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Free Radical Biology & Medicine

Thomas J van T Erve, Fred B Lih, Maria B Kadiiska, Leesa J Deterding, Ronald P Mason
It is widely accepted that free radicals in tobacco smoke lead to oxidative stress and generate the popular lipid peroxidation biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α). However, 8-iso-PGF2α can simultaneously be produced in vivo by the prostaglandin-endoperoxide synthases (PGHS) induced by inflammation. This inflammation-dependent mechanism has never been considered as a source of elevated 8-iso-PGF2α in tobacco smokers. The goal of this study is to quantify the distribution of chemical- and PGHS-dependent 8-iso-PGF2α formation in the plasma of tobacco smokers and non-smokers...
November 18, 2017: Free Radical Biology & Medicine
Eder Barbosa, Ana Oliveira, Alexandra Plácido, Renato Socodato, Camila C Portugal, Ana Carolina Mafud, Alicia S Ombredane, Daniel C Moreira, Nuno Vale, Lucinda J Bessa, Graziella A Joanitti, Cláudia Alves, Paula Gomes, Cristina Delerue-Matos, Yvonne Primerano Mascarenhas, Mariela M Marani, João B Relvas, Manuela Pintado, José Roberto S A Leite
The amphibian skin plays an important role protecting the organism from external harmful factors such as microorganisms or UV radiation. Based on biorational strategies, many studies have investigated the cutaneous secretion of anurans as a source of bioactive molecules. By a peptidomic approach, a novel antioxidant peptide (AOP) with in vitro free radical scavenging ability was isolated from Physalaemus nattereri. The AOP, named antioxidin-I, has a molecular weight [M+H](+) = 1543.69Da and a TWYFITPYIPDK primary amino acid sequence...
November 18, 2017: Free Radical Biology & Medicine
Vanja Cejvanovic, Laura Kofoed Kjær, Helle Kirstine Mørup Bergholdt, Arendse Torp-Pedersen, Trine Henriksen, Allan Weimann, Christina Ellervik, Henrik Enghusen Poulsen
Iron promotes formation of hydroxyl radicals by the Fenton reaction, subsequently leading to potential oxidatively generated damage of nucleic acids. Oxidatively generated damage to RNA, measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine, is increased in patients with genetic iron overload, which have led us to test the hypothesis that high iron status, assessed by iron biomarkers and genetic disposition, increases urinary excretion of 8-oxoGuo. In a general Danish population study we used a Mendelian randomization design with HFE genotypes as a proxy for iron status and supplemented with ex vivo experiments in mice muscle tissue exposed to iron(II) sulfate to attempt to clarify this hypothesis...
November 17, 2017: Free Radical Biology & Medicine
Detao Gao, Eugene A Podrez
High density lipoprotein (HDL) is cardioprotective, unless it is pathologically modified under oxidative stress. Covalent modifications of lipid-free apoA-I, the most abundant apoprotein in HDL, compromise its atheroprotective functions. HDL is enriched in oxidized phospholipids (oxPL) in vivo in oxidative stress. Furthermore, oxidized phospholipids can covalently modify HDL apoproteins. We have now carried out a systematic analysis of modifications of HDL apoproteins by endogenous oxPL. Human HDL or plasma were oxidized using a physiologically relevant MPO-H2O2-NO2(-) system or AIPH, or were exposed to synthetic oxPL...
November 15, 2017: Free Radical Biology & Medicine
Neelam Khaper, Craig D C Bailey, Nilesh R Ghugre, Cristine Reitz, Zikra Awosanmi, Ryan Waines, Tami A Martino
Cell autonomous circadian "clock" mechanisms are present in virtually every organ, and generate daily rhythms that are important for normal physiology. This is especially relevant to the cardiovascular system, for example the circadian mechanism orchestrates rhythms in heart rate, blood pressure, cardiac contractility, metabolism, gene and protein abundance over the 24-hour day and night cycles. Conversely, disturbing circadian rhythms (e.g. via shift work, sleep disorders) increases cardiovascular disease risk, and exacerbates cardiac remodelling and worsens outcome...
November 13, 2017: Free Radical Biology & Medicine
Yeo Jun Yoon, Michelle J Suh, Hyun Young Lee, Hae June Lee, Eun Ha Choi, In Seok Moon, Kiwon Song
Vestibular schwannoma (VS), although a benign intracranial tumor, causes morbidities by brainstem compression. Since chemotherapy is not very effective in most Nf2-negative schwannomas, surgical removal or radiation therapy is required. However, depending on the size and site of the tumor, these approaches may cause loss of auditory or vestibular functions, and severely decrease the post-surgical wellbeing. Here, we examined the feasibility of cold atmospheric pressure plasma (CAP) as an intra-operative adjuvant treatment for VS after surgery...
November 11, 2017: Free Radical Biology & Medicine
Gustavo H Oliveira-Paula, Lucas C Pinheiro, Graziele C Ferreira, Waynice N P Garcia, Riccardo Lacchini, Luis V Garcia, Jose E Tanus-Santos
Propofol anesthesia is usually accompanied by hypotension. Studies have shown that the hypotensive effects of propofol increase in patients treated with angiotensin-converting enzyme inhibitors (ACEi). Given that both propofol and ACEi affect nitric oxide (NO) signaling, the present study tested the hypothesis that ACEi treatment induces pronounced hypotensive responses to propofol by increasing NO bioavailability. In this study we evaluated 65 patients, divided into three groups: hypertensive patients chronically treated with ACEi (HT-ACEi; n = 21), hypertensive patients treated with other antihypertensive drugs instead of ACEi, such as angiotensin II receptor blockers, β-blockers or diuretics (HT; n = 21) and healthy normotensive subjects (NT; n = 23)...
November 11, 2017: Free Radical Biology & Medicine
Alicia R Mathers, Cara D Carey, Meaghan E Killeen, Sonia R Salvatore, Laura K Ferris, Bruce A Freeman, Francisco J Schopfer, Louis D Falo
Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction and gene expression. Nitro-fatty acids and other electrophilic fatty acids may thus be useful for the prevention and treatment of immune-mediated diseases, including inflammatory skin disorders. In this regard, subcutaneous (SC) injections of nitro oleic acid (OA-NO2), an exemplary nitro-fatty acid, inhibit skin inflammation in a model of allergic contact dermatitis (ACD). Given the nitration of unsaturated fatty acids during metabolic and inflammatory processes and the growing use of fatty acids in topical formulations, we sought to further study the effect of nitro-fatty acids on cutaneous inflammation...
November 10, 2017: Free Radical Biology & Medicine
Isabel Heyde, Jana-Thabea Kiehn, Henrik Oster
The 24-hour sleep-wake cycle is one of the most prominent outputs of the circadian clock system. At the same time, changes in sleep-wake behavior feedback on behavioral and physiological circadian rhythms, thus altering the coordination of the body's clock network. Sleep and circadian rhythm disruption have similar physiological endpoints including metabolic, cognitive, and immunologic impairments. This raises the question to which extent these phenomena are causally linked. In this review, we summarize different physiologic outcomes of sleep deprivation and mistimed sleep and discuss the experimental evidence for a mediating role of the circadian clock machinery in this context...
November 10, 2017: Free Radical Biology & Medicine
Song Zhang, Shuai Jiang, Haiping Wang, Wencheng Di, Chao Deng, Zhenxiao Jin, Wei Yi, Xiao Xiao, Yongzhan Nie, Yang Yang
Silent information regulator 6 (SIRT6), a class III histone deacetylase, has been revealed to participate in multiple metabolic processes in the liver, and it plays important roles in protecting against ischemia/reperfusion (I/R) injury in multiple organs. In this study, we explored whether SIRT6 is protective against hepatic I/R injury and elucidated the underlying mechanisms. The expression of SIRT6 was significantly decreased during reperfusion compared with the control group. SIRT6-LKO mice exhibited significantly aggravated oxidative stress, mitochondrial dysfunction, inflammatory responses, mitogen-activated protein kinase (MAPK) signaling activation, and apoptosis and autophagy related hepatocyte death compared with control mice...
November 10, 2017: Free Radical Biology & Medicine
Beatrice Arezzini, Daniela Vecchio, Cinzia Signorini, Blerta Stringa, Concetta Gardi
F2-isoprostanes (F2-IsoPs) have been considered markers of oxidative stress in various pulmonary diseases, but little is known about their possible role in pulmonary fibrosis. In this study, we have investigated the potential key role of F2-IsoPs as markers and mediators of bleomycin (BLM)-induced pulmonary fibrosis in rats. During the in vivo study, plasma F2-IsoPs showed a peak at 7 days and remained elevated for the entire experimental period. Lung F2-IsoP content nearly tripled 7 days following the intratracheal instillation of BLM, and by 28 days, the value increased about fivefold compared to the controls...
November 9, 2017: Free Radical Biology & Medicine
Sundarraj Jayakumar, Raghavendra S Patwardhan, Debojyoti Pal, Babita Singh, Deepak Sharma, Vijay Kumar Kutala, Santosh Kumar Sandur
Mitocurcumin is a derivative of curcumin, which has been shown to selectively enter mitochondria. Here we describe the anti-tumor efficacy of mitocurcumin in lung cancer cells and its mechanism of action. Mitocurcumin, showed 25-50 fold higher efficacy in killing lung cancer cells as compared to curcumin as demonstrated by clonogenic assay, flow cytometry and high throughput screening assay. Treatment of lung cancer cells with mitocurcumin significantly decreased the frequency of cancer stem cells. Mitocurcumin increased the mitochondrial reactive oxygen species (ROS), decreased the mitochondrial glutathione levels and induced strand breaks in the mitochondrial DNA...
November 5, 2017: Free Radical Biology & Medicine
Ewa Jówko, Wilhelm Gromisz, Jerzy Sadowski, Igor Cieśliński, Jadwiga Kotowska
The aim of the study was to analyze the effect of SOD2 Val16Ala polymorphism on blood biochemical response to chronic swimming training. Healthy men (students of physical education) participated in a swimming training program (ST group) or served as a control group (CON group). The swimming training program lasted 12 weeks (1.5h per day; 4 days per week). Fasting blood samples were obtained prior to (pre) and after (post) a 12-week study period, to measure the biomarkers of oxidative stress, muscle damage and lipid profile...
November 3, 2017: Free Radical Biology & Medicine
Huanyuan Wang, Qi Sun, Yi Zhou, Hui Zhang, Chenghua Luo, Jiahui Xu, Yu Dong, Ye Wu, Huirong Liu, Wen Wang
Deficiency of cystathionine β-synthase (CBS) activity is the most common cause of increased homocysteine (Hcy). However, until now the underlying mechanisms why CBS activity decreased still remain unresolved. The goal of this study was to explore the contribution of nitrative stress to deficiency of CBS activity, and further identify the possible nitration sites of CBS protein. Results showed that in elderly people, there was an increased nitrative stress level, which was relative to elevated Hcy level. In natural aging rats and diet-induced hyperhomocysteinemia (HHcy) rats, the levels of Hcy and nitrative stress were both elevated, and interestingly, pretreatment with peroxynitrite (ONOO(-)) scavenger FeTMPyP ameliorated the elevation of Hcy as well as nitrative stress...
November 3, 2017: Free Radical Biology & Medicine
Monica Deiana, Simone Calfapietra, Alessandra Incani, Angela Atzeri, Daniela Rossin, Roberto Loi, Barbara Sottero, Noemi Iaia, Giuseppe Poli, Fiorella Biasi
The emerging role of the diet in the incidence of intestinal inflammatory diseases has stimulated research on the influence of eating habits with pro-inflammatory properties in inducing epithelial barrier disturbance. Cholesterol oxidation products, namely oxysterols, have been shown to promote and sustain oxidative/inflammatory reactions in human digestive tract. This work investigated in an in vitro model the potential ability of a combination of dietary oxysterols representative of a hyper-cholesterol diet to induce the loss of intestinal epithelial layer integrity...
November 2, 2017: Free Radical Biology & Medicine
Huang-Hui Chen, Hsin-Huei Chang, Jang-Yang Chang, Ya-Chu Tang, Yung-Chi Cheng, Li-Mei Lin, Shu-Ying Cheng, Chih-Hsiang Huang, Man-Wu Sun, Chiung-Tong Chen, Ching-Chuan Kuo
Nuclear factor erythroid-2-related factor 2 (NRF2) mainly regulates transcriptional activation through antioxidant-responsive elements (AREs) present in the promoters of NRF2 target genes. Recently, we found that NRF2 was overexpressed in a KB-derived drug-resistant cancer cell panel. In this panel, KB-7D cells, which show acquired resistance to topoisomerase II (Top II) poisons, exhibited the highest NRF2 activation. To investigate whether NRF2 directly contributed to acquired resistance against Top II poisons, we manipulated NRF2 by genetic and pharmacological approaches...
November 2, 2017: Free Radical Biology & Medicine
Isaac K Sundar, Michael T Sellix, Irfan Rahman
At the cellular level, circadian timing is maintained by the molecular clock, a family of interacting clock gene transcription factors, nuclear receptors and kinases called clock genes. Daily rhythms in pulmonary function are dictated by the circadian timing system, including rhythmic susceptibility to the harmful effects of airborne pollutants, exacerbations in patients with chronic airway disease and the immune-inflammatory response to infection. Further, evidence strongly suggests that the circadian molecular clock has a robust reciprocal interaction with redox signaling and plays a considerable role in the response to oxidative/carbonyl stress...
October 31, 2017: Free Radical Biology & Medicine
Dorottya Garai, Bessie B Ríos-González, Paul G Furtmüller, Jon M Fukuto, Ming Xian, Juan López-Garriga, Christian Obinger, Péter Nagy
The interaction of heme proteins with hydrogen sulfide is gaining attention as an important element in sulfide-mediated protection against oxidative stress and in regulation of redox signaling. In our previous study we reported the efficient reversible inhibition of myeloperoxidase (MPO) activity by sulfide and the kinetics of the reactions of sulfide with ferric MPO, Compound I and Compound II. Here we provide several lines of evidence that a central intermediate species in the turnover of MPO by sulfide is the Compound III state...
October 31, 2017: Free Radical Biology & Medicine
Xin Liao, Chao Huang, Dongyun Zhang, Jingjing Wang, Jingxia Li, Honglei Jin, Chuanshu Huang
It's well documented that over-production of reactive oxygen species (ROS) causes detrimental damages to cells. While a low level of ROS, such as H2O2, functions as signaling transducer and motivates cell proliferation in both cancer and non-transformed stem cells. As a double-edged sword, the direct evidence for demonstrating the function of H2O2 in the cause of tumor is barely characterized in intact cells. In our current study, we found that targeted expression of mitochondrial catalase (mCAT), but not catalase, could significantly reduce the accumulation of H2O2 in mouse epithelial JB6 Cl41 cells, consequently led to the cell malignant transformation and anchorage-independent cell growth...
October 31, 2017: Free Radical Biology & Medicine
Robert F Anderson, Dan Li, Francis W Hunter
Hypoxic cells pose a problem in anticancer chemotherapy, in which often drugs require oxygen as an electron acceptor to bring about the death of actively cycling cells. Bioreductive anticancer drugs, which are selectively activated in the hypoxic regions of tumours through enzymatic one-electron reduction, are being developed for combination with chemotherapy-, radiotherapy- and immunotherapy-containing regimens to kill treatment-resistant hypoxic cells. The most clinically-advanced bioreductive drug, evofosfamide (TH-302), which acts by releasing a DNA-crosslinking mustard, failed to extend overall survival in combination with doxorubicin, a topoisomerase II inhibitor, for advanced soft tissue sarcoma in a pivotal clinical trial...
October 28, 2017: Free Radical Biology & Medicine
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