This research aimed to explore the potential involvement of oxidative stress in the onset of migraines. The primary objective was to assess the concentrations of malondialdehyde (MDA), which serves as an indicator of oxidative stress, as well as nitric oxide (NO), a marker for nitrosative stress, and asymmetric dimethylarginine (ADMA), an indicator of endothelial dysfunction. Ninety (90) participants were recruited in this research work from the neurology department's outpatient headache clinic at Al Jumhury Teaching Hospital in Erbil city, the study consisted of (60) patients and (30) as controls. In the migraine group, there were (45) females and (15) males, while the control group was comprised of (20) females and (10) males with age and sex matching. The study was granted ethical approval by the Human Research Ethics Committee (HREC) at the Department of Biology, College of Science, Salahaddin University-Erbil, on February 6th, 2022.The study showed that the migraine patients had significantly greater levels of MDA, NO and ADMA than the control group. Additionally, the number of headache days experienced per month by migraine patients was positively correlated with the serum concentrations of MDA, NO, and ADMA. Specifically, as the frequency of monthly headache days increased, levels of the oxidative stress markers MDA and NO, as well as the endothelial dysfunction marker ADMA, also tended to be higher.
Inherited familial Alzheimer's disease (AD) is characterized by small increases in the ratio of Aβ42 versus Aβ40 peptide which is thought to drive the amyloid plaque formation in the brain of these patients. Little is known however whether ageing, the major risk factor for sporadic AD, affects amyloid beta‐peptide (Aβ) generation as well. Here we demonstrate that the secretion of Aβ is enhanced in an in vitro model of neuronal ageing, correlating with an increase in γ‐secretase complex formation. Moreover we found that peroxynitrite (ONOO−), produced by the reaction of superoxide anion with nitric oxide, promoted the nitrotyrosination of presenilin 1 (PS1), the catalytic subunit of γ‐secretase. This was associated with an increased association of the two PS1 fragments, PS1‐CTF and PS1‐NTF, which constitute the active catalytic centre. Furthermore, we found that peroxynitrite shifted the production of Aβ towards Aβ42 and increased the Aβ42/Aβ40 ratio. Our work identifies nitrosative stress as a potential mechanistic link between ageing and AD. ; This work was made possible by grants from the Fund for Scientific Research, Flanders; the K.U.Leuven; the VIB, Methusalem (K.U.Leuven and the Flemisch government), the Foundation for Alzheimer Research (SAO/FRMA), the European Research council (BDS), NIH AG15379 (OB), Spanish Ministry of Science and Innovation SAF 2010‐14906, Consolider 2010‐00045 (CGD), Spanish Ministery of Health (Fondo de Investigación Sanitaria‐PI10/00587 and Red HERACLES RD06/0009); The European FEDER Fundings; and Fundació La Marató de TV3 (Catalonia; Spain; no. 100310). We would like to acknowledge the Banc de Teixits Neurologics de l' Hospital Clinic de Barcelona and the Unidad de Neuropatología y Banco de Cerebros of Fundación Hospital Alcorcón for providing the brain samples. BDS is the Arthur Bax and Anna Vanluffelen chair for AD. FG obtained a IEF fellowship of the Marie Curie Actions program in FP7 and a Beatriu de Pinos grant of the Generalitat de Catalunya, Spain. TW was supported by EMBO and DFG long‐term fellowships
Elevated greenhouse gases (GHGs) induce adverse conditions directly and indirectly, causing decreases in plant productivity. To deal with climate change effects, plants have developed various mechanisms including the fine-tuning of metabolism. Plant respiratory metabolism is highly flexible due to the presence of various alternative pathways. The mitochondrial alternative oxidase (AOX) respiratory pathway is responsive to these changes, and several lines of evidence suggest it plays a role in reducing excesses of reactive oxygen species (ROS) and reactive nitrogen species (RNS) while providing metabolic flexibility under stress. Here we discuss the importance of the AOX pathway in dealing with elevated carbon dioxide (CO2), nitrogen oxides (NOx), ozone (O3), and the main abiotic stresses induced by climate change. ; This work is supported by the DST-DAAD exchange program between KJG and ARF. This work in the KJG lab is partly supported by a Ramalingaswami Fellowship and IYBA from the Department of Biotechnology, Government of India. IFS has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 753301. ; Peer reviewed
43 Pag., 2 Tabl., 2 Fig. The definitive version is available at: www3.interscience.wiley.com ; Legume root nodules are sites of intense biochemical activity and consequently are at high risk of damage as a result of the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). These molecules can potentially give rise to oxidative and nitrosative damage but, when their concentrations are tightly controlled by antioxidant enzymes and metabolites, they also play positive roles as critical components of signal transduction cascades during nodule development and stress. Thus, recent advances in our understanding of ascorbate and (homo)glutathione biosynthesis in plants have opened up the possibility of enhancing N2 fixation through an increase of their concentrations in nodules. It is now evident that antioxidant proteins other than the ascorbate-glutathione enzymes, such as some isoforms of glutathione peroxidases, thioredoxins, peroxiredoxins, and glutathione S-transferases, are also critical for nodule activity. To avoid cellular damage, nodules are endowed with several mechanisms for sequestration of Fenton-active metals (nicotianamine, phytochelatins, and metallothioneins) and for controlling ROS/RNS bioactivity (hemoglobins). The use of 'omic' technologies has expanded the list of known antioxidants in plants and nodules that participate in ROS/RNS/antioxidant signaling networks, although aspects of developmental variation and subcellular localization of these networks remain to be elucidated. To this end, a critical point will be to define the transcriptional and post-transcriptional regulation of antioxidant proteins. ; The research described here was supported by a grant from the National Science Foundation (IOS-0517688) to D.A.D., and a grant from the Spanish Ministry of Science and Innovation-FEDER (AGL2008-01298) and Government of Aragón (group A53) to M.B. ; Peer reviewed
Antioxidants and Redox Signaling 18.3 (2013): 288-308 ; Significance: In the immune system, nitric oxide (NO) has been mainly associated with antibacterial defenses exerted through oxidative, nitrosative, and nitrative stress and signal transduction through cyclic GMP-dependent mechanisms. However, S-nitrosylation is emerging as a post-translational modification (PTM) involved in NO-mediated cell signaling. Recent Advances: Precise roles for S-nitrosylation in signaling pathways have been described both for innate and adaptive immunity. Denitrosylation may protect macrophages from their own S-nitrosylation, while maintaining nitrosative stress compartmentalized in the phagosomes. Nitrosothiols have also been shown to be beneficial in experimental models of autoimmune diseases, mainly through their role in modulating T-cell differentiation and function. Critical Issues: Relationship between S-nitrosylation, other thiol redox PTMs, and other NO-signaling pathways has not been always taken into account, particularly in the context of immune responses. Methods for assaying S-nitrosylation in individual proteins and proteomic approaches to study the S-nitrosoproteome are constantly being improved, which helps to move this field forward. Future Directions: Integrated studies of signaling pathways in the immune system should consider whether S-nitrosylation/denitrosylation processes are among the PTMs influencing the activity of key signaling and adaptor proteins. Studies in pathophysiological scenarios will also be of interest to put these mechanisms into broader contexts. Interventions modulating nitrosothiol levels in autoimmune disease could be investigated with a view to developing new therapies ; Financed by the Spanish Government grants CSD2007-00020 (RosasNet, Consolider-Ingenio 2010 programme), CP07/00143 (Miguel Servet programme), and PS09/00101; and PI10/02136
AbstractDespite the extraordinary use of silver nanoparticles (AgNPs) in medicinal purposes and the food industry, there is rising worry about potential hazards to human health and the environment. The existing study aims to assess the hepatotoxic effects of different dosages of AgNPs by evaluating hematobiochemical parameters, oxidative stress, liver morphological alterations, immunohistochemical staining, and gene expression to clarify the mechanism of AgNPs' hepatic toxic potential. Forty male Sprague Dawley rats were randomly assigned into control and three AgNPs intraperitoneally treated groups 0.25, 0.5, and 1 mg/kg b.w. daily for 15 and 30 days. AgNP exposure reduced body weight, caused haematological abnormalities, and enhanced hepatic oxidative and nitrosative stress with depletion of the hepatic GSH level. Serum hepatic injury biomarkers with pathological hepatic lesions where cholangiopathy emerges as the main hepatic alteration in a dosage- and duration-dependent manner were also elevated. Furthermore, immunohistochemical labelling of apoptotic markers demonstrated that Bcl-2 was significantly downregulated while caspase-3 was significantly upregulated. In conclusion, the hepatotoxic impact of AgNPs may be regulated by two mechanisms, implying the apoptotic/antiapoptotic pathway via raising BAX and inhibiting Bcl-2 expression levels in a dose-dependent manner. The TGF-β1 and α-SMA pathway which triggered fibrosis with incorporation of iNOS which consequently activates the inflammatory process were also elevated. To our knowledge, there has been no prior report on the experimental administration of AgNPs in three different dosages for short and long durations in rats with the assessment of Bcl-2, BAX, iNOS, TGF-β1, and α-SMA gene expressions. Graphical abstract
AbstractOchratoxin A (OTA) is one of the most dangerous and that pollute agricultural products, inducing a variety of toxic effects in humans and animals. The current study explored the protective effect of different concentrations ofAspergillus awamori(A.awamori) against OTA (0.3 mg/kg diet) induced renal and cardiac damage by exploring its mechanism of action in 60 New Zealand white male rabbits. Dietary supplementation ofA.awamoriat the selected doses of 50, 100, and 150 mg/kg diet, respectively, for 2 months significantly improved the rabbit's growth performance; modulated the suppressed immune response and restored the altered hematological parameters; reduced the elevated levels of renal injury biomarkers such as urea, creatinine, and alkaline phosphatase; and increased serum total proteins concentrations. Moreover, it also declined enzymatic activities of cardiac injury biomarkers, including AST, LDH, and CK-MB.A.awamorialleviated OTA-induced degenerative and necrotic changes in the kidney and heart of rabbits. Interestingly,A.awamoriupregulated Nrf2/OH-1 signaling pathway. Therefore enhanced TAC, CAT, and SOD enzyme activities and reduced OTA-induced oxidative and nitrosative stress by declining iNOS gene expression and consequently lowered MDA and NO levels. In addition to attenuating renal and cardiac inflammation via reducing IL-1β, TNF-α gene expressions in a dose-dependent response. In conclusion,this is the first report to pinpoint that dietary incorporation ofA.awamoricounteracted OTA-induced renal and cardiac damage by potentiating the rabbit's antioxidant defense system through its potent antioxidant, free radical scavenging, and anti-inflammatory properties in a dose-dependent response. Based on our observations,A.awamoricould be utilized as a natural protective agent against ochratoxicosis in rabbits.Graphical abstract
Disruption in membrane excitability contributes to malfunction and differential vulnerability of specific neuronal subpopulations in a number of neurological diseases. The adaptor protein p11, and background potassium channel TASK1, have overlapping distributions in the CNS. Here, we report that the transcription factor Sp1 controls p11 expression, which impacts on excitability by hampering functional expression of TASK1. In the SOD1-G93A mouse model of ALS, Sp1-p11-TASK1 dysregulation contributes to increased excitability and vulnerability of motor neurons. Interference with either Sp1 or p11 is neuroprotective, delaying neuron loss and prolonging lifespan in this model. Nitrosative stress, a potential factor in human neurodegeneration, stimulated Sp1 expression and human p11 promoter activity, at least in part, through a Sp1-binding site. Disruption of Sp1 or p11 also has neuroprotective effects in a traumatic model of motor neuron degeneration. Together our work suggests the Sp1-p11-TASK1 pathway is a potential target for treatment of degeneration of motor neurons. ; Funding grants: SAF2008-01415 (MICINN/FEDER), SAF2011-23633 (MICINN), BFU2015-71422-R (MINECO/FEDER), PI14/00060 (ISCIII/FEDER) from Spain's Government, as well as P07-CTS-02606, P09-CTS-5445, and P11-CTS-7281 (CICE/FEDER) from Junta de Andalucía, Spain. We thank Dr. Douglas A. Bayliss (University of Virginia, USA) for kindly providing the knock-out mice, Drs. Carmen Castro (University of Cadiz, Spain) and Sergey Kasparov (University of Bristol, UK) for supervision on the initial western blotting experiments and on viral constructions and production, respectively, and Ms. Lucia Molanes, Ms. Eugenia Gomez and Mr. Antonio Torres for their skillful technical assistance. We thank Elaine Lilly, Ph.D. (Writer's First Aid), for English language revision.
AbstractChronic diseases and illnesses associated with non-specific symptoms are on the rise. In addition to chronic stress in social and work environments, physical and chemical exposures at home, at work, and during leisure activities are causal or contributing environmental stressors that deserve attention by the general practitioner as well as by all other members of the health care community. It seems necessary now to take "new exposures" like electromagnetic fields (EMF) into account. Physicians are increasingly confronted with health problems from unidentified causes. Studies, empirical observations, and patient reports clearly indicate interactions between EMF exposure and health problems. Individual susceptibility and environmental factors are frequently neglected. New wireless technologies and applications have been introduced without any certainty about their health effects, raising new challenges for medicine and society. For instance, the issue of so-called non-thermal effects and potential long-term effects of low-dose exposure were scarcely investigated prior to the introduction of these technologies. Common electromagnetic field or EMF sources: Radio-frequency radiation (RF) (3 MHz to 300 GHz) is emitted from radio and TV broadcast antennas, Wi-Fi access points, routers, and clients (e.g. smartphones, tablets), cordless and mobile phones including their base stations, and Bluetooth devices. Extremely low frequency electric (ELF EF) and magnetic fields (ELF MF) (3 Hz to 3 kHz) are emitted from electrical wiring, lamps, and appliances. Very low frequency electric (VLF EF) and magnetic fields (VLF MF) (3 kHz to 3 MHz) are emitted, due to harmonic voltage and current distortions, from electrical wiring, lamps (e.g. compact fluorescent lamps), and electronic devices. On the one hand, there is strong evidence that long-term exposure to certain EMFs is a risk factor for diseases such as certain cancers, Alzheimer's disease, and male infertility. On the other hand, the emerging electromagnetic hypersensitivity (EHS) is more and more recognized by health authorities, disability administrators and case workers, politicians, as well as courts of law. We recommend treating EHS clinically as part of the group of chronic multisystem illnesses (CMI), but still recognizing that the underlying cause remains the environment. In the beginning, EHS symptoms occur only occasionally, but over time they may increase in frequency and severity. Common EHS symptoms include headaches, concentration difficulties, sleep problems, depression, a lack of energy, fatigue, and flu-like symptoms. A comprehensive medical history, which should include all symptoms and their occurrences in spatial and temporal terms and in the context of EMF exposures, is the key to making the diagnosis. The EMF exposure is usually assessed by EMF measurements at home and at work. Certain types of EMF exposure can be assessed by asking about common EMF sources. It is very important to take the individual susceptibility into account. The primary method of treatment should mainly focus on the prevention or reduction of EMF exposure, that is, reducing or eliminating all sources of high EMF exposure at home and at the workplace. The reduction of EMF exposure should also be extended to public spaces such as schools, hospitals, public transport, and libraries to enable persons with EHS an unhindered use (accessibility measure). If a detrimental EMF exposure is reduced sufficiently, the body has a chance to recover and EHS symptoms will be reduced or even disappear. Many examples have shown that such measures can prove effective. To increase the effectiveness of the treatment, the broad range of other environmental factors that contribute to the total body burden should also be addressed. Anything that supports homeostasis will increase a person's resilience against disease and thus against the adverse effects of EMF exposure. There is increasing evidence that EMF exposure has a major impact on the oxidative and nitrosative regulation capacity in affected individuals. This concept also may explain why the level of susceptibility to EMF can change and why the range of symptoms reported in the context of EMF exposures is so large. Based on our current understanding, a treatment approach that minimizes the adverse effects of peroxynitrite – as has been increasingly used in the treatment of multisystem illnesses – works best. This EMF Guideline gives an overview of the current knowledge regarding EMF-related health risks and provides recommendations for the diagnosis, treatment and accessibility measures of EHS to improve and restore individual health outcomes as well as for the development of strategies for prevention.
