana Paula

2017-09-01

Corticosterone (CORT) treatment has been evidenced to develop a depression-like state in animals, that mimic hypothalamic-pituitary-adrenal (HPA)-axis dysregulation implicated in the development of depression. The present study aimed to examine the ferulic acid (FA), a natural phenolic compound, antidepressant and antioxidant activities on the CORT chronic model. Mice orally treated with 20mg/kg of CORT for 21days were connsidered control group, while mice treated with FA (1mg/kg) or fluoxetine (10mg/kg) for the last week of CORT treatment, as drug groups. Three weeks of CORT treatment resulted in depressive-like behavior, as indicated by the increase on the immobility time in the tail suspension test, grooming in the splash test and an increase in the oxidative stress markers in the brain. It was observed that FA ameliorated the behavioral and oxidative stress alterations induced by CORT, which may plausibly suggest a mode of action for the FA antidepressant effect. The involvement of FA repairing the stress caused by HPA-axis dysfunction evidenced that this phenolic acid could be further investigated as a novel potential agent to improve the management of depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

PubMed

Langgartner, Dominik; Wachter, Ulrich; Hartmann, Clair; Gröger, Michael; Vogt, Josef; Merz, Tamara; McCook, Oscar; Fink, Marina; Kress, Sandra; Georgieff, Michael; Kunze, Julia F; Radermacher, Peter L; Reber, Stefan O; Wepler, Martin

2018-06-08

Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multiple-organ-failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

PROTEOMIC IDENTIFICATION OF CARBONYLATED PROTEINS AND THEIR OXIDATION SITES

PubMed Central

Madian, Ashraf G.; Regnier, Fred E.

2011-01-01

Excessive oxidative stress leaves a protein carbonylation fingerprint in biological systems. Carbonylation is an irreversible post translational modification (PTM) that often leads to the loss of protein function and can be a component of multiple diseases. Protein carbonyl groups can be generated directly (by amino acids oxidation and the a-amidation pathway) or indirectly by forming adducts with lipid peroxidation products or glycation and advanced glycation end-products. Studies of oxidative stress are complicated by the low concentration of oxidation products and wide array of routes by which proteins are carbonylated. The development of new selection and enrichment techniques coupled with advances in mass spectrometry are allowing identification of hundreds of new carbonylated protein products from a broad range of proteins located at many sites in biological systems. The focus of this review is on the use of proteomics tools and methods to identify oxidized proteins along with specific sites of oxidative damage and the consequences of protein oxidation. PMID:20521848

Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

PubMed Central

Liu, Jia; Litt, Lawrence; Segal, Mark R.; Kelly, Mark J. S.; Pelton, Jeffrey G.; Kim, Myungwon

2011-01-01

Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing “omics”-based, diagnostic tests to help influence therapies. PMID:22072900

Aldose reductase is implicated in high glucose-induced oxidative stress in mouse embryonic neural stem cells.

PubMed

Fu, Jiang; Tay, S S W; Ling, E A; Dheen, S T

2007-11-01

Oxidative stress caused by hyperglycemia is one of the key factors responsible for maternal diabetes-induced congenital malformations, including neural tube defects in embryos. However, mechanisms by which maternal diabetes induces oxidative stress during neurulation are not clear. The present study was aimed to investigate whether high glucose induces oxidative stress in neural stem cells (NSCs), which compose the neural tube during development. We also investigated the mechanism by which high glucose disturbs the growth and survival of NSCs in vitro. NSCs were exposed to physiological d-glucose concentration (PG, 5 mmol/L), PG with l-glucose (25 mmol/L), or high d-glucose concentration (HG, 30 or 45 mmol/l). HG induced reactive oxygen species production and mRNA expression of aldose reductase (AR), which catalyzes the glucose reduction through polyol pathway, in NSCs. Expression of glucose transporter 1 (Glut1) mRNA and protein which regulates glucose uptake in NSCs was increased at early stage (24 h) and became down-regulated at late stage (72 h) of exposure to HG. Inhibition of AR by fidarestat, an AR inhibitor, decreased the oxidative stress, restored the cell viability and proliferation, and reduced apoptotic cell death in NSCs exposed to HG. Moreover, inhibition of AR attenuated the down-regulation of Glut1 expression in NSCs exposed to HG for 72 h. These results suggest that the activation of polyol pathway plays a role in the induction of oxidative stress which alters Glut1 expression and cell cycle in NSCs exposed to HG, thereby resulting in abnormal patterning of the neural tube in embryos of diabetic pregnancy.

Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colacino, Justin A.; Arthur, Anna E.; Ferguson, Kelly K.

Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003–2010 National Health and Nutrition Examination Survey to quantify diet's role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation bymore » multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level. - Highlights: • Cadmium may cause chronic disease through oxidative stress or inflammation. • We developed a score to quantify dietary antioxidant and anti-inflammatory intake. • Cadmium was associated with markers of oxidative stress and inflammation. • Antioxidant and anti-inflammatory intake mitigated the effects of cadmium exposure. • Dietary interventions may be effective against chronic cadmium toxicity.« less

Cardiovagal modulation, oxidative stress, and cardiovascular risk factors in prehypertensive subjects: cross-sectional study.

PubMed

Thiyagarajan, Ramkumar; Pal, Pravati; Pal, Gopal Krushna; Subramanian, Senthil Kumar; Bobby, Zachariah; Das, Ashok Kumar; Trakroo, Madanmohan

2013-07-01

Hypertension, one of the modifiable risk factors for cardiovascular disease (CVD), is known to be associated with increased oxidative stress and reduced cardiovagal modulation. Similar to hypertension, prehypertension is associated with increased risk of adverse cardiovascular (CV) events. We planned this study to find the association between prehypertension, cardiovagal modulation, oxidative stress, and associated CV risk factors. We recruited 178 subjects through hypertension screening camps conducted in Puducherry, India. Subjects were grouped into prehypertensive (n = 97) and normotensive (n = 81) groups. They were further subdivided, based on age, as young (20-39 years) and middle-aged (40-60 years) adults. We measured basal physiological parameters, heart rate variability, oxidative stress (thiobarbituric acid reactive substance and total antioxidant capacity (TAC)), and CV risk factors. We found significant increase in oxidative stress in prehypertensive subjects of both age groups but the cardiovagal modulation decreased significantly in young prehypertensive subjects when compared with normotensive subjects. Correlation of TAC with root mean square of the sum of successive R wave to R wave (RR) interval differences (RMSSD), a cardiovagal modulation parameter (r = 0. 437; P < 0.001), and mean arterial pressure (MAP) (r = -0.318; P < 0.001) was significant even after adjusting for CV risk factors. The correlation between MAP and RMSSD (r = 0.199; P = 0.009) was reduced after adjusting for CV risk factors. Prehypertension in young adults is associated with increased oxidative stress and altered cardiovagal modulation. The risk factors for CVDs in prehypertensive young adults were found to be equivalent to that of middle-aged adults who are in the twilight zone for developing CV dysfunctions.

Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm.

PubMed

Sawada, Hisashi; Hao, Hiroyuki; Naito, Yoshiro; Oboshi, Makiko; Hirotani, Shinichi; Mitsuno, Masataka; Miyamoto, Yuji; Hirota, Seiichi; Masuyama, Tohru

2015-06-01

Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive. Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression. © 2015 American Heart Association, Inc.

Borrelia oxidative stress response regulator, BosR: A distinctive Zn-dependent transcriptional activator

PubMed Central

Boylan, Julie A.; Posey, James E.; Gherardini, Frank C.

2003-01-01

The ability of a pathogen to cause infection depends on successful colonization of the host, which, in turn, requires adaptation to various challenges presented by that host. For example, host immune cells use a variety of mechanisms to control infection by bacterial pathogens, including the production of bactericidal reactive oxygen species. Prokaryotic and eukaryotic cells have developed ways of protecting themselves against this oxidative damage; for instance, Borrelia burgdorferi alters the expression of oxidative-stress-related proteins, such as a Dps/Dpr homolog NapA (BB0690), in response to increasing levels of oxygen and reactive oxygen species. These stress-related genes appear to be regulated by a putative metal-dependent DNA-binding protein (BB0647) that has 50.7% similarity to the peroxide-specific stress response repressor of Bacillus subtilis, PerR. We overexpressed and purified this protein from Escherichia coli and designated it Borrelia oxidative stress regulator, BosR. BosR bound to a 50-nt region 180 bp upstream of the napA transcriptional start site and required DTT and Zn2+ for optimal binding. Unlike the Bacillus subtilis PerR repressor, BosR did not require Fe2+ and Mn2+ for binding, and oxidizing agents, such as t-butyl peroxide, enhanced, not eliminated, BosR binding to the napA promoter region. Surprisingly, transcriptional fusion analysis indicated that BosR exerted a positive regulatory effect on napA that is inducible with t-butyl peroxide. On the basis of these data, we propose that, despite the similarity to PerR, BosR functions primarily as a transcriptional activator, not a repressor of oxidative stress response, in B. burgdorferi. PMID:12975527

Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

PubMed Central

Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2012-01-01

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

Oxidative Stress and NLRP3-Inflammasome Activity as Significant Drivers of Diabetic Cardiovascular Complications: Therapeutic Implications

PubMed Central

Sharma, Arpeeta; Tate, Mitchel; Mathew, Geetha; Vince, James E.; Ritchie, Rebecca H.; de Haan, Judy B.

2018-01-01

It is now increasingly appreciated that inflammation is not limited to the control of pathogens by the host, but rather that sterile inflammation which occurs in the absence of viral or bacterial pathogens, accompanies numerous disease states, none more so than the complications that arise as a result of hyperglycaemia. Individuals with type 1 or type 2 diabetes mellitus (T1D, T2D) are at increased risk of developing cardiac and vascular complications. Glucose and blood pressure lowering therapies have not stopped the advance of these morbidities that often lead to fatal heart attacks and/or stroke. A unifying mechanism of hyperglycemia-induced cellular damage was initially proposed to link elevated blood glucose levels with oxidative stress and the dysregulation of metabolic pathways. Pre-clinical evidence has, in most cases, supported this notion. However, therapeutic strategies to lessen oxidative stress in clinical trials has not proved efficacious, most likely due to indiscriminate targeting by antioxidants such as vitamins. Recent evidence now suggests that oxidative stress is a major driver of inflammation and vice versa, with the latest findings suggesting not only a key role for inflammatory pathways underpinning metabolic and haemodynamic dysfunction in diabetes, but furthermore that these perturbations are driven by activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. This review will address these latest findings with an aim of highlighting the interconnectivity between oxidative stress, NLRP3 activation and inflammation as it pertains to cardiac and vascular injury sustained by diabetes. Current therapeutic strategies to lessen both oxidative stress and inflammation will be emphasized. This will be placed in the context of improving the burden of these diabetic complications. PMID:29515457

A novel porcine ex vivo retina culture model for oxidative stress induced by H₂O₂.

PubMed

Hurst, José; Kuehn, Sandra; Jashari, Adelina; Tsai, Teresa; Bartz-Schmidt, Karl Ulrich; Schnichels, Sven; Joachim, Stephanie C

2017-03-01

Oxidative stress is a key player in many ophthalmic diseases. However, the role of oxidative stress in most degenerative processes is not yet known. Therefore, accurate and practical models are required to efficiently screen for therapeutics. Porcine eyes are closely related to the human eye, and can be obtained from the abattoir as a by-product of the food industry. Therefore, they offer excellent opportunities for the development of culture models with which to pre-screen potential therapies, while reducing the use of laboratory animals. To induce oxidative stress, organotypic cultures of porcine retina were treated with different doses of hydrogen peroxide (H₂O₂; 100, 300 and 500μM) for three hours. On days 3 and 8, the retinas were conserved for histological and Western blotting analyses and for evaluation of gene expression, which determined the number of retinal ganglion cells (RGCs), the activation state of glial cells, and the expression levels of several oxidative stress markers. H₂O₂ treatment led to a reduction in the number of RGCs and to an increase in apoptotic RGCs. In addition, a dose-dependent increase of microglia and an elevation of CD11b expression was observed. On day 3, a reduction of IL-1β, and an increase of iNOS, as well as of HSP70 mRNA were found. On day 8, an increase in TNF-α and IL-1β mRNA expression was detected. In conclusion, this ex vivo model offers an opportunity to study the molecular mechanisms underlying certain eye disorders and to test new therapeutic approaches to diminish the effects of oxidative stress. 2017 FRAME.

Dietary Lycopene Supplementation Improves Cognitive Performances in Tau Transgenic Mice Expressing P301L Mutation via Inhibiting Oxidative Stress and Tau Hyperphosphorylation.

PubMed

Yu, Lixia; Wang, Weiguang; Pang, Wei; Xiao, Zhonghai; Jiang, Yugang; Hong, Yan

2017-01-01

Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies and participates in their development by promoting hyperphosphorylation of microtubule-associated protein tau. Lycopene, as an effective antioxidant, combined with vitamin E seemed to be additive against oxidative stress. The present study was undertaken to examine whether lycopene or lycopene/vitamin E could exert protective effects on memory deficit and oxidative stress in tau transgenic mice expressing P301L mutation. P301L transgenic mice were assigned to three groups: P301L group (P301L), P301L+lycopene (Lyc), and P301L+lycopene/vitamin E (Lyc+VE). Age-matched C57BL/6J mice as wild type controls (Con) were used in the present study. Spatial memory was assessed by radial arm while passive memories were evaluated by step-down and step-through tests. Levels of tau phosphorylation were detected by western blot. Oxidative stress biomarkers were measured in the serum using biochemical assay kits. Compared with the control group, P301L mice displayed significant spatial and passive memory impairments, elevated malondialdehyde (MDA) levels and decreased glutathione peroxidase (GSH-Px) activities in serum, and increased tau phosphorylation at Thr231/Ser235, Ser262, and Ser396 in brain. Supplementations of lycopene or lycopene/vitamin E could significantly ameliorate the memory deficits, observably decreased MDA concentrations and increased GSH-Px activities, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites. Our findings indicated that the combination of lycopene and vitamin E antioxidants acted in a synergistic fashion to bring significant effects against oxidative stress in tauopathies.

The effect of upper gastrointestinal system endoscopy process on serum oxidative stress levels.

PubMed

Turan, Mehmet Nuri; Aslan, Mehmet; Bolukbas, Filiz Fusun; Bolukbas, Cengiz; Selek, Sahbettin; Sabuncu, Tevfik

2016-12-01

Some authors have investigated the effects of oxidative stress in some process such as undergoing laparoscopic. However, the effect of upper gastrointestinal system endoscopy process on oxidative stress is unclear. We evaluated the short-term effect of upper gastrointestinal system endoscopy process on oxidative stress. Thirty patients who underwent endoscopy process and 20 healthy controls were enrolled in the prospective study. Serum total antioxidant capacity and total oxidant status measurements were measured before and after endoscopy process. The ratio percentage of total oxidant status to total antioxidant capacity was regarded as oxidative stress index. Before endoscopy process, serum total antioxidant capacity levels were higher, while serum total oxidant status levels and oxidative stress index values were lower in patients than controls, but this difference was not statistically significant (all, p > 0.05). After endoscopy process, serum total antioxidant capacity and total oxidant status levels were significantly higher in patients than before endoscopy process (both, p < 0.05). However, oxidative stress index values were slight higher in patients but this difference was not statistically significant (p > 0.05). We observed that serum TAC and TOS levels were increased in patients who underwent endoscopy process after endoscopy process. However, short-time upper gastrointestinal system endoscopy process did not cause an important change in the oxidative stress index. Further studies enrolling a larger number of patients are required to clarify the results obtained here.

The role of lager beer yeast in oxidative stability of model beer.

PubMed

Berner, T S; Arneborg, N

2012-03-01

In this study, we investigated the relationship between the ability of lager brewing yeast strains to tolerate oxidative stress and their ability to produce oxidative stable model beer. Screening of 21 lager brewing yeast strains against diamide and paraquat showed that the oxidative stress resistance was strain dependent. Fermentation of model wort in European Brewing Convention tubes using three yeast strains with varying oxidative stress resistances resulted in three model beers with different rates of radical formation as measured by electron spin resonance in forced ageing experiments. Interestingly, the strain with the lowest oxidative stress resistance and lowest secretion of thioredoxin, as measured by Western blotting, resulted in the highest uptake of iron, as measured by inductively coupled plasma-mass spectrometry, and the slowest formation of radicals in the model beers. A more oxidative stable beer is not obtained by a more-oxidative-stress-tolerant lager brewing yeast strain, exhibiting a higher secretion of thioredoxin, but rather by a less-oxidative-stress-tolerant strain, exhibiting a higher iron uptake. To obtain lager beers with enhanced oxidative stability, yeast strains should be screened for their low oxidative stress tolerance and/or high ability to take up iron rather than for their high oxidative stress tolerance and/or high ability to secrete thioredoxin. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

Free Radical Exposure Creates Paler Carotenoid-Based Ornaments: A Possible Interaction in the Expression of Black and Red Traits

PubMed Central

Alonso-Alvarez, Carlos; Galván, Ismael

2011-01-01

Oxidative stress could be a key selective force shaping the expression of colored traits produced by the primary animal pigments in integuments: carotenoids and melanins. However, the impact of oxidative stress on melanic ornaments has only recently been explored, whereas its role in the expression of carotenoid-based traits is not fully understood. An interesting study case is that of those animal species simultaneously expressing both kinds of ornaments, such as the red-legged partridge (Alectoris rufa). In this bird, individuals exposed to an exogenous source of free radicals (diquat) during their development produced larger eumelanin-based (black) plumage traits than controls. Here, we show that the same red-legged partridges exposed to diquat simultaneously developed paler carotenoid-based ornaments (red beak and eye rings), and carried lower circulating carotenoid levels as well as lower levels of some lipids involved in carotenoid transport in the bloodstream (i.e., cholesterol). Moreover, partridges treated with a hormone that stimulates eumelanin production (i.e., alpha-melanocyte-stimulating hormone) also increased blood carotenoid levels, but this effect was not mirrored in the expression of carotenoid-based traits. The redness of carotenoid-based ornaments and the size of a conspicuous eumelanic trait (the black bib) were negatively correlated in control birds, suggesting a physiological trade-off during development. These findings contradict recent studies questioning the sensitivity of carotenoids to oxidative stress. Nonetheless, the impact of free radicals on plasma carotenoids seems to be partially mediated by changes in cholesterol metabolism, and not by direct carotenoid destruction/consumption. The results highlight the capacity of oxidative stress to create multiple phenotypes during development through differential effects on carotenoids and melanins, raising questions about evolutionary constraints involved in the production of multiple ornaments by the same organism. PMID:21556328

Does dietary fat intake influence oocyte competence and embryo quality by inducing oxidative stress in follicular fluid?

PubMed

Kazemi, Ashraf; Ramezanzadeh, Fatemeh; Nasr-Esfahani, Mohammad Hosein; Saboor Yaraghi, Ali Akbar; Ahmadi, Mehdi

2013-12-01

Fat-rich diet may alter oocyte development and maturation and embryonic development by inducing oxidative stress (OS) in follicular environment. To investigate the relationship between fat intake and oxidative stress with oocyte competence and embryo quality. In observational study follicular fluid was collected from 236 women undergoing assisted reproduction program. Malon-di-aldehyde (MDA) levels and total antioxidant capacity (TAC) levels of follicular fluid were assessed as oxidative stress biomarkers. In assisted reproduction treatment cycle fat consumption and its component were assessed. A percentage of metaphase ΙΙ stage oocytes, fertilization rate were considered as markers of oocyte competence and non-fragmented embryo rate, mean of blastomer and good cleavage (embryos with more than 5 cells on 3 days post insemination) rate were considered as markers of embryo quality. The MDA level in follicular fluid was positively related to polyunsaturated fatty acids intake level (p=0.02) and negatively associated with good cleavage rate (p=0.045). Also good cleavage rate (p=0.005) and mean of blastomer (p=0.006) was negatively associated with polyunsaturated fatty acids intake levels. The percentage of metaphase ΙΙ stage oocyte was positively related to the TAC levels in follicular fluid (p=0.046). The relationship between the OS biomarkers in FF and the fertilization rate was not significant. These findings revealed that fat rich diet may induce the OS in oocyte environment and negatively influence embryonic development. This effect can partially be accounted by polyunsaturated fatty acids uptake while oocyte maturation is related to TAC and oocytes with low total antioxidant capacity have lower chance for fertilization and further development.

H2O2 mediates ALA-induced glutathione and ascorbate accumulation in the perception and resistance to oxidative stress in Solanum lycopersicum at low temperatures.

PubMed

Liu, Tao; Hu, Xiaohui; Zhang, Jiao; Zhang, Junheng; Du, Qingjie; Li, Jianming

2018-02-15

Low temperature is a crucial factor influencing plant growth and development. The chlorophyll precursor, 5-aminolevulinic acid (ALA) is widely used to improve plant cold tolerance. However, the interaction between H 2 O 2 and cellular redox signaling involved in ALA-induced resistance to low temperature stress in plants remains largely unknown. Here, the roles of ALA in perceiving and regulating low temperature-induced oxidative stress in tomato plants, together with the roles of H 2 O 2 and cellular redox states, were characterized. Low concentrations (10-25 mg·L - 1 ) of ALA enhanced low temperature-induced oxidative stress tolerance of tomato seedlings. The most effective concentration was 25 mg·L - 1 , which markedly increased the ratio of reduced glutathione and ascorbate (GSH and AsA), and enhanced the activities of superoxide dismutase, catalase, ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. Furthermore, gene expression of respiratory burst oxidase homolog1 and H 2 O 2 content were upregulated with ALA treatment under normal conditions. Treatment with exogenous H 2 O 2 , GSH, and AsA also induced plant tolerance to oxidative stress at low temperatures, while inhibition of GSH and AsA syntheses significantly decreased H 2 O 2 -induced oxidative stress tolerance. Meanwhile, scavenging or inhibition of H 2 O 2 production weakened, but did not eliminate, GSH- or AsA- induced tomato plant tolerance to oxidative stress at low temperatures. Appropriate concentrations of ALA alleviated the low temperature-induced oxidative stress in tomato plants via an antioxidant system. The most effective concentration was 25 mg·L - 1 . The results showed that H 2 O 2 induced by exogenous ALA under normal conditions is crucial and may be the initial step for perception and signaling transmission, which then improves the ratio of GSH and AsA. GSH and AsA may then interact with H 2 O 2 signaling, resulting in enhanced antioxidant capacity in tomato plants at low temperatures.

Reactive oxygen species-activated nanomaterials as theranostic agents.

PubMed

Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

2015-01-01

Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use.

Oxidation stress evolution and relaxation of oxide film/metal substrate system

NASA Astrophysics Data System (ADS)

Dong, Xuelin; Feng, Xue; Hwang, Keh-Chih

2012-07-01

Stresses in the oxide film/metal substrate system are crucial to the reliability of the system at high temperature. Two models for predicting the stress evolution during isothermal oxidation are proposed. The deformation of the system is depicted by the curvature for single surface oxidation. The creep strain of the oxide and metal, and the lateral growth strain of the oxide are considered. The proposed models are compared with the experimental results in literature, which demonstrates that the elastic model only considering for elastic strain gives an overestimated stress in magnitude, but the creep model is consistent with the experimental data and captures the stress relaxation phenomenon during oxidation. The effects of the parameter for the lateral growth strain rate are also analyzed.

Oxidative stress during extracorporeal circulation.

PubMed

McDonald, Charles Ian; Fraser, John Francis; Coombes, Jeff S; Fung, Yoke Lin

2014-12-01

There is an increased oxidative stress response in patients having cardiac surgery, haemodialysis or extracorporeal membrane oxygenation that is related to poorer outcomes and increased mortality. Exposure of the patients' blood to the artificial surfaces of these extracorporeal devices, coupled with inflammatory responses, hyperoxia and the pathophysiological aspects of the underlying illness itself, all contribute to this oxidative stress response. Oxidative stress occurs when there is a disruption of redox signalling and loss of control of redox balance. Ongoing oxidative stress occurring during extracorporeal circulation (ECC) results in damage to lipids, proteins and DNA and contributes to morbidity and mortality. This review discusses reactive species generation and the potential clinical consequences of oxidative stress during ECC as well as provides an overview of some current antioxidant compounds that are available to potentially mitigate the oxidative stress response. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Influence of oxidative stress and grains on sclerotial biomass and carotenoid yield of Penicillium sp. PT95.

PubMed

Chen, Shu-Jun; Wang, Qi; Han, Jian-Rong

2010-08-01

Oxidative stress and grains were evaluated for carotenoid production by solid-state fermentation using Penicillium sp. PT95. When the fungus was grown at high oxidative stress, its sclerotial biomass and carotenoid content in sclerotia increased significantly with respect to low oxidative stress (P < 0.01). High oxidative stress also caused a statistically significant increase in carotenoid yield as compared with low oxidative stress (P < 0.01). Both the sclerotial biomass and the amount of carotenoid accumulated in sclerotia of strain PT95 were strongly dependent on the grain medium used. Among the grain media tested under high oxidative stress, buckwheat medium gave the highest content of carotenoid in sclerotia (828 microg/g dry sclerotia), millet medium gave respectively the highest sclerotial biomass (12.69 g/100 g grain) and carotenoid yield (10.152 mg/100 g grain). Copyright 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Role of oxidative stress in epileptic seizures

PubMed Central

Shin, Eun-Joo; Jeong, Ji Hoon; Chung, Yoon Hee; Kim, Won-Ki; Ko, Kwang-Ho; Bach, Jae-Hyung; Hong, Jau-Shyong; Yoneda, Yukio; Kim, Hyoung-Chun

2013-01-01

Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. Therefore, antioxidant therapies aimed at reducing oxidative stress have received considerable attention in epilepsy treatment. However, much evidence suggests that oxidative stress does not always have the same pattern in all seizures models. Thus, this review provides an overview aimed at achieving a better understanding of this issue. We summarize work regarding seizure models (i.e., genetically epilepsy-prone rats, kainic acid, pilocarpine, pentylenetetrazol, and trimethyltin), oxidative stress as an etiologic factor in epileptic seizures (i.e., impairment of antioxidant systems, mitochondrial dysfunction, involvement of redox-active metals, arachidonic acid pathway activation, and aging), and antioxidant strategies for seizure treatment. Combined, this review highlights pharmacological mechanisms associated with oxidative stress in epileptic seizures and the potential for neuroprotection in epilepsy that targets oxidative stress and is supported by effective antioxidant treatment. PMID:21672578

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.

PubMed

Li, Yibo; Amarachintha, Surya; Wilson, Andrew F; Li, Xue; Du, Wei

2017-06-18

Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G 2 /M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress

PubMed Central

Wilson, Andrew F.; Li, Xue

2017-01-01

ABSTRACT Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G2/M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress. PMID:28475398

Study on the effect of reactive oxygen species-mediated oxidative stress on the activation of mitochondrial apoptosis and the tenderness of yak meat.

PubMed

Wang, Lin-Lin; Yu, Qun-Li; Han, Ling; Ma, Xiu-Li; Song, Ren-De; Zhao, Suo-Nan; Zhang, Wen-Hua

2018-04-01

This study investigated the effect of reactive oxygen species-mediated oxidative stress on activation of mitochondrial apoptosis and tenderness of yak meat during postmortem ageing. Oxidative stress degree, Ca 2+ levels, membrane permeability transition pore opening, mitochondrial membrane potential, apoptotic factors and the shear force were examined. Results showed that the ROS generated by H 2 O 2 significantly increased mitochondrial oxidative stress by decreasing the activities of superoxide dismutase, catalase and glutathione peroxidase, and increasing lipid peroxidation. Furthermore, oxidative stress enhanced Ca 2+ production and cytochrome c release, changed the levels of Bcl-2 family proteins and activated caspase-9 and -3 activities. Ultimately, oxidative stress increased the apoptosis rate and tenderness of yak meat. These observations confirmed that ROS-mediated oxidative stress participates in the activation of the apoptotic cascade reaction involving Ca 2+ and Bcl-2 family proteins. The results further suggested that ROS-mediated oxidative stress plays a significant role in meat tenderization through the mitochondrial apoptotic pathway. Copyright © 2017. Published by Elsevier Ltd.

Oxidative stress and the ageing endocrine system.

PubMed

Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

2013-04-01

Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands.

Effects of flight activity and age on oxidative damage in the honey bee, Apis mellifera.

PubMed

Margotta, Joseph W; Roberts, Stephen P; Elekonich, Michelle M

2018-05-03

Frequent and highly aerobic behaviors likely contribute to naturally occurring stress, accelerate senescence, and limit lifespan. To understand how the physiological and cellular mechanisms that determine the onset and duration of senescence are shaped by behavioral development and behavioral duration, we exploited the tractability of the honey bee ( Apis mellifera ) model system. First, we determined if a cause-effect relationship exists between honey bee flight and oxidative stress by comparing oxidative damage accrued from intense flight bouts to damage accrued from D-galactose ingestion, which induces oxidative stress and limit lifespan in other insects. Second, we experimentally manipulated the duration of honey bee flight across a range of ages to determine their effects on reactive oxygen species (ROS) accumulation and associated enzymatic antioxidant protective mechanisms. In bees fed D-galactose, lipid peroxidation (MDA) was higher than in bees fed sucrose and age-matched bees with high and low flight experience collected from a colony. Bees with high amounts of flight experience exhibited elevated 8-OHdG, a marker of oxidative DNA damage, relative to bees with less flight experience. Bees with high amounts of flight experience also showed increased levels of pro-oxidants (superoxide and H 2 O 2 ) and decreased or unchanged levels of antioxidants (SOD and catalase). These data implicate an imbalance of pro- to antioxidants in flight-associated oxidative stress and reveal how behavior can damage a cell and consequently limit lifespan. © 2018. Published by The Company of Biologists Ltd.

Association between Oxidative Stress, Genetic Factors, and Clinical Severity in Children with Sickle Cell Anemia.

PubMed

Renoux, Céline; Joly, Philippe; Faes, Camille; Mury, Pauline; Eglenen, Buse; Turkay, Mine; Yavas, Gokce; Yalcin, Ozlem; Bertrand, Yves; Garnier, Nathalie; Cuzzubbo, Daniela; Gauthier, Alexandra; Romana, Marc; Möckesch, Berenike; Cannas, Giovanna; Antoine-Jonville, Sophie; Pialoux, Vincent; Connes, Philippe

2018-04-01

To investigate the associations between several sickle cell disease genetic modifiers (beta-globin haplotypes, alpha-thalassemia, and glucose-6-phosphate dehydrogenase deficiency) and the level of oxidative stress and to evaluate the association between oxidative stress and the rates of vaso-occlusive events. Steady-state oxidative and nitrosative stress markers, biological variables, genetic modulators, and vaso-occlusive crisis events requiring emergency admissions were measured during a 2-year period in 62 children with sickle cell anemia (58 SS and 4 Sβ 0 ). Twelve ethnic-matched children without sickle cell anemia also participated as healthy controls (AA) for oxidative and nitrosative stress level measurement. Oxidative and nitrosative stress were greater in patients with sickle cell anemia compared with control patients, but the rate of vaso-occlusive crisis events in sickle cell anemia was not associated with the level of oxidative stress. The presence of alpha-thalassemia, but not glucose-6-phosphate dehydrogenase deficiency or beta-globin haplotype, modulated the level of oxidative stress in children with sickle cell anemia. Mild hemolysis in children with alpha-thalassemia may limit oxidative stress and could explain the protective role of alpha-thalassemia in hemolysis-related sickle cell complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

NASA Technical Reports Server (NTRS)

Bhattacharya, Sharmila; Hosamani, Ravikumar

2015-01-01

Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity-associated insulin resistance and cardiovascular risk.

PubMed

Matsuda, Morihiro; Shimomura, Iichiro

2014-08-01

Obesity leads to the development of type 2 diabetes mellitus, which is a strong risk factor for cardiovascular disease. A better understanding of the molecular basis of obesity will lead to the establishment of effective prevention strategies for cardiovascular diseases. Adipocytes have been shown to generate a variety of endocrine factors termed adipokines/adipocytokines. Obesity-associated changes to these adipocytokines contribute to the development of cardiovascular diseases. Adiponectin, which is one of the most well-characterized adipocytokines, is produced exclusively by adipocytes and exerts insulin-sensitizing and anti-atherogenic effects. Obese subjects have lower levels of circulating adiponectin, and this is recognized as one of the factors involved in obesity-induced insulin resistance and atherosclerosis. Another pathophysiological feature of obesity may involve the low-grade chronic inflammation in adipose tissue. This inflammatory process increases oxidative stress in adipose tissue, which may affect remote organs, leading to the development of diabetes, hypertension, and atherosclerosis. Nuclear hormone receptors (NRs) regulate the transcription of the target genes in response to binding with their ligands, which include metabolic and nutritional substrates. Among the various NRs, peroxisome proliferator-activated receptor γ promotes the transcription of adiponectin and antioxidative enzymes, whereas mineralocorticoid receptor mediates the effects of aldosterone and glucocorticoid to induce oxidative stress in adipocytes. It is hypothesized that both play crucial roles in the pathophysiology of obesity-associated insulin resistance and cardiovascular diseases. Thus, reduced adiponectin and increased oxidative stress play pathological roles in obesity-associated insulin resistance to increase the cardiovascular disease risk, and various NRs may be involved in this pathogenesis.

Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain.

PubMed

Butterfield, D Allan; Di Domenico, Fabio; Barone, Eugenio

2014-09-01

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggests that oxidative stress plays a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data interpreted from the point of view of oxidative stress with the aim of highlighting progresses in this field. Copyright © 2014 Elsevier B.V. All rights reserved.

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts

PubMed Central

2014-01-01

Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities. PMID:24533833

Influence of resveratrol on oxidative stress resistance and life span in Caenorhabditis elegans.

PubMed

Chen, Wei; Rezaizadehnajafi, Leila; Wink, Michael

2013-05-01

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol from red wine, has been reported to be beneficial in cases of ageing-related cardiovascular and neurodegenerative diseases owing to its property to reduce oxidative stress. Previous studies on the longevity promoting effect of resveratrol have been partly inconclusive, therefore we set out to investigate whether resveratrol at least promoted longevity in Caenorhabditis elegans under acute oxidative stress conditions. C. elegans was cultured under standard conditions with or without resveratrol. After exposure to juglone-induced acute oxidative stress, the survival rate and hsp-16.2::GFP expression were measured. The influence of resveratrol on life span was recorded also under oxidative stress induced by high glucose concentrations in the growth medium. No extension of the normal life span of C. elegans was observed either in liquid or solid growth media containing different concentrations of resveratrol. However, resveratrol alleviated juglone-induced lethal oxidative stress, and significantly prolonged the life span of C. elegans under conditions of acute oxidative damage and oxidative stress caused by high concentrations of glucose. Resveratrol, as an antioxidant, ameliorated oxidative stress in vivo but did not extend the life span of C. elegans under normal conditions. However, resveratrol did extend life span under conditions of oxidative stress. © 2013 The Authors. JPP © 2013 Royal Pharmaceutical Society.

Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.

PubMed

Manna, Prasenjit; Jain, Sushil K

2015-12-01

Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits.

Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

PubMed Central

Manna, Prasenjit

2015-01-01

Abstract Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits. PMID:26569333

Comparison of oxidative stress & leukocyte activation in patients with severe sepsis & burn injury

PubMed Central

Mühl, Diana; Woth, Gábor; Drenkovics, Livia; Varga, Adrienn; Ghosh, Subhamay; Csontos, Csaba; Bogár, Lajos; Wéber, György; Lantos, János

2011-01-01

Background & objectives: We evaluated pro- and anti-oxidant disturbances in sepsis and non-sepsis burn patients with systemic inflammatory response syndrome (SIRS). Adhesion molecules and inflammation markers on leukocytes were also analyzed. We hypothesized that oxidative stress and leukocyte activation markers can lead to the severity of sepsis. Methods: In 28 severe sepsis and 27 acute burn injury patients blood samples were collected at admission and 4 days consecutively. Oxidative stress markers: production of reactive oxygen species (ROS), myeloperoxidase, malondialdehyde and endogenous antioxidants: plasma protein sulphydryl groups, reduced glutathione, superoxide dismutase and catalase were measured. Flow cytometry was used to determine CD11a, CD14, CD18, CD49d and CD97 adhesion molecules on leukocytes. Procalcitonin, C-reactive protein, fibrinogen, platelet count and lactate were also analyzed. Results: Pro-oxidant parameters were significantly elevated in sepsis patients at admission, ROS intensity increased in burn patients until the 5th day. Endogenous antioxidant levels except catalase showed increased levels after burn trauma compared to sepsis. Elevated granulocyte activation and suppressed lymphocyte function were found at admission and early activation of granulocytes caused by increasing activation/migration markers in sepsis. Leukocyte adhesion molecule expression confirmed the suppressed lymphocyte and monocyte function in sepsis. Interpretation & conclusions: Severe sepsis is accompanied by oxidative stress and pathological leukocyte endothelial cell interactions. The laboratory parameters used for the evaluation of sepsis and several markers of pro- and antioxidant status were different between sepsis and non-sepsis burn patients. The tendency of changes in these parameters may refer to major oxidative stress in sepsis and developing SIRS in burns. PMID:21808137

Effect of oxidative stress on Rho kinase II and smooth muscle contraction in rat stomach.

PubMed

Al-Shboul, Othman; Mustafa, Ayman

2015-06-01

Recent studies have shown that both Rho kinase signaling and oxidative stress are involved in the pathogenesis of a number of human diseases, such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho kinase pathway. The aim of the current study was to investigate the effect of oxidative stress on Rho kinase II and muscle contraction in rat stomach. The peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2), and peroxynitrite were used to induce oxidative stress. Rho kinase II expression and ACh-induced activity were measured in control and oxidant-treated cells via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits, respectively. Single smooth muscle cell contraction was measured via scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632 dihydrochloride. All oxidant agents significantly increased ACh-induced Rho kinase II activity without affecting its expression level. Most important, oxidative stress induced by all three agents augmented ACh-stimulated muscle cell contraction, which was significantly inhibited by Y-27632. In conclusion, oxidative stress activates Rho kinase II and enhances contraction in rat gastric muscle, suggesting an important role in GI motility disorders associated with oxidative stress.

Analyses of Fatigue Crack Growth and Closure Near Threshold Conditions for Large-Crack Behavior

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.

1999-01-01

A plasticity-induced crack-closure model was used to study fatigue crack growth and closure in thin 2024-T3 aluminum alloy under constant-R and constant-K(sub max) threshold testing procedures. Two methods of calculating crack-opening stresses were compared. One method was based on a contact-K analyses and the other on crack-opening-displacement (COD) analyses. These methods gave nearly identical results under constant-amplitude loading, but under threshold simulations the contact-K analyses gave lower opening stresses than the contact COD method. Crack-growth predictions tend to support the use of contact-K analyses. Crack-growth simulations showed that remote closure can cause a rapid rise in opening stresses in the near threshold regime for low-constraint and high applied stress levels. Under low applied stress levels and high constraint, a rise in opening stresses was not observed near threshold conditions. But crack-tip-opening displacement (CTOD) were of the order of measured oxide thicknesses in the 2024 alloy under constant-R simulations. In contrast, under constant-K(sub max) testing the CTOD near threshold conditions were an order-of-magnitude larger than measured oxide thicknesses. Residual-plastic deformations under both constant-R and constant-K(sub max) threshold simulations were several times larger than the expected oxide thicknesses. Thus, residual-plastic deformations, in addition to oxide and roughness, play an integral part in threshold development.

Potential Role of Endoplasmic Reticulum Stress in Pathogenesis of Diabetic Retinopathy.

PubMed

Sánchez-Chávez, Gustavo; Hernández-Ramírez, Ernesto; Osorio-Paz, Ixchel; Hernández-Espinosa, Claudia; Salceda, Rocío

2016-05-01

Diabetes mellitus is a metabolic disease that leads to several complications which include retinopathy. Multiple biochemical abnormalities have been proposed to explain the development of retinopathy, including oxidative stress. Although the existence of oxidative stress has been established in the retina from long standing diabetic animals, pathogenesis and progression of retinopathy remain unclear. In order to gain insight into the pathogenesis of diabetic retinopathy, we analyzed the levels of different oxidative stress biomarkers in the retina at early stages during the progress of streptozotocin-induced diabetes. No significant changes in glutathione content, expression of NADPH-oxidase, levels of lipid peroxidation, nor production of free radicals were observed in the retina up to 45 days of diabetes induction. Likewise, a transient decrease in aconitase activity, parallel to an increase in the superoxide dismutase activity was observed at 20 days of hyperglycemia, suggesting a high capacity of retina to maintain its redox homeostasis, at least at early stages of diabetes. Nonetheless, we found an early and time-dependent increase in the levels of oxidized proteins, which was not affected by the administration of the antioxidant quercetin. Also, positive immunoreactivity to the reticulum stress protein CHOP was found in glial Müller cells of diabetic rat retinas. These findings suggest the occurrence of endoplasmic reticulum stress as a primary event in retina pathogenesis in diabetes.

METAL BIOSENSORS: DEVELOPMENT AND ENVIRONMENTAL TESTING

EPA Science Inventory

Proteomic and Transcriptional Findings

P. putida cells responded differentially to Cd and Cu exposures at the proteomic and transcriptome levels. The cells displayed different stress responses that correlated with a more intense oxidative stress imposed...

Oxidative stress in organophosphate poisoning: role of standard antidotal therapy.

PubMed

Vanova, Nela; Pejchal, Jaroslav; Herman, David; Dlabkova, Alzbeta; Jun, Daniel

2018-08-01

Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration. Copyright © 2018 John Wiley & Sons, Ltd.

Oxidant/antioxidant status in obese children compared to pediatric patients with type 1 diabetes mellitus.

PubMed

Codoñer-Franch, Pilar; Pons-Morales, Sara; Boix-García, Laura; Valls-Bellés, Victoria

2010-06-01

Type 1 diabetes (T1D) mellitus and obesity are recognized risk factors for cardiovascular disease (CVD). A common mechanism underlying an increased risk for endothelial dysfunction in these two metabolic diseases is oxidative stress. To evaluate and compare the oxidant/antioxidant defense systems in children affected with T1D or obesity in order to determine the importance of oxidative stress before the emergence of complications. Children with T1D (n = 20) or obesity (n = 22), without comorbidities, and age- and sex-matched controls (n = 16). We assessed lipid peroxidation by circulating levels of lipoperoxides and malondialdehyde, as well as protein oxidation by the concentration of plasma carbonyl groups. The endogenous antioxidative defense system was evaluated by the red cell glutathione peroxidase and reduced glutathione. The serum levels of alpha-tocopherol and beta-carotene were determined to assess exogenous antioxidants. Lipid peroxidation was significantly higher in both T1D and obese children when compared with control children. However, T1D patients showed a more elevated level, because their malondialdehyde values were significantly increased with respect to obese children. Protein oxidation was present in both groups of children and did not differ between them. With respect to obese children, the glutathione peroxidase activity and exogenous antioxidants were decreased in T1D patients. Oxidative stress is present in both children with T1D and obesity, although it is more pronounced in the former. Obese children may suffer an additional oxidative stress in the case of developing impaired glucose metabolism.

[Periodonta disease in smokers, and the parameters of oxidative stress].

PubMed

Golusińska-Kardach, Ewelina; Napierała, Marta; Sokalski, Jerzy; Kardachi, Hubert; Florek, Ewa

2015-01-01

Periodontal disease, periodontitis, and caries disease, are the two most common disease occurring in the mouth. They affect a large proportion of the world's population. The causes of periodontitis are varied, but the largest group are those caused by infections. The characteristic long asymptomatic period of development of periodontitis, make that patients are not aware of their condition. In-addition, it was observed that tobacco abuse affects the growth of disease and advancing disease state for periodontal diseases. Free radicals and other reactive particles are capable of destroying many cellular structures. They are produced mostly during the breathing process and the immune response or come from the environment. The evolution of living organisms ensure the proper tools to fight against reactive oxygen species after enzymatic and non-enzymatic by antioxidants. Sometimes this protection is not sufficient and the balance between antioxidants and oxidants is compromised. This condition is called oxidative stress. A number of studies looking for a link between oxidative stress, and diseases affecting human and determined that it is an important risk factor in many diseases. Evaluating the parameters of oxidative stress in the saliva allows for effective monitoring of disease progression, evaluation of the therapy and taking preventive measures in a timely manner.

Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in rat by blocking oxidative stress and apoptosis.

PubMed

Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd Shameel; Maity, Pallab; Adhikari, Susanta S; Bandyopadhyay, Uday

2010-07-15

Nonsteroidal anti-inflammatory drug (NSAID)-induced oxidative stress plays a critical role in gastric mucosal cell apoptosis and gastropathy. NSAIDs induce the generation of hydroxyl radical ((*)OH) through the release of free iron, which plays an important role in developing gastropathy. Thus, molecules having both iron-chelating and antiapoptotic properties will be beneficial in preventing NSAID-induced gastropathy. Gallic acid (GA), a polyphenolic natural product, has the capacity to chelate free iron. Here, we report that GA significantly prevents, as well as heals, NSAID-induced gastropathy. In vivo, GA blocks NSAID-mediated mitochondrial oxidative stress by preventing mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. In vitro, GA scavenges free radicals and blocks (*)OH-mediated oxidative damage. GA also attenuates gastric mucosal cell apoptosis in vivo as well as in vitro in cultured gastric mucosal cells as evident from the TUNEL assay. GA prevents NSAID-induced activation of caspase-9, a marker for the mitochondrial pathway of apoptosis, and restores NSAID-mediated collapse of the mitochondrial transmembrane potential and dehydrogenase activity. Thus, the inhibition of mitochondrial oxidative stress by GA is associated with the inhibition of NSAID-induced mitochondrial dysfunction and activation of apoptosis in gastric mucosal cells, which are responsible for gastric injury or gastropathy. Copyright 2010 Elsevier Inc. All rights reserved.

Tolerance to oxidative stress is required for maximal xylem colonization by the xylem-limited bacterial phytopathogen, Xylella fastidiosa.

PubMed

Wang, Peng; Lee, Yunho; Igo, Michele M; Roper, M Caroline

2017-09-01

Bacterial plant pathogens often encounter reactive oxygen species (ROS) during host invasion. In foliar bacterial pathogens, multiple regulatory proteins are involved in the sensing of oxidative stress and the activation of the expression of antioxidant genes. However, it is unclear whether xylem-limited bacteria, such as Xylella fastidiosa, experience oxidative stress during the colonization of plants. Examination of the X. fastidiosa genome uncovered only one homologue of oxidative stress regulatory proteins, OxyR. Here, a knockout mutation in the X. fastidiosa oxyR gene was constructed; the resulting strain was significantly more sensitive to hydrogen peroxide (H 2 O 2 ) relative to the wild-type. In addition, during early stages of grapevine infection, the survival rate was 1000-fold lower for the oxyR mutant than for the wild-type. This supports the hypothesis that grapevine xylem represents an oxidative environment and that X. fastidiosa must overcome this challenge to achieve maximal xylem colonization. Finally, the oxyR mutant exhibited reduced surface attachment and cell-cell aggregation and was defective in biofilm maturation, suggesting that ROS could be a potential environmental cue stimulating biofilm development during the early stages of host colonization. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Hepatoprotective Role of Wheatgrass on Alcohol and ΔPUFA-Induced Oxidative Stress in Rats.

PubMed

Durairaj, Varalakshmi; Shakya, Garima; Rajagopalan, Rukkumani

2015-06-01

Alcohol abuse is recognized as the most common cause for the development of various abnormalities including liver disease. Excessive free radicals are generated during the metabolism of ethanol. The ingestion of alcohol along with polyunsaturated fatty acid (PUFA) aggravates the production of free radicals and enhances the oxidative stress. Medicinal plants contain active phytocomponents, which are the principal healthcare resources. We aimed to analyze the effect of wheatgrass extract on alcohol and thermally oxidized PUFA (ΔPUFA) induced oxidative stress in male albino Wistar rats. The levels of marker enzymes gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), lipid peroxidative markers; thiobarbutric acid reactive substances (TBARS) and lipid hydroperoxides (LH), the levels of enzymatic (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx]) and nonenzymatic (reduced glutathione [GSH], vitamin E, vitamin C) antioxidants were analyzed in liver to evaluate the effects of wheatgrass. The levels of TBARS and LH were significantly (p ≤ .05) increased in alcohol + ΔPUFA group, which were found to be reduced on treatment with wheatgrass. The levels of both enzymatic and nonenzymatic antioxidants were significantly (p ≤ .05) decreased in alcohol + ΔPUFA group, which were found to be restored on treatment with wheatgrass. From the results obtained, we conclude that wheatgrass protects the liver against alcohol and ΔPUFA induced oxidative stress.

Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus.

PubMed

Foster, Meika; Samman, Samir

2010-11-15

Cellular signal transduction pathways are influenced by the zinc and redox status of the cell. Numerous chronic diseases, including cardiovascular disease (CVD) and diabetes mellitus (DM), have been associated with impaired zinc utilization and increased oxidative stress. In humans, mutations in the MT-1A and ZnT8 genes, both of which are involved in the maintenance of zinc homeostasis, have been linked with DM development. Changes in levels of intracellular free zinc may exacerbate oxidative stress in CVD and DM by impacting glutathione homeostasis, nitric oxide signaling, and nuclear factor-kappa B-dependent cellular processes. Zinc ions have been shown to influence insulin and leptin signaling via the phosphoinositide 3′-kinase/Akt pathway, potentially linking an imbalance of zinc at the cellular level to insulin resistance and dyslipidemia. The oxidative modification of cysteine residues in zinc coordination sites in proteins has been implicated in cellular signaling and regulatory pathways. Despite the many interactions between zinc and cellular stress responses, studies investigating the potential therapeutic benefit of zinc supplementation in the prevention and treatment of oxidative stress-related chronic disease in humans are few and inconsistent. Further well-designed randomized controlled trials are needed to determine the effects of zinc supplementation in populations at various stages of CVD and DM progression.

Alleviation of Rosup-induced oxidative stress in porcine granulosa cells by anthocyanins from red-fleshed apples.

PubMed

Xiang, Ya; Lai, Fangnong; He, Guifang; Li, Yapeng; Yang, Leilei; Shen, Wei; Huo, Heqiang; Zhu, Jun; Dai, Hongyi; Zhang, Yugang

2017-01-01

Anthocyanins are the polyphenolic phytochemicals which have been shown to scavenge free radicals. In this study, we investigated the effects of anthocyanins extracted from red-fleshed apples (Malus sieversii) on reducing oxidative damage by Rosup in porcine granulosa cells (GCs) by measuring intracellular reactive oxygen species (ROS), content of glutathione (GSH), activities of superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase (GPX1) and the gene expression of SOD1, CAT, GPX1. Apoptosis was determined with TdT-mediated dUTP-biotin nick end labeling (TUNEL) and apoptosis-related proteins were quantified with Western blotting. The results indicate that Rosup increases oxidative stress by inducing reactive oxygen species production in porcine GCs and the oxidative stress could be reduced by anthocyanins. The gene expression of SOD1, CAT, GPX1 and the activities of these enzymes were increased when GCs were treated with anthocyanins and Rosup for 6 hours. Anthocyanins inhibit Rosup-induced apoptosis by increasing expression of antiapoptotic protein Bcl-2 and suppressing the expression of pro-apoptotic protein Bax. Collectively, anthocyanins from red-fleshed apples reduce oxidative stress and inhibit apoptosis in porcine GCs in vitro. This approach indicates that antioxidants might be developed from red-fleshed apples.

Alleviation of Rosup-induced oxidative stress in porcine granulosa cells by anthocyanins from red-fleshed apples

PubMed Central

He, Guifang; Li, Yapeng; Yang, Leilei; Shen, Wei; Huo, Heqiang; Zhu, Jun; Dai, Hongyi

2017-01-01

Anthocyanins are the polyphenolic phytochemicals which have been shown to scavenge free radicals. In this study, we investigated the effects of anthocyanins extracted from red-fleshed apples (Malus sieversii) on reducing oxidative damage by Rosup in porcine granulosa cells (GCs) by measuring intracellular reactive oxygen species (ROS), content of glutathione (GSH), activities of superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase (GPX1) and the gene expression of SOD1, CAT, GPX1. Apoptosis was determined with TdT-mediated dUTP-biotin nick end labeling (TUNEL) and apoptosis-related proteins were quantified with Western blotting. The results indicate that Rosup increases oxidative stress by inducing reactive oxygen species production in porcine GCs and the oxidative stress could be reduced by anthocyanins. The gene expression of SOD1, CAT, GPX1 and the activities of these enzymes were increased when GCs were treated with anthocyanins and Rosup for 6 hours. Anthocyanins inhibit Rosup-induced apoptosis by increasing expression of antiapoptotic protein Bcl-2 and suppressing the expression of pro-apoptotic protein Bax. Collectively, anthocyanins from red-fleshed apples reduce oxidative stress and inhibit apoptosis in porcine GCs in vitro. This approach indicates that antioxidants might be developed from red-fleshed apples. PMID:28850606

Role of Oxygen Free Radicals, Nitric Oxide and Mitochondria in Mediating Cardiac Alterations During Liver Cirrhosis Induced by Thioacetamide.

PubMed

Amirtharaj, G Jayakumar; Natarajan, Sathish Kumar; Pulimood, Anna; Balasubramanian, K A; Venkatraman, Aparna; Ramachandran, Anup

2017-04-01

Thioacetamide (TAA) administration is widely used for induction of liver cirrhosis in rats, where reactive oxygen radicals (ROS) and nitric oxide (NO) participate in development of liver damage. Cardiac dysfunction is an important complication of liver cirrhosis, but the role of ROS or NO in cardiac abnormalities during liver cirrhosis is not well understood. This was investigated in animals after TAA-induced liver cirrhosis and temporal changes in oxidative stress, NO and mitochondrial function in the heart evaluated. TAA induced elevation in cardiac levels of nitrate before development of frank liver cirrhosis, without gross histological alterations. This was accompanied by an early induction of P38 MAP kinase, which is influenced by ROS and plays an important signaling role for induction of iNOS. Increased nitrotyrosine, protein oxidation and lipid peroxidation in the heart and cardiac mitochondria, suggestive of oxidative stress, also preceded frank liver cirrhosis. However, compromised cardiac mitochondrial function with a decrease in respiratory control ratio and increased mitochondrial swelling was seen later, when cirrhosis was evident. In conclusion, TAA induces elevations in ROS and NO in the heart in parallel to early liver damage. This leads to later development of functional deficits in cardiac mitochondria after development of liver cirrhosis.

Quantitative Profiling of Protein S-Glutathionylation Reveals Redox-Dependent Regulation of Macrophage Function During Nanoparticle-Induced Oxidative Stress

DOE PAGES

Duan, Jicheng; Kodali, Vamsi K.; Gaffrey, Matthew J.; ...

2015-12-23

Engineered nanoparticles (ENPs) are emerging functional materials increasingly utilized for commercial and medical applications. Due to the potential hazard effects of ENPs to human health, it is significant to assess and understand the underlying mechanisms of nanotoxicity. Here, we investigate protein S-glutathionylation (SSG) as an underlying regulatory mechanism for ENP-induced oxidative stress in macrophages by applying a recently developed quantitative redox proteomics approach for site-specific measurements of SSG. Three high-volume production ENPs (SiO 2, Fe 3O 4 and CoO) were selected as representative ENPs with low, moderate, and high reactive oxygen species (ROS) activity, respectively. Among these nanoparticles, we observemore » that CoO led to the most significant dose-dependent oxidative stress and increase of protein SSG modifications in macrophages. Our site-specific SSG changes highlighted a broad set of redox sensitive proteins and their specific Cys residues potentially implicated in stress response. Functional analysis revealed that the most significantly enriched functional categories for SSG-modified proteins were stress response, cellular structure change, and cell death or survival. Moreover, ENPs-induce oxidative stress levels (CoO > Fe 3O 4 > SiO 2) were found to correlate well with the levels of impairment of macrophage phagocytic activity and the overall degrees of increases in SSG. RNA silencing knockdown experiment of glutaredoxin 1 (Grx1) also led to a decreased phagocytic activity in macrophages, which suggested a regulatory role of SSG in phagocytosis. Together, the results provided valuable insights of protein SSG as a potential regulatory mechanism in response to nanomaterial-induced oxidative stress and immunity dysfunction.« less

Quantitative Profiling of Protein S-Glutathionylation Reveals Redox-Dependent Regulation of Macrophage Function During Nanoparticle-Induced Oxidative Stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Jicheng; Kodali, Vamsi K.; Gaffrey, Matthew J.

Engineered nanoparticles (ENPs) are emerging functional materials increasingly utilized for commercial and medical applications. Due to the potential hazard effects of ENPs to human health, it is significant to assess and understand the underlying mechanisms of nanotoxicity. Here, we investigate protein S-glutathionylation (SSG) as an underlying regulatory mechanism for ENP-induced oxidative stress in macrophages by applying a recently developed quantitative redox proteomics approach for site-specific measurements of SSG. Three high-volume production ENPs (SiO 2, Fe 3O 4 and CoO) were selected as representative ENPs with low, moderate, and high reactive oxygen species (ROS) activity, respectively. Among these nanoparticles, we observemore » that CoO led to the most significant dose-dependent oxidative stress and increase of protein SSG modifications in macrophages. Our site-specific SSG changes highlighted a broad set of redox sensitive proteins and their specific Cys residues potentially implicated in stress response. Functional analysis revealed that the most significantly enriched functional categories for SSG-modified proteins were stress response, cellular structure change, and cell death or survival. Moreover, ENPs-induce oxidative stress levels (CoO > Fe 3O 4 > SiO 2) were found to correlate well with the levels of impairment of macrophage phagocytic activity and the overall degrees of increases in SSG. RNA silencing knockdown experiment of glutaredoxin 1 (Grx1) also led to a decreased phagocytic activity in macrophages, which suggested a regulatory role of SSG in phagocytosis. Together, the results provided valuable insights of protein SSG as a potential regulatory mechanism in response to nanomaterial-induced oxidative stress and immunity dysfunction.« less

Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells.

PubMed

Aguilar, Edenil C; Santos, Lana Claudinez Dos; Leonel, Alda J; de Oliveira, Jamil Silvano; Santos, Elândia Aparecida; Navia-Pelaez, Juliana M; da Silva, Josiane Fernandes; Mendes, Bárbara Pinheiro; Capettini, Luciano S A; Teixeira, Lilian G; Lemos, Virginia S; Alvarez-Leite, Jacqueline I

2016-08-01

Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site. Copyright © 2016 Elsevier Inc. All rights reserved.

Measuring the residual stress of transparent conductive oxide films on PET by the double-beam shadow Moiré interferometer

NASA Astrophysics Data System (ADS)

Chen, Hsi-Chao; Huang, Kuo-Ting; Lo, Yen-Ming; Chiu, Hsuan-Yi; Chen, Guan-Jhen

2011-09-01

The purpose of this research was to construct a measurement system which can fast and accurately analyze the residual stress of the flexible electronics. The transparent conductive oxide (TCO) films, tin-doped indium oxide (ITO), were deposited by radio frequency (RF) magnetron sputtering using corresponding oxide targets on PET substrate. As we know that the shadow Moiré interferometry is a useable way to measure the large deformation. So we set up a double beam shadow Moiré interferometer to measure and analyze the residual stress of TCO films on PET. The feature was to develop a mathematical model and combine the image processing software. By the LabVIEW graphical software, we could measure the distance which is between the left and right fringe on the pattern to solve the curvature of deformed surface. Hence, the residual stress could calculate by the Stoney correction formula for the flexible electronics. By combining phase shifting method with shadow Moiré, the measurement resolution and accuracy have been greatly improved. We also had done the error analysis for the system whose relative error could be about 2%. Therefore, shadow Moiré interferometer is a non-destructive, fast, and simple system for the residual stress on TCO/PET films.

Silicon (Si) alleviates cotton (Gossypium hirsutum L.) from zinc (Zn) toxicity stress by limiting Zn uptake and oxidative damage.

PubMed

Anwaar, Shad Ali; Ali, Shafaqat; Ali, Skhawat; Ishaque, Wajid; Farid, Mujahid; Farooq, Muhammad Ahsan; Najeeb, Ullah; Abbas, Farhat; Sharif, Muhammad

2015-03-01

Silicon (Si) is as an important fertilizer element, which has been found effective in enhancing plant tolerance to variety of biotic and a-biotic stresses. This study investigates the Si potential to alleviate zinc (Zn) toxicity stress in cotton (Gossypium hirsutum L.). Cotton plants were grown in hydroponics and exposed to different Zn concentration, 0, 25, and 50 μM, alone and/or in combination with 1 mM Si. Incremental Zn concentration in growth media instigated the cellular oxidative damage that was evident from elevated levels of hydrogen peroxide (H2O2), electrolyte leakage, and malondialdehyde (MDA) and consequently inhibited cotton growth, biomass, chlorophyll pigments, and photosynthetic process. Application of Si significantly suppressed Zn accumulation in various plant parts, i.e., roots, stems, and leaves and thus promoted biomass, photosynthetic, growth parameters, and antioxidant enzymes activity of Zn-stressed as well unstressed plants. In addition, Si reduced the MDA and H2O2 production and electrolyte leakage suggesting its role in protecting cotton plants from Zn toxicity-induced oxidative damage. Thus, the study indicated that exogenous Si application could improve growth and development of cotton crop experiencing Zn toxicity stress by limiting Zn bioavailability and oxidative damage.

Identification and characterization of an Apis cerana cerana Delta class glutathione S-transferase gene ( AccGSTD) in response to thermal stress

NASA Astrophysics Data System (ADS)

Yan, Huiru; Jia, Haihong; Wang, Xiuling; Gao, Hongru; Guo, Xingqi; Xu, Baohua

2013-02-01

Glutathione S-transferases (GSTs) are members of a multifunctional enzyme super family that plays a pivotal role in both insecticide resistance and protection against oxidative stress. In this study, we identified a single-copy gene, AccGSTD, as being a Delta class GST in the Chinese honey bee ( Apis cerana cerana). A predicted antioxidant response element, CREB, was found in the 1,492-bp 5'-flanking region, suggesting that AccGSTD may be involved in oxidative stress response pathways. Real-time PCR and immunolocalization studies demonstrated that AccGSTD exhibited both developmental- and tissue-specific expression patterns. During development, AccGSTD transcript was increased in adults. The AccGSTD expression level was the highest in the honey bee brain. Thermal stress experiments demonstrated that AccGSTD could be significantly upregulated by temperature changes in a time-dependent manner. It is hypothesized that high expression levels might be due to the increased levels of oxidative stress caused by the temperature challenges. Additionally, functional assays of the recombinant AccGSTD protein revealed that AccGSTD has the capability to protect DNA from oxidative damage. Taken together, these data suggest that AccGSTD may be responsible for antioxidant defense in adult honey bees.

Oxidative stress status accompanying diabetic bladder cystopathy results in the activation of protein degradation pathways

PubMed Central

Kanika, Nirmala; Chang, Jinsook; Tong, Yuehong; Tiplitsky, Scott; Lin, Juan; Yohannes, Elizabeth; Tar, Moses; Chance, Mark; Christ, George J.; Melman, Arnold; Davies, Kelvin

2010-01-01

Objectives To investigate the role that oxidative stress plays in the development of diabetic cystopathy. Materials and methods Comparative gene expression in the bladder of non-diabetic and streptozotocin (STZ)-induced 2-month-old diabetic rats was carried out using microarray analysis. Evidence of oxidative stress was investigated in the bladder by analyzing glutathione S-transferase activity, lipid peroxidation, and carbonylation and nitrosylation of proteins. The activity of protein degradation pathways was assessed using western blot analysis. Results Analysis of global gene expression showed that detrusor smooth muscle tissue of STZ-induced diabetes undergoes significant enrichment in targets involved in the production or regulation of reactive oxygen species (P = 1.27 × 10−10). The microarray analysis was confirmed by showing that markers of oxidative stress were all significantly increased in the diabetic bladder. It was hypothesized that the sequelae to oxidative stress would be increased protein damage and apoptosis. This was confirmed by showing that two key proteins involved in protein degradation (Nedd4 and LC3B) were greatly up-regulated in diabetic bladders compared to controls by 12.2 ± 0.76 and 4.4 ± 1.0-fold, respectively, and the apoptosis inducing protein, BAX, was up-regulated by 6.76 ± 0.76-fold. Conclusions Overall, the findings obtained in the present study add to the growing body of evidence showing that diabetic cystopathy is associated with oxidative damage of smooth muscle cells, and results in protein damage and activation of apoptotic pathways that may contribute to a deterioration in bladder function. PMID:21518418

Ethnic-specific relationships between haemostatic and oxidative stress markers in black and white South Africans: The SABPA study.

PubMed

Lammertyn, Leandi; Mels, Catharina M C; Pieters, Marlien; Schutte, Aletta E; Schutte, Rudolph

2015-01-01

Haemostatic- and oxidative stress markers are associated with increased cardiovascular risk. In the black population, evidence exists that both an imbalance in the haemostatic system and oxidative stress link with the development of hypertension. However, it is unclear whether these two risk components function independently or are related, specifically in the black population, who is known to have a high prevalence of stroke. We aimed to investigate associations between the haemostatic system and oxidative stress in black and white South Africans. We performed a cross-sectional study including 181 black (mean age, 44; 51.4% women) and 209 white (mean age, 45; 51.7% women) teachers. Several markers of the haemostatic- (von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1, d-dimer and clot lysis time) and oxidant-antioxidant (serum peroxides, total glutathione, glutathione peroxidase- and glutathione reductase activities) systems were measured. Along with a worsened cardiovascular profile, the black group had higher haemostatic-, inflammation- and oxidative stress markers as well as decreased glutathione peroxidase activity. In multiple regression analyses, fibrinogen was positively associated with serum peroxides (p < 0.001) in both ethnic groups. In the black population, we found negative associations of von Willebrand factor and clot lysis time with glutathione peroxidase activity (p ≤ 0.008), while a positive association existed between clot lysis time and serum peroxides (p = 0.011) in the white population. We conclude that in the black population, decreased GPx activity accompanies an altered haemostatic profile, while in the white population associations may suggest that serum peroxides impair fibrin clot lysis.

Apigenin-7-diglucuronide protects retinas against bright light-induced photoreceptor degeneration through the inhibition of retinal oxidative stress and inflammation.

PubMed

Bian, Minjuan; Zhang, Yong; Du, Xiaoye; Xu, Jing; Cui, Jingang; Gu, Jiangping; Zhu, Weiliang; Zhang, Teng; Chen, Yu

2017-05-15

Vision impairment in retinal degenerative diseases such as age-related macular degeneration is primarily associated with photoreceptor degeneration, in which oxidative stress and inflammatory responses are mechanistically involved as central players. Therapies with photoreceptor protective properties remain to be developed. Apigenin-7-diglucuronide (A7DG), a flavonoid glycoside, is present in an assortment of medicinal plants with anti-inflammatory or ant-oxidant activities. However, the pharmacological significance of A7DG remains unknown in vivo. The current study isolated A7DG from Glechoma longituba (Nakai) Kuprian and investigated the retinal protective effect A7DG in mice characterized by bright light-induced photoreceptor degeneration. The results showed that A7DG treatment led to remarkable photoreceptor protection in bright light-exposed BALB/c mice. Moreover, A7DG treatment alleviated photoreceptor apoptosis, mitigated oxidative stress, suppressed reactive gliosis and microglial activation and attenuated the expression of proinflammatory genes in bright light-exposed retinas. The results demonstrated for the first time remarkable photoreceptor protective activities of A7DG in vivo. Inhibition of bright light-induced retinal oxidative stress and retinal inflammatory responses was associated with the retinal protection conferred by A7DG. The work here warrants further evaluation of A7DG as a pharmacological candidate for the treatment of vision-threatening retinal degenerative disorders. Moreover, given the general implication of oxidative stress and inflammation in the pathogenesis of neurodegeneration, A7DG could be further tested for the treatment of other neurodegenerative disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

A review of the health benefits of cherries

USDA-ARS?s Scientific Manuscript database

Increased oxidative stress contributes to development and progression of several human chronic inflammatory diseases. Cherries are a rich source of polyphenols and vitamin C which have anti-oxidant and anti-inflammatory properties. Our aim is to summarize results from human studies regarding health ...

You're Only as Old as Your Arteries: Translational Strategies for Preserving Vascular Endothelial Function with Aging

PubMed Central

Kaplon, Rachelle E.; Gioscia-Ryan, Rachel A.; LaRocca, Thomas J.

2014-01-01

Endothelial dysfunction develops with age and increases the risk of age-associated vascular disorders. Nitric oxide insufficiency, oxidative stress, and chronic low-grade inflammation, induced by upregulation of adverse cellular signaling processes and imbalances in stress resistance pathways, mediate endothelial dysfunction with aging. Healthy lifestyle behaviors preserve endothelial function with aging by inhibiting these mechanisms, and novel nutraceutical compounds that favorably modulate these pathways hold promise as a complementary approach for preserving endothelial health. PMID:24985329

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism

PubMed Central

Hornik, Chi Dang; Bilbo, Staci; Holzknecht, Zoie E.; Gentry, Lauren; Rao, Rasika; Lin, Shu S.; Herbert, Martha R.; Nevison, Cynthia D.

2017-01-01

The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic breakdown of pharmaceuticals during early development. Thus, one explanation for the increased prevalence of autism is that increased exposure to acetaminophen, exacerbated by inflammation and oxidative stress, is neurotoxic in babies and small children. This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth. PMID:28415925

Aging, Atherosclerosis, and IGF-1

PubMed Central

Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung

2012-01-01

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1–induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging. PMID:22491965

Imaging of Oxidative Stress in Prostate Cancer

DTIC Science & Technology

2013-10-01

transformative imaging agent. 15. SUBJECT TERMS Positron Emission Tomography, Oxidative Stress, Hydrogen Peroxide, 18F, 124I, Prostate...AD_________________ Award Number: W81XWH-12-1-0029 TITLE: Imaging of Oxidative Stress in...27September2012-26September2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Imaging of Oxidative Stress in Prostate Cancer 5b. GRANT NUMBER

Ceramic Composite Intermediate Temperature Stress-Rupture Properties Improved Significantly

NASA Technical Reports Server (NTRS)

Morscher, Gregory N.; Hurst, Janet B.

2002-01-01

Silicon carbide (SiC) composites are considered to be potential materials for future aircraft engine parts such as combustor liners. It is envisioned that on the hot side (inner surface) of the combustor liner, composites will have to withstand temperatures in excess of 1200 C for thousands of hours in oxidizing environments. This is a severe condition; however, an equally severe, if not more detrimental, condition exists on the cold side (outer surface) of the combustor liner. Here, the temperatures are expected to be on the order of 800 to 1000 C under high tensile stress because of thermal gradients and attachment of the combustor liner to the engine frame (the hot side will be under compressive stress, a less severe stress-state for ceramics). Since these composites are not oxides, they oxidize. The worst form of oxidation for strength reduction occurs at these intermediate temperatures, where the boron nitride (BN) interphase oxidizes first, which causes the formation of a glass layer that strongly bonds the fibers to the matrix. When the fibers strongly bond to the matrix or to one another, the composite loses toughness and strength and becomes brittle. To increase the intermediate temperature stress-rupture properties, researchers must modify the BN interphase. With the support of the Ultra-Efficient Engine Technology (UEET) Program, significant improvements were made as state-of-the-art SiC/SiC composites were developed during the Enabling Propulsion Materials (EPM) program. Three approaches were found to improve the intermediate-temperature stress-rupture properties: fiber-spreading, high-temperature silicon- (Si) doped boron nitride (BN), and outside-debonding BN.

The impact of match-play tennis in a hot environment on indirect markers of oxidative stress and antioxidant status.

PubMed

Knez, Wade L; Périard, Julien D; Périard, J P

2014-04-01

The purpose of this study was to determine the impact of changes in oxidative stress and antioxidant status in response to playing tennis in HOT (∼36°C and 35% relative humidity (RH)) and COOL (∼22°C and 70% RH) conditions. 10 male tennis players undertook two matches for an effective playing time (ie, ball in play) of 20 min, corresponding to ∼122 and ∼107 min of total play in HOT and COOL conditions, respectively. Core body temperature, body mass and indirect markers of oxidative stress (diacrons reactive oxygen metabolic test) and antioxidant status (biological antioxidant potential test) were assessed immediately prematch, midmatch and postmatch, and 24 and 48 h into recovery. Regardless of the condition, oxidative stress remained similar throughout play and into recovery. Likewise, match-play tennis in the COOL had no impact on antioxidant status. However, antioxidants status increased significantly in the HOT compared with COOL environment (p<0.05). Body mass losses (∼0.5 kg) were similar between conditions. Rectal temperature increased during both matches (p<0.05), but with a greater magnitude in the HOT (39.3±0.5°C) versus COOL (38.7±0.2°C) environment (p<0.05). Match-play tennis in the heat does not exacerbate the development of oxidative stress, but significantly increases antioxidant status. These data suggest that the heat stress observed in the HOT environment may provide a necessary signal for the upregulation of antioxidant defence, dampening cellular damage.

Marine Carotenoids against Oxidative Stress: Effects on Human Health.

PubMed

Gammone, Maria Alessandra; Riccioni, Graziano; D'Orazio, Nicolantonio

2015-09-30

Carotenoids are lipid-soluble pigments that are produced in some plants, algae, fungi, and bacterial species, which accounts for their orange and yellow hues. Carotenoids are powerful antioxidants thanks to their ability to quench singlet oxygen, to be oxidized, to be isomerized, and to scavenge free radicals, which plays a crucial role in the etiology of several diseases. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. In this respect, various novel marine carotenoids have recently been isolated from marine organisms and displayed several utilizations as nutraceuticals and pharmaceuticals. Marine carotenoids (astaxanthin, fucoxanthin, β-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. This review aims to describe the role of marine carotenoids against oxidative stress and their potential applications in preventing and treating inflammatory diseases.

Marine Carotenoids against Oxidative Stress: Effects on Human Health

PubMed Central

Gammone, Maria Alessandra; Riccioni, Graziano; D’Orazio, Nicolantonio

2015-01-01

Carotenoids are lipid-soluble pigments that are produced in some plants, algae, fungi, and bacterial species, which accounts for their orange and yellow hues. Carotenoids are powerful antioxidants thanks to their ability to quench singlet oxygen, to be oxidized, to be isomerized, and to scavenge free radicals, which plays a crucial role in the etiology of several diseases. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. In this respect, various novel marine carotenoids have recently been isolated from marine organisms and displayed several utilizations as nutraceuticals and pharmaceuticals. Marine carotenoids (astaxanthin, fucoxanthin, β-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. This review aims to describe the role of marine carotenoids against oxidative stress and their potential applications in preventing and treating inflammatory diseases. PMID:26437420

An oral absorbent, surface-deacetylated chitin nano-fiber ameliorates renal injury and oxidative stress in 5/6 nephrectomized rats.

PubMed

Anraku, Makoto; Tabuchi, Ryo; Ifuku, Shinsuke; Nagae, Tomone; Iohara, Daisuke; Tomida, Hisao; Uekama, Kaneto; Maruyama, Toru; Miyamura, Shigeyuki; Hirayama, Fumitoshi; Otagiri, Masaki

2017-04-01

In this study, we report that surface-deacetylated chitin nano-fibers (SDACNFs) are more effective in decreasing renal injury and oxidative stress than deacetylated chitin powder (DAC) in 5/6 nephrectomized rats. An oral administration of low doses of SDACNFs (40mg/kg/day) over a 4 week period resulted in a significant decrease in serum indoxyl sulfate, creatinine and urea nitrogen levels, compared with a similar treatment with DAC or AST-120. The SDACNFs treatment also resulted in an increase in antioxidant potential, compared with that for DAC or AST-120. Immunohistochemical analyses also demonstrated that SDACNFs treated CRF rats showed a decrease in the amount of accumulated 8-OHdG compared with the CRF group. These results suggest that the ingestion of SDCH-NF results in a significant reduction in the levels of pro-oxidants, such as uremic toxins, in the gastrointestinal tract, thereby inhibiting the subsequent development of oxidative stress in the systemic circulation. Copyright © 2016. Published by Elsevier Ltd.

Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications.

PubMed

Porter, Joseph J; Mehl, Ryan A

2018-01-01

Posttranslational modifications resulting from oxidation of proteins (Ox-PTMs) are present intracellularly under conditions of oxidative stress as well as basal conditions. In the past, these modifications were thought to be generic protein damage, but it has become increasingly clear that Ox-PTMs can have specific physiological effects. It is an arduous task to distinguish between the two cases, as multiple Ox-PTMs occur simultaneously on the same protein, convoluting analysis. Genetic code expansion (GCE) has emerged as a powerful tool to overcome this challenge as it allows for the site-specific incorporation of an Ox-PTM into translated protein. The resulting homogeneously modified protein products can then be rigorously characterized for the effects of individual Ox-PTMs. We outline the strengths and weaknesses of GCE as they relate to the field of oxidative stress and Ox-PTMs. An overview of the Ox-PTMs that have been genetically encoded and applications of GCE to the study of Ox-PTMs, including antibody validation and therapeutic development, is described.

Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases.

PubMed

Islam, Md Asiful; Alam, Fahmida; Solayman, Md; Khalil, Md Ibrahim; Kamal, Mohammad Amjad; Gan, Siew Hua

2016-01-01

Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro , in vivo , and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.

Diabetes and Kidney Disease: Role of Oxidative Stress

PubMed Central

Jha, Jay C.; Banal, Claudine; Chow, Bryna S.M.; Cooper, Mark E.

2016-01-01

Abstract Significance: Intrarenal oxidative stress plays a critical role in the initiation and progression of diabetic kidney disease (DKD). Enhanced oxidative stress results from overproduction of reactive oxygen species (ROS) in the context of concomitant, insufficient antioxidant pathways. Renal ROS production in diabetes is predominantly mediated by various NADPH oxidases (NOXs), but a defective antioxidant system as well as mitochondrial dysfunction may also contribute. Recent Advances: Effective agents targeting the source of ROS generation hold the promise to rescue the kidney from oxidative damage and prevent subsequent progression of DKD. Critical Issues and Future Directions: In the present review, we summarize and critically analyze molecular and cellular mechanisms that have been demonstrated to be involved in NOX-induced renal injury in diabetes, with particular focus on the role of increased glomerular injury, the development of albuminuria, and tubulointerstitial fibrosis, as well as mitochondrial dysfunction. Furthermore, novel agents targeting NOX isoforms are discussed. Antioxid. Redox Signal. 25, 657–684. PMID:26906673

Interaction of plant cell signaling molecules, salicylic acid and jasmonic acid, with the mitochondria of Helicoverpa armigera.

PubMed

Akbar, S M D; Sharma, H C; Jayalakshmi, S K; Sreeramulu, K

2012-02-01

The cotton bollworm, Helicoverpa armigera is a polyphagous pest in Asia, Africa, and the Mediterranean Europe. Salicylic acid (SA) and jasmonic acid (JA) are the cell signaling molecules produced in response to insect attack in plants. The effect of these signaling molecules was investigated on the oxidative phosphorylation and oxidative stress of H. armigera. SA significantly inhibited the state III and state IV respiration, respiratory control index (RCI), respiratory complexes I and II, induced mitochondrial swelling, and cytochrome c release in vitro. Under in vivo conditions, SA induced state IV respiration as well as oxidative stress in time- and dose-dependent manner, and also inhibited the larval growth. In contrast, JA did not affect the mitochondrial respiration and oxidative stress. SA affected the growth and development of H. armigera, in addition to its function as signaling molecules involved in both local defense reactions at feeding sites and the induction of systemic acquired resistance in plants.

Relationships between Psychosocial Difficulties and Oxidative Stress Biomarkers in Women Subject to Intimate Partner Violence.

PubMed

Kim, Jae Yop; Lee, Ji Hyeon; Song, Hyang Joo; Kim, Dong Goo; Yim, Yeong Shin

2017-02-01

Women subject to violence by their intimate partners often experience a range of psychosocial problems such as depression, excessive alcohol use, and stressful life events that, in turn, lead to health issues. This study examined psychosocial difficulties and oxidative stress levels in abused and non-abused Korean women and analyzed the relationship between psychosocial outcomes and oxidative stress levels. Markers were determined in 16 women (seven abused, nine non-abused). The two groups of women (abused and non-abused) were compared with respect to scores in depression, alcohol use, life stress events, and oxidative stress biomarkers using the Mann-Whitney U test. Correlations between depression, alcohol use, life stress events, and oxidative stress biomarkers were tested by the Spearman rank correlation coefficient. The abused women had significantly higher levels of oxidative stress markers and significantly lower levels of antioxidants than the non-abused women. Life stress events and oxidative biomarker levels were significantly correlated. These findings have implications for both social services providers and medical personnel when assessing abused women to ensure that they receive the most appropriate service. © 2016 National Association of Social Workers.

Nanomaterial induction of oxidative stress in lung epithelial cells and macrophages

NASA Astrophysics Data System (ADS)

Wang, Lin; Pal, Anoop K.; Isaacs, Jacqueline A.; Bello, Dhimiter; Carrier, Rebecca L.

2014-09-01

Oxidative stress in the lung epithelial A549 cells and macrophages J774A.1 due to contact with commercially important nanomaterials [i.e., nano-silver (nAg), nano-alumina (nAl2O3), single-wall carbon nanotubes (CNT), and nano-titanium oxide anatase (nTiO2)] was evaluated. Nanomaterial-induced intracellular oxidative stress was analyzed by both H2DCFDA fluorescein probe and GSH depletion, extracellular oxidative stress was assessed by H2HFF fluorescein probes, and the secretion of chemokine IL-8 by A549 cells due to elevation of cellular oxidative stress was also monitored, in order to provide a comprehensive in vitro study on nanomaterial-induced oxidative stress in lung. In addition, results from this study were also compared with an acellular "ferric reducing ability of serum" (FRAS) assay and a prokaryotic cell-based assay in evaluating oxidative damage caused by the same set of nanomaterials, for comparison purposes. In general, it was found that nanomaterial-induced oxidative stress is highly cell-type dependent. In A549 lung epithelial cells, nAg appeared to induce highest level of oxidative stress and cell death followed by CNT, nTiO2, and nAl2O3. Different biological oxidative damage (BOD) assays' (i.e., H2DCFA, GSH, and IL-8 release) results generally agreed with each other, and the same trends of nanomaterial-induced BOD were also observed in acellular FRAS and prokaryotic E. coli K12-based assay. In macrophage J774A.1 cells, nAl2O3 and nTiO2 appeared to induce highest levels of oxidative stress. These results suggest that epithelial and macrophage cell models may provide complimentary information when conducting cell-based assays to evaluate nanomaterial-induced oxidative damage in lung.

Responses of Aspergillus flavus to oxidative stress are related to fungal development regulator, antioxidant enzyme, and secondary metabolite biosynthetic gene expression

USDA-ARS?s Scientific Manuscript database

The infection of maize and peanut with Aspergillus flavus and subsequent contamination with aflatoxin pose a threat to global food safety and human health, and is exacerbated by drought stress. Drought stress-responding compounds such as reactive oxygen species (ROS) are associated with fungal stres...

Oxidative Stress, Nitric Oxide, and Diabetes

PubMed Central

Pitocco, Dario; Zaccardi, Francesco; Di Stasio, Enrico; Romitelli, Federica; Santini, Stefano A.; Zuppi, Cecilia; Ghirlanda, Giovanni

2010-01-01

In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the “final common pathway”, through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients. PMID:20703435

Liver antioxidant stores protect the brain from electromagnetic radiation (900 and 1800 MHz)-induced oxidative stress in rats during pregnancy and the development of offspring.

PubMed

Çetin, Hasan; Nazıroğlu, Mustafa; Çelik, Ömer; Yüksel, Murat; Pastacı, Nural; Özkaya, Mehmet Okan

2014-12-01

The present study determined the effects of mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in the brain and liver as well as the element levels in growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their offspring were equally divided into three different groups: the control, 900 MHz, and 1800 MHz groups. The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/d during pregnancy and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain samples were obtained. Brain and liver glutathione peroxidase activities, as well as liver vitamin A and β-carotene concentrations decreased in the EMR groups, although brain iron, vitamin A, and β-carotene concentrations increased in the EMR groups. In the 6th week, selenium concentrations in the brain decreased in the EMR groups. There were no statistically significant differences in glutathione, vitamin E, chromium, copper, magnesium, manganese, and zinc concentrations between the three groups. EMR-induced oxidative stress in the brain and liver was reduced during the development of offspring. Mobile phone-induced EMR could be considered as a cause of oxidative brain and liver injury in growing rats.

Melatonin protect the development of preimplantation mouse embryos from sodium fluoride-induced oxidative injury.

PubMed

Zhao, Jiamin; Fu, Beibei; Peng, Wei; Mao, Tingchao; Wu, Haibo; Zhang, Yong

2017-09-01

Recently study shows that melatonin can protect embryos from the culture environment oxidative stress. However, the protective effect of melatonin on the mouse development of preimplantation embryos under sodium fluoride (NaF) induced oxidative stress is still unclear. Here, we showed that exposure to NaF significantly increased the reactive oxygen species (ROS) level, decreased the blastocyst formation rates, and increased the fragmentation, apoptosis and retardation of blastocysts in the development of mouse preimplantation embryos. However, the protective of melatonin remarkable increased the of blastocyst formation rates, maintained mitochondrial function and total antioxidant capacity by clearing ROS. Importantly the data showed that melatonin improved the activity of enzymatic antioxidants, including glutathione(GSH), superoxide dismutase(SOD), and malonaldehyde (MDA), and increased the expression levels of antioxidative genes. Taken together, our results indicate that melatonin prevent NaF-induced oxidative damage to mouse preimplantation embryo through down regulation of ROS level, stabilization of mitochondrial function and modulation of the activity of antioxidases and antioxidant genes. Copyright © 2017 Elsevier B.V. All rights reserved.

[The correlations between aging of the human body, oxidative stress and reduced efficiency of repair systems].

PubMed

Michalak, Aleksandra; Krzeszowiak, Jakub; Markiewicz-Górka, Iwona

2014-12-15

The article presents an current knowledge overview about the importance of oxidative stress and reduced efficiency of repair processes during the aging process of the human body. Oxidative damage to cellular macromolecules (proteins, lipids, nucleic acids), are formed under the influence of reactive oxygen species (ROS). They are the part of important mechanism which is responsible for the process of aging and the development of many diseases. The most important effects result from DNA damage, due to the mutations formation, which can lead to the development of tumors. However, a well-functioning repair systems (i.a. homologous recombination) remove the damage and prevent harmful changes in the cells. Lipid peroxidation products also cause oxidative modification of nucleic acids (and proteins). Proteins and fats also have repair systems, but much simpler than those responsible for the repair of nucleic acids. Unfortunately, with increasing age, they are more weakened, which contributes to increase numbers of cell damage, and consequently development of diseases specific to old age: cancer, neurodegenerative diseases or atherosclerosis.

Roles of Inflammation, Oxidative Stress, and Vascular Dysfunction in Hypertension

PubMed Central

Dinh, Quynh N.; Drummond, Grant R.; Sobey, Christopher G.

2014-01-01

Hypertension is a complex condition and is the most common cardiovascular risk factor, contributing to widespread morbidity and mortality. Approximately 90% of hypertension cases are classified as essential hypertension, where the precise cause is unknown. Hypertension is associated with inflammation; however, whether inflammation is a cause or effect of hypertension is not well understood. The purpose of this review is to describe evidence from human and animal studies that inflammation leads to the development of hypertension, as well as the evidence for involvement of oxidative stress and endothelial dysfunction—both thought to be key steps in the development of hypertension. Other potential proinflammatory conditions that contribute to hypertension—such as activation of the sympathetic nervous system, aging, and elevated aldosterone—are also discussed. Finally, we consider the potential benefit of anti-inflammatory drugs and statins for antihypertensive therapy. The evidence reviewed suggests that inflammation can lead to the development of hypertension and that oxidative stress and endothelial dysfunction are involved in the inflammatory cascade. Aging and aldosterone may also both be involved in inflammation and hypertension. Hence, in the absence of serious side effects, anti-inflammatory drugs could potentially be used to treat hypertension in the future. PMID:25136585

Microbial interference mitigates Meloidogyne incognita mediated oxidative stress and augments bacoside content in Bacopa monnieri L.

PubMed

Gupta, Rupali; Singh, Akanksha; Ajayakumar, P V; Pandey, Rakesh

2017-06-01

Microbial interference plays an imperative role in plant development and response to various stresses. However, its involvement in mitigation of oxidative stress generated by plant parasitic nematode in plants remains elusive. In the present investigation, the efficacy of microbe's viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 single and in combinations was examined to mitigate oxidative stress generated by M. incognita in medicinal plant, Bacopa monnieri. Microbial combination with and without pathogen also enhanced the growth parameters along with secondary metabolites (bacoside) of B. monnieri than the pathogen inoculated control. The study showed that initially the production of hydrogen peroxide (H 2 O 2 ) was higher in dual microbes infected with pathogen which further declined over M. incognita inoculated control plants. Superoxide dismutase and free radical scavenging activity were also highest in the same treatment which was linearly related with least lipid peroxidation and root gall formation in B. monnieri under the biotic stress. Microscopic visualization of total reactive oxygen species (ROS), H 2 O 2 , superoxide radical and programmed cell death in host plant further extended our knowledge and corroborated well with the above findings. Furthermore, scanning electron microscopy confirmed good microbial colonization on the host root surface around nematode penetration sites in plants treated with dual microbes under pathogenic stress. The findings offer novel insight into the mechanism adopted by the synergistic microbial strains in mitigating oxidative stress and simultaneously stimulating bacoside production under pathogenic stress. Copyright © 2017 Elsevier GmbH. All rights reserved.

Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease

PubMed Central

Cao, Stewart Siyan

2014-01-01

Abstract Significance: The endoplasmic reticulum (ER) is a specialized organelle for the folding and trafficking of proteins, which is highly sensitive to changes in intracellular homeostasis and extracellular stimuli. Alterations in the protein-folding environment cause accumulation of misfolded proteins in the ER that profoundly affect a variety of cellular signaling processes, including reduction–oxidation (redox) homeostasis, energy production, inflammation, differentiation, and apoptosis. The unfolded protein response (UPR) is a collection of adaptive signaling pathways that evolved to resolve protein misfolding and restore an efficient protein-folding environment. Recent Advances: Production of reactive oxygen species (ROS) has been linked to ER stress and the UPR. ROS play a critical role in many cellular processes and can be produced in the cytosol and several organelles, including the ER and mitochondria. Studies suggest that altered redox homeostasis in the ER is sufficient to cause ER stress, which could, in turn, induce the production of ROS in the ER and mitochondria. Critical Issues: Although ER stress and oxidative stress coexist in many pathologic states, whether and how these stresses interact is unknown. It is also unclear how changes in the protein-folding environment in the ER cause oxidative stress. In addition, how ROS production and protein misfolding commit the cell to an apoptotic death and contribute to various degenerative diseases is unknown. Future Directions: A greater fundamental understanding of the mechanisms that preserve protein folding homeostasis and redox status will provide new information toward the development of novel therapeutics for many human diseases. Antioxid. Redox Signal. 21, 396–413. PMID:24702237

The Effect of Interface Roughness and Oxide Film Thickness on the Inelastic Response of Thermal Barrier Coatings to Thermal Cycling

NASA Technical Reports Server (NTRS)

Pindera, Marek-Jerzy; Aboudi, Jacob; Arnold, Steven M.

1999-01-01

The effects of interfacial roughness and oxide film thickness on thermally-induced stresses in plasma-sprayed thermal barrier coatings subjected to thermal cycling are investigated using the recently developed higher-order theory for functionally graded materials. The higher-order theory is shown to be a viable alternative to the finite-element approach, capable of modeling different interfacial roughness architectures in the presence of an aluminum oxide layer and capturing the high stress gradients that occur at the top coat/bond coat interface. The oxide layer thickness is demonstrated to have a substantially greater effect on the evolution of residual stresses than local variations in interfacial roughness. Further, the location of delamination initiation in the top coat is predicted to change with increasing oxide layer thickness. This result can be used to optimize the thickness of a pre-oxidized layer introduced at the top coat/bond coat interface in order to enhance TBC durability as suggested by some researchers. The results of our investigation also support a recently proposed hypothesis regarding delamination initiation and propagation in the presence of an evolving bond coat oxidation, while pointing to the importance of interfacial roughness details and specimen geometry in modeling this phenomenon.

Abdominal aorta aneurysm (AAA): Is there a role for prevention and therapy using antioxidants?

PubMed

Pincemail, Joël; Defraigne, Jean-Olivier; Courtois, Audrey; Albert, Adelin; Cheramy-Bien, Jean-Paul; Sakalihasan, Natzi

2017-09-18

Abdominal aortic aneurysm (AAA) is a degenerative disease that cause mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seems to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. Reducing oxidative stress by antioxidants has been shown to be a potential strategy for limiting AAA development. Human studies confirmed that oxidative stress and endothelial dysfunction are well associated with AAA development. Unfortunately, there is currently no evidence showing that strategies using low molecular weight antioxidants (vitamins C and E, β-carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function but also their capacity to stimulate enzymatic antioxidants trough activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. Clinical studies are therefore urgently necessary to confirm such a suggestion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiriyama, Takao; Hirano, Makito; Asai, Hirohide

Triple A syndrome is an autosomal recessive neurological disease, mimicking motor neuron disease, and is caused by mutant ALADIN, a nuclear-pore complex component. We recently discovered that the pathogenesis involved impaired nuclear import of DNA repair proteins, including DNA ligase I and the cerebellar ataxia causative protein aprataxin. Such impairment was overcome by fusing classical nuclear localization signal (NLS) and 137-aa downstream sequence of XRCC1, designated stretched NLS (stNLS). We report here that the minimum essential sequence of stNLS (mstNLS) is residues 239-276, downsized by more than 100 aa. mstNLS enabled efficient nuclear import of DNA repair proteins in patientmore » fibroblasts, functioned under oxidative stress, and reduced oxidative-stress-induced cell death, more effectively than stNLS. The stress-tolerability of mstNLS was also exerted in control fibroblasts and neuroblastoma cells. These findings may help develop treatments for currently intractable triple A syndrome and other oxidative-stress-related neurological diseases, and contribute to nuclear compartmentalization study.« less

Decrease of Total Antioxidative Capacity in Developed Low Cardiac Output Syndrome

PubMed Central

Kunt, Alper Sami; Andac, Mehmet Halit

2012-01-01

Background. It has been known that cardiac surgery induces an oxidative stress. The persistent oxidative stress during reperfusion may lead to depressed myocardial function resulting in low cardiac output syndrome (LCOS) necessitating inotropic or intra-aortic balloon counterpulsation support. Total antioxidant capacity (TAC) is a measurement of oxidative stress in tissues. The purpose of this study was to examine the TAC differences during coronary artery bypass graft (CABG) operation in patients who have developed LCOS and who have not. Material and Methods. Seventy-nine patients were enrolled in the study. Central venous blood samples were obtained immediately before surgery, during operation, and at the end of surgery to assess TAC. Clinical data regarding patient demographics and operative outcomes were prospectively collected and entered into our clinical database. Results. LCOS developed in 8 patients (10.12%). The TAC has decreased sharply in the LCOS patients compared with those who did not develop LCOS (P < 0.001) during operation. In addition, the receiver operating characteristic (ROC) area was 0.879. Conclusion. TAC has decreased during operation in a significant proportion of patients undergoing isolated CABG, and this is more prominent and serious and might be an independent variable in patients who have developed LCOS. This may be related to intraoperative misadventure or inadequate myocardial antioxidative protection. Routine measurement of the TAC during operation may provide information for assessment of the LCOS development. PMID:23251720

Multiple Low-Dose Radiation Prevents Type 2 Diabetes-Induced Renal Damage through Attenuation of Dyslipidemia and Insulin Resistance and Subsequent Renal Inflammation and Oxidative Stress

PubMed Central

Shao, Minglong; Lu, Xuemian; Cong, Weitao; Xing, Xiao; Tan, Yi; Li, Yunqian; Li, Xiaokun; Jin, Litai; Wang, Xiaojie; Dong, Juancong; Jin, Shunzi; Zhang, Chi; Cai, Lu

2014-01-01

Background Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress. Objective The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. Methods Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured. Results HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks. Conclusion These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress. PMID:24651118

Nuclear factor erythroid-2-related factor regulates LRWD1 expression and cellular adaptation to oxidative stress in human embryonal carcinoma cells.

PubMed

Hung, Jui-Hsiang; Wee, Shi-Kae; Omar, Hany A; Su, Chia-Hui; Chen, Hsing-Yi; Chen, Pin-Shern; Chiu, Chien-Chih; Wu, Ming-Syuan; Teng, Yen-Ni

2018-05-01

Leucine-rich repeats and WD repeat domain-containing protein 1 (LRWD1) is implicated in the regulation of signal transduction, transcription, RNA processing and tumor development. However, LRWD1 transcriptional regulation is not fully understood. This study aimed to investigate the relationship between LRWD1 expression and reactive oxygen species (ROS) level in human embryonal carcinoma cell line, NT2/D1 cells, which will help in understanding the transcriptional regulatory role of ROS in cells. Results showed that the exposure of NT2/D1 cells to various concentrations of hydrogen peroxide (H 2 O 2 ) and the nitric oxide (NO) donor sodium nitroprusside (SNP) caused a significant increase in the mRNA and protein expression of LRWD1. In addition, LRWD1 promoter luciferase reporter assay, and Chromatin Immunoprecipitation assay (CHIP assay) showed that nuclear factor erythroid-2-related factor (Nrf2) was involved in the regulation of LRWD1 expression in response to oxidative stress. The involvement of Nrf2 was confirmed by shRNA-mediated knockdown of Nrf2 in NT2/D1 cells, which caused a significant decrease in LRWD1 expression in response to oxidative stress. Similarly, LRWD1 knockdown resulted in the accumulation of H 2 O 2 and superoxide anion radical (O2-). Blocking ROS production by N-acetyl cysteine (NAC) protected NT2/D1 shLRWD1cells from H 2 O 2 -induced cell death. Collectively, oxidative stress increased LRWD1 expression through a Nrf2-dependent mechanism, which plays an important role in cellular adaptation to oxidative stress. These results highlight an evidence, on the molecular level, about LRWD1 transcriptional regulation under oxidative stress. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

A Molecular Web: Endoplasmic Reticulum Stress, Inflammation, and Oxidative Stress

PubMed Central

Chaudhari, Namrata; Talwar, Priti; Parimisetty, Avinash; Lefebvre d’Hellencourt, Christian; Ravanan, Palaniyandi

2014-01-01

Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded-protein response (UPR) through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS). Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress. PMID:25120434

NIP/DuoxA is essential for Drosophila embryonic development and regulates oxidative stress response.

PubMed

Xie, Xiaojun; Hu, Jack; Liu, Xiping; Qin, Hanjuan; Percival-Smith, Anthony; Rao, Yong; Li, Shawn S C

2010-05-11

NIP/DuoxA, originally cloned as a protein capable of binding to the cell fate determinant Numb in Drosophila, was recently identified as a modulator of reactive oxygen species (ROS) production in mammalian systems. Despite biochemical and cellular studies that link NIP/DuoxA to the generation of ROS through the dual oxidase (Duox) enzyme, the in vivo function of NIP/DuoxA has not been characterized to date. Here we report a genetic and functional characterization of nip in Drosophila melanogaster. We show that nip is essential for Drosophila development as nip null mutants die at the 1(st) larval instar. Expression of UAS-nip, but not UAS-Duox, rescued the lethality. To understand the function of nip beyond the early larval stage, we generated GAL4 inducible UAS-RNAi transgenes. da(G32)-GAL4 driven, ubiquitous RNAi-mediated silencing of nip led to profound abnormality in pre-adult development, crinkled wing and markedly reduced lifespan at 29 degrees C. Compared to wild type flies, da-GAL4 induced nip-RNAi transgenic flies exhibited significantly reduced ability to survive under oxidative stress and displayed impaired mitochondrial aconitase function. Our work provides in vivo evidence for a critical role for nip in the development and oxidative stress response in Drosophila.

Difference in oxidative stress tolerance between rice cultivars estimated with chlorophyll fluorescence analysis.

PubMed

Kasajima, Ichiro

2017-04-26

Oxidative stress is considered to be involved in growth retardation of plants when they are exposed to a variety of biotic and abiotic stresses. Despite its potential importance in improving crop production, comparative studies on oxidative stress tolerance between rice (Oryza sativa L.) cultivars are limited. This work describes the difference in term of oxidative stress tolerance between 72 rice cultivars. 72 rice cultivars grown under naturally lit greenhouse were used in this study. Excised leaf discs were subjected to a low concentration of methyl viologen (paraquat), a chemical reagent known to generate reactive oxygen species in chloroplast. Chlorophyll fluorescence analysis using a two-dimensional fluorescence meter, ion leakage analysis as well as the measurement of chlorophyll contents were used to evaluate the oxidative stress tolerance of leaf discs. Furthermore, fluorescence intensities were finely analyzed based on new fluorescence theories that we have optimized. Treatment of leaf discs with methyl viologen caused differential decrease of maximum quantum yield of photosystem II (Fv/Fm) between cultivars. Decrease of Fv/Fm was also closely correlated with increase of ion leakage and decrease of chlorophyll a/b ratio. Fv/Fm was factorized into photochemical and non-photochemical parameters to classify rice cultivars into sensitive and tolerant ones. Among the 72 compared rice cultivars, the traditional cultivar Co13 was identified as the most tolerant to oxidative stress. Koshihikari, a dominant modern Japonica cultivar in Japan as well as IR58, one of the modern Indica breeding lines exhibited a strong tolerance to oxidative stress. Close correlation between Fv/Fm and chlorophyll a/b ratio provides a simple method to estimate oxidative stress tolerance, without measurement of chlorophyll fluorescence with special equipment. The fact that modern cultivars, especially major cultivars possessed tolerance to oxidative stress suggests that oxidative stress tolerance is one of the agricultural traits prerequisite for improvement of modern rice cultivars. Data presented in this study would enable breeding of rice cultivars having strong tolerance to oxidative stress.