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Free Radical Biology & Medicine

Lorena Perdices, Lorena Fuentes-Broto, Francisco Segura, Neyla Ben Gdara, Ana Isabel Sánchez-Cano, Gema Insa Sánchez, Elvira Orduna Hospital, Isabel Pinilla
Retinitis pigmentosa (RP) comprises a group of inherited retinal degenerative conditions characterized by primary degeneration of the rod photoreceptors. Increased oxidative damage is observed in the retina, aqueous humor, and plasma of RP animal models and patients. The hepatic oxidative status may also be affected in RP due to oxidative damage influencing soluble macromolecules exiting the retina or to alterations in the melanopsin system resulting in chronic circadian desynchronization that negatively alters the oxidative stress defense system...
July 10, 2018: Free Radical Biology & Medicine
Tasuku Hirayama
Iron (Fe) is the most abundant redox-active metal ion in the human body, and its redox-active property inter-convertible multiple oxidation states contributes to numerous essential biological processes. Moreover, iron overload can potentially cause cellular damage and death, as wel as numerous diseases through the aberrant production of highly reactive oxidative species (hROS). Protein-free or weakly-protein-bound Fe ions play a pivotal role as catalytic reactants of the Fenton reaction. In this reaction, hROS, such as hydroxyl radicals and high valent-iron-oxo species, are generated by a reaction between hydrogen peroxide and Fe(II), which is re-generated through reduction using abundant intracellular reductants, such as glutathione...
July 7, 2018: Free Radical Biology & Medicine
Tomas Ganz
Erythropoiesis is the predominant consumer of iron in humans and other vertebrates. By decreasing the transcription of the gene encoding the iron-regulatory hormone hepcidin, erythropoietic activity stimulates iron absorption, as well as the release of iron from recycling macrophages and from stores in hepatocytes. The main erythroid regulator of hepcidin is erythroferrone (ERFE), synthesized and secreted by erythroblasts in the marrow and extramedullary sites. The production of ERFE is induced by erythropoietin (EPO) and is also proportional to the total number of responsive erythroblasts...
July 5, 2018: Free Radical Biology & Medicine
Veena Sangkhae, Elizabeta Nemeth
As the interface between the fetal and maternal circulation, the placenta facilitates both nutrient and waste exchange for the developing fetus. Iron is essential for healthy pregnancy, and transport of iron across the placenta is required for fetal growth and development. Perturbation of this transfer can lead to adverse pregnancy outcomes. Despite its importance, our understanding of how a large amount of iron is transported across placental membranes, how this process is regulated, and which iron transporter proteins function in different placental cells remains rudimentary...
July 5, 2018: Free Radical Biology & Medicine
Kaikai Xu, Hai Yao, Jinhui Hu, Jiahong Zhou, Lin Zhou, Shaohua Wei
In photodynamic therapy (PDT), the elevated glutathione (GSH) of cancer cells have two sides for treatment efficacy, activation pre-drug by removing activity suppressor part (advantages) and consumption reactive oxygen species (ROS) to confer PDT resistance (disadvantages). Preparation all-in-one system by simple method to make best use of the advantages and bypass the disadvantages still were remains a technical challenge. Herein, we report a robust PDT nanoparticle with above function based on a self-assembled pyridine modified Zinc phthalocyanine (ZnPc-DTP)...
July 4, 2018: Free Radical Biology & Medicine
Hiroshi Kawabata
In vertebrates, transferrin (Tf) safely delivers iron through circulation to cells. Tf-bound iron is incorporated through Tf receptor (TfR) 1-mediated endocytosis. TfR1 can mediate cellular uptake of both Tf and H-ferritin, an iron storage protein. New World arenaviruses, which cause hemorrhagic fever, and Plasmodium vivax use TfR1 for entry into host cells. Human TfR2, another receptor for Tf, is predominantly expressed in hepatocytes and erythroid precursors, and holo-Tf dramatically upregulates its expression...
June 30, 2018: Free Radical Biology & Medicine
Faji Yang, Shuai Wang, Yang Liu, Yuan Zhou, Longcheng Shang, Min Feng, Xianwen Yuan, Wei Zhu, Xiaolei Shi
Fatty liver is one of the widely accepted marginal donor for liver transplantation, but is also more sensitive to ischemia and reperfusion injury (IRI) and produces more reactive oxygen species (ROS). Moreover, so far, no effective method has been developed to alleviate it. Endoplasmic reticulum stress (ER-stress) of hepatocyte is associated with the occurrence of fatty liver disease, but ER-stress of kupffer cells (KCs) in fatty liver is not clear at all. This study evaluates whether ER-stress of KCs is activated in fatty liver and accelerate IRI of fatty livers...
June 30, 2018: Free Radical Biology & Medicine
Qin Yang, Fan-Rong Wu, Jia-Nan Wang, Li Gao, Ling Jiang, Hai-Di Li, Qiuying Ma, Xue-Qi Liu, Biao Wei, Luyu Zhou, Jiagen Wen, Tao Tao Ma, Jun Li, Xiao-Ming Meng
Reactive oxygen species derived from NADPH oxidase contribute to a wide variety of renal diseases. Nox4, the major NADPH isoform in kidney, produces mainly H2 O2 that regulates physiological functions. Nox4 contributes to redox processes involved in diabetic nephropathy, acute kidney injury, obstructive nephropathy, hypertensive nephropathy, renal cell carcinoma and other renal diseases by activating multiple signaling pathways. Although Nox4 is found in a variety of cell types, including epithelial cells, podocytes, mesangial cells, endothelial cells and fibroblasts, its role is not clear and even controversial...
June 30, 2018: Free Radical Biology & Medicine
Carmen Peña-Bautista, Claire Vigor, Jean-Marie Galano, Camille Oger, Thierry Durand, Inés Ferrer, Ana Cuevas, Rogelio López-Cuevas, Miguel Baquero, Marina López-Nogueroles, Máximo Vento, David Hervás, Ana García-Blanco, Consuelo Cháfer-Pericás
INTRODUCTION: Alzheimer Disease (AD) standard diagnosis is based on evaluations and biomarkers that are non-specific, expensive, or requires invasive sampling. Therefore, an early, and non-invasive diagnosis is required. As regards molecular mechanisms, recent research has shown that lipid peroxidation plays an important role. METHODS: Well-defined participants groups were recruited. Lipid peroxidation compounds were determined in plasma using a validated analytical method...
June 30, 2018: Free Radical Biology & Medicine
Guglielmina Chimienti, Anna Picca, Giuseppe Sirago, Flavio Fracasso, Riccardo Calvani, Roberto Bernabei, Francesco Russo, Christy S Carter, Christiaan Leeuwenburgh, Vito Pesce, Emanuele Marzetti, Angela Maria Serena Lezza
The well-known age-related mitochondrial dysfunction deeply affects heart because of the tissue's large dependence on mitochondrial ATP provision. Our study revealed in aged rat heart a significant 25% decrease in mtDNA relative content, a significant 29% increase in the 4.8 Kb mtDNA deletion relative content, and a significant inverse correlation between such contents as well as a significant 38% decrease in TFAM protein amount. The TFAM-binding activity to specific mtDNA regions increased at those encompassing the mtDNA replication origins, D-loop and Ori-L...
June 30, 2018: Free Radical Biology & Medicine
Bradly M Bauman, Chang Jeong, Matthew Savage, Anna L Briker, Nicholas G Janigian, Linda L Nguyen, Zachary A Kemmerer, Aimee L Eggler
The transcription factor Nrf2 is a master regulator of antioxidant and cytoprotective genes, binding to antioxidant response elements (AREs) in their promoter regions. Due to the therapeutic role of the Nrf2/ARE system in oxidative homeostasis, its activation has been investigated in many pre-clinical and clinical trials for common chronic diseases. One of the most promising Nrf2 activators is sulforaphane, the subject of over 50 clinical trials. In this work, we examine the effect of reactive oxygen species (ROS) on sulforaphane's Nrf2/ARE activation in the non-tumorigenic keratinocyte cell line HaCaT, with the non-arylating oxidizable phenol, 2,5-di-tert-butylhydroquinone (dtBHQ), as the source of ROS...
June 30, 2018: Free Radical Biology & Medicine
Xiangsheng Zhang, Qi Wu, Yue Lu, Jieru Wan, Haibin Dai, Xiaoming Zhou, Shengyin Lv, Xuemei Chen, Xin Zhang, Chunhua Hang, Jian Wang
Salvianolic acid B (SalB), a natural polyphenolic compound extracted from the herb of Salvia miltiorrhiza, possesses antioxidant and neuroprotective properties and has been shown to be beneficial for diseases that affect vasculature and cognitive function. Here we investigated the protective effects of SalB against subarachnoid hemorrhage (SAH)-induced oxidative damage, and the involvement of underlying molecular mechanisms. In a rat model of SAH, SalB inhibited SAH-induced oxidative damage. The reduction in oxidative damage was associated with suppressed reactive oxygen species generation; decreased lipid peroxidation; and increased glutathione peroxidase, glutathione, and superoxide dismutase activities...
June 29, 2018: Free Radical Biology & Medicine
Ekaterina S Kharechkina, Anna B Nikiforova, Alexey G Kruglov
The permeabilization of mitochondrial membranes via permeability transition pore opening or by the pore-forming peptide alamethicin causes a flash of superoxide anion (SA) and hydrogen peroxide production and the inhibition of matrix aconitase. It was shown using the SA probe 3,7-dihydro-2-methyl-6-(4-methoxyphenyl)imidazol[1,2-a]pyrazine-3-one (MCLA) that the substrates of NAD-dependent dehydrogenases, inhibitors of the respiratory chain, and NAD(P)H at millimolar concentrations suppressed or delayed SA flashes...
June 29, 2018: Free Radical Biology & Medicine
Tamil S Anthonymuthu, Elizabeth M Kenny, Andrew M Lamade, Valerian E Kagan, Hülya Bayır
Oxidative stress is a major contributor to secondary injury signaling cascades following traumatic brain injury (TBI). The role of lipid peroxidation in the pathophysiology of a traumatic insult to neural tissue is increasingly recognized. As the methods to quantify lipid peroxidation have gradually improved, so has the understanding of mechanistic details of lipid peroxidation and related signaling events in the injury pathogenesis. While free-radical mediated, non-enzymatic lipid peroxidation has long been studied, recent advances in redox lipidomics have demonstrated the significant contribution of enzymatic lipid peroxidation to TBI pathogenesis...
June 29, 2018: Free Radical Biology & Medicine
Domenico Lapenna, Giuliano Ciofani, Antonio Maria Calafiore, Francesco Cipollone, Ettore Porreca
We studied the specific enzymatic activities of selenium-dependent (GSH-Px) and -independent (GST-Px) glutathione peroxidase, glutathione reductase (GSSG-Red), and glutathione S-transferase (GST) in internal mammary arteries (IMArt) specimens obtained during coronary artery bypass surgery in 18 patients with type 2 diabetes mellitus as compared to 18 non-diabetic controls; vascular lipid peroxidation, namely fluorescent damage products of lipid peroxidation (FDPL) as 4-hydroxynonenal-related oxidative stress indicators, was also studied...
June 29, 2018: Free Radical Biology & Medicine
Irena Krga, Radu Tamaian, Sylvie Mercier, Celine Boby, Laurent-Emanuel Monfoulet, Marija Glibetic, Christine Morand, Dragan Milenkovic
Cardioprotective effects of dietary anthocyanins are partly attributed to their ability to maintain endothelial function. However, the underlying cellular and molecular mechanisms of action are not fully understood. This study aimed to evaluate the effect of anthocyanins and their gut metabolites, at physiologically-relevant conditions, on endothelial cell (EC) function and decipher the underlying molecular mechanisms of action using integrated omics approaches. Primary EC were treated with a mixture of 0.1μM cyanidin-3-arabinoside, 0...
June 28, 2018: Free Radical Biology & Medicine
Junduo Wu, Ziping Jiang, Haina Zhang, Wenzhao Liang, Wenlin Huang, Huan Zhang, Ying Li, Zhaohui Wang, Junnan Wang, Ye Jia, Bin Liu, Hao Wu
Oxidative stress and inflammation are major contributors to diabetes-induced endothelial dysfunction which is the critical first step to the development of diabetic macrovascular complications. Nuclear factor erythroid 2-related factor 2 (NRF2) plays a key role in combating diabetes-induced oxidative stress and inflammation. Sodium butyrate (NaB) is an inhibitor of histone deacetylase (HDAC) and an activator of NRF2. However, NaB's effect on diabetes-induced aortic injury was unknown. It was also not known whether or to what extent NRF2 is required for both self-defense and NaB's protection in the diabetic aorta...
June 28, 2018: Free Radical Biology & Medicine
Laura C D Pomatto, Kelvin J A Davies
The Free Radical Theory of Ageing, was first proposed by Denham Harman in the mid-1950's, based largely on work conducted by Rebeca Gerschman and Daniel Gilbert. At its core, the Free Radical Theory of Ageing posits that free radical and related oxidants, from the environment and internal metabolism, cause damage to cellular constituents that, over time, result in an accumulation of structural and functional problems. Several variations on the original concept have been advanced over the past six decades, including the suggestion of a central role for mitochondria-derived reactive species, and the proposal of an age-related decline in the effectiveness of protein, lipid, and DNA repair systems...
June 27, 2018: Free Radical Biology & Medicine
Xianwen Zhang, Liping Bai, Se Zhang, Xiaoshuang Zhou, Ye Li, Jie Bai
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra(SNpc), characteristic motor symptoms and cognitive impairment. Thioredoxin-1 (Trx-1) is a redox protein and protects neurons from various injuries. Our previous study has shown that Trx-1 overexpression attenuates movement disorder in PD. However, whether Trx-1 ameliorates cognitive deficits in PD is still unknown. In the present study, we investigated the effects of Trx-1 on learning and memory in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in mice...
June 27, 2018: Free Radical Biology & Medicine
Jose Viña, Consuelo Borras, Mari Carmen Gomez-Cabrera
The free radical theory of ageing provided an intellectual framework for many laboratories working on ageing. However, experimental and clinical evidence showing that high doses of antioxidants do not have an effect on ageing or on age-associated diseases, cast doubts on the validity of this theory. Data from our own laboratory show that oxidative damage does not correlate with age, especially in the geriatric population, but rather with the frailty state. This has led us to postulate the free radical theory of frailty that proposes that oxidative damage is associated with frailty, but not with chronological age itself...
June 26, 2018: Free Radical Biology & Medicine
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