scholarly journals Hypermetabolism of glutathione, glutamate and ornithine via redox imbalance in methylglyoxal-induced peritoneal injury rats

2019 ◽  
Author(s):  
Ichiro Hirahara ◽  
Eiji Kusano ◽  
Denan Jin ◽  
Shinji Takai
Keyword(s):  
Oxidative Stress ◽  
Intraperitoneal Administration ◽  
Methionine Sulfoxide ◽  
Mesenchymal Cell ◽  
Oxidative Stress Marker ◽  
Peritoneal Fibrosis ◽  
Metabolome Analysis ◽  
Glycation End Products ◽  
Excessive Proliferation

Abstract Peritoneal dialysis (PD) is a blood purification treatment for patients with reduced renal function. However, the peritoneum is exposed to oxidative stress during PD and long-term PD results in peritoneal damage, leading to the termination of PD. Methylglyoxal (MGO) contained in commercial PD fluids is a source of strong oxidative stress. The aim of this study was to clarify the mechanism of MGO-induced peritoneal injury using metabolome analysis in rats. We prepared peritoneal fibrosis rats by intraperitoneal administration of PD fluids containing MGO for 21 days. As a result, MGO-induced excessive proliferation of mesenchymal cells with an accumulation of advanced glycation end-products (AGEs) at the surface of the thickened peritoneum in rats. The effluent levels of methionine sulfoxide, an oxidative stress marker and glutathione peroxidase activity were increased in the MGO-treated rats. The levels of glutathione, glutamate, aspartate, ornithine and AGEs were also increased in these rats. MGO upregulated the gene expression of transporters and enzymes related to the metabolism of glutathione, glutamate and ornithine in the peritoneum. These results suggest that MGO may induce peritoneal injury with mesenchymal cell proliferation via increased redox metabolism, directly or through the formation of AGEs during PD.

scholarly journals Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma

Endocrinology ◽  
2018 ◽  
Vol 159 (8) ◽  
pp. 2836-2849 ◽  
Author(s):  
Vasileios Chortis ◽  
Angela E Taylor ◽  
Craig L Doig ◽  
Mark D Walsh ◽  
Eirini Meimaridou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adrenocortical Carcinoma ◽  
Reduced Form ◽  
Polyamine Metabolism ◽  
Metabolome Analysis ◽  
Nucleotide Synthesis ◽  
Treatment Target ◽  
Nicotinamide Nucleotide Transhydrogenase ◽  
Response To Chemotherapy

Abstract Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized that NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry–based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and nontargeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding, and polyamine metabolism. This study provides preclinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress.

Alteration of Energy Metabolism and Antioxidative Processing in the Hippocampus of Rats Reared in Long-Term Environmental Enrichment

2016 ◽  
Vol 38 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Hee Kang ◽  
Dong-Hee Choi ◽  
Su-Kang Kim ◽  
Jongmin Lee ◽  
Youn-Jung Kim
Keyword(s):  
Oxidative Stress ◽  
Energy Metabolism ◽  
Protein Expression ◽  
Environmental Enrichment ◽  
Synaptic Activity ◽  
Antioxidant Defenses ◽  
Laboratory Animals ◽  
Oxidative Stress Marker ◽  
Altered Expression

Environmental enrichment (EE) is a typical experimental method that promotes levels of novelty and complexity that enhance experience-dependent neuroplasticity and cognitive behavior function in laboratory animals. Early EE is associated with resilience in the face of later-life challenges. Since increased synaptic activity enhances endogenous neuronal antioxidant defenses, we hypothesized that long-term EE beginning at an early stage may alter the levels of oxidative stress. We investigated global protein expression and oxidative stress in hippocampal proteins from rats nurtured for a 6-month EE beginning in the prenatal period. The analysis of protein expression was carried out using 2-dimensional gel electrophoresis with matrix-associated laser desorption ionization time-of-flight mass spectrometry. Proteins with altered expression were involved in energy metabolism (phosphoglycerate mutase 1, α-enolase isoform 1, adenylate kinase 1, and triose phosphate isomerase) and antioxidant enzymes (superoxide dismutase 1, glutathione S-transferase ω type 1, peroxiredoxin 5, DJ-1, and glial maturation factor β). Using Western blot assays, some of the proteins with altered expression and NADPH oxidase 2 were confirmed to be decreased. Further confirmation was demonstrated with attenuated expression of 7,8-dihydro-8-oxo-deoxyguanine, a DNA oxidative stress marker, in the hippocampus of EE group rats. Our data demonstrate that a long-term EE program beginning in the prenatal and early postnatal phase of development modulates energy metabolism and reduced oxidant stress possibly through enhanced synaptic activity. We provide evidence that EE can be developed as a tool to protect the brain from oxidative stress-induced injury.

scholarly journals Asymptomatic HIV People Present Different Profiles of sCD14, sRAGE, DNA Damage, and Vitamins, according to the Use of cART and CD4+ T Cell Restoration

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Karen Ingrid Tasca ◽  
Camila Renata Correa ◽  
Juliana Trindade Caleffi ◽  
Monica Banwart Mendes ◽  
Mariana Gatto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Immune Activation ◽  
Antiretroviral Treatment ◽  
High Mobility ◽  
Soluble Cd14 ◽  
Glycation End Products ◽  
And Oxidative Stress ◽  
Asymptomatic Hiv

We aimed to analyze markers of immune activation, inflammation, and oxidative stress in 92 asymptomatic HIV-infected patients according to the adequate (AR, >500 cells/mm3) or inadequate (IR, <500 cells/mm3) CD4+ T recovery and the presence or absence of antiretroviral treatment (cART). In relation to those newly diagnosed, they were divided into two groups, cART-naïve IR (nIR) and cART-naïve AR (nAR). Among those diagnosed more than five years ago, the following division was made: the cART-naïve long-term nonprogressors (LTNP); patient under cART and AR (tAR); and patients under cART and IR (tIR). We investigated the expression of soluble receptor for advanced glycation end products (sRAGE), high-mobility group-box protein −1 (HMGB1), soluble CD14 (sCD14), IL-8, IL-10, 8-isoprostane, vitamins, and DNA damage. We observed higher levels of sRAGE in tAR as compared to nIR, nAR, LTNP, and more sCD14 than in nIR and nAR. As for IL-10 levels, we found nIR > nAR > LTNP > tAR > tIR. Higher levels of 8-isoprostane were observed in nIR. LTNP presented a higher retinol dosage than tAR and less genotoxic damage induced by oxidative stress than the other groups. We suggest that the therapy, despite being related to lesser immune activation and inflammation, alters the vitamin profile and consequently increases the oxidative stress of patients. In addition, the lowest genotoxic index for LTNP indicates that both VL and cART could be responsible for the increased DNA damage. More studies are needed to understand the influence of cART on persistent immune activation and inflammation.

scholarly journals Az oxidatív stressz szerepe a diabeteses neuropathia kialakulásában

2016 ◽  
Vol 157 (49) ◽  
pp. 1939-1946 ◽  
Author(s):  
Ferenc Sztanek ◽  
Ágnes Molnárné Molnár ◽  
Zoltán Balogh
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Neuropathy ◽  
Microvascular Complications ◽  
Advanced Glycation ◽  
Complications Of Diabetes ◽  
Kinase C ◽  
Glycation End Products ◽  
Comparative Trials

Diabetic neuropathy may be one of the most common and severe complications of diabetes mellitus. Oxidative stress plays a pivotal role in the development of microvascular complications of diabetes. The majority of related pathways like polyol and hexosamine, advanced glycation end products, poly-ADP-ribose polymerase, and protein kinase-C all originated from initial oxidative stress. In this review, the authors present the current oxidative stress hypothesis in diabetes mellitus and summarize the pathophysiological mechanisms of diabetic neuropathy associated with increased oxidative stress. The development of modern medicines to treat diabetic neuropathy needs intensive long-term comparative trials in the future. Orv. Hetil., 2016, 157(49), 1939–1946.

scholarly journals Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury

2016 ◽  
Vol 311 (2) ◽  
pp. F268-F277 ◽  
Author(s):  
Nataliya I. Skrypnyk ◽  
Paul Voziyan ◽  
Haichun Yang ◽  
Christian R. de Caestecker ◽  
Marie-Claude Theberge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Oxidative Damage ◽  
Functional Recovery ◽  
Kidney Injury ◽  
Oxidative Stress Marker ◽  
Severity Of Injury ◽  
Dose Dependent

Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI.

Formula-derived advanced glycation end products are involved in the development of long-term inflammation and oxidative stress in kidney of IUGR piglets

2015 ◽  
Vol 59 (5) ◽  
pp. 939-947 ◽  
Author(s):  
Ghada Elmhiri ◽  
Dler F. D. Mahmood ◽  
Celine Niquet-Leridon ◽  
Philippe Jacolot ◽  
Stephane Firmin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

scholarly journals Unfavorable Effects of Peritoneal Dialysis Solutions on the Peritoneal Membrane: The Role of Oxidative Stress

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 768
Author(s):  
Stefanos Roumeliotis ◽  
Evangelia Dounousi ◽  
Marios Salmas ◽  
Theodoros Eleftheriadis ◽  
Vassilios Liakopoulos
Keyword(s):  
Oxidative Stress ◽  
Peritoneal Dialysis ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Structural Alterations ◽  
And Function ◽  
Dialysis Solutions ◽  
Harmful Effects

One of the main limitations to successful long-term use of peritoneal dialysis (PD) as a renal replacement therapy is the harmful effects of PD solutions to the structure and function of the peritoneal membrane (PM). In PD, the PM serves as a semipermeable membrane that, due to exposure to PD solutions, undergoes structural alterations, including peritoneal fibrosis, vasculopathy, and neoangiogenesis. In recent decades, oxidative stress (OS) has emerged as a novel risk factor for mortality and cardiovascular disease in PD patients. Moreover, it has become evident that OS plays a pivotal role in the pathogenesis and development of the chronic, progressive injury of the PM. In this review, we aimed to present several aspects of OS in PD patients, including the pathophysiologic effects on the PM, clinical implications, and possible therapeutic antioxidant strategies that might protect the integrity of PM during PD therapy.

Oxidative injury associated with stenting of asymptomatic carotid artery stenosis

VASA ◽  
2017 ◽  
Vol 46 (4) ◽  
pp. 268-274
Author(s):  
Erhan Saraçoğlu ◽  
Ertan Vuruşkan ◽  
Yusuf Çekici ◽  
Salih Kiliç ◽  
Halil Ay ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carotid Artery ◽  
Oxidative Damage ◽  
Carotid Artery Stenosis ◽  
Artery Stenosis ◽  
Oxidative Stress Marker ◽  
Asymptomatic Carotid ◽  
Imaging Methods ◽  
Neurological Findings ◽  
Asymptomatic Carotid Artery Stenosis

Abstract. Background: After carotid artery stenting (CAS), neurological complications that cannot be explained with imaging methods may develop. In our study we aimed to show, using oxidative stress markers, isolated oxidative damage and resulting neurological findings following CAS in patients with asymptomatic carotid artery stenosis. Patients and methods: We included 131 neurologically asymptomatic patients requiring CAS. The neurological findings were evaluated using the modified Rankin Scale (mRS) prior to the procedure, one hour post-procedure, and two days after. Patients with elevated mRS scores but with or without typical hyperintense lesions observed on an MRI and with changes of oxidative stress marker levels at the time (Δtotal-thiol, Δtotal antioxidative status [TAS], and Δtotal oxidant status [TOS]) were evaluated. Results: In the neurological examination carried out one hour prior to the procedure, there were 92 patients with mRS = 0, 20 with mRS = 1, and 12 with mRS = 2. When Δtotal-thiol, ΔTAS, and ΔTOS values and the mRS were compared, it was observed that as the difference in oxidative parameters increased, clinical deterioration also increased proportionally (p = 0.001). Conclusions: We demonstrate a possible correlation between oxidative damage and neurological findings after CAS which could not be explained by routine imaging methods.

Trace elements as an oxidative stress marker in women with gestational diabetes and their neonates

2017 ◽  
Author(s):  
Georgios Boutzios ◽  
Eleni Koukoulioti ◽  
Ioannis Papoutsis ◽  
Sotirios Athanaselis ◽  
Gerasimos Tsourouflis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Trace Elements ◽  
Gestational Diabetes ◽  
Oxidative Stress Marker ◽  
Stress Marker
Sign in / Sign up

Export Citation Format

Share Document