Science captured by storytelling: the oxidative stress narrative.

Oxidative stress results from an imbalance between the production of reactive oxygen species and the antioxidants defences, in favour of the former. In recent years, the association between oxidative processes, environmental change and life histories has received much attention. However, most studies have focused on avian and mammalian taxonomic groups, with less attention given to fish, despite their ecological and socio‐economic relevance. Here we present a review of the extrinsic and intrinsic factors that influence oxidative processes in fish, using a comparative and evolutionary approach. We demonstrate that oxidative stress plays a key role in shaping fish's responses to environmental change as well as life history strategies. We focus on representative examples to compare and contrast how levels of oxidative stress respond to changes in temperature, salinity and oxygen availability. Furthermore, we describe how emerging threats (i.e. pollution) affect oxidative stress parameters in fish. Oxidative stress indicators are increasingly being used as biomarkers to understand the mechanisms of various human‐induced stressors, but also to understand the physiological consequences of how animals are distributed in space and time and influenced by different life stages. Despite the expansion of the field of ecological oxidative stress, we are only beginning to understand the complex ways in which oxidative stress may interact with both extrinsic and intrinsic factors in fish. We conclude with a research agenda for oxidative research on fish and note that there is need for further research particularly in the area of life history strategies and ecological implications of oxidative status, as this type of research has the potential to help us understand patterns and dynamics relevant to fish conservation.

A major goal of the 2006 NIEHS Strategic Plan encompasses the institute’s desire to “recruit and train the next generation of environmental health scientists.” To begin to achieve that goal, the NIEHS has unveiled a new annual grants program called the Outstanding New Environmental Scientist (ONES) Award. The five-year grants are designed to identify, encourage, inspire, and support outstanding investigators early in their careers, who have not yet received their first R01 grant. The first ONES grants, totaling $3.6 million, were awarded in September 2006 to eight promising young scientists chosen from more than 70 applicants through a rigorous application, review, and interview process. The program is the brainchild of NIEHS director David Schwartz, who has been concerned for some time about the loss of promising young scientific talent from the field for lack of support. “As a faculty member at Duke,” he says, “I found that the individuals who were particularly vulnerable in terms of their career development were those at that transitional stage between mentored and independent research, and that many very bright, creative people simply were not supported in ways that enhanced their career development.” Schwartz says the awards are also intended to help attract innovative young investigators to the NIEHS and the environmental health sciences, as well as to support the institutions that are helping new scientists develop their careers. The program’s long-term impact on the field, in terms of both the science and the scientists, could be significant. “These individuals represent very promising early career trajectories that are likely to have a substantial effect on environmental health sciences, and hopefully will evolve into the leaders in the field in the future,” says Schwartz. To ease that tricky early-career transition, ONES grantees are encouraged to establish and meet annually with an advisory committee comprising senior experts in their disciplines. According to Pat Mastin, chief of the NIEHS Cellular, Organ, and Systems Pathobiology Branch, who helped coordinate the initial ONES process, the grants represent a hybrid between mentored career development awards and independent R01 grants. “We think the young investigators should continue to be mentored,” Mastin says. “So we encouraged them to identify not a specific mentor, but an advisory committee, to give not only scientific advice but also career path advice.” The grantees recognize and appreciate the value of this hybrid approach to mentoring. “It gives us access to people we wouldn’t normally be interacting with,” says ONES grantee Thomas Begley, an assistant professor in the Department of Biomedical Sciences at the University at Albany State University of New York. “Having a mechanism to ensure that will promote good science on my end, and also will help me network with others in the field.” Grantee Patricia Opresko, an assistant professor in the Department of Environmental and Occupational Health at the University of Pittsburgh, agrees. “The grant has funds that will allow the four investigators on my advisory committee to come to Pittsburgh and meet with me once a year to focus on my project and offer their ideas, insight, input, and criticisms,” she says. “It adds an additional layer of mentoring that is really critical for a young investigator’s development.”

Proliferating mammalian cells exhibit a broad spectrum of responses to oxidative stress, depending on the stress level encountered. Very low levels of hydrogen peroxide, e.g., 3 to 15 microM, or 0.1 to 0.5 micromol/10(7) cells, cause a significant mitogenic response, 25% to 45 % growth stimulation. Greater concentrations of H2O2, 120 to 150 microM, or 2 to 5 micromol/10(7) cells, cause a temporary growth arrest that appears to protect cells from excess energy use and DNA damage. After 4-6 h of temporary growth arrest, many cells will exhibit up to a 40-fold transient adaptive response in which genes for oxidant protection and damage repair are preferentially expressed. After 18 h of H2O2 adaptation (including the 4-6 h of temporary growth arrest) cells exhibit maximal protection against oxidative stress. The H2O2 originally added is metabolized within 30-40 min, and if no more is added the cells will gradually de-adapt, so that by 36 h after the initial H2O2 stimulus they have returned to their original level of H2O2 sensitivity. At H2O2 concentrations of 250 to 400 microM, or 9 to 14 micromol/10(7) cells, mammalian fibroblasts are not able to adapt but instead enter a permanently growth-arrested state in which they appear to perform most normal cell functions but never divide again. This state of permanent growth arrest has often been confused with cell death in toxicity studies relying solely on cell proliferation assays as measures of viability. If the oxidative stress level is further increased to 0.5 to 1.0 mM H2O2, or 15 to 30 micromol/10(7) cells, apoptosis results. This oxidative stress-induced apoptosis involves nuclear condensation, loss of mitochondrial transmembrane potential, degradation/down-regulation of mitochondrial mRNAs and rRNAs, and degradation/laddering of both nuclear and mitochondrial DNA. At very high H2O2 concentrations of 5.0 to 10.0 mM, or 150 to 300 micromol/10(7) cells and above, cell membranes disintegrate, proteins and nucleic acids denature, and necrosis swiftly follows. Cultured cells grown in 20% oxygen are essentially preadapted or preselected to survive under conditions of oxidative stress. If cells are instead grown in 3% oxygen, much closer to physiological cellular levels, they are more sensitive to an oxidative challenge but exhibit far less accumulated oxidant damage. This broad spectrum of cellular responses to oxidant stress, depending on the amount of oxidant applied and the concentration of oxygen in the cell culture system, provides for a new paradigm of cellular oxidative stress responses.

Oxidative Stress for an Acute Bout of Bikram Yoga in Healthy, Trained Adults by Kimberly Trocio Dr. Antonio Santo, Thesis Committee Chair Professor of Kinesiology and Nutrition Sciences University of Nevada, Las Vegas BACKGROUND: Generation of free radicals resulting in oxidative damage has been linked to cellular damage, aging, and human disease. Many studies have reported that physical exercise can contribute to oxidative stress. Further, exercise in a hyperthermic environment can promote additional oxidative stress. It is important to consider that practices in yoga may be beneficial in reducing oxidative stress according to some studies. The compound effects of exercise and hyperthermic exposure are experienced in the practice of Bikram yoga, the original “hot” yoga. Because Bikram yoga and other hot exercise classes are an increasingly growing fitness trend, it is necessary to investigate whether there are benefits and inherent risks associated with participation. Specifically, markers of oxidative stress may provide insight into the safety and benefit for practical application of Bikram yoga. The proposed research will acknowledge two products of oxidative stress by means of lipid peroxidation and the antioxidant defense mechanism. PURPOSE: The purpose of this study is to examine the effect of one Bikram Yoga session on oxidative stress markers in healthy, trained adults. METHODS: Fourteen healthy, Bikram yoga trained adults (7 females & 7 males) with a mean age, height, weight, BMI, and % body fat of 35.86 ± 9.09 y, 171.51 ± 9.37 cm, 76.23 ± 15.03 kg, 25.90 ± 4.83, and 20.96 ± 5.17 respectively, with 2.13 ± 1.82 years of experience, iii completed a Bikram yoga session in its standard hot environment (approximately 40.6°Celcius, 40% humidity)(HOT) and a Bikram yoga session in a thermoneutral environment (22.2°Celcius and 50% humidity)(CON) on two separate laboratory visits. Oxidative stress variables, plasma thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) were investigated. Hematocrit (HMT), heart rate (HR), and oral body temperature (TEMP) were also observed. PASW Statistics 20 software was used to analyze the data. RESULTS: Oxidative stress in participation of one session of Bikram yoga performed in its standard hot environment is not significantly different when performed in a thermoneutral environment by healthy, trained adults. There was no significant interaction or main effects for TBARS (time: p=0.886, condition: p=0.480, interaction: p=0.507), GSH(time: p=0.161, condition: p=0.414, interaction: p=0.525), or hematocrit (time: p=0.581, condition: p=0.148, interaction: p=0.106). The practice of Bikram yoga in the HOT revealed elevated HR (60 min: p=0.005, 75 min: p=0.034, 105 min: p=0.033) and TEMP (15-90min: p<0.001 throughout testing in comparison to CON. HR was significantly different dependent upon the specific Bikram yoga pose. Oral temperatures reached significance throughout class participation. CONCLUSION: The lack of significant change observed in TBARS, GSH, and hematocrit indicates that the trained participants did not undergo significant oxidative stress regardless of increased oral body temperature or heart rates from the practice of Bikram yoga in the heat. Explanation of comparable levels of oxidative stress may be due to the experience and acclimatization to the practice. These data suggests that while the hyperthermic environment provides cardiovascular benefits, it does not significantly contribute to more oxidative stress in an acute bout of Bikram yoga for the Bikram trained.

Research attention has been drawn to honey's nutritional status and beneficial properties for human health. This study aimed to provide a bibliometric analysis of honey's antioxidant and antimicrobial properties. The research advancements within this field from 2001 to 2022 were addressed using the Scopus database, R, and VOSviewer. Of the 383 results, articles (273) and reviews (81) were the most common document types, while the annual growth rate of published manuscripts reached 17.5%. The most relevant topics about honey's antimicrobial and antioxidant properties were related to the agricultural and biological sciences, biochemistry, and pharmacology. According to a keyword analysis, the most frequent terms in titles, abstracts, and keywords were honey, antimicrobial, antioxidant, bee, propolis, phenolic compounds, wound, antibacterial, anti-inflammatory, and polyphenols. A trend topic analysis showed that the research agenda mainly encompassed antioxidants, pathogens, and anti-infection and chemical agents. In a co-occurrence analysis, antioxidants, anti-infection agents, and chemistry were connected to honey research. The initial research focus of this domain was primarily on honey's anti-inflammatory and antineoplastic activity, wound healing, and antibacterial agents. The research agenda was enriched in the subsequent years by pathogens, propolis, oxidative stress, and flavonoids. It was possible to pinpoint past trends and ongoing developments and provide a valuable insight into the field of honey research.

The crosstalk between different organelles allows for the exchange of proteins, lipids and ions. Endoplasmic reticulum (ER) and mitochondria are physically linked and signal through the mitochondria-associated membrane (MAM) to regulate the transfer of Ca2+ from ER stores into the mitochondrial matrix, thereby affecting mitochondrial function and intracellular Ca2+ homeostasis. The chaperone glucose-regulated protein 75 (GRP75) is a key protein expressed at the MAM interface which regulates ER–mitochondrial Ca2+ transfer. Previous studies revealed that modulation of GRP75 expression largely affected mitochondrial integrity and vulnerability to cell death. In the present study, we show that genetic ablation of GRP75, by weakening ER–mitochondrial junctions, provided protection against mitochondrial dysfunction and cell death in a model of glutamate-induced oxidative stress. Interestingly, GRP75 silencing attenuated both cytosolic and mitochondrial Ca2+ overload in conditions of oxidative stress, blocked the formation of reactive oxygen species and preserved mitochondrial respiration. These data revealed a major role for GRP75 in regulating mitochondrial function, Ca2+ and redox homeostasis. In line, GRP75 overexpression enhanced oxidative cell death induced by glutamate. Overall, our findings suggest weakening ER–mitochondrial connectivity by GRP75 inhibition as a novel protective approach in paradigms of oxidative stress in neuronal cells.

1. Reactive oxygen species and oxidative state are slowly gaining acceptance in having a physiological relevance rather than just being the culprits in pathophysiological processes. The control of the redox environment of the cell provides for additional regulation in relation to signal transduction pathways. Conversely, aberrant regulation of oxidative state manifesting as oxidative stress can predispose a cell to adverse outcome. 2. The phosphatidylinositol 3-kinase/akt pathway is one such pathway that is partially regulated via oxidative state and, in an oxidative stress paradigm such as ischaemic-reperfusion injury, may be inactivated, which can lead to exacerbation of cell death. 3. Activation of nuclear factor (NF)-kappaB has been associated with oxidative stress. The role of NF-kappaB in neuronal cell death is widely debated, with major studies highlighting both a pro- and anti-apoptotic role for NF-kappaB, with the outcome being region, stimulus, dose and duration specific. 4. Oxidative state plays a key role in the regulation and control of numerous signal transduction pathways in the cell. Elucidating the mechanisms behind oxidative stress-mediated neuronal cell death is important in identifying potential putative targets for the treatment of diseases such as stroke.

Ca(2+) is well known for its role as crucial second messenger in modulating many cellular physiological functions, Ca(2+) overload is detrimental to cellular function and may present as an important cause of cellular oxidative stress generation and apoptosis. The aim of this study is to investigate the effects of selenium on lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), cytosolic Ca(2+) release, cell viability (MTT) and apoptosis values in dorsal root ganglion (DRG) sensory neurons of rats. DRG cells were divided into four groups namely control, H(2)O(2) (as a model substance used as a paradigm for oxidative stress), selenium, selenium + H(2)O(2). Moderate doses and times of H(2)O(2) and selenium were determined by MTT test. Cells were preterated 200 nM selenium for 30 h before incubatation with 1 μM H(2)O(2) for 2 h. Lipid peroxidation levels were lower in the control, selenium, selenium + H(2)O(2) groups than in the H(2)O(2) group. GSH-Px activities were higher in the selenium groups than in the H(2)O(2) group. GSH levels were higher in the control, selenium, selenium + H(2)O(2) groups than in the H(2)O(2) group. Cytosolic Ca(2+) release was higher in the H(2)O(2) group than in the control, selenium, selenium + H(2)O(2) groups. Cytosolic Ca(2+) release was lower in the selenium + H(2)O(2) group than in the H(2)O(2). In conclusion, the present study demonstrates that selenium induced protective effects on oxidative stress, [Ca(2+)](c) release and apoptosis in DRG cells. Since selenium deficiency is a common feature of oxidative stress-induced neurological diseases of sensory neurons, our findings are relevant to the etiology of pathology in oxidative stress-induced neurological diseases of the DRG neurons.

Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

LOW-FLOW DOMICILIARY OXYGEN AS A MECHANISM OF ONGOING OXIDATIVE STRESS IN COPD PATIENTS Jill Stulce, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Health Related Sciences at Virginia Commonwealth University. Virginia Commonwealth University, 2015 Clarence Biddle, Ph.D., Department of Nurse Anesthesia Healthcare costs are escalating in the U.S., with a projected 48 trillion dollars by 2021. More than ever medical researches are obligated to ensure that costly treatment modalities are safe and effective. Chronic obstructive pulmonary disease (COPD) is a costly and debilitating disease, ranked as the third leading cause of death in America. Currently, treatment for COPD consists of anti-inflammatory agents, bronchodilators, antibiotics and supplemental oxygen when hypoxemia or clinical manifestations ensue. Oxidative stress is central to the pathology of COPD. Supplemental oxygen has been substantiated as an instigator of oxidative stress; however, LFDO has not been evaluated as a mechanism of ongoing oxidative stress in individuals with COPD. Isofuran (IsoF), a biosynthetic relative of the validated oxidative stress biomarker 8-isoprostane, is preferentially synthesized during periods of increased tissue oxygen tension. This sort of specificity allows for refinement in the assessment of supplemental oxygen as a source of oxidative stress. To address this potential this study evaluated individuals diagnosed with COPD utilizing LFDO. The study also aimed to determine if IsoF possessed clinical application in predicting the standard pulmonary function test (PFT) parameters of FEV1, FVC, FEV1/FVC and FEF25-75. The exhaled breath condensate (EBC) of 52 individuals with COPD was evaluated for the presence of IsoF. An active control group not receiving LFDO (n=26) was compared to an active treatment group receiving LFDO for a minimum of 6 hrs/day (n=26). The groups showed no statistically significant demographic differences in age, gender, height, weight, ethnicity or smoking history or in the pulmonary function test parameters of FEV1, FVC, and FEV1/FVC, with the exception of the FEF25-75 (P=0.03). The active control group generated a mean EBC IsoF level of 35.81 ± 4.91 pg/ml (± SEM) compared to the active treatment group mean EBC IsoF level of 51.37 ± 8.27 pg/ml (P=0.057). Currently, no research has been conducted that defines baseline EBC IsoF levels in healthy or diseased lungs. No statistically significant differences in mean EBC IsoF levels were noted between the control and treatment groups; however, the results, in conjunction with the only two studies available utilizing EBC IsoF as an oxidative stress biomarker, may serve to provide benchmark information for future research regarding individuals with diseased lungs, specifically COPD.

Neurodegenerative disorders, brain injury, and the decline in cognitive function with aging are accompanied by a reduced capacity of cells in the brain to cope with oxidative stress and inflammation. In this study, we focused on the response to oxidative stress in SH-SY5Y, a human neuroblastoma cell line. We monitored the viability of the cells in the presence of oxidative stress. Such stress was induced by hydrogen peroxide or by Sin1 (3-morpholinosydnonimine) that generates reactive oxygen and nitrogen species (ROS and RNS). Both stressors caused significant cell death. Our results from the RNA-seq experiments show that SH-SY5Y cells treated with Sin1 for 24 h resulted in 94 differently expressed long non-coding RNAs (lncRNAs), including many abundant ones. Among the abundant lncRNAs that were upregulated by exposing the cells to Sin1 were those implicated in redox homeostasis, energy metabolism, and neurodegenerative diseases (e.g., MALAT1, MIAT, GABPB1-AS1, NEAT1, MIAT, GABPB1-AS1, and HAND2-AS1). Another group of abundant lncRNAs that were significantly altered under oxidative stress included cancer-related SNHG family members. We tested the impact of ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, on the lncRNA expression levels. Ladostigil was previously shown to enhance learning and memory in the brains of elderly rats. In SH-SY5Y cells, several lncRNAs involved in transcription regulation and the chromatin structure were significantly induced by ladostigil. We anticipate that these poorly studied lncRNAs may act as enhancers (eRNA), regulating transcription and splicing, and in competition for miRNA binding (ceRNA). We found that the induction of abundant lncRNAs, such as MALAT1, NEAT-1, MIAT, and SHNG12, by the Sin1 oxidative stress paradigm specifies only the undifferentiated cell state. We conclude that a global alteration in the lncRNA profiles upon stress in SH-SY5Y may shift cell homeostasis and is an attractive in vitro system to characterize drugs that impact the redox state of the cells and their viability.

ZnO NPs (zinc oxide nanoparticles) has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species) production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

In multiple sclerosis (MS), mitochondrial alterations appear to contribute to disease progression. The sphingosine-1-phosphate receptor modulator siponimod is approved for treating secondary progressive MS. Its preceding compound fingolimod was shown to prevent oxidative stress-induced alterations in mitochondrial morphology. Here, we assessed the effects of siponimod, compared to fingolimod, on neuronal mitochondria in oxidatively stressed hippocampal slices. We have also advanced the model of chronic organotypic hippocampal slices for live imaging, enabling semi-automated monitoring of mitochondrial alterations. The slices were prepared from B6.Cg-Tg(Thy1-CFP/COX8A)S2Lich/J mice that display fluorescent neuronal mitochondria. They were treated with hydrogen peroxide (oxidative stress paradigm) ± 1 nM siponimod or fingolimod for 24 h. Afterwards, mitochondrial dynamics were investigated. Under oxidative stress, the fraction of motile mitochondria decreased and mitochondria were shorter, smaller, and covered smaller distances. Siponimod partly prevented oxidatively induced alterations in mitochondrial morphology; for fingolimod, a similar trend was observed. Siponimod reduced the decrease in mitochondrial track displacement, while both compounds significantly increased track speed and preserved motility. The novel established imaging and analysis tools are suitable for assessing the dynamics of neuronal mitochondria ex vivo. Using these approaches, we showed that siponimod at 1 nM partially prevented oxidatively induced mitochondrial alterations in chronic brain slices.

Cyclophilin 1 (Cyp1) mutation ameliorates oxidative stress-induced defects in a Drosophila DJ-1 null mutant

Reactive oxygen species and the modulation of stroke