LAS0811: From Combinatorial Chemistry to Activation of Antioxidant Response Element

PubMed Central

Zhu, Ming; Baek, Hyounggee; Liu, Ruiwu; Song, Aimin; Lam, Kit; Lau, Derick

2009-01-01

The antioxidant response element (ARE) and its transcription factor, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), are potential targets for cancer chemoprevention. We sought to screen small molecules synthesized with combinatorial chemistry for activation of ARE. By high-throughput screening of 9400 small molecules from 10 combinatorial chemical libraries using HepG2 cells with an ARE-driven reporter, we have identified a novel small molecule, 1,2-dimethoxy-4,5-dinitrobenzene (LAS0811), as an activator of the ARE. LAS0811 upregulated the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1), a representative antioxidative enzyme regulated by ARE. It enhanced production of an endogenous reducing agent, glutathione (GSH). In addition, LAS0811 induced expression of heme oxygenase 1 (HO1), which is an ARE-regulated enzyme with anti-inflammatory activity. Furthermore, LAS0811 reduced cell death due to the cytotoxic stress of a strong oxidant, t-butyl hydroperoxide (t-BOOH). Mechanistically, LAS0811 upregulated the expression of Nrf2 and promoted its translocation into the nuclei leading to subsequent ARE activation. Taken together, LAS0811 is a novel activator of the ARE and its associated detoxifying genes and, thus, a potential agent for cancer chemoprevention. PMID:19794825

Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures.

PubMed

Yoshino, Atsushi; Polouliakh, Natalia; Meguro, Akira; Takeuchi, Masaki; Kawagoe, Tatsukata; Mizuki, Nobuhisa

2016-01-01

Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients.

Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using Antioxidant Response Element Reporter Gene Assay Models and Big Data.

PubMed

Kim, Marlene Thai; Huang, Ruili; Sedykh, Alexander; Wang, Wenyi; Xia, Menghang; Zhu, Hao

2016-05-01

Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program. The ARE-bla computational model and HTS data from a big data source (PubChem) were used to profile environmental and pharmaceutical compounds with hepatotoxicity data. Quantitative structure-activity relationship (QSAR) models were developed based on ARE-bla data. The models predicted the potential oxidative stress response for known liver toxicants when no ARE-bla data were available. Liver toxicants were used as probe compounds to search PubChem Bioassay and generate a response profile, which contained thousands of bioassays (> 10 million data points). By ranking the in vitro-in vivo correlations (IVIVCs), the most relevant bioassay(s) related to hepatotoxicity were identified. The liver toxicants profile contained the ARE-bla and relevant PubChem assays. Potential toxicophores for well-known toxicants were created by identifying chemical features that existed only in compounds with high IVIVCs. Profiling chemical IVIVCs created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources. Kim MT, Huang R, Sedykh A, Wang W, Xia M, Zhu H. 2016. Mechanism profiling of hepatotoxicity caused by oxidative stress using antioxidant response element reporter gene assay models and big data. Environ Health Perspect 124:634-641; http://dx.doi.org/10.1289/ehp.1509763.

Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using Antioxidant Response Element Reporter Gene Assay Models and Big Data

PubMed Central

Kim, Marlene Thai; Huang, Ruili; Sedykh, Alexander; Wang, Wenyi; Xia, Menghang; Zhu, Hao

2015-01-01

Background: Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program. Objective: The ARE-bla computational model and HTS data from a big data source (PubChem) were used to profile environmental and pharmaceutical compounds with hepatotoxicity data. Methods: Quantitative structure–activity relationship (QSAR) models were developed based on ARE-bla data. The models predicted the potential oxidative stress response for known liver toxicants when no ARE-bla data were available. Liver toxicants were used as probe compounds to search PubChem Bioassay and generate a response profile, which contained thousands of bioassays (> 10 million data points). By ranking the in vitro–in vivo correlations (IVIVCs), the most relevant bioassay(s) related to hepatotoxicity were identified. Results: The liver toxicants profile contained the ARE-bla and relevant PubChem assays. Potential toxicophores for well-known toxicants were created by identifying chemical features that existed only in compounds with high IVIVCs. Conclusion: Profiling chemical IVIVCs created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources. Citation: Kim MT, Huang R, Sedykh A, Wang W, Xia M, Zhu H. 2016. Mechanism profiling of hepatotoxicity caused by oxidative stress using antioxidant response element reporter gene assay models and big data. Environ Health Perspect 124:634–641; http://dx.doi.org/10.1289/ehp.1509763 PMID:26383846

Nitrate, ascorbic acid, mineral and antioxidant activities of Cosmos caudatus in response to organic and mineral-based fertilizer rates.

PubMed

Hassan, Siti Aishah; Mijin, Salumiah; Yusoff, Umi Kalsom; Ding, Phebe; Wahab, Puteri Edaroyati Megat

2012-06-28

The source and quantity of nutrients available to plants can affect the quality of leafy herbs. A study was conducted to compare quality of Cosmos caudatus in response to rates of organic and mineral-based fertilizers. Organic based fertilizer GOBI (8% N:8% P₂O₅:8% K₂O) and inorganic fertilizer (15% N, 15% P₂O₅, 15% K₂O) were evaluated based on N element rates at 0, 30, 60, 90, 120 kg h⁻¹. Application of organic based fertilizer reduced nitrate, improved vitamin C, antioxidant activity as well as nitrogen and calcium nutrients content. Antioxidant activity and chlorophyll content were significantly higher with increased fertilizer application. Fertilization appeared to enhance vitamin C content, however for the maximum ascorbic acid content, regardless of fertilizer sources, plants did not require high amounts of fertilizer.

Licochalcone E activates Nrf2/antioxidant response element signaling pathway in both neuronal and microglial cells: therapeutic relevance to neurodegenerative disease.

PubMed

Kim, Sa Suk; Lim, Juhee; Bang, Yeojin; Gal, Jiyeong; Lee, Sang-Uk; Cho, Young-Chang; Yoon, Goo; Kang, Bok Yun; Cheon, Seung Hoon; Choi, Hyun Jin

2012-10-01

Oxidative stress and neuroinflammation are hallmarks of neurodegenerative diseases, which do not play independently but work synergistically through complex interactions exacerbating neurodegeneration. Therefore, the mechanism that is directly implicated in controlling oxidative stress and inflammatory response could be an attractive strategy to prevent the onset and/or delay the progression of neurodegenerative diseases. The transcription factor nuclear factor-E2-related factor-2 (Nrf2) is the guardian of redox homeostasis by regulating a battery of antioxidant and phase II detoxification genes, which are relevant to defense mechanism against oxidative stress and inflammatory responses. In this study, we show that a recently identified Glycyrrhiza-inflata-derived chalcone, licochalcone E (Lico-E), attenuates lipopolysaccharide-induced inflammatory responses in microglial BV2 cells and protects dopaminergic SH-SY5Y cells from 6-hydroxydopamine cytotoxicity. Lico-E activates Nrf2-antioxidant response element (ARE) system and up-regulates downstream NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Anti-inflammatory and cytoprotective effects of Lico-E are attenuated in siRNA-mediated Nrf2-silencing cells as well as in the presence with specific inhibitor of HO-1 or NQO1, respectively. Lico-E also has neuroprotective effect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal dopaminergic neurodegeneration in mice, with up-regulation of HO-1 and NQO1 in the substantia nigra of the brain. This study demonstrates that Lico-E is a potential activator of the Nrf2/ARE-dependent pathway and is therapeutically relevant not only to oxidative-stress-related neurodegeneration but also inflammatory responses of microglial cells both in vitro and in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yanyan; The First Affiliated Hospital, China Medical University, Shenyang 110001; Xue, Peng

2013-12-15

Transcriptional signaling through the antioxidant response element (ARE), orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major cellular defense mechanism against oxidative or electrophilic stress. Here, we reported that isoniazid (INH), a widely used antitubercular drug, displays a substantial inhibitory property against ARE activities in diverse mouse and human cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE-luciferase reporter activity and mRNA expression of various ARE-dependent antioxidant genes under basal and oxidative stressed conditions. In keeping with our previous findings that Nrf2-ARE plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein β (C/EBPβ) andmore » peroxisome proliferator-activated receptor γ (PPARγ), suppression of ARE signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced levels of lipid accumulation and attenuated expression of C/EBPα and PPARγ. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by INH occurred in the early stage of terminal adipogenic differentiation, where reduced expression of C/EBPβ and C/EBPδ was observed. To our knowledge, the present study is the first to demonstrate that INH suppresses ARE signaling and interrupts with the transcriptional network of adipogenesis, leading to impaired adipogenic differentiation. The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. - Highlights: • Isoniazid suppresses ARE-mediated transcriptional activity. • Isoniazid inhibits adipogenesis in preadipocytes. • Isoniazid suppresses adipogenic gene expression during adipogenesis.« less

10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki

Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductasemore » 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.« less

Trace elements and antioxidant enzymes in Behçet's disease.

PubMed

Saglam, K; Serce, A F; Yilmaz, M I; Bulucu, F; Aydin, A; Akay, C; Sayal, A

2002-07-01

Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of Behçet's disease (BD). Trace elements function as cofactors to antioxidant enzymes. The antioxidant system and trace elements were investigated in many different studies, including BD, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in BD to contribute to the knowledge of pathogenesis and treatment of this disease. We examined glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities together with selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) levels in plasma and erythrocytes of 50 patients with BD and 30 healthy controls. It was found that in patients with BD, erythrocyte GSH-Px and SOD activities and erythrocyte Se, plasma Fe, Mn, and Zn levels were significantly lower than those of controls and that plasma Cu, erythrocyte Zn, and Mn levels were significantly higher in patients with BD. Insufficient antioxidant enzyme activities were observed in patients with BD. The mechanism(s) of this phenomenon is not clear. Therefore, supplementation with trace elements involved in the antioxidative processes may increase scavenger enzyme activities, and consequently, an improvement in clinical symptoms may be expected.

Antioxidant Vitamins and Trace Elements in Critical Illness.

PubMed

Koekkoek, W A C Kristine; van Zanten, Arthur R H

2016-08-01

This comprehensive narrative review summarizes relevant antioxidant mechanisms, the antioxidant status, and effects of supplementation in critically ill patients for the most studied antioxidant vitamins A, C, and E and the enzyme cofactor trace elements selenium and zinc. Over the past 15 years, oxidative stress-mediated cell damage has been recognized to be fundamental to the pathophysiology of various critical illnesses such as acute respiratory distress syndrome, ischemia-reperfusion injury, and multiorgan dysfunction in sepsis. Related to these conditions, low plasma levels of antioxidant enzymes, vitamins, and trace elements have been frequently reported, and thus supplementation seems logical. However, low antioxidant plasma levels per se may not indicate low total body stores as critical illness may induce redistribution of antioxidants. Furthermore, low antioxidant levels may even be beneficial as pro-oxidants are essential in bacterial killing. The reviewed studies in critically ill patients show conflicting results. This may be due to different patient populations, study designs, timing, dosing regimens, and duration of the intervention and outcome measures evaluated. Therefore, at present, it remains unclear whether supplementation of antioxidant micronutrients has any clinical benefit in critically ill patients as some studies show clear benefits, whereas others demonstrate neutral outcomes and even harm. Combination therapy of antioxidants seems logical as they work in synergy and function as elements of the human antioxidant network. Further research should focus on defining the normal antioxidant status for critically ill patients and to study optimal supplement combinations either by nutrition enrichment or by enteral or parenteral pharmacological interventions. © 2016 American Society for Parenteral and Enteral Nutrition.

Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

PubMed Central

Kulkarni, Supriya R.; Donepudi, Ajay C.; Xu, Jialin; Wei, Wei; Cheng, Qiuqiong C.; Driscoll, Maureen V.; Johnson, Delinda A.; Johnson, Jeffrey A.; Li, Xiaoling

2014-01-01

Abstract Aims: The purpose of this study was to determine whether 3′-5′-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2–4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2- and SIRT1–dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20, 15–30. PMID:23725046

Novel oxindole derivatives prevent oxidative stress-induced cell death in mouse hippocampal HT22 cells.

PubMed

Hirata, Yoko; Yamada, Chika; Ito, Yuki; Yamamoto, Shotaro; Nagase, Haruna; Oh-Hashi, Kentaro; Kiuchi, Kazutoshi; Suzuki, Hiromi; Sawada, Makoto; Furuta, Kyoji

2018-03-15

The current medical and surgical therapies for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease offer symptomatic relief but do not provide a cure. Thus, small synthetic compounds that protect neuronal cells from degeneration are critically needed to prevent and treat these. Oxidative stress has been implicated in various pathophysiological conditions, including neurodegenerative diseases. In a search for neuroprotective agents against oxidative stress using the murine hippocampal HT22 cell line, we found a novel oxindole compound, GIF-0726-r, which prevented oxidative stress-induced cell death, including glutamate-induced oxytosis and erastin-induced ferroptosis. This compound also exerted a protective effect on tunicamycin-induced ER stress to a lesser extent but had no effect on campthothecin-, etoposide- or staurosporine-induced apoptosis. In addition, GIF-0726-r was also found to be effective after the occurrence of oxidative stress. GIF-0726-r was capable of inhibiting reactive oxygen species accumulation and Ca 2+ influx, a presumed executor in cell death, and was capable of activating the antioxidant response element, which is a cis-acting regulatory element in promoter regions of several genes encoding phase II detoxification enzymes and antioxidant proteins. These results suggest that GIF-0726-r is a low-molecular-weight compound that prevents neuronal cell death through attenuation of oxidative stress. Among the more than 200 derivatives of the GIF-0726-r synthesized, we identified the 11 most potent activators of the antioxidant response element and characterized their neuroprotective activity in HT22 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures

PubMed Central

Yoshino, Atsushi; Polouliakh, Natalia; Meguro, Akira; Takeuchi, Masaki; Kawagoe, Tatsukata; Mizuki, Nobuhisa

2016-01-01

Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients. PMID:27621603

The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases

PubMed Central

Smith, Robert E.; Tran, Kevin; Smith, Cynthia C.; McDonald, Miranda; Shejwalkar, Pushkar; Hara, Kenji

2016-01-01

It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However, many antioxidants behave quite differently in vivo. Some of them, such as resveratrol (in red wine) and epigallocatechin gallate or EGCG (in green tea) can activate the nuclear erythroid-2 like factor-2 (Nrf2) transcription factor. It is a master regulator of endogenous cellular defense mechanisms. Nrf2 controls the expression of many antioxidant and detoxification genes, by binding to antioxidant response elements (AREs) that are commonly found in the promoter region of antioxidant (and other) genes, and that control expression of those genes. The mechanisms by which Nrf2 relieves oxidative stress and limits cardiac injury as well as the progression to heart failure are described. Also, the ability of statins to induce Nrf2 in the heart, brain, lung, and liver is mentioned. However, there is a negative side of Nrf2. When over-activated, it can cause (not prevent) cardiovascular diseases and multi-drug resistance cancer. PMID:28933413

Multielement analysis and antioxidant capacity of Merlot wine clones developed in Montenegro.

PubMed

Đorđević, Neda O; Pejin, Boris; Novaković, Miroslav M; Stanković, Dalibor M; Mutić, Jelena J; Pajović, Snežana B; Tešević, Vele V

2018-02-01

The overall aim of this paper was to compare the multielement composition and antioxidant capacity of two Montenegrin Merlot wines obtained from specific vine clones (VCR1 and VCR 101) along with commercial Merlot wine throughout the consecutive vintages in 2010 and 2011. Elemental composition was analysed using inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). Additionally, antioxidant capacity was assessed by cyclic voltammetry. VCR 1 wine from 2011 stood out for its elemental composition. On the other hand, antioxidant capacity of VCR 101 wines was the highest one for the both vintages. According to the experimental data obtained, all three wines are good source of essential elements and products with a significant antioxidant activity and specific geographical origin.

Abiotic Stress Tolerance in Plants: Myriad Roles of Ascorbate Peroxidase

PubMed Central

Pandey, Saurabh; Fartyal, Dhirendra; Agarwal, Aakrati; Shukla, Tushita; James, Donald; Kaul, Tanushri; Negi, Yogesh K.; Arora, Sandeep; Reddy, Malireddy K.

2017-01-01

One of the most significant manifestations of environmental stress in plants is the increased production of Reactive Oxygen Species (ROS). These ROS, if allowed to accumulate unchecked, can lead to cellular toxicity. A battery of antioxidant molecules is present in plants for keeping ROS levels under check and to maintain the cellular homeostasis under stress. Ascorbate peroxidase (APX) is a key antioxidant enzyme of such scavenging systems. It catalyses the conversion of H2O2 into H2O, employing ascorbate as an electron donor. The expression of APX is differentially regulated in response to environmental stresses and during normal plant growth and development as well. Different isoforms of APX show differential response to environmental stresses, depending upon their sub-cellular localization, and the presence of specific regulatory elements in the upstream regions of the respective genes. The present review delineates role of APX isoforms with respect to different types of abiotic stresses and its importance as a key antioxidant enzyme in maintaining cellular homeostasis. PMID:28473838

Chamomile confers protection against hydrogen peroxide-induced toxicity through activation of Nrf2-mediated defense response.

PubMed

Bhaskaran, Natarajan; Srivastava, Janmejai K; Shukla, Sanjeev; Gupta, Sanjay

2013-01-01

Oxidative stress plays an important role in the development of various human diseases. Aqueous chamomile extract is used as herbal medicine, in the form of tea, demonstrated to possess antiinflammatory and antioxidant properties. We demonstrate the cytoprotective effects of chamomile on hydrogen peroxide (H₂O₂)-induced cellular damage in macrophage RAW 264.7 cells. Pretreatment of cells with chamomile markedly attenuated H₂O₂-induced cell viability loss in a dose-dependent manner. The mechanisms by which chamomile-protected macrophages from oxidative stress was through the induction of several antioxidant enzymes including NAD(P)H:quinone oxidoreductase, superoxide dismutase, and catalase and increase nuclear accumulation of the transcription factor Nrf2 and its binding to antioxidant response elements. Furthermore, chamomile dose-dependently reduced H₂O₂-mediated increase in the intracellular levels of reactive oxygen species. Our results, for the first time, demonstrate that chamomile has protective effects against oxidative stress and might be beneficial to provide defense against cellular damage. Copyright © 2012 John Wiley & Sons, Ltd.

Chamomile Confers Protection against Hydrogen Peroxide-Induced Toxicity through Activation of Nrf2-Mediated Defense Response

PubMed Central

Bhaskaran, Natarajan; Srivastava, Janmejai K.; Shukla, Sanjeev; Gupta, Sanjay

2014-01-01

Oxidative stress plays an important role in the development of various human diseases. Aqueous chamomile extract is used as herbal medicine, in the form of tea, demonstrated to possess antiinflammatory and antioxidant properties. We demonstrate the cytoprotective effects of chamomile on hydrogen peroxide (H2O2)-induced cellular damage in macrophage RAW 264.7 cells. Pretreatment of cells with chamomile markedly attenuated H2O2-induced cell viability loss in a dose-dependent manner. The mechanisms by which chamomile-protected macrophages from oxidative stress was through the induction of several antioxidant enzymes including NAD (P)H:quinone oxidoreductase, superoxide dismutase, and catalase and increase nuclear accumulation of the transcription factor Nrf2 and its binding to antioxidant response elements. Furthermore, chamomile dose-dependently reduced H2O2-mediated increase in the intracellular levels of reactive oxygen species. Our results, for the first time, demonstrate that chamomile has protective effects against oxidative stress and might be beneficial to provide defense against cellular damage. PMID:22511316

Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway.

PubMed

Cheng, Xinghua; Siow, Richard C M; Mann, Giovanni E

2011-02-01

Type 2 diabetes is an age-related disease associated with vascular pathologies, including severe blindness, renal failure, atherosclerosis, and stroke. Reactive oxygen species (ROS), especially mitochondrial ROS, play a key role in regulating the cellular redox status, and an overproduction of ROS may in part underlie the pathogenesis of diabetes and other age-related diseases. Cells have evolved endogenous defense mechanisms against sustained oxidative stress such as the redox-sensitive transcription factor nuclear factor E2-related factor 2 (Nrf2), which regulates antioxidant response element (ARE/electrophile response element)-mediated expression of detoxifying and antioxidant enzymes and the cystine/glutamate transporter involved in glutathione biosynthesis. We hypothesize that diminished Nrf2/ARE activity contributes to increased oxidative stress and mitochondrial dysfunction in the vasculature leading to endothelial dysfunction, insulin resistance, and abnormal angiogenesis observed in diabetes. Sustained hyperglycemia further exacerbates redox dysregulation, thereby providing a positive feedback loop for severe diabetic complications. This review focuses on the role that Nrf2/ARE-linked gene expression plays in regulating endothelial redox homeostasis in health and type 2 diabetes, highlighting recent evidence that Nrf2 may provide a therapeutic target for countering oxidative stress associated with vascular disease and aging.

Paeonol extracted from Paeonia suffruticosa Andr. ameliorated UVB-induced skin photoaging via DLD/Nrf2/ARE and MAPK/AP-1 pathway.

PubMed

Sun, ZhengWang; Du, Juan; Hwang, Eunson; Yi, Tae-Hoo

2018-05-10

Paeonia suffruticosa Andr. (PS) has been used in traditional Chinese medicine for a long time. However, there are no studies that investigate the preventive effects of PS on ultraviolet B (UVB)-induced photoaging. In this study, paeonol (PA) was detected the main compound in PS root. In vitro, PS and PA significantly inhibited UVB-induced phosphorylation of mitogen-activated protein kinase and activator protein 1 in keratinocytes, which consequently led to degradation of procollagen type I. On the other hand, PS and PA increased NAD(P)H:quinone oxidoreductase 1 and heme oxygenase-1 expression, confirmed by greater nuclear accumulation of nuclear factor E2-releated factor 2 (Nrf2). Furthermore, this study proved that the endogenous antioxidant system Nrf2/antioxidant response element was regulated by dihydrolipoamide dehydrogenase, a tricarboxylic acid (TCA) cycle-associated protein whose level was decreased after UVB exposure. PS and PA promoted the production of dihydrolipoamide dehydrogenase, as well as the activation of Nrf2 and antioxidant response element, resulting in preventing procollagen type I ruined caused by UVB. In vivo, topical application of PS and PA attenuated UVB-induced matrix metalloproteinase-1 production and promoted procollagen type I in hairless mice. These results suggested PA a promising botanical in protecting skin from UVB-induced photoaging. Copyright © 2018 John Wiley & Sons, Ltd.

INDUCTION OF HEME OXYGENASE-1 EXPRESSION IN MACROPHAGES BY DIESEL EXHAUST PARTICLE CHEMICALS AND QUINONES VIA THE ANTIOXIDANT-RESPONSIVE ELEMENT. (R827352C001)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Complex of vitamins and antioxidants protects low-density lipoproteins in blood plasma from free radical oxidation and activates antioxidants enzymes in erythrocytes from patients with coronary heart disease.

PubMed

Konovalova, G G; Lankin, V Z; Tikhaze, A K; Nezhdanova, I B; Lisina, M O; Kukharchuk, V V

2003-08-01

We studied the effect of a complex containing antioxidant vitamins C and E, provitamin A, and antioxidant element selenium on the contents of primary (lipid peroxides) and secondary products (malonic dialdehyde) of free radical lipid oxidation in low-density lipoproteins isolated from the plasma of patients with coronary heart disease and hypercholesterolemia by means of preparative ultracentrifugation. Activity of key antioxidant enzymes in the blood was measured during treatment with the antioxidant preparation. Combination treatment with antioxidant vitamins and antioxidant element selenium sharply decreased the contents of primary and secondary free radical oxidation products in circulating low-density lipoproteins and increased activity of antioxidant enzymes in erythrocytes. Activities of superoxide dismutase and selenium-containing glutathione peroxidase increased 1 and 2 months after the start of therapy, respectively.

Essential trace elements and antioxidant status in relation to severity of HIV in Nigerian patients.

PubMed

Olaniyi, J A; Arinola, O G

2007-01-01

This study was designed to determine the plasma levels of some antioxidants and trace elements in three severity groups of HIV patients compared with non-HIV-infected controls. The plasma levels of antioxidants (total antioxidant, albumin, bilirubin and uric acid) and trace elements (Mg, Fe, Zn, Mn, Cu, Cr, Cd and Se) were estimated spectrophotometrically in controls and patients with CD4 counts of <200; 200-499 and > or =500 cells/microl. Uric acid and Zn were significantly higher, while vitamin E and all the trace elements (except Zn) were significantly lower in HIV-infected patients compared to healthy controls. The highest level of uric acid was observed in those with CD4 counts of <200 cells/microl. All the trace elements (except Zn) were higher in HIV subjects with a CD4 count of 200-499 cells/microl compared to >500 cells/microl. Only uric acid and Zn showed significant correlation with CD4 count. Based on the results of this study, we recommend routine assessment and appropriate supplementation of antioxidants/trace elements in HIV subjects. This supplementation is hoped to strengthen the immune system and reduce the adverse consequences of HIV- related oxidative stress. Copyright 2007 S. Karger AG, Basel.

Extracts of Fruits and Vegetables Activate the Antioxidant Response Element in IMR-32 Cells.

PubMed

Orena, Stephen; Owen, Jennifer; Jin, Fuxia; Fabian, Morgan; Gillitt, Nicholas D; Zeisel, Steven H

2015-09-01

The biological effects of antioxidant nutrients are mediated in part by activation of antioxidant response elements (AREs) on genes for enzymes involved in endogenous pathways that prevent free radical damage. Traditional approaches for identifying antioxidant molecules in foods, such as total phenolic compound (TP) content or oxygen radical absorption capacity (ORAC), do not measure capacity to activate AREs. The goal of this study was to develop an assay to assess the ARE activation capacity of fruit and vegetable extracts and determine whether such capacity was predicted by TP content and/or ORAC activity. Fruits and vegetables were homogenized, extracted with acidified ethanol, lyophilized, and resuspended in growth medium. Human IMR-32 neuroblastoma cells, transfected with an ARE-firefly luciferase reporter, were exposed to extracts for 5 h. Firefly luciferase was normalized to constitutively expressed Renilla luciferase with tertiary butylhydroquinone (tBHQ) as a positive control. TP content and ORAC activity were measured for each extract. Relations between TPs and ORAC and ARE activity were determined. A total of 107 of 134 extracts tested significantly activated the ARE-luciferase reporter from 1.2- to 58-fold above that of the solvent control (P < 0.05) in human IMR-32 cells. ARE activity, TP content, and ORAC ranked higher in peels than in associated flesh. Despite this relation, ARE activity did not correlate with TP content (Spearman ρ = 0.05, P = 0.57) and only modestly but negatively correlated with ORAC (Spearman ρ = -0.24, P < 0.01). Many extracts activated the ARE more than predicted by the TP content or ORAC. The ARE reporter assay identified many active fruit and vegetable extracts in human IMR-32 cells. There are components of fruits and vegetables that activate the ARE but are not phenolic compounds and are low in ORAC. The ARE-luciferase reporter assay is likely a better predictor of the antioxidant benefits of fruits and vegetables than TP or ORAC. © 2015 American Society for Nutrition.

Characterization of Nrf2 activation and heme oxygenase-1 expression in NIH3T3 cells exposed to aqueous extracts of cigarette smoke.

PubMed

Knörr-Wittmann, Constanze; Hengstermann, Arnd; Gebel, Stephan; Alam, Jawed; Müller, Thomas

2005-12-01

Cigarette smoke (CS) is a complex chemical mixture estimated to be composed of up to 5000 different chemicals, many of which are prooxidant. Here we show that, at least in vitro, the cellular response designed to combat oxidative stress resulting from CS exposure is primarily controlled by the transcription factor Nrf2, a principal inducer of antioxidant and phase II-related genes. The prominent role of Nrf2 in the cellular response to CS is substantiated by the following observations: In NIH3T3 cells exposed to aqueous extracts of CS (i) Nrf2 is strongly stabilized and becomes detectable in nuclear extracts. (ii) Nuclear localization of Nrf2 coincides with increased DNA binding of a putative Nrf2/MafK heterodimer to its cognate cis-regulatory site, i.e., the antioxidant-responsive element (ARE). (iii) Studies on the regulatory elements of the oxidative stress-inducible gene heme oxygenase-1 (hmox1) using various hmox1 promoter/luciferase reporter constructs revealed that the strong CS-dependent expression of this gene is primarily governed by the distal enhancers 1 ("E1") and 2 ("E2"), which both contain three canonical ARE-like stress-responsive elements (StREs). Notably, depletion of Nrf2 levels caused by RNA interference significantly compromised CS-induced hmox1 promoter activation, based on the distinct Nrf2 sensitivity exhibited by E1 and E2. Finally, (iv) siRNA-dependent knock-down of Nrf2 completely abrogated CS-induced expression of phase II-related genes. Taken together, these results confirm the outstanding role of Nrf2 both in sensing (oxidant) stress and in orchestrating an efficient transcriptional response aimed at resolving the stressing conditions.

Overexpression of the OsIMP Gene Increases the Accumulation of Inositol and Confers Enhanced Cold Tolerance in Tobacco through Modulation of the Antioxidant Enzymes' Activities.

PubMed

Zhang, Rong-Xiang; Qin, Li-Jun; Zhao, De-Gang

2017-07-20

Inositol is a cyclic polyol that is involved in various physiological processes, including signal transduction and stress adaptation in plants. l- myo -inositol monophosphatase (IMPase) is one of the metal-dependent phosphatase family members and catalyzes the last reaction step of biosynthesis of inositol. Although increased IMPase activity induced by abiotic stress has been reported in chickpea plants, the role and regulation of the IMP gene in rice ( Oryza sativa L.) remains poorly understood. In the present work, we obtained a full-length cDNA sequence coding IMPase in the cold tolerant rice landraces in Gaogonggui, which is named as OsIMP . Multiple alignment results have displayed that this sequence has characteristic signature motifs and conserved enzyme active sites of the phosphatase super family. Phylogenetic analysis showed that IMPase is most closely related to that of the wild rice Oryza brachyantha , while transcript analysis revealed that the expression of the OsIMP is significantly induced by cold stress and exogenous abscisic acid (ABA) treatment. Meanwhile, we cloned the 5' flanking promoter sequence of the OsIMP gene and identified several important cis -acting elements, such as LTR (low-temperature responsiveness), TCA-element (salicylic acid responsiveness), ABRE-element (abscisic acid responsiveness), GARE-motif (gibberellin responsive), MBS (MYB Binding Site) and other cis -acting elements related to defense and stress responsiveness. To further investigate the potential function of the OsIMP gene, we generated transgenic tobacco plants overexpressing the OsIMP gene and the cold tolerance test indicated that these transgenic tobacco plants exhibit improved cold tolerance. Furthermore, transgenic tobacco plants have a lower level of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), and a higher content of total chlorophyll as well as increased antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), when compared to wild type (WT) tobacco plants under normal and cold stress conditions.

Induction of activation of the antioxidant response element and stabilization of Nrf2 by 3-(3-pyridylmethylidene)-2-indolinone (PMID) confers protection against oxidative stress-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Jia-Wei; Beijing Institute of Radiation Medicine, Beijing 100850; Liu, Jing

2012-03-01

The antioxidant response elements (ARE) are a cis-acting enhancer sequence located in regulatory regions of antioxidant and detoxifying genes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a member of the Cap ‘n’ Collar family of transcription factors that binds to the ARE and regulates the transcription of specific ARE-containing genes. Under oxidative stress, Nrf2/ARE induction is fundamental to defense against reactive oxygen species (ROS) and serves as a key factor in the protection against toxic xenobiotics. 3-(3-Pyridylmethylidene)-2-Indolinone (PMID) is a derivative of 2-indolinone compounds which act as protein kinase inhibitors and show anti-tumor activity. However, the role of PMID inmore » the oxidative stress remains unknown. In the present study, we showed that PMID induced the activation of ARE-mediated transcription, increased the DNA-binding activity of Nrf2 and then up-regulated the expression of antioxidant genes such as HO-1, SOD, and NQO1. The level of Nrf2 protein was increased in cells treated with PMID by a post-transcriptional mechanism. Under CHX treatment, the stability of Nrf2 protein was enhanced by PMID with decreased turnover rate. We showed that PMID reduced the ubiquitination of Nrf2 and disrupted the Cullin3 (Cul3)-Keap1 interaction. Furthermore, cells treated with PMID showed resistance to cytotoxicity by H{sub 2}O{sub 2} and pro-oxidant 6-OHDA. PMID also up-regulated the antioxidant level in BALB/c mice. Taken together, the compound PMID induces the ARE-mediated gene expression through stabilization of Nrf2 protein and activation of Nrf2/ARE pathway and protects against oxidative stress-mediated cell death. -- Highlights: ► PMID up-regulates ARE-mediated antioxidant gene expression in vitro and in vivo. ► PMID enhances the stabilization of Nrf2 protein, decreasing Nrf2 turnover rate. ► PMID disrupted the Cullin3 (Cul3)-Keap1 interaction. ► PMID protects against cell death induced by H{sub 2}O{sub 2} and pro-oxidant 6-OHDA.« less

Vegetarian diets and public health: biomarker and redox connections.

PubMed

Benzie, Iris F F; Wachtel-Galor, Sissi

2010-11-15

Vegetarian diets are rich in antioxidant phytochemicals. However, they may not act as antioxidants in vivo, and yet still have important signaling and regulatory functions. Some may act as pro-oxidants, modulating cellular redox tone and oxidizing redox sensitive sites. In this review, evidence for health benefits of vegetarian diets is presented from different perspectives: epidemiological, biomarker, evolutionary, and public health, as well as antioxidant. From the perspective of molecular connections between diet and health, evidence of a role for plasma ascorbic acid as a biomarker for future disease risk is presented. Basic concepts of redox-based cell signaling are presented, and effects of antioxidant phytochemicals on signaling, especially via redox tone, sulfur switches and the Antioxidant Response Element (ARE), are explored. Sufficient scientific evidence exists for public health policy to promote a plant-rich diet for health promotion. This does not need to wait for science to provide all the answers as to why and how. However, action and interplay of dietary antioxidants in the nonequilibrium systems that control redox balance, cell signaling, and cell function provide rich ground for research to advance understanding of orthomolecular nutrition and provide science-based evidence to advance public health in our aging population.

Salicylic acid improves root antioxidant defense system and total antioxidant capacities of flax subjected to cadmium.

PubMed

Belkadhi, Aïcha; De Haro, Antonio; Soengas, Pilar; Obregon, Sara; Cartea, Maria Elena; Djebali, Wahbi; Chaïbi, Wided

2013-07-01

Cadmium (Cd) disrupts the normal growth and development of plants, depending on their tolerance to this toxic element. The present study was focused on the impacts of exogenous salicylic acid (SA) on the response and regulation of the antioxidant defense system and membrane lipids to 16-day-old flax plantlets under Cd stress. Exposure of flax to high Cd concentrations led to strong inhibition of root growth and enhanced lipid peroxides, membrane permeability, protein oxidation, and hydrogen peroxide (H2O2) production to varying degrees. Concomitantly, activities of the antioxidant enzymes catalase (CAT, EC 1.11.1.6), guaïcol peroxydase (GPX, EC 1.11.1.7), ascorbate peroxydase (APX, EC 1.11.1.11), and superoxide dismutase (SOD, EC 1.15.1.1), and the total antioxidant capacities (2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP)) were significantly altered by Cd. In contrast, exogenous SA greatly reduced the toxic effects of Cd on the root growth, antioxidant system, and membrane lipid content. The Cd-treated plantlets pre-soaked with SA exhibited less lipid and protein oxidation and membrane alteration, as well as a high level of total antioxidant capacities and increased activities of antioxidant enzymes except of CAT. These results may suggest that SA plays an important role in triggering the root antioxidant system, thereby preventing membrane damage as well as the denaturation of its components.

Role of antioxidants and trace elements in health and immunity of transition dairy cows.

PubMed

Spears, Jerry W; Weiss, William P

2008-04-01

A number of antioxidants and trace minerals have important roles in immune function and may affect health in transition dairy cows. Vitamin E and beta-carotene are important cellular antioxidants. Selenium (Se) is involved in the antioxidant system via its role in the enzyme glutathione peroxidase. Inadequate dietary vitamin E or Se decreases neutrophil function during the perpariturient period. Supplementation of vitamin E and/or Se has reduced the incidence of mastitis and retained placenta, and reduced duration of clinical symptoms of mastitis in some experiments. Research has indicated that beta-carotene supplementation may enhance immunity and reduce the incidence of retained placenta and metritis in dairy cows. Marginal copper deficiency resulted in reduced neutrophil killing and decreased interferon production by mononuclear cells. Copper supplementation of a diet marginal in copper reduced the peak clinical response during experimental Escherichia coli mastitis. Limited research indicated that chromium supplementation during the transition period may increase immunity and reduce the incidence of retained placenta.

Role of antioxidants in redox regulation of diabetic cardiovascular complications.

PubMed

Turan, Belma

2010-12-01

Cardiovascular dysfunction is leading cause for the mortality of diabetic individuals, in part due to a specific cardiomyopathy, and due to altered endothelial dependent/independent vascular reactivity. Cardiovascular complications result from multiple parameters including glucotoxicity, lipotoxicity, fibrosis and mitochondrial uncoupling. Oxidative stress arises from an imbalance between the production of reactive oxygen and nitrogen species (ROS and RNS) and the capability of biological system to readily detoxify reactive intermediates. Several studies have reported beneficial effects of a therapy with antioxidant agents, including trace elements and other antioxidants, against the cardiovascular system dysfunction due to the diabetes. Antioxidants act through different mechanisms to prevent oxidant-induced cell damages acting either directly or indirectly. They can reduce the generation of ROS, scavenge ROS, or interfere with ROS-induced alterations. Modulating mitochondrial activity is an important possibility to control ROS production. Hence, the use of PPARα agonist to reduce fatty acid oxidation and of trace elements such as selenium as antioxidant and other antioxidants such as vitamins E and C, contribute to the prevention of diabetes-induced cardiovascular dysfunction. The paradigm that, inhibiting the overproduction of superoxides and peroxides would prevent cardiac dysfunction in diabetes has been difficult to verify using conventional antioxidants like vitamins E and C. That led to use of catalytic antioxidants such as SOD/CAT mimetics. Hence, well-tuned, balanced and responsive antioxidant defence systems are vital for proper prevention against diabetic damage. Myocardial cell death is observed in the hearts of diabetic patients and animal models; however, its importance in the development of diabetic cardiomyopathy is not completely understood. This review aims to summarize our present knowledge on various strategies to control oxidative stress and antagonize cardiovascular dysfunction during diabetes. In here, we consider aspects of redox signaling in the cardiovascular system, focusing on the molecular basis of redox sensing by proteins and the array of post-translational oxidative modifications that can occur. In addition, we discuss studies identify redox-sensitive cardiac proteins, as well as those assessing redox signalling in cardiovascular disease.

Characterization of carotenoid hydroxylase gene promoter in Haematococcus pluvialis.

PubMed

Meng, C X; Wei, W; Su, Z- L; Qin, S

2006-10-01

Astaxanthin, a high-value ketocarotenoid is mainly used in fish aquaculture. It also has potential in human health due to its higher antioxidant capacity than beta-carotene and vitamin E. The unicellular green alga Haematococcus pluvialis is known to accumulate astaxanthin in response to environmental stresses, such as high light intensity and salt stress. Carotenoid hydroxylase plays a key role in astaxanthin biosynthesis in H. pluvialis. In this paper, we report the characterization of a promoter-like region (-378 to -22 bp) of carotenoid hydroxylase gene by cloning, sequence analysis and functional verification of its 919 bp 5'-flanking region in H. pluvialis. The 5'-flanking region was characterized using micro-particle bombardment method and transient expression of LacZ reporter gene. Results of sequence analysis showed that the 5'-flanking region might have putative cis-acting elements, such as ABA (abscisic acid)-responsive element (ABRE), C-repeat/dehydration responsive element (C-repeat/DRE), ethylene-responsive element (ERE), heat-shock element (HSE), wound-responsive element (WUN-motif), gibberellin-responsive element (P-box), MYB-binding site (MBS) etc., except for typical TATA and CCAAT boxes. Results of 5' deletions construct and beta-galactosidase assays revealed that a highest promoter-like region might exist from -378 to -22 bp and some negative regulatory elements might lie in the region from -919 to -378 bp. Results of site-directed mutagenesis of a putative C-repeat/DRE and an ABRE-like motif in the promoter-like region (-378 to -22 bp) indicated that the putative C-repeat/DRE and ABRE-like motif might be important for expression of carotenoid hydroxylase gene.

Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line.

PubMed

Park, Hae-Ryung; Loch-Caruso, Rita

2014-11-15

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20μM BDE-47 for 24h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20μM BDE-47 for 24h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells.

PubMed

Tan, Xin; Sidell, Neil; Mancini, Alessandra; Huang, Ruo-Pan; Shenming Wang; Horowitz, Ira R; Liotta, Dennis C; Taylor, Robert N; Wieser, Friedrich

2010-10-01

Curcumin, a component of turmeric, has been reported to exhibit potential antitumor activities. This study assessed the effects of a novel synthetic curcumin analog, EF24, on proliferation, apoptosis, and vascular endothelial growth factor (VEGF) regulation in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells. EF24 time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis. Although treatment with EF24 had no significant effect on VEGF messenger RNA (mRNA) expression,VEGF protein secretion into conditioned media was dose-dependently reduced with EF24 demonstrating ∼8-fold greater potency than curcumin (P < .05). EF24 significantly inhibited hydrogen peroxide (H(2)O(2))-induced VEGF expression, as did the phenolic antioxidant tert-butylhydroquinone (t-BHQ). EF24 upregulated cellular antioxidant responses as observed by the suppression of reactive oxygen species (ROS) generation and activation of antioxidant response element (ARE)-dependent gene transcription. Given its high potency, EF24 is an excellent lead candidate for further development as an adjuvant therapeutic agent in preclinical models of ovarian cancer.

Silicon Regulates Antioxidant Activities of Crop Plants under Abiotic-Induced Oxidative Stress: A Review

PubMed Central

Kim, Yoon-Ha; Khan, Abdul L.; Waqas, Muhammad; Lee, In-Jung

2017-01-01

Silicon (Si) is the second most abundant element in soil, where its availability to plants can exhilarate to 10% of total dry weight of the plant. Si accumulation/transport occurs in the upward direction, and has been identified in several crop plants. Si application has been known to ameliorate plant growth and development during normal and stressful conditions over past two-decades. During abiotic (salinity, drought, thermal, and heavy metal etc) stress, one of the immediate responses by plant is the generation of reactive oxygen species (ROS), such as singlet oxygen (1O2), superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (OH), which cause severe damage to the cell structure, organelles, and functions. To alleviate and repair this damage, plants have developed a complex antioxidant system to maintain homeostasis through non-enzymatic (carotenoids, tocopherols, ascorbate, and glutathione) and enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)]. To this end, the exogenous application of Si has been found to induce stress tolerance by regulating the generation of ROS, reducing electrolytic leakage, and malondialdehyde (MDA) contents, and immobilizing and reducing the uptake of toxic ions like Na, under stressful conditions. However, the interaction of Si and plant antioxidant enzyme system remains poorly understood, and further in-depth analyses at the transcriptomic level are needed to understand the mechanisms responsible for the Si-mediated regulation of stress responses. PMID:28428797

Mesenchymal stem cells restore CCl4-induced liver injury by an antioxidative process.

PubMed

Cho, Kyung-Ah; Woo, So-Youn; Seoh, Ju-Young; Han, Ho-Seong; Ryu, Kyung-Ha

2012-01-01

We have investigated BM (bone marrow)-derived MSCs (mesenchymal stem cells) for the treatment of liver injury. It was hypothesized that MSC-mediated resolution of liver injury could occur through an antioxidative process. After being injected with CCl4 (carbon tetrachloride), mice were injected with syngenic BM-derived MSCs or normal saline. Oxidative stress activity of the MSCs was determined by the analysis of ROS (reactive oxygen species) and SOD (superoxide dismutase) activity. In addition, cytoprotective genes of the liver tissue were assessed by real-time PCR and ARE (antioxidant-response element) reporter assay. Up-regulated ROS of CCl4-treated liver cells was attenuated by co-culturing with MSCs. Suppression of SOD by adding an SOD inhibitor decreased the effect of MSCs on injured liver cells. MSCs significantly increased SOD activity and inhibited ROS production in the injured liver. The gene expression levels of Hmox-1 (haem oxygenase-1), BI-1 (Bax inhibitor-1), HGF (hepatocyte growth factor), GST (glutathione transferase) and Nrf2 (nuclear factor-erythoid 2 p45 subunit-related factor 20), attenuated by CCl4, were increased up to basal levels after MSC transplantation. In addition, MSCs induced an ARE, shown by luciferase activity, which represented a cytoprotective response in the injured liver. Evidence of a new cytoprotective effect is shown in which MSCs promote an antioxidant response and supports the potential of using MSC transplantation as an effective treatment modality for liver disease.

Low cytotoxicity of inorganic nanotubes and fullerene-like nanostructures in human bronchial epithelial cells: relation to inflammatory gene induction and antioxidant response.

PubMed

Pardo, Michal; Shuster-Meiseles, Timor; Levin-Zaidman, Smadar; Rudich, Assaf; Rudich, Yinon

2014-03-18

The cytotoxicity of tungsten disulfide nano tubes (INT-WS2) and inorganic fullerene-like molybdenum disulfide (IF-MoS2) nanoparticles (NPs) used in industrial and medical applications was evaluated in comparison to standard environmental particulate matter. The IF-MoS2 and INT-WS2 reside in vesicles/inclusion bodies, suggestive of endocytic vesicles. In cells representing the respiratory, immune and metabolic systems, both IF-MoS2 and INT-WS2 NPs remained nontoxic compared to equivalent concentrations (up to 100 μg/mL in the medium) of silica dioxide (SiO2), diesel engine-derived and carbon black NPs, which induced cell death. Associating with this biocompatibility of IF-MoS2\\INT-WS2, we demonstrate in nontransformed human bronchial cells (NL-20) relative low induction of the pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α. Moreover, IF-MoS2 and INT-WS2 activated antioxidant response as measured by the antioxidant response element (ARE) using a luciferase reporter, and induced Nrf2-mediated Phase II detoxification genes. Collectively, our findings suggest that the lower cytotoxicity of IF-MoS2 and INT-WS2 NPs does not reflect general biological inertness. Rather, compared to other NP's, it likely results from decreased pro-inflammatory activation, but a comparable significant capacity to induce protective antioxidant/detoxification defense mechanisms.

Silicon Regulates Antioxidant Activities of Crop Plants under Abiotic-Induced Oxidative Stress: A Review.

PubMed

Kim, Yoon-Ha; Khan, Abdul L; Waqas, Muhammad; Lee, In-Jung

2017-01-01

Silicon (Si) is the second most abundant element in soil, where its availability to plants can exhilarate to 10% of total dry weight of the plant. Si accumulation/transport occurs in the upward direction, and has been identified in several crop plants. Si application has been known to ameliorate plant growth and development during normal and stressful conditions over past two-decades. During abiotic (salinity, drought, thermal, and heavy metal etc) stress, one of the immediate responses by plant is the generation of reactive oxygen species (ROS), such as singlet oxygen ( 1 O 2 ), superoxide ([Formula: see text]), hydrogen peroxide (H 2 O 2 ), and hydroxyl radicals (OH), which cause severe damage to the cell structure, organelles, and functions. To alleviate and repair this damage, plants have developed a complex antioxidant system to maintain homeostasis through non-enzymatic (carotenoids, tocopherols, ascorbate, and glutathione) and enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)]. To this end, the exogenous application of Si has been found to induce stress tolerance by regulating the generation of ROS, reducing electrolytic leakage, and malondialdehyde (MDA) contents, and immobilizing and reducing the uptake of toxic ions like Na, under stressful conditions. However, the interaction of Si and plant antioxidant enzyme system remains poorly understood, and further in-depth analyses at the transcriptomic level are needed to understand the mechanisms responsible for the Si-mediated regulation of stress responses.

Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein Endothelial Cells by Generating Trace Amounts of ROS.

PubMed

Niu, Tingting; Xuan, Rongrong; Jiang, Ligang; Wu, Wei; Zhen, Zhanghe; Song, Yuling; Hong, Lili; Zheng, Kaiqin; Zhang, Jiaxing; Xu, Qingshan; Tan, Yinghong; Yan, Xiaojun; Chen, Haimin

2018-02-14

Astaxanthin is a powerful antioxidant that possesses potent protective effects against various human diseases and physiological disorders. However, the mechanisms underlying its antioxidant functions in cells are not fully understood. In the present study, the effects of astaxanthin on reactive oxygen species (ROS) production and antioxidant enzyme activity, as well as mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K)/Akt, and the nuclear factor erythroid 2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) pathways in human umbilical vein endothelial cells (HUVECs), were examined. It was shown that astaxanthin (0.1, 1, and 10 μM) induced ROS production by 9.35%, 14.8%, and 18.06% compared to control, respectively, in HUVECs. In addition, astaxanthin increased the mRNA levels of phase II enzymes HO-1 and also promoted GSH-Px enzyme activity. Furthermore, we observed ERK phosphorylation, nuclear translocation of Nrf-2, and activation of antioxidant response element-driven luciferase activity upon astaxanthin treatment. Knockdown of Nrf-2 by small interfering RNA inhibited HO-1 mRNA expression by 60%, indicating that the Nrf-2/ARE signaling pathway is activated by astaxanthin. Our results suggest that astaxanthin activates the Nrf-2/HO-1 antioxidant pathway by generating small amounts of ROS.

Influence of heavy metal stress on antioxidant status and DNA damage in Urtica dioica.

PubMed

Gjorgieva, Darinka; Kadifkova Panovska, Tatjana; Ruskovska, Tatjana; Bačeva, Katerina; Stafilov, Trajče

2013-01-01

Heavy metals have the potential to interact and induce several stress responses in the plants; thus, effects of heavy metal stress on DNA damages and total antioxidants level in Urtica dioica leaves and stems were investigated. The samples are sampled from areas with different metal exposition. Metal content was analyzed by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES), for total antioxidants level assessment the Ferric-Reducing Antioxidant Power (FRAP) assay was used, and genomic DNA isolation from frozen plant samples was performed to obtain DNA fingerprints of investigated plant. It was found that heavy metal contents in stems generally changed synchronously with those in leaves of the plant, and extraneous metals led to imbalance of mineral nutrient elements. DNA damages were investigated by Random Amplified Polymorphic DNA (RAPD) technique, and the results demonstrated that the samples exposed to metals yielded a large number of new fragments (total 12) in comparison with the control sample. This study showed that DNA stability is highly affected by metal pollution which was identified by RAPD markers. Results suggested that heavy metal stress influences antioxidant status and also induces DNA damages in U. dioica which may help to understand the mechanisms of metals genotoxicity.

Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression.

PubMed

Mann, Giovanni E; Rowlands, David J; Li, Francois Y L; de Winter, Patricia; Siow, Richard C M

2007-07-15

The endothelium plays a key role in the maintenance of vascular homeostasis, and increased oxidative stress in vascular disease leads to reduced nitric oxide bioavailability and impaired endothelium-dependent relaxation of resistance vessels. Although epidemiological evidence suggests that diets containing high amounts of natural antioxidants afford protection against coronary heart disease (CHD), antioxidant supplementation trials have largely reported only marginal health benefits. There is controversy concerning the cardiovascular benefits of prolonged estrogen/progestin or soy isoflavone therapy for postmenopausal women and patients with an increased risk of CHD. Research on the potential health benefits of soy isoflavones and other polyphenols contained in red wine, green and black tea and dark chocolate developed rapidly during the 1990's, and recent clinical trials and studies in animal models and cultured endothelial cells provide important and novel insights into the mechanisms by which dietary polyphenols afford protection against oxidative stress. In this review, we highlight that NO and reactive oxygen radicals may mediate dietary polyphenol induced activation of Nrf2, which in turn triggers antioxidant response element (ARE) driven transcription of phase II detoxifying and antioxidant defense enzymes in vascular cells.

Substoichiometric hydroxynonenylation of a single protein recapitulates whole-cell-stimulated antioxidant response.

PubMed

Parvez, Saba; Fu, Yuan; Li, Jiayang; Long, Marcus J C; Lin, Hong-Yu; Lee, Dustin K; Hu, Gene S; Aye, Yimon

2015-01-14

Lipid-derived electrophiles (LDEs) that can directly modify proteins have emerged as important small-molecule cues in cellular decision-making. However, because these diffusible LDEs can modify many targets [e.g., >700 cysteines are modified by the well-known LDE 4-hydroxynonenal (HNE)], establishing the functional consequences of LDE modification on individual targets remains devilishly difficult. Whether LDE modifications on a single protein are biologically sufficient to activate discrete redox signaling response downstream also remains untested. Herein, using T-REX (targetable reactive electrophiles and oxidants), an approach aimed at selectively flipping a single redox switch in cells at a precise time, we show that a modest level (∼34%) of HNEylation on a single target is sufficient to elicit the pharmaceutically important antioxidant response element (ARE) activation, and the resultant strength of ARE induction recapitulates that observed from whole-cell electrophilic perturbation. These data provide the first evidence that single-target LDE modifications are important individual events in mammalian physiology.

Acute toxicity of arsenic and oxidative stress responses in the embryonic development of the common South American toad Rhinella arenarum.

PubMed

Mardirosian, Mariana Noelia; Lascano, Cecilia Inés; Ferrari, Ana; Bongiovanni, Guillermina Azucena; Venturino, Andrés

2015-05-01

Arsenic (As), a natural element of ecological relevance, is found in natural water sources throughout Argentina in concentrations between 0.01 mg/L and 15 mg/L. The autochthonous toad Rhinella arenarum was selected to study the acute toxicity of As and the biochemical responses elicited by the exposure to As in water during its embryonic development. The median lethal concentration (LC50) value averaged 24.3 mg/L As and remained constant along the embryonic development. However, As toxicity drastically decreased when embryos were exposed from heartbeat-stage on day 4 of development, suggesting the onset of detoxification mechanisms. Given the environmental concentrations of As in Argentina, there is a probability of exceeding lethal levels at 1% of sites. Arsenic at sublethal concentrations caused a significant decrease in the total antioxidant potential but generated an increase in endogenous glutathione (GSH) content and glutathione S-transferase (GST) activity. This protective response might prevent a deeper decline in the antioxidant system and further oxidative damage. Alternatively, it might be linked to As conjugation with GSH for its excretion. The authors conclude that toad embryos are more sensitive to As during early developmental stages and that relatively high concentrations of this toxic element are required to elicit mortality, but oxidative stress may be an adverse effect at sublethal concentrations. © 2014 SETAC.

Protection by Chrysanthemum zawadskii extract from liver damage of mice caused by carbon tetrachloride is maybe mediated by modulation of QR activity

PubMed Central

Seo, Ji Yeon; Lim, Soon Sung; Park, Jia; Lim, Ji-Sun; Kim, Hyo Jung; Kang, Hui Jung; Yoon Park, Jung Han

2010-01-01

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by CCl4 treatment to the control level. Hepatic injury induced by CCl4 was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by CCl4. PMID:20461196

Protection by Chrysanthemum zawadskii extract from liver damage of mice caused by carbon tetrachloride is maybe mediated by modulation of QR activity.

PubMed

Seo, Ji Yeon; Lim, Soon Sung; Park, Jia; Lim, Ji-Sun; Kim, Hyo Jung; Kang, Hui Jung; Yoon Park, Jung Han; Kim, Jong-Sang

2010-04-01

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by CCl(4) treatment to the control level. Hepatic injury induced by CCl(4) was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by CCl(4).

Impact of a trace element supplementation programme on health and performance of cross-breed (Bos indicus x Bos taurus) dairy cattle under tropical farming conditions: a double-blinded randomized field trial.

PubMed

Dermauw, V; Dierenfeld, E; Du Laing, G; Buyse, J; Brochier, B; Van Gucht, S; Duchateau, L; Janssens, G P J

2015-06-01

Small-scale urban dairy farms (n = 16) in and around Jimma, Ethiopia with cross-bred (Bos indicus × Bos taurus) cows were enrolled in a double-blinded intervention study to investigate the effect of a trace element supplementation programme on trace element status and milk concentrations as well as performance [body condition score (BCS), milk yield, leptin], milk composition, antioxidant status (ferric-reducing ability of plasma (FRAP), thiobarbituric acid-reactive substances (TBARS)], blood biochemistry, serum proteins and immune response (antibody titre upon rabies vaccination). The farms were allocated to a (1) placebo or (2) Cu, Zn, Se, Co and I supplementation treatment for 150 d. On days 0 and 120, four lactating cows per farm were sampled for milk and plasma, and on day 150 for serum, following primo-vaccination. Cu deficiency was present in 17% and marginal Se deficiency in 30% of initially sampled cows, while no Zn shortage was detected. Over 120 days, trace element supplementation caused a bigger increase in plasma Se and Cu concentrations, but also a larger decrease of plasma Fe concentrations. A larger increase in milk Se concentrations was observed in the supplemented group, whereas none of the other elements were affected. BCS decreased more over time in the supplemented group. None of the other parameters of performance and antioxidant status nor milk composition or blood biochemistry was affected by treatment. Antibody response to rabies vaccination did not differ between groups, whereas α1-globulins tended to be lower and β-globulins tended to be higher in the supplemented group. In conclusion, despite improved Cu and Se status and Se concentrations in milk, cows on tropical urban dairy farms did not seem to benefit from trace element supplementation, with respect to the parameters investigated. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Ethanol Extract of Cirsium japonicum var. ussuriense Kitamura Exhibits the Activation of Nuclear Factor Erythroid 2-Related Factor 2-dependent Antioxidant Response Element and Protects Human Keratinocyte HaCaT Cells Against Oxidative DNA Damage.

PubMed

Yoo, Ok-Kyung; Choi, Bu Young; Park, Jin-Oh; Lee, Ji-Won; Park, Byoung-Kwon; Joo, Chul Gue; Heo, Hyo-Jung; Keum, Young-Sam

2016-03-01

Keratinocytes are constantly exposed to extracellular insults, such as ultraviolet B, toxic chemicals and mechanical stress, all of which can facilitate the aging of keratinocytes via the generation of intracellular reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a critical role in protecting keratinocytes against oxidants and xenobiotics by binding to the antioxidant response element (ARE), a cis-acting element existing in the promoter of most phase II cytoprotective genes. In the present study, we have attempted to find novel ethanol extract(s) of indigenous plants of Jeju island, Korea that can activate the Nrf2/ARE-dependent gene expression in human keratinocyte HaCaT cells. As a result, we identified that ethanol extract of Cirsium japonicum var. ussuriense Kitamura (ECJUK) elicited strong stimulatory effect on the ARE-dependent gene expression. Supporting this observation, we found that ECJUK induced the expression of Nrf2, hemoxygenase-1, and quinone oxidoreductase-1 and this event was correlated with Akt1 phosphorylation. We also found that ECJUK increased the intracellular reduced glutathione level and suppressed 12-O-tetradecanoylphorbol acetate-induced 8-hydroxyguanosine formation without affecting the overall viability. Collectively, our results provide evidence that ECJUK can protect against oxidative stress-mediated damages through the activation of Nrf2/ARE-dependent phase II cytoprotective gene expression.

Cyclo(His-Pro) promotes cytoprotection by activating Nrf2-mediated up-regulation of antioxidant defence

PubMed Central

Minelli, Alba; Conte, Carmela; Grottelli, Silvia; Bellezza, Maria; Cacciatore, Ivana; Bolaños, Juan P

2009-01-01

Hystidyl-proline [cyclo(His-Pro)] is an endogenous cyclic dipeptide produced by the cleavage of thyrotropin releasing hormone. Previous studies have shown that cyclo(His-Pro) protects against oxidative stress, although the underlying mechanism has remained elusive. Here, we addressed this issue and found that cyclo(His-Pro) triggered nuclear accumulation of NF-E2-related factor-2 (Nrf2), a transcription factor that up-regulates antioxidant-/electrophile-responsive element (ARE-EpRE)-related genes, in PC12 cells. Cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion caused by glutamate, rotenone, paraquat and β-amyloid treatment. Moreover, real-time PCR analyses revealed that cyclo(His-Pro) induced the expression of a number of ARE-related genes and protected cells against hydrogen peroxide-mediated apoptotic death. Furthermore, these effects were abolished by RNA interference-mediated Nrf2 knockdown. Finally, pharmacological inhibition of p-38 MAPK partially prevented both cyclo(His-Pro)-mediated Nrf2 activation and cellular protection. These results suggest that the signalling mechanism responsible for the cytoprotective actions of cyclo(His-Pro) would involve p-38 MAPK activation leading to Nrf2-mediated up-regulation of antioxidant cellular defence. PMID:18373731

SPBP Is a Sulforaphane Induced Transcriptional Coactivator of NRF2 Regulating Expression of the Autophagy Receptor p62/SQSTM1

PubMed Central

Darvekar, Sagar Ramesh; Elvenes, Julianne; Brenne, Hanne Britt; Johansen, Terje; Sjøttem, Eva

2014-01-01

Organisms exposed to oxidative stress respond by orchestrating a stress response to prevent further damage. Intracellular levels of antioxidant agents increase, and damaged components are removed by autophagy induction. The KEAP1-NRF2 signaling pathway is the main pathway responsible for cell defense against oxidative stress and for maintaining the cellular redox balance at physiological levels. Sulforaphane, an isothiocyanate derived from cruciferous vegetables, is a potent inducer of KEAP1-NRF2 signaling and antioxidant response element driven gene expression. In this study, we show that sulforaphane enhances the expression of the transcriptional coregulator SPBP. The expression curve peaks 6–8 hours post stimulation, and parallels the sulforaphane-induced expression of NRF2 and the autophagy receptor protein p62/SQSTM1. Reporter gene assays show that SPBP stimulates the expression of p62/SQSTM1 via ARE elements in the promoter region, and siRNA mediated knock down of SPBP significantly decreases the expression of p62/SQSTM1 and the formation of p62/SQSTM1 bodies in HeLa cells. Furthermore, SPBP siRNA reduces the sulforaphane induced expression of NRF2, and the expression of the autophagy marker protein LC3B. Both these proteins contain ARE-like elements in their promoter regions. Over-expressed SPBP and NRF2 acts synergistically on the p62/SQSTM1 promoter and colocalize in nuclear speckles in HeLa cells. Collectively, these results suggest that SPBP is a coactivator of NRF2, and hence may be important for securing enhanced and sustained expression of NRF2 induced genes such as proteins involved in selective autophagy. PMID:24416372

Ferulic Acid Orchestrates Anti-Oxidative Properties of Danggui Buxue Tang, an Ancient Herbal Decoction: Elucidation by Chemical Knock-Out Approach

PubMed Central

Gong, Amy G. W.; Huang, Vincent Y.; Wang, Huai Y.; Lin, Huang Q.; Dong, Tina T. X.; Tsim, Karl W. K.

2016-01-01

Ferulic acid, a phenolic acid derived mainly from a Chinese herb Angelica Sinensis Radix (ASR), was reported to reduce the formation of free radicals. Danggui Buxue Tang (DBT), a herbal decoction composing of Astragali Radix (AR) and ASR, has been utilized for more than 800 years in China having known anti-oxidative property. Ferulic acid is a major active ingredient in DBT; however, the role of ferulic acid within the herbal mixture has not been resolved. In order to elucidate the function of ferulic acid within this herbal decoction, a ferulic acid-depleted herbal decoction was created and named as DBTΔfa. The anti-oxidative properties of chemically modified DBT decoction were systemically compared in cultured H9C2 rat cardiomyoblast cell line. The application of DBT and DBTΔfa into the cultures showed functions in (i) decreasing the reactive oxygen species (ROS) formation, detected by laser confocal; (ii) increasing of the activation of Akt; (iii) increasing the transcriptional activity of anti-oxidant response element (ARE); and (iv) increasing the expressions of anti-oxidant enzymes, i.e. NQO1 and GCLM. In all scenario, the aforementioned anti-oxidative properties of DBTΔfa in H9C2 cells were significantly reduced, as compared to authentic DBT. Thus, ferulic acid could be an indispensable chemical in DBT to orchestrate multi-components of DBT as to achieve maximal anti-oxidative functions. PMID:27824860

Ferulic Acid Orchestrates Anti-Oxidative Properties of Danggui Buxue Tang, an Ancient Herbal Decoction: Elucidation by Chemical Knock-Out Approach.

PubMed

Gong, Amy G W; Huang, Vincent Y; Wang, Huai Y; Lin, Huang Q; Dong, Tina T X; Tsim, Karl W K

2016-01-01

Ferulic acid, a phenolic acid derived mainly from a Chinese herb Angelica Sinensis Radix (ASR), was reported to reduce the formation of free radicals. Danggui Buxue Tang (DBT), a herbal decoction composing of Astragali Radix (AR) and ASR, has been utilized for more than 800 years in China having known anti-oxidative property. Ferulic acid is a major active ingredient in DBT; however, the role of ferulic acid within the herbal mixture has not been resolved. In order to elucidate the function of ferulic acid within this herbal decoction, a ferulic acid-depleted herbal decoction was created and named as DBTΔfa. The anti-oxidative properties of chemically modified DBT decoction were systemically compared in cultured H9C2 rat cardiomyoblast cell line. The application of DBT and DBTΔfa into the cultures showed functions in (i) decreasing the reactive oxygen species (ROS) formation, detected by laser confocal; (ii) increasing of the activation of Akt; (iii) increasing the transcriptional activity of anti-oxidant response element (ARE); and (iv) increasing the expressions of anti-oxidant enzymes, i.e. NQO1 and GCLM. In all scenario, the aforementioned anti-oxidative properties of DBTΔfa in H9C2 cells were significantly reduced, as compared to authentic DBT. Thus, ferulic acid could be an indispensable chemical in DBT to orchestrate multi-components of DBT as to achieve maximal anti-oxidative functions.

Gravitropism of cut shoots is mediated by oxidative processes: A physiological and molecular study

NASA Astrophysics Data System (ADS)

Philosoph-Hadas, Sonia; Friedman, Haya; Meir, Shimon

2012-07-01

The signal transduction events occurring during shoot gravitropism are mediated through amyloplasts sedimentation, reorientation of actin filaments in the endodermis, and differential changes in level and action of auxin, associated with differential growth leading to shoot curvature. Since increase in reactive oxygen species (ROS) was shown to be associated with growth, we examined the possible use of antioxidants in controlling the gravitropic response, via their interaction with events preceding shoot bending. Reoriented snapdragon (Antirrhinum majus L.) spikes and tomato (Solanum lycopersicum cv. MicroTom) shoots showed a visual upward bending after a lag period of 3 or 5 h, respectively, which was inhibited by the antioxidants N-acetyl-cysteine (NAC) and reduced glutathione (GSH). This suggests the involvement of oxidative reactions in the process. The two antioxidants prevented the sedimentation of amyloplasts to the bottom of the endodermis cells following 0.5-5 h of snapdragon shoot reorientation, suggesting that oxidative reactions are involved already at a very early signal perception stage prior to the visual bending. In addition, a differential distribution in favor of the lower shoot side of various oxidative elements, including H2O2 concentrations and activity of the NADPH-oxidase enzyme, was observed during reorientation of snapdragon spikes. Application of the two antioxidants reduced the levels of these elements and abolished their differential distribution across the shoot. On the other hand, the activity of the antioxidative enzyme, superoxide dismutase (SOD), which was not differentially distributed across the shoot, increased significantly following application of the two antioxidants. The auxin redistribution in reoriented shoots was analyzed using transgenic tomato plants expressing the GUS reporter gene under the Aux/IAA4 promoter (a generous gift of M. Bouzayen, France). GUS response, detected in control shoots 4 h after their reorientation in favor of the lower shoot side was completely eliminated in the NAC-treated shoots, in which the bending response was inhibited. These results suggest that the gravitropic-induced asymmetric auxin redistribution precedes shoot bending, and NAC inhibits this response by abolishing the auxin gradient across the shoot. Our microarray analysis of tomato shoots, using the Affymetrix Tomato GeneChip, revealed differential changes in expression of 266 genes, occurring during the initial 0.5-5 h of shoot reorientation prior to bending. The differential changes in expression of auxin-related genes in favor of the lower shoot side occurred already following 0.5 h of reorientation, while those of cell wall-related genes, associated with shoot bending, occurred only 3 h following shoot reorientation. Among the identified genes, 11 genes were related to auxin, and 36 genes were associated with oxidative processes, demonstrating the involvement of ROS in early events of shoot gravitropism. Taken together, our results suggest that ROS mediate the early gravity-induced amyloplast sedimentation required for signal perception, as well as the lateral auxin movement across the shoot, which is necessary for the auxin asymmetric distribution leading to shoot upward bending.

Association of Serum Concentration of Different Trace Elements with Biomarkers of Systemic Oxidant Status in Dairy Cattle.

PubMed

Abuelo, Angel; Hernandez, Joaquín; Alves-Nores, Víctor; Benedito, José L; Castillo, Cristina

2016-12-01

There has been some recent criticism about the reliability of the assays commonly used to measure oxidant status in cattle, because some recent publications suggested that the concentration of different trace elements influences the results of these assays. The aim of this study was to test the correlation in 502 bovine serum samples between the concentration of several trace elements (Br, Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se, Sr, V and Zn) and markers of oxidant status (reactive oxygen species (ROS) and total serum antioxidant capacity (SAC)). The Oxidative Stress index (OSi) was also calculated as ROS/SAC. Some significant correlations were found, although weak (|ρ| < 0.50). Therefore, the relationships observed might be attributed to the different pro- and antioxidant effect of the different elements rather than to the assays detecting these elements instead of the oxidised molecules or total antioxidant potential, respectively. The OSi was poorly correlated (|ρ| ≤ 0.36) with the concentration of the studied trace elements, and therefore, its use is recommended to assess shifts in the systemic redox balance.

Physical activity does not influence the effect of antioxidant supplementation at nutritional doses on the incidence of impaired fasting glucose: a 7.5 year post-hoc analysis from the SU.VI.MAX study.

PubMed

Fezeu, L; Henegar, A; Kesse-Guyot, E; Julia, C; Galan, P; Hercberg, S; Ristow, M; Czernichow, S

2010-10-01

Supplementation with high doses of antioxidant vitamins prevents the insulin-sensitizing effects of physical exercise. However, little is known whether antioxidant supplementation affects the incidence of impaired fasting glucose (IFG). Data from 8938 subjects included in a randomized controlled trial on supplementation with antioxidants vitamins and trace elements at nutritional doses (SU.VI.MAX) were used to examine the effects of antioxidants on incident IFG after 7.5 years of follow-up, with and without stratification for daily physical exercise. The odds-ratio (95% CI) for developing an IFG among study participants receiving antioxidant supplementation was 1.34 (0.90-1.97) (p=0.33), in comparison to placebo. This risk did not vary significantly according to physical activity level (p for homogeneity=0.10). Supplementation with trace elements and antioxidants at nutritional doses apparently does not affect the incidence of IFG irrespective of self-reported physical exercise habits. © Georg Thieme Verlag KG Stuttgart · New York.

Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of antioxidant defenses.

PubMed

Schriner, Samuel E; Avanesian, Agnesa; Liu, Yanxia; Luesch, Hendrik; Jafari, Mahtab

2009-09-01

Rhodiola rosea root has been long used in traditional medical systems in Europe and Asia as an adaptogen to increase an organism's resistance to physical stress. Recent research has demonstrated its ability to improve mental and physical stamina, to improve mood, and to help alleviate high-altitude sickness. We have also recently found that R. rosea is able to extend the life span of Drosophila melanogaster. The mode of action of R. rosea is currently unknown; it has been suggested by some to act as an antioxidant, whereas others have argued that it may actually be a pro-oxidant and act through a hormetic mechanism. We found that R. rosea supplementation could protect cultured cells against ultraviolet light, paraquat, and H(2)O(2). However, it did not alter the levels of the major antioxidant defenses nor did it markedly activate the antioxidant response element or modulate heme-oxygenase-1 expression levels at relevant concentrations. In addition, R. rosea extract was not able to significantly degrade H(2)O(2) in vitro. These results suggest that in human cultured cells R. rosea does not act as an antioxidant and that its mode of action cannot be sufficiently explained through a pro-oxidant hormetic mechanism.

Influence of Heavy Metal Stress on Antioxidant Status and DNA Damage in Urtica dioica

PubMed Central

Kadifkova Panovska, Tatjana; Bačeva, Katerina; Stafilov, Trajče

2013-01-01

Heavy metals have the potential to interact and induce several stress responses in the plants; thus, effects of heavy metal stress on DNA damages and total antioxidants level in Urtica dioica leaves and stems were investigated. The samples are sampled from areas with different metal exposition. Metal content was analyzed by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES), for total antioxidants level assessment the Ferric-Reducing Antioxidant Power (FRAP) assay was used, and genomic DNA isolation from frozen plant samples was performed to obtain DNA fingerprints of investigated plant. It was found that heavy metal contents in stems generally changed synchronously with those in leaves of the plant, and extraneous metals led to imbalance of mineral nutrient elements. DNA damages were investigated by Random Amplified Polymorphic DNA (RAPD) technique, and the results demonstrated that the samples exposed to metals yielded a large number of new fragments (total 12) in comparison with the control sample. This study showed that DNA stability is highly affected by metal pollution which was identified by RAPD markers. Results suggested that heavy metal stress influences antioxidant status and also induces DNA damages in U. dioica which may help to understand the mechanisms of metals genotoxicity. PMID:23862140

2',5'-Dihydroxychalcone-induced glutathione is mediated by oxidative stress and kinase signaling pathways.

PubMed

Kachadourian, Remy; Pugazhenthi, Subbiah; Velmurugan, Kalpana; Backos, Donald S; Franklin, Christopher C; McCord, Joe M; Day, Brian J

2011-09-15

Hydroxychalcones are naturally occurring compounds that continue to attract considerable interest because of their anti-inflammatory and antiangiogenic properties. They have been reported to inhibit the synthesis of the inducible nitric oxide synthase and to induce the expression of heme oxygenase-1. This study examines the mechanisms by which 2',5'-dihydroxychalcone (2',5'-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant-response elements (MCF-7/AREc32). The 2',5'-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP(5+), suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2',5'-DHC treatment induced phosphorylation of the c-Jun N-terminal kinase (JNK) pathway, which was also inhibited by MnTDE-1,3-IP(5+). These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, whereas 2',5'-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, cotreatment with MnTDE-1,3-IP(5+) did not decrease 2',5'-DHC-induced Nrf2/ARE activity, showing that this pathway is not dependent on ROS. Moreover, pharmacological inhibitors of mitogen-activated protein kinase (MAPK) pathways showed a role for JNK and p38MAPK in mediating the 2',5'-DHC-induced Nrf2 response. These findings suggest that the 2',5'-DHC-induced increase in GSH levels results from a combination of ROS-dependent and ROS-independent pathways. Copyright © 2011 Elsevier Inc. All rights reserved.

Hepatoprotective effect of grape seed oil against carbon tetrachloride induced oxidative stress in liver of γ-irradiated rat.

PubMed

Ismail, Amel F M; Salem, Asmaa A M; Eassawy, Mamdouh M T

2016-07-01

Carbon tetrachloride (CCl4) and ionizing radiation are well known environmental pollutants that generate free radicals and induce oxidative stress. The liver is the primary and major target organ responsible for the metabolism of drugs, toxic chemicals and affected by irradiation. This study investigated the effect of grape seed oil (GSO) on acute liver injury induced by carbon tetrachloride (CCl4) in γ-irradiated rats (7Gy). CCl4-intoxicated rats exhibited an elevation of ALT, AST activities, IL-6 and TNF-α level in the serum. Further, the levels of MDA, NO, NF-κB and the gene expression of CYP2E1, iNOS and Caspase-3 were increased, and SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Furthermore, silent information regulator protein 1 (SIRT1) gene expression was markedly down-regulated. Additionally, alterations of the trace elements; copper, manganese, zinc and DNA fragmentation was observed in the hepatic tissues of the intoxicated group. These effects were augmented in CCl4-intoxicated-γ-irradiated rats. However, the administration of GSO ameliorated these parameters. GSO exhibit protective effects on CCl4 induced acute liver injury in γ-irradiated rats that could be attributed to its potent antioxidant, anti-inflammatory and anti-apoptotic activities. The induction of the antioxidant enzymes activities, down-regulation of the CYP2E1, iNOS, Caspase-3 and NF-κB expression, up-regulation of the trace elements concentration levels and activation of SIRT1 gene expression are responsible for the improvement of the antioxidant and anti-inflammatory status in the hepatic tissues and could be claimed to be the hepatoprotective mechanism of GSO. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia.

PubMed

Lee, Yu Young; Lee, Eun-Jung; Park, Jin-Sun; Jang, Se-Eun; Kim, Dong-Hyun; Kim, Hee-Sun

2016-06-01

Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, but further study is necessary for elucidating the detailed mechanisms of these effects. In this study, we examined the anti-inflammatory effect of tangeretin in lipopolysaccharide (LPS)-stimulated microglia. We first observed that tangeretin inhibited LPS-induced production of nitric oxide, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, as well as LPS-induced mRNA expression of inducible nitric oxide synthases and cytokines. Additionally, we found that the activities, mRNA levels, and protein levels of matrix metalloproteinase (MMP)-3 and MMP-8 were inhibited, while the expression of tissue inhibitor of metalloproteinase-2 was enhanced by tangeretin in LPS-stimulated microglia. Further mechanistic study showed that tangeretin suppressed LPS-induced phosphorylation of mitogen-activated protein kinases and Akt. Also, tangeretin inhibited nuclear factor-κB by upregulating sirtuin 1 and 5'-adenosine monophosphate-activated protein kinase. We further demonstrated the antioxidant effect of tangeretin by showing that tangeretin inhibited reactive oxygen species production and p47(phox) phosphorylation, while enhancing the expression of heme oxygenase-1 and the DNA binding activity of nuclear factor-erythroid 2-related factor 2 to the antioxidant response element in LPS-stimulated microglia. Taken together, the results of the present study demonstrate that tangeretin possesses a potent anti-inflammatory and antioxidant effect in microglia.

Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Hae-Ryung, E-mail: heaven@umich.edu; Loch-Caruso, Rita

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20 μM BDE-47more » for 24 h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20 μM BDE-47 for 24 h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. - Highlights: • BDE-47 stimulated ARE reporter activity and GSH production. • BDE-47 resulted in differential expression of redox-sensitive genes. • Nrf2 inducers upregulated Nrf2-mediated oxidative stress responses. • Nrf2 inducers reduced BDE-47-stimulated IL-6 release and NF-κB activity.« less

Nrf2: bane or blessing in cancer?

PubMed

Xiang, MingJun; Namani, Akhileshwar; Wu, ShiJun; Wang, XiaoLi

2014-08-01

The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element pathway serves a major function in endogenous cytoprotection in normal cells. Nrf2 is a transcription factor that mainly regulates the expression of a wide array of genes that produce the antioxidants and other proteins responsible for the detoxification of xenobiotics and reactive oxygen species. Nrf2 mediates the chemoprevention of cancer in normal cells. Growing body of evidence suggests that Nrf2 is not only involved in the chemoprevention of normal cells but also promotes the growth of cancer cells. However, the mechanism underlying the function of Nrf2 in oncogenesis and tumor protection in cancer cells remains unclear and thus requires further study. This review aims to rationalize the existing functions of Nrf2 in chemoprevention and tumorigenesis, as well as the somatic mutations of Nrf2 and Keap1 in cancer and Nrf2 cross talk with miRNAs. This review also discusses the future challenges in Nrf2 research.

Elemental Zinc Is Inversely Associated with C-Reactive Protein and Oxidative Stress in Chronic Liver Disease.

PubMed

Uddin, Md Giash; Hossain, Mohammad Salim; Rahman, Md Atiqur; Uddin, A H M Mazbah; Bhuiyan, Md Shafiullah

2017-08-01

Chronic liver disease (CLD) is associated with the destruction of liver parenchyma cell. It is the main cause of morbidity and mortality in most of the developed countries. Oxidative stress and altered levels of different trace elements in serum have been documented for different diseases including inflammation and many liver diseases. This study aims to evaluate the serum level of malondialdehyde (MDA), nitric oxide (NO), antioxidant vitamin C, C-reactive protein (CRP), and zinc (Zn) in CLD patients and to establish a correlation among the study parameters with the severity of inflammatory conditions of CLD. In this study, CLD patients and healthy volunteers were recruited. Total cholesterol and triglyceride were determined by colorimeter using enzymatic method. Serum non-enzymatic antioxidant vitamin C, reactive oxygen species nitric oxide (NO), and malondialdehyde (MDA) were determined by UV-spectrophotometric method. Trace element (Zn) levels were determined by graphite furnace atomic absorption spectroscopy. Independent sample t test and Pearson's correlation test were performed for statistical analysis using the statistical software package SPSS, Version 20. Studies showed that the MDA (p < 0.001), NO (p < 0.001), and CRP levels were significantly higher in CLD patients than in control subjects. The antioxidant vitamin C (p < 0.001) and trace element zinc (p < 0.001) were comparatively lower in the CLD patients than in control subjects. Elemental Zn showed an inverse relationship with MDA, NO, and CRP but positively correlated with antioxidant capacity, whereas MDA showed a positive correlation with CRP level. Thus, we conclude that attenuated level of Zn and antioxidant in serum play an important role in the inflammatory status of CLD patients by elevating the concentration of MDA, NO, and CRP.

Effect of lipid peroxidation, antioxidants, macro minerals and trace elements on eczema.

PubMed

Amin, Mohammad Nurul; Liza, Kaniz Fatema; Sarwar, Md Shahid; Ahmed, Jamiuddin; Adnan, Md Tareek; Chowdhury, Manjurul Islam; Hossain, Mohammad Zahid; Islam, Mohammad Safiqul

2015-09-01

The exact etiology and pathogenesis of eczema are not yet fully understood, although different factors are considered as pathogenic mechanisms in the development of eczema. Our study was designed to determine extent of serum lipid peroxidation, antioxidants, macro minerals and trace elements in patients with eczema, and thereby, find any pathophysiological correlation. The study was conducted as a case-control study with 65 eczema patients as cases and 65 normal healthy individuals as controls. Lipid peroxidation was assessed by measuring the serum level of malondialdehyde (MDA). Antioxidants- vitamin A and E concentration was determined by RP-HPLC method whereas vitamin C was evaluated for serum ascorbic acid by UV spectrophotometric method. Serum macro minerals (Na, K, Ca) and trace elements (Zn, Fe) were determined by Atomic Absorption Spectroscopy (AAS). This study found significantly higher level of MDA (p < 0.001) and lower level of antioxidants (p < 0.05) in patients in comparison to the control subjects. Analysis of serum macro minerals (Na, K and Ca) and trace elements (Zn, Fe) found that the mean values of Na, K, Ca, Zn and Fe were 2771.60 ± 75.64, 66.33 ± 3.03, 48.41 ± 2.50, 0.30 ± 0.02 and 0.29 ± 0.009 mg/L for the patient group and 3284.81 ± 34.51, 162.18 ± 3.72, 87.66 ± 2.10, 0.75 ± 0.06 and 0.87 ± 0.06 mg/L for the control group, accordingly. There was a significant difference for all the minerals between the patients and controls (p < 0.001). This study suggests a strong association between the pathogenesis of eczema with the elevated level of MDA and depleted level of antioxidants, macro minerals, and trace elements.

Elevated serum MDA and depleted non-enzymatic antioxidants, macro-minerals and trace elements are associated with bipolar disorder.

PubMed

Chowdhury, Manjurul Islam; Hasan, Maimuna; Islam, Mohammad Safiqul; Sarwar, Md Shahid; Amin, Mohammad Nurul; Uddin, S M Naim; Rahaman, Md Zahedur; Banik, Sujan; Hussain, Md Saddam; Yokota, Kazushige; Hasnat, Abul

2017-01-01

Genetic and neurobiological factors are considered to be the major causes of mood and mental disorders. However, over the past few years, increased levels of serum malondialdehyde and altered levels of various non-enzymatic antioxidants and essential minerals involved in abnormal functional activity have been identified as major contributing factors to the pathogenesis of several neurological disorders. The aim of this study was to determine the levels of the serum lipid peroxidation product malondialdehyde (MDA), antioxidants (vitamin A, E and C), macro-minerals (calcium, potassium and sodium) and trace elements (zinc, iron and selenium) in patients with bipolar disorder and to explore their role in disease progression. This is a prospective case-control study that evaluated 55 patients with bipolar disorder and 55 healthy volunteers matched by age and sex. Serum MDA levels were determined by UV spectrophotometry as a marker of lipid peroxidation. RP-HPLC was employed to investigate the serum vitamin A and E concentrations, whereas UV spectrophotometry was used to quantify levels of vitamin C. Serum macro-minerals and trace elements were analyzed by atomic absorption spectroscopy (AAS). Statistical analysis was performed with independent sample t-tests and Pearson's correlation test. We found significantly higher concentrations of MDA (p<0.05) and significantly lower concentrations of antioxidants (vitamin A, E and C) (p<0.05) in the patient group compared with control group. Regarding trace elements and macro-minerals, lower concentrations of zinc, calcium, iron, selenium, sodium and potassium were found in the patient group compared with control subjects (p<0.05). Our study suggests that high serum MDA concentrations and low serum concentrations of antioxidants, macro-minerals and trace elements are strongly associated with bipolar disorder. Copyright © 2016 Elsevier GmbH. All rights reserved.

Dimethyl fumarate modulation of immune and antioxidant responses: application to HIV therapy

PubMed Central

Gill, Alexander J.; Kolson, Dennis L.

2013-01-01

The persistence of chronic immune activation and oxidative stress in human immunodeficiency virus (HIV)-infected, antiretroviral drug-treated individuals are major obstacles to fully preventing HIV disease progression. The immune modulator and antioxidant dimethyl fumarate (DMF) is effective in treating immune-mediated diseases and it also has potential applications to limiting HIV disease progression. Among the relevant effects of DMF and its active metabolite monomethyl fumarate (MMF) are induction of a Th1 → Th2 lymphocyte shift, inhibition of pro-inflammatory cytokine signaling, inhibition of NF-κB nuclear translocation, inhibition of dendritic cell maturation, suppression of lymphocyte and endothelial cell adhesion molecule expression, and induction of the Nrf2-dependent antioxidant response element (ARE) and effector genes. Associated with these effects are reduced lymphocyte and monocyte infiltration into psoriatic skin lesions in humans and immune-mediated demyelinating brain lesions in rodents, which confirms potent systemic and central nervous system (CNS) effects. In addition, DMF and MMF limit HIV infection in macrophages in vitro, albeit by unknown mechanisms. Finally, DMF and MMF also suppress neurotoxin production from HIV-infected macrophages, which drives CNS neurodegeneration. Thus, DMF might protect against systemic and CNS complications in HIV infection through its effective suppression of immune activation, oxidative stress, HIV replication, and macrophage-associated neuronal injury. PMID:23971529

Clinical Effects of a Dietary Antioxidant Silicate Supplement, Microhydrin((R)), on Cardiovascular Responses to Exercise.

PubMed

Purdy Lloyd, Kimberly L.; Wasmund, Wendy; Smith, Leonard; Raven, Peter B.

2001-01-01

Amorphous silicate minerals, often described as rock flour, were once common in natural water sources and abundant in glacial stream waters. Not only do the silica mineral particles bond water and other elements for transport; they also can be adsorbed with reduced hydrogen, which releases electrons, providing antioxidant or reducing potential to surrounding fluids. The purpose of this investigation was to examine the cardiovascular responses during exercise after consumption of a dietary silicate mineral antioxidant supplement, Microhydrin((R)) (Royal BodyCare, Inc., Irving, TX). A clinical trial incorporating a double-blind, placebo-controlled, crossover experimental design was employed. Subjects received either active agent or placebo, four capsules per day, for 7 days before the trial. The trial evaluated six exercise bicycle-trained subjects performing a 40-km bicycling time trial. Ratings of perceived exertion and measurements of oxygen uptake, heart rate, performance workload, and preexercise and postexercise blood lactate concentrations were obtained. Although there were no differences (P >/=.05) in work performed, heart rate, oxygen uptake, and ratings of perceived exertion during the time trial, the postexercise blood lactate concentrations were significantly lower (P

The effect of Mastin® on expression of Nrf2 in the rat heart with subtotally nephrectomy chronic Kidney disease model

NASA Astrophysics Data System (ADS)

Nathania, J.; Soetikno, V.

2017-08-01

Chronic kidney disease (CKD) is increasingly prevalent in Indonesia and worldwide. One of the major causes of morbidity and mortality in CKD is the complication of cardiovascular disease. Mastin® is a supplement that is locally produced in Indonesia and is made from extract of mangosteen pericarp, which is reported to have antioxidative, anti-inflammatory, and antitumor properties. The present study aimed to investigate whether Mastin® could improve antioxidant responses in the rat heart during CKD by measuring the expression of nuclear factor erythroid-2-related factor (Nrf)2, a master regulator of antioxidant response elements. RNA was extracted from the heart tissue of three groups of rats: a normal group, a nephrectomy group, and a nephrectomy with Mastin® group. Two-step real-time RT-PCR was then conducted to calculate the relative expression of the Nrf2 gene. Nrf2 expression was markedly decreased in the nephrectomy group vs the normal group, but slightly increas ed in the nephrectomy with Mastin® group vs the nephrectomy group. CKD resulted in impaired activation of the Nrf2 pathway in the rat heart. Although the administration of Mastin® slightly increased Nrf2 expression, it was not enough to confer cardioprotective effects through the Nrf2 pathway.

A microfluidic device for evaluating the dynamics of the metabolism-dependent antioxidant activity of nutrients.

PubMed

Lee, Jungwoo; Choi, Jong-ryul; Ha, Sang Keun; Choi, Inwook; Lee, Seung Hwan; Kim, Donghyun; Choi, Nakwon; Sung, Jong Hwan

2014-08-21

Various food components are known for their health-promoting effects. However, their biochemical effects are generally evaluated in vitro, and their actual in vivo effect can vary significantly, depending on their metabolic profiles. To evaluate the effect of the liver metabolism on the antioxidant activity, we have developed a two-compartment microfluidic system that integrates the dynamics of liver metabolism and the subsequent antioxidant activity of food components. In the first compartment of the device, human liver enzyme fractions were immobilized inside a poly(ethylene glycol) diacrylate (PEGDA) hydrogel to mimic the liver metabolism. The radical scavenging activity was evaluated by the change of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) absorbance in the second compartment. Reaction engineering and fluid mechanics principles were used to develop a simplified analytical model and a more complex finite element model, which were used to design the chip and determine the optimal flow conditions. For real-time measurements of the reaction on a chip, we developed a custom-made photospectrometer system with an LED light source. The developed microfluidic system showed a linear and dose-dependent antioxidant activity in response to increasing concentration of flavonoid. We also compared the antioxidant activity of flavonoid after various liver metabolic reactions. This microfluidic system can serve as a novel in vitro platform for predicting the antioxidant activity of various food components in a more physiologically realistic manner, as well as for studying the mechanism of action of such food components.

2′,5′-Dihydroxychalcone-induced glutathione is mediated by oxidative stress and kinase signaling pathways

PubMed Central

Kachadourian, Remy; Pugazhenthi, Subbiah; Velmurugan, Kalpana; Backos, Donald S.; Franklin, Christopher C.; McCord, Joe M.; Day, Brian J.

2011-01-01

Hydroxychalcones are naturally occurring compounds that continue to attract considerable interest due to their anti-inflammatory and anti-angiogenic properties. They have been reported to inhibit the synthesis of the inducible nitric oxide (NO) synthase and to induce the expression of heme oxygenase-1 (HO-1). This study examines the mechanisms by which 2′,5′-dihydroxychalcone (2′,5′-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant response elements (MCF-7/AREc32). 2′,5′-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP5+, suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2′,5′-DHC treatment induced the phosphorylation of c-Jun N-terminal kinase (JNK) pathway that was also inhibited by MnTDE-1,3-IP5+. These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, while 2′,5′-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, co-treatment with MnTDE-1,3-IP5+ did not decrease 2′,5′-DHC-induced Nrf2/ARE activity, showing that this pathway is not dependent on ROS. Moreover, pharmacological inhibitors of mitogen-activated protein (MAP) kinase pathways showed a role for JNK and p38MAPK in mediating the 2′,5′-DHC-induced Nrf2 response. These findings suggest that the 2′,5′-DHC-induced increase in GSH levels results from a combination of ROS-dependent and ROS-independent pathways. PMID:21712085

Reduction of facial wrinkles by hydrolyzed water-soluble egg membrane associated with reduction of free radical stress and support of matrix production by dermal fibroblasts

PubMed Central

Jensen, Gitte S; Shah, Bijal; Holtz, Robert; Patel, Ashok; Lo, Donald C

2016-01-01

Objective The aim of this study was to evaluate the effects of water-soluble egg membrane (WSEM) on wrinkle reduction in a clinical pilot study and to elucidate specific mechanisms of action using primary human immune and dermal cell-based bioassays. Methods To evaluate the effects of topical application of WSEM (8%) on human skin, an open-label 8-week study was performed involving 20 healthy females between the age of 45 years and 65 years. High-resolution photography and digital analysis were used to evaluate the wrinkle depth in the facial skin areas beside the eye (crow’s feet). WSEM was tested for total antioxidant capacity and effects on the formation of reactive oxygen species by human polymorphonuclear cells. Human keratinocytes (HaCaT cells) were used for quantitative polymerase chain reaction analysis of the antioxidant response element genes Nqo1, Gclm, Gclc, and Hmox1. Evaluation of effects on human primary dermal fibroblasts in vitro included cellular viability and production of the matrix components collagen and elastin. Results Topical use of a WSEM-containing facial cream for 8 weeks resulted in a significant reduction of wrinkle depth (P<0.05). WSEM contained antioxidants and reduced the formation of reactive oxygen species by inflammatory cells in vitro. Despite lack of a quantifiable effect on Nrf2, WSEM induced the gene expression of downstream Nqo1, Gclm, Gclc, and Hmox1 in human keratinocytes. Human dermal fibroblasts treated with WSEM produced more collagen and elastin than untreated cells or cells treated with dbcAMP control. The increase in collagen production was statistically significant (P<0.05). Conclusion The topical use of WSEM on facial skin significantly reduced the wrinkle depth. The underlying mechanisms of this effect may be related to protection from free radical damage at the cellular level and induction of several antioxidant response elements, combined with stimulation of human dermal fibroblasts to secrete high levels of matrix components. PMID:27789968

The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: Aging and anti-aging.

PubMed

Luo, Cheng; Urgard, Egon; Vooder, Tõnu; Metspalu, Andres

2011-08-01

Oxidative stress and inflammation are constant features of many chronic diseases and complications, and have been linked to carcinogenesis. Cyclooxygenase 2 (COX-2), a rate-limiting enzyme for the synthesis of prostaglandins, plays important roles in physiology and pathology, but has been a source of controversy within the scientific and clinical community. However, recent work has shown that nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against oxidative stress. Furthermore, COX-2-dependent electrophile oxo-derivative (EFOX) molecules have been shown to act as anti-inflammatory mediators via activation of the Nrf2-dependent antioxidant response element (ARE). These studies have provided more insight into COX-2-mediated events. The function of all tissues, especially epithelial and endothelial tissues, declines with age, leading to the production of reactive oxygen species (ROS). COX-2 expression increases with aging in most tissues, due in part to ROS, chemical reactions, physical shearing, and dietary molecules. Here we discuss new findings related to COX-2 inflammatory and anti-inflammatory responses. Taken together, we hypothesize that COX-2 levels increase during the aging process because increasing levels of ROSs necessitate the involvement of COX-2-dependent EFOXs for anti-inflammation and Nrf2/ARE signaling for antioxidation. We also propose that COX-2 may act as an intrinsic biological aging clock due to its role in balancing inflammatory and anti-inflammatory responses. Copyright © 2011 Elsevier Ltd. All rights reserved.

Partial contribution of the Keap1–Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shinkai, Yasuhiro; Kimura, Tomoki; Itagaki, Ayaka

Cadmium is an environmental electrophile that modifies protein reactive thiols such as Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of nuclear factor-erythroid 2-related factor 2 (Nrf2). In the present study, we investigated a role of the Keap1–Nrf2 system in cellular response to cadmium in vascular endothelial cells. Exposure of bovine aortic endothelial cells to cadmium resulted in modification of Keap1 and Nrf2 activation, thereby up-regulating not only its typical downstream proteins but also metallothionein-1/2. Experiments with siRNA-mediated knockdown of Nrf2 or Keap1 supported participation of the Keap1–Nrf2 system in the modulation of metallothionein-1/2 expression. Furthermore, chromatin immunoprecipitation assay showedmore » that Nrf2 was recruited to the antioxidant response element of the promoter region of the bovine metallothionein-2 gene in the presence of cadmium. These results suggest that the transcription factor Nrf2 plays, at least in part, a role in the changes in metallothionein expression mediated by exposure to cadmium. - Highlights: • Role of the Keap1–Nrf2 system in cellular response to cadmium was examined. • We used bovine aortic endothelial cells as a model of the vascular endothelium. • Exposure of cells to cadmium resulted in modification of Keap1 and Nrf2 activation. • Keap1–Nrf2 system participated in the modulation of metallothionein-1/2 expression. • Nrf2 was recruited to the antioxidant response element of MT2 promoter region.« less

NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.

PubMed

Ziros, Panos G; Habeos, Ioannis G; Chartoumpekis, Dionysios V; Ntalampyra, Eleni; Somm, Emmanuel; Renaud, Cédric O; Bongiovanni, Massimo; Trougakos, Ioannis P; Yamamoto, Masayuki; Kensler, Thomas W; Santisteban, Pilar; Carrasco, Nancy; Ris-Stalpers, Carrie; Amendola, Elena; Liao, Xiao-Hui; Rossich, Luciano; Thomasz, Lisa; Juvenal, Guillermo J; Refetoff, Samuel; Sykiotis, Gerasimos P

2018-06-01

The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated by cell-autonomous regulation of Tg gene expression by Nrf2 via its direct binding to two evolutionarily conserved antioxidant response elements in an upstream enhancer. Yet, despite upregulating Tg levels, Nrf2 limits Tg iodination both under basal conditions and in response to excess iodide. Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide.

Analysis of the influences of short-term levosimendan exposure on oxidant/antioxidant status and trace-element levels in the physiological status of the thoracic aorta of rats.

PubMed

Aydin, Cemalettin; Ay, Yasin; Basel, Halil; Kavak, Servet; Inan, Bekir; Bektaş, Hava; Gümrükçüoğlu, Hasan Ali; Ekim, Hasan; Demir, Halit

2012-12-01

The objective of this study was to evaluate the effect of levosimendan (chemical formula C₁₄H₁₂N₆O) exposure on oxidant/antioxidant status and trace-element levels in the thoracic aorta of rats. Eighteen male Wistar albino rats were randomly divided into two groups of eight animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.5 % dextrose was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their thoracic aortae were harvested for determination of changes in tissue oxidant/antioxidant status and trace-element levels. The animals in both groups were killed 72 h after levosimendan exposure, and thoracic aortae were harvested for determination of the lipid peroxidation product MDA and antioxidant GSH levels and the activities of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA, GSH and CAT enzyme levels increased in thoracic aortae of rats after levosimendan administration. SOD and CA enzyme activities and the level of antioxidant GSH decreased in thoracic aortae of rats after levosimendan treatment. Pb, Cd and Fe levels of thoracic aortae were significantly higher (P < 0.001) and Mg, Mn, Zn and Cu were significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that short-term levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in thoracic aortae of levosimendan-treated rats. It also causes a decrease or increase in many mineral levels of the thoracic aorta, which is an undesirable condition for normal pharmacological function.

Activation of AMPK stimulates heme oxygenase-1 gene expression and human endothelial cell survival

PubMed Central

Liu, Xiao-ming; Peyton, Kelly J.; Shebib, Ahmad R.; Wang, Hong; Korthuis, Ronald J.

2011-01-01

The present study determined whether AMP-activated protein kinase (AMPK) regulates heme oxygenase (HO)-1 gene expression in endothelial cells (ECs) and if HO-1 contributes to the biological actions of this kinase. Treatment of human ECs with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) stimulated a concentration- and time-dependent increase in HO-1 protein and mRNA expression that was associated with a prominent increase in nuclear factor-erythroid 2-related factor 2 (Nrf2) protein. Induction of HO-1 was also observed in rat carotid arteries after the in vivo application of AICAR. Induction of HO-1 by AICAR was blocked by the AMPK inhibitor compound C, the adenosine kinase inhibitor 5′-iodotubercidin, and by silencing AMPK-α1/2 and was mimicked by the AMPK activator A-769662 and by infecting ECs with an adenovirus expressing constitutively active AMPK-α1. AICAR also induced a significant rise in HO-1 promoter activity that was abolished by mutating the antioxidant responsive elements of the HO-1 promoter or by the overexpression of dominant negative Nrf2. Finally, activation of AMPK inhibited cytokine-mediated EC death, and this was prevented by the HO inhibitor tin protoporphyrin-IX or by silencing HO-1 expression. In conclusion, AMPK stimulates HO-1 gene expression in human ECs via the Nrf2/antioxidant responsive element signaling pathway. The induction of HO-1 mediates the antiapoptotic effect of AMPK, and this may provide an important adaptive response to preserve EC viability during periods of metabolic stress. PMID:21037234

Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway.

PubMed

Mascuch, Samantha J; Boudreau, Paul D; Carland, Tristan M; Pierce, N Tessa; Olson, Joshua; Hensler, Mary E; Choi, Hyukjae; Campanale, Joseph; Hamdoun, Amro; Nizet, Victor; Gerwick, William H; Gaasterland, Teresa; Gerwick, Lena

2018-03-23

The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-l-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keap1. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.

Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats.

PubMed

Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

2006-02-16

Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.

Growth at elevated ozone or elevated carbon dioxide concentration alters antioxidant capacity and response to acute oxidative stress in soybean (Glycine max)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillespie, K.M.; Rogers, A.; Ainsworth, E. A.

2011-01-31

Soybeans (Glycine max Merr.) were grown at elevated carbon dioxide concentration ([CO{sub 2}]) or chronic elevated ozone concentration ([O{sub 3}]; 90 ppb), and then exposed to an acute O{sub 3} stress (200 ppb for 4 h) in order to test the hypothesis that the atmospheric environment alters the total antioxidant capacity of plants, and their capacity to respond to an acute oxidative stress. Total antioxidant metabolism, antioxidant enzyme activity, and antioxidant transcript abundance were characterized before, immediately after, and during recovery from the acute O{sub 3} treatment. Growth at chronic elevated [O{sub 3}] increased the total antioxidant capacity of plants,more » while growth at elevated [CO{sub 2}] decreased the total antioxidant capacity. Changes in total antioxidant capacity were matched by changes in ascorbate content, but not phenolic content. The growth environment significantly altered the pattern of antioxidant transcript and enzyme response to the acute O{sub 3} stress. Following the acute oxidative stress, there was an immediate transcriptional reprogramming that allowed for maintained or increased antioxidant enzyme activities in plants grown at elevated [O{sub 3}]. Growth at elevated [CO{sub 2}] appeared to increase the response of antioxidant enzymes to acute oxidative stress, but dampened and delayed the transcriptional response. These results provide evidence that the growth environment alters the antioxidant system, the immediate response to an acute oxidative stress, and the timing over which plants return to initial antioxidant levels. The results also indicate that future elevated [CO{sub 2}] and [O{sub 3}] will differentially affect the antioxidant system.« less

Protective effect of sulforaphane against oxidative stress: recent advances.

PubMed

Guerrero-Beltrán, Carlos Enrique; Calderón-Oliver, Mariel; Pedraza-Chaverri, José; Chirino, Yolanda Irasema

2012-07-01

Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage. Studies on this compound is increasing because its anticarcinogenic and cytoprotective properties in several in vivo experimental paradigms associated with oxidative stress such as focal cerebral ischemia, brain inflammation, intracerebral hemorrhage, ischemia and reperfusion induced acute renal failure, cisplatin induced-nephrotoxicity, streptozotocin-induced diabetes, carbon tetrachloride-induced hepatotoxicity and cardiac ischemia and reperfusion. This protective effect also has been observed in in vitro studies in different cell lines such as human neuroblastoma SH-SY5Y, renal epithelial proximal tubule LLC-PK1 cells and aortic smooth muscle A10 cells. Sulforaphane is considered an indirect antioxidant; this compound is able to induce many cytoprotective proteins, including antioxidant enzymes, through the Nrf2-antioxidant response element pathway. Heme oxygenase-1, NAD(P)H: quinone oxidoreductase, glutathione-S-transferase, gamma-glutamyl cysteine ligase, and glutathione reductase are among the cytoprotective proteins induced by sulforaphane. In conclusion, sulforaphane is a promising antioxidant agent that is effective to attenuate oxidative stress and tissue/cell damage in different in vivo and in vitro experimental paradigms. Copyright © 2010 Elsevier GmbH. All rights reserved.

Effects of molybdenum on water utilization, antioxidative defense system and osmotic-adjustment ability in winter wheat (Triticum aestivum) under drought stress.

PubMed

Wu, Songwei; Hu, Chengxiao; Tan, Qiling; Nie, Zhaojun; Sun, Xuecheng

2014-10-01

Molybdenum (Mo), as an essential trace element in plants, plays an essential role in abiotic stress tolerance of plants. To obtain a better understanding of drought tolerance enhanced by Mo, a hydroponic trial was conducted to investigate the effects of Mo on water utilization, antioxidant enzymes, non-enzymatic antioxidants, and osmotic-adjustment products in the Mo-efficient '97003' and Mo-inefficient '97014' under PEG simulated drought stress. Our results indicate that Mo application significantly enhanced Pn, chlorophyll, dry matter, grain yield, biomass, RWC and WUE and decreased Tr, Gs and water loss of wheat under drought stress, suggesting that Mo application improved the water utilization capacity in wheat. The activities of antioxidant enzymes such as superoxide dismutase, peroxidase, catalase, ascorbate peroxidase and the contents of non-enzymatic antioxidants content such as ascorbic acid, reduced glutathione, carotenoid were significantly increased and malonaldehyde contents were decreased by Mo application under PEG simulated drought stress, suggesting that Mo application enhanced the ability of scavenging active oxygen species. The osmotic-adjustment products such as soluble protein, proline and soluble sugar were also increased by Mo application under PEG simulated drought stress, indicating that Mo improved the osmotic adjustment ability in wheat. It is hypothesized that Mo application might improve the drought tolerance of wheat by enhancing water utilization capability and the abilities of antioxidative defense and osmotic adjustment. Similarities and differences between the Mo-efficient and Mo-inefficient cultivars wheat in response to Mo under drought stress are discussed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Bifunctional Alkylating Agent-Induced p53 and Nonclassical Nuclear Factor kB Responses and Cell Death are Altered by Caffeic Acid Phenethyl Ester: A Potential Role for Antioxidant/Electrophilic Response-Element Signaling

DTIC Science & Technology

2007-01-01

Methods. To establish the maximal LDH 2,3,7,8-tetrachloro- activity achievable from these cells, untreated control cells were grown dibenzo-p- dioxin to the...to modulated by AhR (Miao et al., 2005). Curcumin has been induce apoptosis. CAPE may be involved in anoikis, that is, shown to compete with dioxin ...the AhR directly binds (Miao et al., 2005). adhesion kinase (Weyant et al., 2000). Also, CAPE-induced Exposure of Hepalclc7 cells to dioxin results in

Identification and characterization of an Apis cerana cerana Delta class glutathione S-transferase gene ( AccGSTD) in response to thermal stress

NASA Astrophysics Data System (ADS)

Yan, Huiru; Jia, Haihong; Wang, Xiuling; Gao, Hongru; Guo, Xingqi; Xu, Baohua

2013-02-01

Glutathione S-transferases (GSTs) are members of a multifunctional enzyme super family that plays a pivotal role in both insecticide resistance and protection against oxidative stress. In this study, we identified a single-copy gene, AccGSTD, as being a Delta class GST in the Chinese honey bee ( Apis cerana cerana). A predicted antioxidant response element, CREB, was found in the 1,492-bp 5'-flanking region, suggesting that AccGSTD may be involved in oxidative stress response pathways. Real-time PCR and immunolocalization studies demonstrated that AccGSTD exhibited both developmental- and tissue-specific expression patterns. During development, AccGSTD transcript was increased in adults. The AccGSTD expression level was the highest in the honey bee brain. Thermal stress experiments demonstrated that AccGSTD could be significantly upregulated by temperature changes in a time-dependent manner. It is hypothesized that high expression levels might be due to the increased levels of oxidative stress caused by the temperature challenges. Additionally, functional assays of the recombinant AccGSTD protein revealed that AccGSTD has the capability to protect DNA from oxidative damage. Taken together, these data suggest that AccGSTD may be responsible for antioxidant defense in adult honey bees.

Effect of vitamin E and C supplementation on oxidative damage and total antioxidant capacity in lead-exposed workers.

PubMed

Rendón-Ramírez, Adela-Leonor; Maldonado-Vega, María; Quintanar-Escorza, Martha-Angelica; Hernández, Gerardo; Arévalo-Rivas, Bertha-Isabel; Zentella-Dehesa, Alejandro; Calderón-Salinas, José-Víctor

2014-01-01

The molecular response of the antioxidant system and the effects of antioxidant supplementation against oxidative insult in lead-exposed workers has not been sufficiently studied. In this work, antioxidants (vitamin E 400 IU+vitamin C 1g/daily) were supplemented for one year to 15 workers exposed to lead (73 μg of lead/dl of blood) and the results were compared with those on 19 non-lead exposed workers (6.7 μg of lead/dl). Lead intoxication was accompanied by a high oxidative damage and an increment in the erythrocyte antioxidant response due to increased activity of catalase and superoxide dismutase. Antioxidant supplementations decreased significantly the oxidative damage as well as the total antioxidant capacity induced by lead intoxication with reduction of the antioxidant enzyme activities. We conclude that antioxidant supplementation is effective in reducing oxidative damage and induces modifications in the physiopathological status of the antioxidant response in lead-exposed workers. Copyright © 2013 Elsevier B.V. All rights reserved.

Activation of the Nrf2-ARE pathway by siRNA knockdown of Keap1 reduces oxidative stress and provides partial protection from MPTP-mediated neurotoxicity.

PubMed

Williamson, Tracy P; Johnson, Delinda A; Johnson, Jeffrey A

2012-06-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that binds to the antioxidant response element, a cis-acting regulatory element that increases expression of detoxifying enzymes and antioxidant proteins. Kelch-like ECH associating protein 1 (Keap1) protein is a negative regulator of Nrf2. Previous work has shown that genetic overexpression of Nrf2 is protective in vitro and in vivo. To modulate the Nrf2-ARE system without overexpressing Nrf2, we used short interfering RNA (siRNA) directed against Keap1. Keap1 siRNA administration in primary astrocytes increased the levels of Nrf2-ARE driven genes and protected against oxidative stress. Moreover, Keap1 siRNA resulted in a persistent upregulation of the Nrf2-ARE pathway and protection against oxidative stress in primary astrocytes. Keap1 siRNA injected into the striatum was also modestly protective against MPTP-induced dopaminergic terminal damage. These data indicate that activation of endogenous intracellular levels of Nrf2 is sufficient to protect in models of oxidative stress and Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of rutin supplementation on antioxidant status and iron, copper, and zinc contents in mouse liver and brain.

PubMed

Gao, Zhonghong; Xu, Huibi; Huang, Kaixun

2002-09-01

The effect of rutin on total antioxidant status as well as on trace elements such as iron, copper, and zinc in mouse liver and brain were studied. Mice were administrated with 0.75 g/kg or 2.25 g/kg P. O. of rutin for 30 d consecutively. Following the treatment, the activity of total antioxidant status, catalase, Cu,Zn-superoxide dismutase, Mn-superoxide dismutase, zinc, copper, and iron were measured in mouse liver and brain. The results showed that rutin significantly increased the antioxidant status and Mn-superoxide dismutase activities in mouse liver, but it had no effect on these variables in the brain. Treatment with a higher concentration of rutin significantly decreased catalase activity and iron, zinc, and copper contents in mouse liver; it also resulted in a slower weight gain for the first 20 d. These results indicate that rutin taken in proper amount can effectively improve antioxidant status, whereas at an increased dosage, it may cause trace element (such as iron, zinc, and copper) deficiencies and a decrease in the activities of related metal-containing enzymes.

Oxidative stress contributes to the tamoxifen-induced killing of breast cancer cells: implications for tamoxifen therapy and resistance

PubMed Central

Bekele, Raie T.; Venkatraman, Ganesh; Liu, Rong-Zong; Tang, Xiaoyun; Mi, Si; Benesch, Matthew G. K.; Mackey, John R.; Godbout, Roseline; Curtis, Jonathan M.; McMullen, Todd P. W.; Brindley, David N.

2016-01-01

Tamoxifen is the accepted therapy for patients with estrogen receptor-α (ERα)-positive breast cancer. However, clinical resistance to tamoxifen, as demonstrated by recurrence or progression on therapy, is frequent and precedes death from metastases. To improve breast cancer treatment it is vital to understand the mechanisms that result in tamoxifen resistance. This study shows that concentrations of tamoxifen and its metabolites, which accumulate in tumors of patients, killed both ERα-positive and ERα-negative breast cancer cells. This depended on oxidative damage and anti-oxidants rescued the cancer cells from tamoxifen-induced apoptosis. Breast cancer cells responded to tamoxifen-induced oxidation by increasing Nrf2 expression and subsequent activation of the anti-oxidant response element (ARE). This increased the transcription of anti-oxidant genes and multidrug resistance transporters. As a result, breast cancer cells are able to destroy or export toxic oxidation products leading to increased survival from tamoxifen-induced oxidative damage. These responses in cancer cells also occur in breast tumors of tamoxifen-treated mice. Additionally, high levels of expression of Nrf2, ABCC1, ABCC3 plus NAD(P)H dehydrogenase quinone-1 in breast tumors of patients at the time of diagnosis were prognostic of poor survival after tamoxifen therapy. Therefore, overcoming tamoxifen-induced activation of the ARE could increase the efficacy of tamoxifen in treating breast cancer. PMID:26883574

Measurement of the total antioxidant response using a novel automated method in subjects with nonalcoholic steatohepatitis.

PubMed

Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Fusun F; Sabuncu, Tevfik; Aslan, Mehmet; Sarifakiogullari, Serpil; Gunaydin, Necla; Erel, Ozcan

2005-11-11

Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of nonalcoholic steatohepatitis. We aimed to investigate the total antioxidant response using a novel automated method in nonalcoholic steatohepatitis subjects. As a reciprocal measure, we also aimed to determine total peroxide level in the same plasma samples. Twenty-two subjects with biopsy proven nonalcoholic steatohepatitis and 22 healthy controls were enrolled. Total antioxidant response and total peroxide level measurements were done in all participants. The ratio percentage of total peroxide level to total antioxidant response was regarded as oxidative stress index. Total antioxidant response of subjects with nonalcoholic steatohepatitis was significantly lower than controls (p < 0.05), while mean total peroxide level and mean oxidative stress index were higher (all p < 0.05). In subjects with nonalcoholic steatohepatitis, fibrosis score was significantly correlated with total peroxide level, total antioxidant response and oxidative stress index (p < 0.05, r = 0.607; p < 0.05, r = -0.506; p < 0.05, r = 0.728, respectively). However, no correlation was observed between necroimflamatory grade and those oxidative status parameters (all p > 0.05). Nonalcoholic steatohepatitis is associated with increased oxidant capacity, especially in the presence of liver fibrosis. The novel automated assay is a reliable and easily applicable method for total plasma antioxidant response measurement in nonalcoholic steatohepatitis.

Targeting of the Glutathione, Thioredoxin, and Nrf2 Antioxidant Systems in Head and Neck Cancer.

PubMed

Roh, Jong-Lyel; Jang, Hyejin; Kim, Eun Hye; Shin, Daiha

2017-07-10

The glutathione (GSH), thioredoxin (Trx), and Nrf2 systems represent a major defense against reactive oxygen species (ROS), the cellular imbalance of which in cancer promotes growth and therapeutic resistance. This study investigated whether targeting the GSH, Trx, and Nrf2 antioxidant systems effectively eliminated head and neck cancer (HNC). At high concentrations, auranofin, but not buthionine sulfoximine (BSO) alone, decreased the viability of HNC, whereas even at low concentrations, auranofin plus BSO synergized to kill HNC cells. Dual silencing of the genes for GCLM and TrxR1 induced GSH depletion, Trx activity inhibition, and ROS accumulation, synergistically killing HNC cells. Inhibition of the GSH and Trx systems resulted in activation of the Nrf2-antioxidant response element (ARE) pathway, which may result in suboptimal GSH and Trx inhibition where HNC is resistant. Genetic inhibition of Nrf2 and/or HO-1 or trigonelline enhanced growth suppression, ROS accumulation, and cell death from GSH and Trx inhibition. The in vivo effects of GSH, Trx, and Nrf2 system inhibition were confirmed in a mouse HNC xenograft model by achieving growth inhibition >60% compared with those of control. Innovations: This study is the first to show that triple inhibition of GSH, Trx, and Nrf2 pathways could be an effective method to overcome the resistance of HNC. Inhibition of the Nrf2-ARE pathway in addition to dual inhibition of the GSH and Trx antioxidant systems can effectively eliminate resistant HNC. Antioxid. Redox Signal. 27, 106-114.

Induction of heme oxygenase-1 by chamomile protects murine macrophages against oxidative stress.

PubMed

Bhaskaran, Natarajan; Shukla, Sanjeev; Kanwal, Rajnee; Srivastava, Janmejai K; Gupta, Sanjay

2012-06-27

Protection of cells from oxidative insult may be possible through direct scavenging of reactive oxygen species, or through stimulation of intracellular antioxidant defense mechanisms by induction of antioxidant gene expression. In this study we investigated the cytoprotective effect of chamomile and elucidated the underlying mechanisms. The cytoprotective effect of chamomile was examined on H(2)O(2)-induced cellular stress in RAW 264.7 murine macrophages. RAW 264.7 murine macrophages treated with chamomile were protected from cell death caused by H(2)O(2). Treatment with 50μM H(2)O(2) for 6h caused significant increase in cellular stress accompanied by cell death in RAW 264.7 macrophages. Pretreatment with chamomile at 10-20μg/mL for 16h followed by H(2)O(2) treatment protected the macrophages against cell death. Chamomile exposure significantly increased the expression of antioxidant enzymes viz. heme oxygenase-1 (HO-1), peroxiredoxin-1 (Prx-1), and thioredoxin-1 (Trx-1) in a dose-dependent manner, compared with their respective controls. Chamomile increased nuclear translocation of Nrf2 with increased phosphorylated Nrf2 levels, and binding to the antioxidant response element in the nucleus. These molecular findings for the first time provide insights into the mechanisms underlying the induction of phase 2 enzymes through the Keap1-Nrf2 signaling pathway by chamomile, and provide evidence that chamomile possesses antioxidant and cytoprotective properties. Copyright © 2012 Elsevier Inc. All rights reserved.

Induction of heme oxygenase-1 by chamomile protects murine macrophages against oxidative stress

PubMed Central

Bhaskaran, Natarajan; Shukla, Sanjeev; Kanwal, Rajnee; Srivastava, Janmejai K; Gupta, Sanjay

2012-01-01

Aims Protection of cells from oxidative insult may be possible through direct scavenging of reactive oxygen species, or through stimulation of intracellular antioxidant defense mechanisms by induction of antioxidant gene expression. In this study we investigated the cytoprotective effect of chamomile and elucidated the underlying mechanisms. Main Methods The cytoprotective effect of chamomile was examined on H2O2-induced cellular stress in RAW 264.7 murine macrophages. Key Findings RAW 264.7 murine macrophages treated with chamomile were protected from cell death caused by H2O2. Treatment with 50 μM H2O2 for 6 h caused significant increase in cellular stress accompanied by cell death in RAW 264.7 macrophages. Pretreatment with chamomile at 10-20 μg/mL for 16 h followed by H2O2 treatment protected the macrophages against cell death. Chamomile exposure significantly increased the expression of antioxidant enzymes viz. heme oxygenase-1 (HO-1), peroxiredoxin-1 (Prx-1), and thioredoxin-1 (Trx-1) in a dose-dependent manner, compared with their respective controls. Chamomile increased nuclear translocation of Nrf2 with increased phosphorylated Nrf2 levels, and binding to the antioxidant response element in the nucleus. Significance These molecular findings for the first time provide insights into the mechanisms underlying the induction of phase 2 enzymes through the Keap1-Nrf2 signaling pathway by chamomile, and provide evidence that chamomile possesses antioxidant and cytoprotective properties. PMID:22683429

Activation of the nuclear factor E2-related factor 2/anitioxidant response element alleviates the nitroglycerin-induced hyperalgesia in rats.

PubMed

Di, Wei; Shi, Xiaolei; Lv, Hua; Liu, Jun; Zhang, Hong; Li, Zhiwei; Fang, Yannan

2016-12-01

Antioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats. The expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot. Immunofluorescence was used to demonstrate the cell-specific localization of Nrf2 in TNC. Sulforaphane, a Nrf2 activator, was administered to NTG-induced rats. Then, the number of c-Fos- and nNOS-immunoreactive neurons in TNC was evaluated using immunofluorescence, and c-Fos and nNOS protein levels were quantified using western blot. Von Frey hair testing was used to evaluate the tactile thresholds of rats at different time points in different groups. Total cellular and nuclear levels of the proteins Nrf2, HO1, and NQO1 were elevated in TNC after NTG injection, and Nrf2 was found to be located in the nucleus and cytoplasm of the neurons. Sulforaphane pretreatment significantly increased the nuclear Nrf2, HO1, and NQO1 levels in TNC. In addition, sulforaphane exposure effectively inhibited the expression of nNOS and c-Fos, reduced the number of nNOS and c-Fos immunoreactive neurons in TNC, and attenuated the tactile thresholds induced by NTG injection. Oxidative stress was involved in nitroglycerin-induced hyperalgesia. Activation of the Nrf2/ARE pathway inhibited the activation of TGVS and prevented the induction of hyperalgesia. Sulforaphane might therefore be an effective agent for hyperalgesia. Further studies are needed to discover the underlying mechanisms of the process.

Platelet-released growth factors can accelerate tenocyte proliferation and activate the anti-oxidant response element.

PubMed

Tohidnezhad, M; Varoga, D; Wruck, C J; Brandenburg, L O; Seekamp, A; Shakibaei, M; Sönmez, T T; Pufe, Thomas; Lippross, S

2011-05-01

Little is know about the pathophysiology of acute and degenerative tendon injuries. Although most lesions are uncomplicated, treatment is long and unsatisfactory in a considerable number of cases. Besides the common growth factors that were shown to be relevant for tendon integrity more recently protection against oxidative stress was shown to promote tendon healing. To improve tendon regeneration, many have advocated the use of platelet-rich plasma (PRP), a thrombocyte concentrate that can serve as an autologous source of growth factors. In this study, we investigated the effect of platelet-released growth factors (PRGF) on tenocytes. Tenocytes were isolated from the Achilles tendon of postnatal rats. Tenocyte cell cultures were stimulated with PRGF. We used a CyQuant assay and WST assay to analyse tendon cell growth and viability in different concentrations of PRGF. Migration and proliferation of cells grown in PRGF were assessed by a scratch test. A dual-luciferase assay was used to demonstrate the activation of the anti-oxidant response element (ARE) in tenocytes. A positive effect of PRGF could be shown on tendon cell growth and migratory capacity. PRGF activated the Nrf2-ARE pathway in a dose-dependent manner. Here, we provide evidence of a biological effect of PRGF on tenocytes by the promotion of tenocyte growth and activation of the Nrf2-ARE pathway. This is a novel aspect of the action of platelet concentrates on tendon growth.

Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve.

PubMed

Radak, Zsolt; Ishihara, Kazunari; Tekus, Eva; Varga, Csaba; Posa, Aniko; Balogh, Laszlo; Boldogh, Istvan; Koltai, Erika

2017-08-01

It is debated whether exercise-induced ROS production is obligatory to cause adaptive response. It is also claimed that antioxidant treatment could eliminate the adaptive response, which appears to be systemic and reportedly reduces the incidence of a wide range of diseases. Here we suggest that if the antioxidant treatment occurs before the physiological function-ROS dose-response curve reaches peak level, the antioxidants can attenuate function. On the other hand, if the antioxidant treatment takes place after the summit of the bell-shaped dose response curve, antioxidant treatment would have beneficial effects on function. We suggest that the effects of antioxidant treatment are dependent on the intensity of exercise, since the adaptive response, which is multi pathway dependent, is strongly influenced by exercise intensity. It is further suggested that levels of ROS concentration are associated with peak physiological function and can be extended by physical fitness level and this could be the basis for exercise pre-conditioning. Physical inactivity, aging or pathological disorders increase the sensitivity to oxidative stress by altering the bell-shaped dose response curve. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Physiological and biochemical responses of Suaeda fruticosa to cadmium and copper stresses: growth, nutrient uptake, antioxidant enzymes, phytochelatin, and glutathione levels.

PubMed

Bankaji, I; Caçador, I; Sleimi, N

2015-09-01

Environmental pollution by trace metal elements (TMEs) is a serious problem worldwide, increasing in parallel with the development of human technology. The present research aimed to examine the response of halophytic species Suaeda fruticosa to oxidative stress posed by combined abiotic stresses. Plants have been grown for 1 month with an irrigation solution supplemented with 200 mM NaCl and 400 μM Cd(2+) or 400 μM Cu(2+). The level of glutathione (GSH), phytochelatins (PCs), and antioxidant enzyme activities [ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and catalase (CAT)] as well as lipid peroxidation was studied to see the stress exerted by the TME and the level of tolerance and detoxification strategy adopted by S. fruticosa. Relative growth rate (RGR) decreased under Cd(2+) stress in this species, whereas Cu(2+) did not have any impact on S. fruticosa performance. Cd(2+) or Cu(2+) enhanced malondialdehyde, suggesting reactive oxygen species-induced disruption of membrane integrity and oxidative stress in S. fruticosa. On the other hand, the activities of the antioxidant enzymes CAT, APX, and GPX diminished and mineral nutrition was disturbed by metal stress. S. fruticosa was able to synthesize PCs in response to TME toxicity. However, data indicate that GSH levels underwent a significant decrease in roots and leaves of S. fruticosa stressed by Cd(2+) or Cu(2+). The GSH depletion accompanied by the increase of phytochelatin concentration suggests the involvement of GSH in the synthesis of phytochelatins.

Comparison of hepatic NRF2 and AHR binding in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated mice demonstrates NRF2-independent PKM2 induction.

PubMed

Nault, Rance; Doskey, Claire M; Fader, Kelly A; Rockwell, Cheryl E; Zacharewski, Timothy R

2018-05-11

2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD) induces hepatic oxidative stress following activation of the aryl hydrocarbon receptor (AhR). Our recent studies showed TCDD induced pyruvate kinase muscle isoform 2 ( Pkm2 ) as a novel antioxidant response in normal differentiated hepatocytes. To investigate cooperative regulation between nuclear factor, erythroid derived 2, like 2 ( Nrf2 ) and the AhR in the induction of Pkm2 , hepatic ChIP-seq analyses were integrated with RNA-seq time course data from mice treated with TCDD for 2 - 168h. ChIP-seq analysis 2h after TCDD treatment identified genome-wide NRF2 enrichment. Approximately 842 NRF2 enriched regions were located in the regulatory region of differentially expressed genes (DEGs) while 579 DEGs showed both NRF2 and AhR enrichment. Sequence analysis of regions with overlapping NRF2 and AhR enrichment showed over-representation of either antioxidant or dioxin response elements (ARE and DRE, respectively), although 18 possessed both motifs. NRF2 exhibited negligible enrichment within a closed Pkm chromatin region while the AhR was enriched 29-fold. Furthermore, TCDD induced Pkm2 in primary hepatocytes from wild-type and Nrf2 null mice, indicating NRF2 is not required. Although NRF2 and AhR cooperate to regulate numerous antioxidant gene expression responses, the induction of Pkm2 by TCDD is independent of ROS-mediated NRF2 activation. The American Society for Pharmacology and Experimental Therapeutics.

Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells.

PubMed

Eren, Erden; Tufekci, Kemal Ugur; Isci, Kamer Burak; Tastan, Bora; Genc, Kursad; Genc, Sermin

2018-01-01

Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes. SFN induced translocation of Nrf2 to the nucleus via extracellular signal-regulated kinase 1/2 (ERK1/2) pathway activation. siRNA-mediated knockdown study showed that the effects of SFN on LPS-induced reactive oxygen species, reactive nitrogen species, and pro-inflammatory cytokine production and cell death are partly Nrf2 dependent. Mox phenotype is a novel microglial phenotype that has roles in oxidative stress responses. Our results suggested that SFN induced the Mox phenotype in murine microglia through Nrf2 pathway. SFN also alleviated LPS-induced expression of inflammatory microRNA, miR-155. Finally, SFN inhibits microglia-mediated neurotoxicity as demonstrated by conditioned medium and co-culture experiments. In conclusion, SFN exerts protective effects on microglia and modulates the microglial activation state.

Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2–Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells

PubMed Central

Eren, Erden; Tufekci, Kemal Ugur; Isci, Kamer Burak; Tastan, Bora; Genc, Kursad; Genc, Sermin

2018-01-01

Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes. SFN induced translocation of Nrf2 to the nucleus via extracellular signal-regulated kinase 1/2 (ERK1/2) pathway activation. siRNA-mediated knockdown study showed that the effects of SFN on LPS-induced reactive oxygen species, reactive nitrogen species, and pro-inflammatory cytokine production and cell death are partly Nrf2 dependent. Mox phenotype is a novel microglial phenotype that has roles in oxidative stress responses. Our results suggested that SFN induced the Mox phenotype in murine microglia through Nrf2 pathway. SFN also alleviated LPS-induced expression of inflammatory microRNA, miR-155. Finally, SFN inhibits microglia-mediated neurotoxicity as demonstrated by conditioned medium and co-culture experiments. In conclusion, SFN exerts protective effects on microglia and modulates the microglial activation state. PMID:29410668

Ultraviolet-B Protective Effect of Flavonoids from Eugenia caryophylata on Human Dermal Fibroblast Cells.

PubMed

Patwardhan, Juilee; Bhatt, Purvi

2015-10-01

The exposure of skin to ultraviolet-B (UV-B) radiations leads to deoxyribonucleic acid (DNA) damage and can induce production of free radicals which imbalance the redox status of the cell and lead to increased oxidative stress. Clove has been traditionally used for its analgesic, anti-inflammatory, anti-microbial, anti-viral, and antiseptic effects. To evaluate the UV-B protective activity of flavonoids from Eugenia caryophylata (clove) buds on human dermal fibroblast cells. Protective ability of flavonoid-enriched (FE) fraction of clove was studied against UV-B induced cytotoxicity, anti-oxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2-related factor 2 antioxidant response element (Nrf2 ARE) pathway. FE fraction showed a significant antioxidant potential. Pretreatment of cells with FE fraction (10-40 μg/ml) reversed the effects of UV-B induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1. The present study demonstrated for the first time that the FE fraction from clove could confer UV-B protection probably through the Nrf2-ARE pathway, which included the down-regulation of Nrf2 and HO-1. These findings suggested that the flavonoids from clove could potentially be considered as UV-B protectants and can be explored further for its topical application to the area of the skin requiring protection. Pretreatment of human dermal fibroblast with flavonoid-enriched fraction of Eugenia caryophylata attenuated effects of ultraviolet-B radiationsIt also conferred protection through nuclear factor E2-related factor 2-antioxidant response pathway and increased tolerance of cells against oxidative stressFlavonoid-enriched fraction can be explored further for topical application to the skin as a ultraviolet-B protectant. Abbreviations used: ABTS: 2,2'-azino-bis-(3-ethylbenzothiazoline- 6-sulphonic acid), AO: Acridine orange, Analysis of variance, ARE: Antioxidant response elements, BSA: Bovine serum albumin, CAPE: Caffeic acid phenethyl ester, CAT: Catalase, DCFH-DA: 2',7'-dichlorofluorescein diacetate, DMEM: Dulbecco's Modified Eagle's Medium, DMSO: Dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DPBS: Dulbecco's phosphate buffered saline, DPPH: 2,2-diphenyl-1-picrylhydrazyl, ECL: Enhanced chemiluminescence, EDTA: Ethylenediaminetetraacetic acid, ELISA: Enzyme-linked immunesorbent assay, EtBr: Ethidium bromide, FBS: Fetal bovine serum, FE fraction: Flavonoid-enriched fraction, FRAP: Ferric reducing antioxidant power, GPx: Glutathione peroxidase, GR: Glutathione reductase, GST: Glutathione-S-transferase, GSH: Reduced glutathione, GSSG: Oxidized glutathione, HDF: Human dermal fibroblast, HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid, HRP: Horseradish peroxidase, HO-1: Heme oxygenase-1, HPTLC: High-performance thin layer chromatography, Keap-1: Kelch-like ECH-associated protein-1, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NaCl: Sodium chloride, NFDM: Nonfat dry milk, Nrf2: Nuclear factor E2-related factor 2, NQO1: NAD (P) H: Quinine oxidoreductase 1, OH: Hydroxyl ions, PBST: Phosphate buffered saline with 0.1% tween 20, PCR: Polymerase chain reaction, PMSF: Phenylmethanesulfonyl fluoride, Rf: Retention factor, ROS: Reactive oxygen species, rRNA: Ribosomal ribonucleic acid, SDS: Sodium dodecyl sulfate, SOD: Superoxide dismutase, TLC: Thin layer chromatography, TLC-DPPH: Thin layer chromatography-2,2-diphenyl-1-picrylhydrazyl, UV: Ultraviolet, UV-A: Ultraviolet-A, UV-B: Ultraviolet-B, UV-C: Ultraviolet-C, and qPCR: Quantitative polymerase chain reaction.

Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.

PubMed

Choi, Mi-Ran; Lee, Min Young; Hong, Ji Eun; Kim, Jeong Eun; Lee, Jae-Yong; Kim, Tae Hwan; Chun, Jang Woo; Shin, Hyun Kyung; Kim, Eun Ji

2014-10-01

The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.

The effects of levosimendan exposure on oxidant/antioxidant status and trace element levels in the pulmonary artery of rats.

PubMed

Ay, Yasin; Aydın, Cemalettin; Basel, Halil; Bektaş, Hava; Bülüt, Gülay; Inan, Bekir; Ay, Nuray Kahraman; Demir, Ismail

2013-06-01

We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.

Measurement of the total antioxidant response using a novel automated method in subjects with nonalcoholic steatohepatitis

PubMed Central

Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Fusun F; Sabuncu, Tevfik; Aslan, Mehmet; Sarifakiogullari, Serpil; Gunaydin, Necla; Erel, Ozcan

2005-01-01

Background Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of nonalcoholic steatohepatitis. We aimed to investigate the total antioxidant response using a novel automated method in nonalcoholic steatohepatitis subjects. As a reciprocal measure, we also aimed to determine total peroxide level in the same plasma samples. Methods Twenty-two subjects with biopsy proven nonalcoholic steatohepatitis and 22 healthy controls were enrolled. Total antioxidant response and total peroxide level measurements were done in all participants. The ratio percentage of total peroxide level to total antioxidant response was regarded as oxidative stress index. Results Total antioxidant response of subjects with nonalcoholic steatohepatitis was significantly lower than controls (p < 0.05), while mean total peroxide level and mean oxidative stress index were higher (all p < 0.05). In subjects with nonalcoholic steatohepatitis, fibrosis score was significantly correlated with total peroxide level, total antioxidant response and oxidative stress index (p < 0.05, r = 0.607; p < 0.05, r = -0.506; p < 0.05, r = 0.728, respectively). However, no correlation was observed between necroimflamatory grade and those oxidative status parameters (all p > 0.05). Conclusion Nonalcoholic steatohepatitis is associated with increased oxidant capacity, especially in the presence of liver fibrosis. The novel automated assay is a reliable and easily applicable method for total plasma antioxidant response measurement in nonalcoholic steatohepatitis. PMID:16283935

Antioxidant responses and cellular adjustments to oxidative stress.

PubMed

Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

2015-12-01

Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. Copyright © 2015. Published by Elsevier B.V.

Antioxidant capacity and mineral contents of edible wild Australian mushrooms.

PubMed

Zeng, X; Suwandi, J; Fuller, J; Doronila, A; Ng, K

2012-08-01

Five selected edible wild Australian mushrooms, Morchella elata, Suillus luteus, Pleurotus eryngii, Cyttaria gunnii, and Flammulina velutipes, were evaluated for their antioxidant capacity and mineral contents. The antioxidant capacities of the methanolic extracts of the dried caps of the mushrooms were determined using a number of different chemical reactions in evaluating multi-mechanistic antioxidant activities. These included the Trolox equivalent antioxidant capacity, ferric ion reducing antioxidant power, and ferrous ion chelating activity. Mineral contents of the dried caps of the mushrooms were also determined by inductively coupled plasma-optical emission spectroscopy. The results indicated that these edible wild mushrooms have a high antioxidant capacity and all, except C. gunnii, have a high level of several essential micro-nutrients such as copper, magnesium, and zinc. It can be concluded that these edible wild mushrooms are good sources of nutritional antioxidants and a number of mineral elements.

Hederagenin Induces Apoptosis in Cisplatin-Resistant Head and Neck Cancer Cells by Inhibiting the Nrf2-ARE Antioxidant Pathway.

PubMed

Kim, Eun Hye; Baek, Seungho; Shin, Daiha; Lee, Jaewang; Roh, Jong-Lyel

2017-01-01

Acquired resistance to cisplatin is the most common reason for the failure of cisplatin chemotherapy. Hederagenin, triterpenoids extracted from ivy leaves, exhibits antitumor activity in various types of cancer. However, the therapeutic potential of hederagenin in head and neck cancer (HNC) has remained unclear. Therefore, we examined the effects of hederagenin in cisplatin-resistant HNC cells and characterized its molecular mechanisms of action in this context. We evaluated the effects of hederagenin treatment on cell viability, apoptosis, reactive oxygen species (ROS) production, glutathione levels, mitochondrial membrane potential (Δ Ψ m), and protein and mRNA expression in HNC cells. The antitumor effect of hederagenin in mouse tumor xenograft models was also analyzed. Hederagenin selectively induced cell death in both cisplatin-sensitive and cisplatin-resistant HNC cells by promoting changes in Δ Ψ m and inducing apoptosis. Hederagenin inhibited the Nrf2-antioxidant response element (ARE) pathway and activated p53 in HNC cells, thereby enhancing ROS production and promoting glutathione depletion. These effects were reversed by the antioxidant trolox. Hederagenin activated intrinsic apoptotic pathways via cleaved PARP, cleaved caspase-3, and Bax. The selective inhibitory effects of hederagenin were confirmed in cisplatin-resistant HNC xenograft models. These data suggest that hederagenin induces cell death in resistant HNC cells via the Nrf2-ARE antioxidant pathway.

Selenium-Dependent Antioxidant Enzymes: Actions and Properties of Selenoproteins

PubMed Central

Zoidis, Evangelos; Seremelis, Isidoros; Kontopoulos, Nikolaos

2018-01-01

Unlike other essential trace elements that interact with proteins in the form of cofactors, selenium (Se) becomes co-translationally incorporated into the polypeptide chain as part of 21st naturally occurring amino acid, selenocysteine (Sec), encoded by the UGA codon. Any protein that includes Sec in its polypeptide chain is defined as selenoprotein. Members of the selenoproteins family exert various functions and their synthesis depends on specific cofactors and on dietary Se. The Se intake in productive animals such as chickens affect nutrient utilization, production performances, antioxidative status and responses of the immune system. Although several functions of selenoproteins are unknown, many disorders are related to alterations in selenoprotein expression or activity. Selenium insufficiency and polymorphisms or mutations in selenoproteins’ genes and synthesis cofactors are involved in the pathophysiology of many diseases, including cardiovascular disorders, immune dysfunctions, cancer, muscle and bone disorders, endocrine functions and neurological disorders. Finally, heavy metal poisoning decreases mRNA levels of selenoproteins and increases mRNA levels of inflammatory factors, underlying the antagonistic effect of Se. This review is an update on Se dependent antioxidant enzymes, presenting the current state of the art and is focusing on results obtained mainly in chicken. PMID:29758013

Neuroprotective effects of dietary supplement Kang-fu-ling against high-power microwave through antioxidant action.

PubMed

Hu, Shaohua; Peng, Ruiyun; Wang, Changzhen; Wang, Shuiming; Gao, Yabing; Dong, Ji; Zhou, Hongmei; Su, Zhentao; Qiao, Shanyi; Zhang, Shouguo; Wang, Lin; Wen, Xiaoxue

2014-09-01

Kang-fu-ling (KFL) is a polybotanical dietary supplement with antioxidant properties. This study aimed to evaluate the potential protective effects of KFL on cognitive deficit induced by high-power microwave (HPM) and the underlying mechanism for this neuroprotection. The electron spin resonance technique was employed to evaluate the free radical scavenging activity of KFL in vitro and KFL exhibited scavenging hydroxyl radical activity. KFL at doses of 0.75, 1.5 and 3 g kg(-1) and vehicle were administered orally once daily for 14 days to male Wistar rats after being exposed to 30 mW cm(-2) HPM for 15 minutes. KFL reversed HPM-induced memory loss and the histopathological changes in hippocampus of rats. In addition, KFL displayed a protective effect against HPM-induced oxidative stress and activated the nuclear factor-E2-related factor 2 (Nrf2) and its target genes in the hippocampus of rats. The Nrf2-antioxidant response element (ARE) signaling pathway may be involved in the neuroprotective effects of KFL against HPM-induced oxidative stress. In summary, the dietary supplement KFL is a promising natural complex, which ameliorates oxidative stress, with neuroprotective effects against HPM.

Fucoxanthin enhances HO-1 and NQO1 expression in murine hepatic BNL CL.2 cells through activation of the Nrf2/ARE system partially by its pro-oxidant activity.

PubMed

Liu, Cheng-Ling; Chiu, Yu-Ting; Hu, Miao-Lin

2011-10-26

To determine whether fucoxanthin, a major carotenoid in brown sea algae, may activate cellular antioxidant enzymes via up-regulation of the Nrf2/antioxidant-response element (ARE) pathway, we incubated mouse hepatic BNL CL.2 cells with fucoxanthin (0.5-20 μM) for 0-24 h. We found that fucoxanthin (≥5 μM) significantly increased cellular reactive oxygen species (ROS) at 6 h of incubation, whereas preincubation with α-d-tocopherol (30 μM) significantly attenuated the increase of ROS, indicating the pro-oxidant nature of fucoxanthin. Fucoxanthin significantly increased the phosphorylation of ERK and p38 and markedly increased nuclear Nrf2 protein accumulation after incubation for 12 h. Moreover, fucoxanthin significantly enhanced binding activities of nuclear Nrf2 with ARE and increased mRNA and protein expression of HO-1 and NQO1 after incubation for 12 h. siRNA inhibition of Nrf2 led to markedly decreased HO-1 and NQO1 protein expression. Thus, fucoxanthin may exert its antioxidant activity, at least partly, through its pro-oxidant actions.

Antioxidative Dietary Compounds Modulate Gene Expression Associated with Apoptosis, DNA Repair, Inhibition of Cell Proliferation and Migration

PubMed Central

Wang, Likui; Gao, Shijuan; Jiang, Wei; Luo, Cheng; Xu, Maonian; Bohlin, Lars; Rosendahl, Markus; Huang, Wenlin

2014-01-01

Many dietary compounds are known to have health benefits owing to their antioxidative and anti-inflammatory properties. To determine the molecular mechanism of these food-derived compounds, we analyzed their effect on various genes related to cell apoptosis, DNA damage and repair, oxidation and inflammation using in vitro cell culture assays. This review further tests the hypothesis proposed previously that downstream products of COX-2 (cyclooxygenase-2) called electrophilic oxo-derivatives induce antioxidant responsive elements (ARE), which leads to cell proliferation under antioxidative conditions. Our findings support this hypothesis and show that cell proliferation was inhibited when COX-2 was down-regulated by polyphenols and polysaccharides. Flattened macrophage morphology was also observed following the induction of cytokine production by polysaccharides extracted from viili, a traditional Nordic fermented dairy product. Coix lacryma-jobi (coix) polysaccharides were found to reduce mitochondrial membrane potential and induce caspase-3- and 9-mediated apoptosis. In contrast, polyphenols from blueberries were involved in the ultraviolet-activated p53/Gadd45/MDM2 DNA repair system by restoring the cell membrane potential. Inhibition of hypoxia-inducible factor-1 by saponin extracts of ginsenoside (Ginsen) and Gynostemma and inhibition of S100A4 by coix polysaccharides inhibited cancer cell migration and invasion. These observations suggest that antioxidants and changes in cell membrane potential are the major driving forces that transfer signals through the cell membrane into the cytosol and nucleus, triggering gene expression, changes in cell proliferation and the induction of apoptosis or DNA repair. PMID:25226533

Responses of antioxidant systems after exposition to rare earths and their role in chilling stress in common duckweed (Lemna minor L.): a defensive weapon or a boomerang?

PubMed

Ippolito, M P; Fasciano, C; d'Aquino, L; Morgana, M; Tommasi, F

2010-01-01

Extensive agriculture application of rare earth elements (REEs) in Far East countries might cause spreading of these metals in aquatic and terrestrial ecosystems, thus inducing a growing concern about their environmental impact. In this work the effects of a mix of different REE nitrate (RE) and of lanthanum nitrate (LA) on catalase and antioxidant systems involved in the ascorbate-glutathione cycle were investigated in common duckweed Lemna minor L. The results indicated that L. minor shows an overall good tolerance to the presence of REEs in the media. Treatments at concentrations up to 5 mM RE and 5 mM LA did not cause either visible symptoms on plants or significant effects on reactive oxygen species (ROS) production, chlorophyll content, and lipid peroxidation. Toxic effects were observed after 5 days of exposition to 10 mM RE and 10 mM LA. A remarkable increase in glutathione content as well as in enzymatic antioxidants was observed before the appearance of the stress symptoms in treated plants. Duckweed plants pretreated with RE and LA were also exposed to chilling stress to verify whether antioxidants variations induced by RE and LA improve plant resistance to the chilling stress. In pretreated plants, a decrease in ascorbate and glutathione redox state and in chlorophyll content and an increase in lipid peroxidation and ROS production levels were observed. The use of antioxidant levels as a stress marker for monitoring REE toxicity in aquatic ecosystems by means of common duckweed is discussed.

Nrf2-Mediated Antioxidant Defense and Peroxiredoxin 6 Are Linked to Biosynthesis of Palmitic Acid Ester of 9-Hydroxystearic Acid.

PubMed

Kuda, Ondrej; Brezinova, Marie; Silhavy, Jan; Landa, Vladimir; Zidek, Vaclav; Dodia, Chandra; Kreuchwig, Franziska; Vrbacky, Marek; Balas, Laurence; Durand, Thierry; Hübner, Norbert; Fisher, Aron B; Kopecky, Jan; Pravenec, Michal

2018-06-01

Fatty acid esters of hydroxy fatty acids (FAHFAs) are lipid mediators with promising antidiabetic and anti-inflammatory properties that are formed in white adipose tissue (WAT) via de novo lipogenesis, but their biosynthetic enzymes are unknown. Using a combination of lipidomics in WAT, quantitative trait locus mapping, and correlation analyses in rat BXH/HXB recombinant inbred strains, as well as response to oxidative stress in murine models, we elucidated the potential pathway of biosynthesis of several FAHFAs. Comprehensive analysis of WAT samples identified ∼160 regioisomers, documenting the complexity of this lipid class. The linkage analysis highlighted several members of the nuclear factor, erythroid 2 like 2 ( Nrf2 )-mediated antioxidant defense system ( Prdx6, Mgst1, Mgst3 ), lipid-handling proteins ( Cd36, Scd6, Acnat1, Acnat2, Baat ), and the family of flavin containing monooxygenases ( Fmo ) as the positional candidate genes. Transgenic expression of Nrf2 and deletion of Prdx6 genes resulted in reduction of palmitic acid ester of 9-hydroxystearic acid (9-PAHSA) and 11-PAHSA levels, while oxidative stress induced by an inhibitor of glutathione synthesis increased PAHSA levels nonspecifically. Our results indicate that the synthesis of FAHFAs via carbohydrate-responsive element-binding protein-driven de novo lipogenesis depends on the adaptive antioxidant system and suggest that FAHFAs may link activity of this system with insulin sensitivity in peripheral tissues. © 2018 by the American Diabetes Association.

Use of Iodine to Biofortify and Promote Growth and Stress Tolerance in Crops

PubMed Central

Medrano-Macías, Julia; Leija-Martínez, Paola; González-Morales, Susana; Juárez-Maldonado, Antonio; Benavides-Mendoza, Adalberto

2016-01-01

Iodine is not considered essential for land plants; however, in some aquatic plants, iodine plays a critical role in antioxidant metabolism. In humans, iodine is essential for the metabolism of the thyroid and for the development of cognitive abilities, and it is associated with lower risks of developing certain types of cancer. Therefore, great efforts are made to ensure the proper intake of iodine to the population, for example, the iodization of table salt. In the same way, as an alternative, the use of different iodine fertilization techniques to biofortify crops is considered an adequate iodine supply method. Hence, biofortification with iodine is an active area of research, with highly relevant results. The agricultural application of iodine to enhance growth, environmental adaptation, and stress tolerance in plants has not been well explored, although it may lead to the increased use of this element in agricultural practice and thus contribute to the biofortification of crops. This review systematically presents the results published on the application of iodine in agriculture, considering different environmental conditions and farming systems in various species and varying concentrations of the element, its chemical forms, and its application method. Some studies report beneficial effects of iodine, including better growth, and changes in the tolerance to stress and antioxidant capacity, while other studies report that the applications of iodine cause no response or even have adverse effects. We suggested different assumptions that attempt to explain these conflicting results, considering the possible interaction of iodine with other trace elements, as well as the different physicochemical and biogeochemical conditions that give rise to the distinct availability and the volatilization of the element. PMID:27602033

Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzymes. 15-deoxy-delta(12,14)-prostaglandin j2-induced expression of glutathione S-transferases.

PubMed

Kawamoto, Y; Nakamura, Y; Naito, Y; Torii, Y; Kumagai, T; Osawa, T; Ohigashi, H; Satoh, K; Imagawa, M; Uchida, K

2000-04-14

Exposure of cells to a wide variety of chemoprotective compounds confers resistance to a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes, such as glutathione S-transferases (GSTs). In the present study, we developed a cell culture system that potently responds to phenolic antioxidants and found that antitumor prostaglandins (PGs) are potential inducers of GSTs. We screened primary hepatocytes and multiple cell lines for inducing GST activity upon incubation with the phenolic antioxidant (tert-butylhydroquinone) and found that rat liver epithelial RL34 cells most potently responded. Based on an extensive screening of diverse chemical agents on the induction of GST activity in RL34 cells, the J2 series of PGs, 15-deoxy-Delta(12,14)-prostaglandin J2 (15-deoxy-Delta(12,14)-PGJ2) in particular, were found to be potential inducers of GST. Enhanced gene expression of Class pi GST isozyme (GSTP1) by 15-deoxy-Delta(12,14)-PGJ2 was evident as a drastic elevation of the mRNA level. Hence, we examined the molecular mechanism underlying the 15-deoxy-Delta(12, 14)-PGJ2-induced GSTP1 gene expression. From functional analysis of various deletion mutant genes, we found that the 15-deoxy-Delta(12, 14)-PGJ2 reponse element was localized in a region containing a GSTP1 enhancer I (GPEI) that consists of two imperfect phorbol 12-O-tetradecanoylphorbol-13-acetate response elements. When the GPEI was combined with the minimum GSTP1 promoter, the element indeed showed an enhancer activity in response to 15-deoxy-Delta(12, 14)-PGJ2. Point mutations of either of the two imperfect 12-O-tetradecanoylphorbol-13-acetate response elements in GPEI completely abolished the enhancer activity. Gel mobility shift assays demonstrated that 15-deoxy-Delta(12,14)-PGJ2 specifically stimulated the binding of nuclear proteins including the transcription factor c-Jun, but not Nrf2, to GPEI. These results suggest that 15-deoxy-Delta(12,14)-PGJ2 induces the expression of the rat GSTP1 gene through binding of proteins, including c-Jun, to a specific GPEI.

Novel oxime based flavanone, naringin-oxime: synthesis, characterization and screening for antioxidant activity.

PubMed

Ozyürek, Mustafa; Akpınar, Damla; Bener, Mustafa; Türkkan, Baki; Güçlü, Kubilay; Apak, Reşat

2014-04-05

Recent interest in polyphenolic antioxidants due to their involvement in health benefits has led to the investigation of new polyphenolic compounds with enhanced antioxidant activity. Naringin (4',5,7-trihydroxyflavanone-7-β-l-rhamnoglucoside-(1,2)-α-d-glucopyranoside) is one of the major flavanones in citrus and grapefruit. The present study aimed to synthesize naringin oxime from naringin and to evaluate its antioxidant and anticancer potential using in vitro assay system. The structure of the synthesized compound, naringin oxime, was elucidated by FT-IR, (1)H NMR, elemental analysis and UV-vis spectroscopy. Antioxidant capacity of naringin oxime, as measured by the cupric reducing antioxidant capacity (CUPRAC) method, was found to be higher than that of the parent compound naringin. Other parameters of antioxidant activity (scavenging effects on OH, O2(-), and H2O2) of naringin and naringin oxime were also determined. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice.

PubMed

Wang, Huali; Zhang, Jinsong; Yu, Hanqing

2007-05-15

Glutathione peroxidase and thioredoxin reductase are major selenoenzymes through which selenium exerts powerful antioxidant effects. Selenium also elicits pro-oxidant effects at toxic levels. The antioxidant and pro-oxidant effects, or bioavailability and toxicity, of selenium depend on its chemical form. Selenomethionine is considered to be the most appropriate supplemental form due to its excellent bioavailability and lower toxicity compared to various selenium compounds. The present studies reveal that, compared with selenomethionine, elemental selenium at nano size (Nano-Se) possesses equal efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase but has much lower toxicity as indicated by median lethal dose, acute liver injury, and short-term toxicity. Our results suggest that Nano-Se can serve as an antioxidant with reduced risk of selenium toxicity.

Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction☆

PubMed Central

Chepelev, Nikolai L.; Zhang, Hongqiao; Liu, Honglei; McBride, Skye; Seal, Andrew J.; Morgan, Todd E.; Finch, Caleb E.; Willmore, William G.; Davies, Kelvin J.A.; Forman, Henry Jay

2013-01-01

Although the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2) regulated expression of multiple antioxidant and cytoprotective genes through the electrophile responsive element (EpRE) is well established, interaction of Nrf2/EpRE with Nrf1, a closely-related transcription factor, is less well understood. Due to either proteolysis or alternative translation, Nrf1 has been found as proteins of varying size, p120, p95, and p65, which have been described as either activators of EpRE or competitive inhibitors of Nrf2. We investigated the effect of Nrf1 on EpRE-regulated gene expression using the catalytic and modifier subunits of glutamate cysteine ligase (GCLC and GCLM) as models and explored the potential role of Nrf1 in altering their expression in aging and upon chronic exposure to airborne nano-sized particulate matter (nPM). Nrf1 knockout resulted in the increased expression of GCLC and GCLM in human bronchial epithelial (HBE1) cells. Overexpression Nrf2 in combination with either p120 or p65 diminished or failed to further increase the GCLC- and GLCM-EpRE luciferase activity. All known forms of Nrf1 protein, remained unchanged in the lungs of mice with age or in response to nPM. Our study shows that Nrf1 could inhibit EpRE activity in vitro, whereas the precise role of Nrf1 in vivo requires further investigations. We conclude that Nrf1 may not be directly responsible for the loss of Nrf2-dependent inducibility of antioxidant and cytoprotective genes observed in aged animals. PMID:24024152

Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1.

PubMed

Eggler, Aimee L; Small, Evan; Hannink, Mark; Mesecar, Andrew D

2009-07-29

Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that activates transcription of a battery of cytoprotective genes by binding to the ARE (antioxidant response element). Nrf2 is repressed by the cysteine-rich Keap1 (kelch-like ECH-associated protein 1) protein, which targets Nrf2 for ubiquitination and subsequent degradation by a Cul3 (cullin 3)-mediated ubiquitination complex. We find that modification of Cys(151) of human Keap1, by mutation to a tryptophan, relieves the repression by Keap1 and allows activation of the ARE by Nrf2. The Keap1 C151W substitution has a decreased affinity for Cul3, and can no longer serve to target Nrf2 for ubiquitination, though it retains its affinity for Nrf2. A series of 12 mutant Keap1 proteins, each containing a different residue at position 151, was constructed to explore the chemistry required for this effect. The series reveals that the extent to which Keap1 loses the ability to target Nrf2 for degradation, and hence the ability to repress ARE activation, correlates well with the partial molar volume of the residue. Other physico-chemical properties do not appear to contribute significantly to the effect. Based on this finding, a structural model is proposed whereby large residues at position 151 cause steric clashes that lead to alteration of the Keap1-Cul3 interaction. This model has significant implications for how electrophiles which modify Cys(151), disrupt the repressive function of Keap1.

Exercise-Induced Oxidative Stress Responses in the Pediatric Population

PubMed Central

Avloniti, Alexandra; Chatzinikolaou, Athanasios; Deli, Chariklia K.; Vlachopoulos, Dimitris; Gracia-Marco, Luis; Leontsini, Diamanda; Draganidis, Dimitrios; Jamurtas, Athanasios Z.; Mastorakos, George; Fatouros, Ioannis G.

2017-01-01

Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty. PMID:28106721

Heavy Metal Stress and Some Mechanisms of Plant Defense Response

PubMed Central

Emamverdian, Abolghassem; Ding, Yulong; Mokhberdoran, Farzad; Xie, Yinfeng

2015-01-01

Unprecedented bioaccumulation and biomagnification of heavy metals (HMs) in the environment have become a dilemma for all living organisms including plants. HMs at toxic levels have the capability to interact with several vital cellular biomolecules such as nuclear proteins and DNA, leading to excessive augmentation of reactive oxygen species (ROS). This would inflict serious morphological, metabolic, and physiological anomalies in plants ranging from chlorosis of shoot to lipid peroxidation and protein degradation. In response, plants are equipped with a repertoire of mechanisms to counteract heavy metal (HM) toxicity. The key elements of these are chelating metals by forming phytochelatins (PCs) or metallothioneins (MTs) metal complex at the intra- and intercellular level, which is followed by the removal of HM ions from sensitive sites or vacuolar sequestration of ligand-metal complex. Nonenzymatically synthesized compounds such as proline (Pro) are able to strengthen metal-detoxification capacity of intracellular antioxidant enzymes. Another important additive component of plant defense system is symbiotic association with arbuscular mycorrhizal (AM) fungi. AM can effectively immobilize HMs and reduce their uptake by host plants via binding metal ions to hyphal cell wall and excreting several extracellular biomolecules. Additionally, AM fungi can enhance activities of antioxidant defense machinery of plants. PMID:25688377

The Protective Effect of Hydroalcoholic Extract of Zingiber officinale Roscoe (Ginger) on Ethanol-Induced Reproductive Toxicity in Male Rats.

PubMed

Akbari, Abolfazl; Nasiri, Khadijeh; Heydari, Mojtaba; Mosavat, Seyed Hamdollah; Iraji, Aida

2017-10-01

This study was conducted to evaluate the prophylactic effect of ginger extract on ethanol-induced reproductive toxicity in male rats. Twenty-eight adult male Sprague-Dawley rats were randomly divided into 4 groups and treated daily for 28 days as follows: control, control-ginger (1 g/kg of body weight [BW]/day by gavage), ethanol group (ethanol 4 g/kg of BW/day by gavage), and ginger-ethanol group. At the end of the experiment, all the rats were sacrificed and their testes were removed and used for measurement of the total homocysteine (tHcy), trace elements, antioxidant enzymes activity, and malondialdehyde (MDA). The results in the ethanol group indicate that ethanol decreased antioxidant enzymes activity and increased MDA and tHcy compared with the control groups ( P < .05). In ginger-ethanol group, ginger improved antioxidant enzymes activity and reduced tHcy and MDA compared to ethanol group ( P < .05). It can be concluded that ginger protects the ethanol-induced testicular damage and improves the hormonal levels, trace elements, antioxidant enzymes activity, and decreases tHcy and MDA.

Nuclear factor erythroid-derived 2-related factor 2 activates glutathione S-transferase expression in the midgut of Spodoptera litura (Lepidoptera: Noctuidae) in response to phytochemicals and insecticides.

PubMed

Chen, S; Lu, M; Zhang, N; Zou, X; Mo, M; Zheng, S

2018-05-10

Detoxication enzymes play an important role in insect resistance to xenobiotics such as insecticides and phytochemicals. We studied the pathway for activating the expression of glutathione S-transferases (GSTs) in response to selected xenobiotics. An assay of the promoter activity of GST epsilon 1 (Slgste1) of Spodoptera litura led to the discovery of a cis-regulating element. An antioxidant response element was activated in response to indole-3-carbinol (I3C) and chlorpyrifos (CPF) and was able to bind with the xenobiotic sensor protein nuclear factor erythroid-derived 2-related factor 2 (SlNrf2). SlNrf2 and Slgste1 were responsive to reactive oxygen species induced by I3C and CPF in a S. litura cell line, as well as in S. litura midguts. SlNrf2 RNA interference (RNAi) reduced the message RNA levels of Slgste1 and the peroxidase activity of GSTs in response to I3C, xanthotoxin, CPF and deltamethrin. SlNrf2 RNAi and inhibitor treatment of GST activity decreased the viability of I3C-treated cells. These results indicate that SlNrf2 activates the expression of GSTs in response to oxidative stresses caused by exposure to xenobiotics. © 2018 The Royal Entomological Society.

Antioxidant response and carboxylate metabolism in Brassica rapa exposed to different external Zn, Ca, and Mg supply.

PubMed

Blasco, Begoña; Graham, Neil S; Broadley, Martin R

2015-03-15

Zinc (Zn), calcium (Ca), and magnesium (Mg) malnutrition are common deficiencies in many developed and developing countries, resulting in a widespread health problem. Biofortification of food crops is an agricultural strategy that can be used to increase the levels of these elements in the edible portions of crops. Deficiency or toxicity of these cations in soils reduces plant growth, crop yield, and the quality of plant foodstuff. The aim of this study was to investigate the effect of external Zn, Ca, and Mg supply on accumulation and distribution of this elements as well as antioxidant response and organic acid composition of Brassica rapa ssp. trilocularis line R-o-18. Plants were grown at low Zn (0.05 μM Zn) and high Zn (500 μM Zn), low Ca (0.4 mM) and high Ca (40 mM), and low Mg (0.2 mM), and high Mg (20 mM) to simulate deficiency and toxicity conditions. Larger shoot biomass reductions were observed under high Zn, Ca and Mg treatments, and superoxide dismutase (SOD), ascorbate peroxidase (APX), H2O2, malondialdehyde (MDA), and total ascorbate (AA) showed a marked increase in these treatments. Therefore, Brassica plants might be more sensitive to excess of these elements in the nutrient solution. The translocation factor (TF) and distribution coefficient (DC) values of Zn, Ca, and Mg indicated higher translocation and accumulation in deficient conditions. High biosynthesis and citrate content in Brassica plants may be associated mainly with a high-nutrient solution extraction ability of these plants. These results provide background data, which will be used to characterize TILLING mutants to study the effects of mutations in genes involved in regulating Zn, Ca, and Mg distribution and accumulation in plants. Copyright © 2014 Elsevier GmbH. All rights reserved.

ACTIVATION OF DIOXIN RESPONSE ELEMENT (DRE)-ASSOCIATED GENES BY BENZO(A)PYRENE 3,6-QUINONE AND BENZO(A)PYRENE 1,6-QUINONE IN MCF-10A HUMAN MAMMARY EPITHELIAL CELLS

PubMed Central

Burchiel, Scott W.; Thompson, Todd A.; Lauer, Fredine T.; Oprea, Tudor I.

2007-01-01

Benzo(a)pyrene (BaP) is a known human carcinogen and a suspected breast cancer complete carcinogen. BaP is metabolized by several metabolic pathways, some having bioactivation and others detoxification properties. BaP-quinones (BPQs) are formed via cytochrome P450 and peroxidase dependent pathways. Previous studies by our laboratory have shown that BPQs have significant growth promoting and anti-apoptotic activities in human MCF-10A mammary epithelial cells examined in vitro. Previous results suggest that BPQs act via redox-cycling and oxidative stress. However, because two specific BPQs (1,6-BPQ and 3,6-BPQ) differed in their ability to produce reactive oxygen species (ROS) and yet both had strong proliferative and EGF receptor activating activity, we utilized mRNA expression arrays and qRT-PCR to determine potential pathways and mechanisms of gene activation. The results of the present studies demonstrated that 1,6-BPQ and 3,6-BPQ activate dioxin response elements (DRE, also known as xenobiotic response elements, XRE) and anti-oxidant response elements (ARE, also known and electrophile response elements, EpRE). 3,6-BPQ had greater DRE activity than 1,6-BPQ, whereas the opposite was true for the activation of ARE. Both 3,6-BPQ and 1,6-BPQ induced oxidative stress associated genes (HMOX1, GCLC, GCLM, and SLC7A11), phase 2 enzyme genes (NQO1, NQO2, ALDH3A1) PAH metabolizing genes (CYP1B1, EPHX1, AKR1C1), and certain EGF receptor associated genes (EGFR, IER3, ING1, SQSTM1 and TRIM16). The results of these studies demonstrate that BPQs activate numerous pathways in human mammary epithelial cells associated with increased cell growth and survival that may play important roles in tumor promotion. PMID:17466351

Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases.

PubMed

Kumar, Hemant; Kim, In-Su; More, Sandeep Vasant; Kim, Byung-Wook; Choi, Dong-Kug

2014-01-01

Covering: 2000 to 2013. Oxidative stress is the central component of chronic diseases. The nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway is vital in the up-regulation of cytoprotective genes and enzymes in response to oxidative stress and treatment with certain dietary phytochemicals. Herein, we classify bioactive compounds derived from natural products that are Nrf2/ARE pathway activators and recapitulate the molecular mechanisms for inducing Nrf2 to provide favorable effects in experimental models of chronic diseases. Moreover, pharmacological inhibition of Nrf2 signalling has emerged as promising strategy against multi-drug resistance thereby improving the treatment efficacy. We have also enlisted natural product-derived inhibitors of Nrf2/ARE pathway.

[Chosen non-enzymatic substances that participate in a protection against overproduction of free radicals].

PubMed

Gałecka, Elzbieta; Mrowicka, Małgorzata; Malinowska, Katarzyna; Gałecki, Piotr

2008-09-01

Free radicals are substantial elements that take part in proper function of metabolic pathways of human cells and tissues in hydrophobic as well as in hydrophilic environment. Nevertheless overproduction of above molecules causes oxidative stress, a process which is very harmful for lipids, proteins, and others molecules what reduces their normal function. To protect against adverse effects of free radicals and theirs derivatives to human body there is a group of antioxidants divided into enzymatic and non-enzymatic substances. Enzymatic antioxidants are represented mainly by enzymes such as: copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). Glutathione (GSH), thioredoxin (Trx), vitamins, melatonin, polyphenols, trace elements, albumin, and others function as non-enzymatic free radicals scavengers. This work in a brief way describes properties of chosen representants of non-enzymatic antioxidant system.

Changes in element accumulation, phenolic metabolism, and antioxidative enzyme activities in the red-skin roots of Panax ginseng.

PubMed

Zhou, Ying; Yang, Zhenming; Gao, Lingling; Liu, Wen; Liu, Rongkun; Zhao, Junting; You, Jiangfeng

2017-07-01

Red-skin root disease has seriously decreased the quality and production of Panax ginseng (ginseng). To explore the disease's origin, comparative analysis was performed in different parts of the plant, particularly the epidermis, cortex, and/or fibrous roots of 5-yr-old healthy and diseased red-skin ginseng. The inorganic element composition, phenolic compound concentration, reactive oxidation system, antioxidant concentrations such as ascorbate and glutathione, activities of enzymes related to phenolic metabolism and oxidation, and antioxidative system particularly the ascorbate-glutathione cycle were examined using conventional methods. Aluminum (Al), iron (Fe), magnesium, and phosphorus were increased, whereas manganese was unchanged and calcium was decreased in the epidermis and fibrous root of red-skin ginseng, which also contained higher levels of phenolic compounds, higher activities of the phenolic compound-synthesizing enzyme phenylalanine ammonia-lyase and the phenolic compound oxidation-related enzymes guaiacol peroxidase and polyphenoloxidase. As the substrate of guaiacol peroxidase, higher levels of H 2 O 2 and correspondingly higher activities of superoxide dismutase and catalase were found in red-skin ginseng. Increased levels of ascorbate and glutathione; increased activities of l-galactose 1-dehydrogenase, ascorbate peroxidase, ascorbic acid oxidase, and glutathione reductase; and lower activities of dehydroascorbate reductase, monodehydroascorbate reductase, and glutathione peroxidase were found in red-skin ginseng. Glutathione- S -transferase activity remained constant. Hence, higher element accumulation, particularly Al and Fe, activated multiple enzymes related to accumulation of phenolic compounds and their oxidation. This might contribute to red-skin symptoms in ginseng. It is proposed that antioxidant and antioxidative enzymes, especially those involved in ascorbate-glutathione cycles, are activated to protect against phenolic compound oxidation.

Plasma Selenium Levels in First Trimester Pregnant Women with Hyperthyroidism and the Relationship with Thyroid Hormone Status.

PubMed

Arikan, Tugba Atilan

2015-10-01

The thyroid gland has the highest selenium (Se) concentration per unit weight among all tissues. The aims of the present study were to evaluate the Se levels in the plasma of hyperthyroidic pregnant women and to investigate the association between maternal plasma Se concentrations and thyroid hormone levels. The study population consisted of 107 pregnant women, 70 healthy pregnant women (group 1) and 37 pregnant women with hyperthyroidism (group 2). The plasma free triiodothyronine (fT3) and free thyroxine (fT4) levels were significantly higher, and the plasma thyroid-stimulating hormone (TSH) and Se levels were significantly lower in group 2 than in group 1 (p < 0.05). A correlation analysis showed a positive correlation between Se and fT4 in group 1 and with TSH in group 2 (p < 0.05). Decreased maternal serum antioxidant trace element Se in hyperthyroidic pregnant women compared with normal pregnant women supported the hypothesis that hyperthyroidism was associated with decreased antioxidant response.

Procyanidins from wild grape (Vitis amurensis) seeds regulate ARE-mediated enzyme expression via Nrf2 coupled with p38 and PI3K/Akt pathway in HepG2 cells.

PubMed

Bak, Min-Ji; Jun, Mira; Jeong, Woo-Sik

2012-01-01

Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles in inducing phase II detoxifying/antioxidant enzymes as well as in modulating the upstream kinases. Ethanolic extract of V. amurensis seeds was fractionated with a series of organic solvents and finally separated into six fractions, F1-F6. Chemical properties of the procyanidins were analyzed by vanillin assay, BuOH-HCl test, and depolymerization with phloroglucinol followed by LC/MS analysis. The F5 had the highest procyanidin content among all the fractions and strongly induced the reporter activity of antioxidant response element as well as the protein expression of nuclear factor E2-related factor (Nrf2) in HepG2 human hepatocarcinoma cells. The procyanidin-rich F5 also strongly induced the expression of the phase II detoxifying and antioxidant enzymes such as NAD(P)H:quinone oxidoreductase1 and hemeoxygenase1. Phosphorylations of the upstream kinases such as MAPKs and PI3K/Akt were significantly increased by treatment with procyanidin fraction. In addition, the procyanidin-mediated Nrf2 expression was partly attenuated by PI3K inhibitor LY294002, and almost completely by p38 inhibitor SB202190, but neither by JNK inhibitor SP600125 nor by MEK1/2 inhibitor U0126. Taken together, the procyanidins from wild grape seeds could be used as a potential natural chemopreventive agent through Nrf2/ARE-mediated phase II detoxifying/antioxidant enzymes induction via p38 and PI3K/Akt pathway.

Protective effects of glutamine on human melanocyte oxidative stress model.

PubMed

Jiang, Liya; Guo, Zhen; Kong, Yulong; Liang, Jianhua; Wang, Yi; Wang, Keyu

2018-01-01

Vitiligo is a disorder caused by the loss of the melanocyte activity on melanin pigment generation. Studies show that oxidative-stress induced apoptosis in melanocytes is closely related to the pathogenesis of vitiligo. Glutamine is a well known antioxidant with anti-apoptotic effects, and is used in a variety of diseases. However, it is unclear whether glutamine has an antioxidant or anti-apoptotic effect on melanocytes. The aim of this study was to investigate the protective effects of glutamine on a human melanocyte oxidative stress model. The oxidative stress model was established on human melanocytes using hydrogen peroxide. The morphology and viability of melanocytes, levels of oxidants [reactive oxygen species and malondialdehyde], levels of antioxidants [superoxide dismutase and glutathione-S-transferase], and apoptosis-related indicators (caspase-3, bax and bcl-2) were examined after glutamine exposure at various concentrations. Expressions of nuclear factor-E2-related factor 2, heme oxygenase-1, and heat shock protein 70 were detected using western blot technique after glutamine exposure at various concentrations. Our results demonstrate that pre-treatment and post-treatment with glutamine promoted melanocyte viability, increased levels of superoxide dismutase, glutathione-S-transferase and bcl-2, decreased levels of reactive oxygen species, malondialdehyde, bax and caspase-3, and enhanced nuclear factor-E2-related factor 2, heme oxygenase-1, and heat shock protein 70 expression in a dose dependent manner. The effect of pre-treatment was more significant than post-treatment, at the same concentration. The mechanisms of glutamine activated nuclear factor-E2-related factor 2 antioxidant responsive element signaling pathway need further investigation. Glutamine enhances the antioxidant and anti-apoptotic capabilities of melanocytes and protects them against oxidative stress.

Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells

PubMed Central

Wu, Jian-Zhang; Cheng, Chan-Chan; Shen, Lai-Lai; Wang, Zhan-Kun; Wu, Shou-Biao; Li, Wu-Lan; Chen, Su-Hua; Zhou, Rong-Ping; Qiu, Pei-Hong

2014-01-01

Chalcone derivatives (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one (Compounds 1 and 2) have been demonstrated to be potent anti-inflammatory agents in our previous study. In light of the relationship of intracellular mechanisms between anti-inflammatories and antioxidants, we further designed and synthesized a series of chalcone derivatives based on 1 and 2, to explore their antioxidant efficacy. The majority of the derivatives exhibited strong protective effects on PC12 (PC12 rat pheochromocytoma) cells exposed to H2O2, and all compounds were nontoxic. A preliminary structure-activity relationship was proposed. Compounds 1 and 1d ((E)-2-methoxy-4-(3-(4-methoxyphenyl)-3-oxoprop-1-en-1-yl) phenyl acrylate) exerted the action in a good dose-dependent manner. Quantitative RT-PCR (qRT-PCR) and western blot analysis showed that 1 and 1d significantly improve the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant genes g-Glutamylcysteine Ligase Catalytic Subunit (GCLC) and heme oxygenase-1 (HO-1) and their corresponding proteins (γ-glutamyl cysteine synthase (γ-GCS) and HO-1) in PC12 cells. Inhibition of GCLC and HO-1 by specific inhibitors, l-buthionine-S-sulfoximine (BSO) and zinc protoporphyrin (ZnPP), respectively, partially reduce the protective effect of 1 and 1d. These data present a series of novel chalcone analogs, especially compounds 1 and 1d, as candidates for treating oxidative stress-related disease by activating the Nrf2-antioxidant responsive element (ARE) pathway. PMID:25318055

Antioxidative and Anti-Melanogenic Activities of Bamboo Stems (Phyllostachys nigra variety henosis) via PKA/CREB-Mediated MITF Downregulation in B16F10 Melanoma Cells.

PubMed

Choi, Moon-Hee; Jo, Han-Gyo; Yang, Ji Hye; Ki, Sung Hwan; Shin, Hyun-Jae

2018-01-30

Phyllostachys nigra var. henosis, a domestic bamboo species, has been attracting much attention; its bioactive compounds (especially in the leaf) show antioxidant, anti-inflammatory, and anti-obesity activities. Little information is available on the antioxidative and anti-melanogenetic activities of the bioactive compounds in bamboo stems. The anti-melanogenic and antioxidative activities of the EtOAc fraction (PN3) of a P. nigra stem extract were investigated in a cell-free system and in B16F10 melanoma cells. PN3 consisted of a mixture of flavonoids, such as catechin, chlorogenic acid, caffeic acid, and p -coumaric acid. The antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)), and hydroxyl radical scavenging) was evaluated, as well as the inhibition of reactive oxygen species (ROS) produced by the Fenton reaction. PN3 showed in vitro tyrosinase inhibition activity with the half maximal inbihitory concentration (IC 50 ) values of 240 μg/mL, and in vivo cytotoxic concentration ranges > 100 μg/mL. The protein expression levels and mRNA transcription levels of TYR , TRP-1 , and MITF were decreased in a dose-dependent manner by the treatment with PN3. PN3 interfered with the phosphorylation of intracellular protein kinase A (PKA)/cAMP response element-binding protein (CREB), demonstrating potent anti-melanogenic effects. PN3 could inhibit PKA/CREB and the subsequent degradation of microphthalmia-associated transcription factor (MITF), resulting in the suppression of melanogenic enzymes and melanin production, probably because of the presence of flavonoid compounds. These properties make it a candidate as an additive to whitening cosmetics.

Antioxidative and Anti-Melanogenic Activities of Bamboo Stems (Phyllostachys nigra variety henosis) via PKA/CREB-Mediated MITF Downregulation in B16F10 Melanoma Cells

PubMed Central

Choi, Moon-Hee; Jo, Han-Gyo; Yang, Ji Hye; Ki, Sung Hwan

2018-01-01

Phyllostachys nigra var. henosis, a domestic bamboo species, has been attracting much attention; its bioactive compounds (especially in the leaf) show antioxidant, anti-inflammatory, and anti-obesity activities. Little information is available on the antioxidative and anti-melanogenetic activities of the bioactive compounds in bamboo stems. The anti-melanogenic and antioxidative activities of the EtOAc fraction (PN3) of a P. nigra stem extract were investigated in a cell-free system and in B16F10 melanoma cells. PN3 consisted of a mixture of flavonoids, such as catechin, chlorogenic acid, caffeic acid, and p-coumaric acid. The antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)), and hydroxyl radical scavenging) was evaluated, as well as the inhibition of reactive oxygen species (ROS) produced by the Fenton reaction. PN3 showed in vitro tyrosinase inhibition activity with the half maximal inbihitory concentration (IC50) values of 240 μg/mL, and in vivo cytotoxic concentration ranges > 100 μg/mL. The protein expression levels and mRNA transcription levels of TYR, TRP-1, and MITF were decreased in a dose-dependent manner by the treatment with PN3. PN3 interfered with the phosphorylation of intracellular protein kinase A (PKA)/cAMP response element-binding protein (CREB), demonstrating potent anti-melanogenic effects. PN3 could inhibit PKA/CREB and the subsequent degradation of microphthalmia-associated transcription factor (MITF), resulting in the suppression of melanogenic enzymes and melanin production, probably because of the presence of flavonoid compounds. These properties make it a candidate as an additive to whitening cosmetics. PMID:29385729

In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids.

PubMed

Peng, Sui; Huo, Xiaofang; Rezaei, Davood; Zhang, Qiuyang; Zhang, Xi; Yu, Chunhua; Asanuma, Kiyotaka; Cheng, Edaire; Pham, Thai H; Wang, David H; Chen, Minhu; Souza, Rhonda F; Spechler, Stuart Jon

2014-07-15

Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA damage and activate NF-κB in Barrett's metaplasia, might contribute to carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced injury in vivo in patients and in vitro using nonneoplastic, telomerase-immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from 21 patients before and after esophageal perfusion with DCA (250 μM) at baseline and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX expression, neutral CometAssay, and phospho-H2AX nuclear foci formation. Quantitative PCR was performed for antioxidants including catalase and GPX1. Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were performed using a plasmid construct containing antioxidant responsive element. In patients, baseline esophageal perfusion with DCA significantly increased phospho-H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing DNA damage and NF-κB activation. In cells, DCA-induced DNA damage and NF-κB activation was prevented by 24-h pretreatment with UDCA, but not by mixing UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase expression, and protective effects of UDCA pretreatment were blocked by siRNA knockdown of these antioxidants. UDCA increases expression of antioxidants that prevent toxic bile acids from causing DNA damage and NF-κB activation in Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection provides rationale for clinical trials on UDCA for chemoprevention in Barrett's esophagus. Copyright © 2014 the American Physiological Society.

In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids

PubMed Central

Peng, Sui; Huo, Xiaofang; Rezaei, Davood; Zhang, Qiuyang; Zhang, Xi; Yu, Chunhua; Asanuma, Kiyotaka; Cheng, Edaire; Pham, Thai H.; Wang, David H.; Chen, Minhu; Spechler, Stuart Jon

2014-01-01

Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA damage and activate NF-κB in Barrett's metaplasia, might contribute to carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced injury in vivo in patients and in vitro using nonneoplastic, telomerase-immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from 21 patients before and after esophageal perfusion with DCA (250 μM) at baseline and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX expression, neutral CometAssay, and phospho-H2AX nuclear foci formation. Quantitative PCR was performed for antioxidants including catalase and GPX1. Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were performed using a plasmid construct containing antioxidant responsive element. In patients, baseline esophageal perfusion with DCA significantly increased phospho-H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing DNA damage and NF-κB activation. In cells, DCA-induced DNA damage and NF-κB activation was prevented by 24-h pretreatment with UDCA, but not by mixing UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase expression, and protective effects of UDCA pretreatment were blocked by siRNA knockdown of these antioxidants. UDCA increases expression of antioxidants that prevent toxic bile acids from causing DNA damage and NF-κB activation in Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection provides rationale for clinical trials on UDCA for chemoprevention in Barrett's esophagus. PMID:24852569

Oxidative stress suppression by luteolin-induced heme oxygenase-1 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Gui-bo; Sun, Xiao; Wang, Min

Luteolin, a flavonoid that exhibits antioxidative properties, exerts myocardial protection effects. However, the underlying molecular mechanisms are not yet fully understood. To investigate the effects of luteolin on myocardial injury protection and its possible mechanisms, a myocardial injury model was established with intragastric administration of 4 mg/kg isoproterenol (ISO) to male Sprague–Dawley rats (200–220 g) daily for 2 days. We found that pretreatment of luteolin (160, 80 and 40 mg/kg, i.g., respectively) daily for 15 days can prevent ISO-induced myocardial damage, including decrease of serum cardiac enzymes, improvement electrocardiography and heart vacuolation. Luteolin also improved the free radical scavenging andmore » antioxidant potential, suggesting one possible mechanism of luteolin-induced cardio-protection is mediated by blocking the oxidative stress. To clarify the mechanisms, we performed the in vitro study by hydrogen peroxide (H{sub 2}O{sub 2})-induced cytotoxicty model in H9c2 cells. We found that luteolin pretreatment prevented apoptosis, increased the expression of heme oxygenase-1 (HO-1), and enhanced the binding of Nrf2 to the antioxidant response element, providing an adaptive survival response against H{sub 2}O{sub 2}-derived oxidative cytotoxicity. The addition of Znpp, a selective HO-1 competitive inhibitor, reduced the cytoprotective ability of luteolin, indicating the vital role of HO-1 on these effects. Luteolin also activated Akt and ERK, whereas the addition of LY294002 and U0126, the pharmacologic inhibitors of PI3K and ERK, attenuated luteolin-induced HO-1 expression and cytoprotective effect. Taken together, the above findings suggest that luteolin protects against myocardial injury and enhances cellular antioxidant defense capacity through the activation of Akt and ERK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction. -- Highlights: ► Luteolin prevents isoproterenol-induced myocardial damage. ► Luteolin enhances cellular antioxidant defense capacity. ► Luteolin increases the expression of heme oxygenase-1 protein levels. ► Luteolin activates Akt and ERK signal pathways.« less

Developmental characterization and environmental stress responses of Y-box binding protein 1 gene (AccYB-1) from Apis cerana cerana.

PubMed

Li, Guilin; Wang, Lijun; Wang, Ying; Li, Han; Liu, Zhenguo; Wang, Hongfang; Xu, Baohua; Guo, Xingqi

2018-06-22

Y-box binding protein 1 (YB-1) is a member of the cold shock domain protein superfamily and is involved in development, environmental stresses and DNA oxidative damage in many organisms. However, the precise functions of YB-1 are still not well understood in various insects, including bees. In the current study, we identified a YB-1 gene in Apis cerana cerana (AccYB-1). The predicted cis-acting elements in the promoter sequence of AccYB-1 indicated its possible roles in development and stress responses. AccYB-1 expression was higher in one-day-old larvae and dark-eyed pupae than in other development stages. Tissue-specific expression analysis showed that the mRNA level of AccYB-1 was higher in the thorax and midgut than in other tissues. The results from real-time PCR showed that AccYB-1 was induced by many environmental stresses. Silencing AccYB-1 downregulated the transcriptional level of some growth- and development-related genes and antioxidant genes and decreased the enzyme activities of several antioxidant-related enzymes, further indicating a possible function of AccYB-1 in growth, development and stress responses. Taken together, our findings suggest that AccYB-1 may play an indispensable role in growth and development and environmental stress responses in Apis cerana cerana. To our knowledge, this is the first paper to explore the role of YB-1 in bees. Copyright © 2018. Published by Elsevier B.V.

Antioxidant status in vivo: the case for regular consumption of antioxidant rich fruits and vegetables

USDA-ARS?s Scientific Manuscript database

Since metabolism of energy is a major source of reactive oxygen species, the quantity of dietary antioxidants needed may be related to energy consumption. Antioxidant status in vivo can be altered by diet, but the postprandial response is dependent upon factors such as 1) antioxidant capacity (AOC) ...

Carotenoids: biochemistry, pharmacology and treatment.

PubMed

Milani, Alireza; Basirnejad, Marzieh; Shahbazi, Sepideh; Bolhassani, Azam

2017-06-01

Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, the Wnt/β-catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B- and T-lymphocytes, the activity of macrophages and cytotoxic T-cells, effector T-cell function and the production of cytokines. Recently, the beneficial effects of carotenoid-rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β-carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time- and dose-dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

Carotenoids: biochemistry, pharmacology and treatment

PubMed Central

Milani, Alireza; Basirnejad, Marzieh; Shahbazi, Sepideh

2016-01-01

Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation‐related proteins, retinoid‐like receptors, antioxidant response element, nuclear receptors, AP‐1 transcriptional complex, the Wnt/β‐catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B‐ and T‐lymphocytes, the activity of macrophages and cytotoxic T‐cells, effector T‐cell function and the production of cytokines. Recently, the beneficial effects of carotenoid‐rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β‐carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time‐ and dose‐dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:27638711

CDDO and Its Role in Chronic Diseases.

PubMed

Mathis, Bryan J; Cui, Taixing

2016-01-01

There has been a continued interest in translational research focused on both natural products and manipulation of functional groups on these compounds to create novel derivatives with higher desired activities. Oleanolic acid, a component of traditional Chinese medicine used in hepatitis therapy, was modified by chemical processes to form 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO). This modification increased anti-inflammatory activity significantly and additional functional groups on the CDDO backbone have shown promise in treating conditions ranging from kidney disease to obesity to diabetes. CDDO's therapeutic effect is due to its upregulation of the master antioxidant transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) through conformational change of Nrf2-repressing, Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) and multiple animal and human studies have verified subsequent activation of Nrf2-controlled antioxidant genes via upstream Antioxidant Response Element (ARE) regions. At the present time, positive results have been obtained in the laboratory and clinical trials with CDDO derivatives treating conditions such as lung injury, inflammation and chronic kidney disease. However, clinical trials for cancer and cardiovascular disease have not shown equally positive results and further exploration of CDDO and its derivatives is needed to put these shortcomings into context for the purpose of future therapeutic modalities.

Impact of proline application on cadmium accumulation, mineral nutrition and enzymatic antioxidant defense system of Olea europaea L. cv Chemlali exposed to cadmium stress.

PubMed

Zouari, Mohamed; Ben Ahmed, Chedlia; Elloumi, Nada; Bellassoued, Khaled; Delmail, David; Labrousse, Pascal; Ben Abdallah, Ferjani; Ben Rouina, Bechir

2016-06-01

Proline plays an important role in plant response to various environmental stresses. However, its involvement in mitigation of heavy metal stress in plants remains elusive. In this study, we examined the effectiveness of exogenous proline (10 and 20 mM) in alleviating cadmium induced inhibitory effects in young olive plants (Olea europaea L. cv. Chemlali) exposed to two Cd levels (10 and 30 mg CdCl2 kg(-1) soil). The Cd treatment induced substantial accumulation of Cd in both root and leaf tissues and a decrease in gas exchange, photosynthetic pigments contents, uptake of essential elements (Ca, Mg and K) and plant biomass. Furthermore, an elevation of antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxydase) and proline content in association with relatively high amounts of hydrogen peroxide, thiobarbituric acid reactive substances and electrolyte leakage were observed. Interestingly, the application of exogenous proline alleviated the oxidative damage induced by Cd accumulation. In fact, Cd-stressed olive plants treated with proline showed an increase of antioxidant enzymes activities, photosynthetic activity, nutritional status, plant growth and oil content of olive fruit. Generally, it seems that proline supplementation alleviated the deleterious effects of young olive plants exposed to Cd stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals.

PubMed

Qin, Si; Hou, De-Xing

2016-08-01

Keap1/Nrf2 system plays a critical role on cellular protection by regulating many antioxidant and detoxification enzyme genes through the antioxidant response element (ARE). Thus, it must work constantly to prevent the accumulation of reactive oxygen species (ROS) because excess ROS are associated with many diseases such as cancer, cardiovascular complications, inflammation, and neurodegeneration. Dietary phytochemicals widely distributing in fruits and vegetables have been considered to possess cancer chemopreventive potential through the induction of Keap1/Nrf2 system-mediated antioxidant and detoxification enzymes in a variety of manners. The data are extensive and are not well classified on the molecular mechanisms. In this review, we first briefly introduce the current knowledge on Keap1/Nrf2 system regulation including Keap1-dependent and Keap1-independent cascades, and epigenetic pathway. Then, we summarize the molecular targets of Keap1/Nrf2 system by dietary phytochemicals, and finally review the crosstalk between Keap1/Nrf2 system and other cellular signaling pathways to regulate diverse chronic diseases by dietary phytochemicals. These comprehensive data will help us to understand the potential effects of dietary phytochemicals on the prevention of chronic diseases and maintenance of human health. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interleukin-6 Reduces β-Cell Oxidative Stress by Linking Autophagy With the Antioxidant Response.

PubMed

Marasco, Michelle R; Conteh, Abass M; Reissaus, Christopher A; Cupit V, John E; Appleman, Evan M; Mirmira, Raghavendra G; Linnemann, Amelia K

2018-05-21

Production of reactive oxygen species (ROS) is a key instigator of β-cell dysfunction in diabetes. The pleiotropic cytokine IL-6 has previously been linked to β-cell autophagy but has not been studied in the context of β-cell antioxidant response. We used a combination of animal models of diabetes and analysis of cultured human islets and rodent β-cells to study how IL-6 influences antioxidant response. We show that IL-6 couples autophagy to antioxidant response to reduce β-cell and human islet ROS. β cell-specific loss of IL-6 signaling in vivo renders mice more susceptible to oxidative damage and cell death by the selective β-cell toxins streptozotocin and alloxan. IL-6-driven ROS reduction is associated with an increase in the master antioxidant factor NRF2, which rapidly translocates to the mitochondria to decrease mitochondrial activity and stimulate mitophagy. IL-6 also initiates a robust transient drop in cellular cAMP, likely contributing to the stimulation of mitophagy for ROS mitigation. Our findings suggest that coupling autophagy to antioxidant response in the β cell leads to stress adaptation that can reduce cellular apoptosis. These findings have implications for β-cell survival under diabetogenic conditions and present novel targets for therapeutic intervention. © 2018 by the American Diabetes Association.

The antioxidant effect of derivatives pyroglutamic lactam

NASA Astrophysics Data System (ADS)

Rohadi, Atisya; Lazim, Azwani Mat; Hasbullah, Siti Aishah

2013-11-01

Diphenylpicrylhydrazyl (DPPH) is widely used for quickly accessing the ability of polyphenols to transfer labile H atoms to radicals. The antioxidant activity of all the synthesized compounds was screened by DPPH method. Compound (4) showed 54% antioxidant potential while all other compounds were found to have moderate to have moderate to mild antioxidant activity ranging from 47-52%. Pyroglutamic lactams have been synthesized stereoselectively in racemic form from levulinic acid as bifunctional adduct using convertible isocyanide in one-pot Ugi 4-center-3-component condensation reaction (U-4C-3CR). The product formed provides biologically interesting products in excellent yields in a short reaction time. The structures of the synthesized compounds were elucidated using spectroscopic data and elemental analysis.

Flavone-resistant Leishmania donovani Overexpresses LdMRP2 Transporter in the Parasite and Activates Host MRP2 on Macrophages to Circumvent the Flavone-mediated Cell Death*

PubMed Central

Chowdhury, Sayan; Mukhopadhyay, Rupkatha; Saha, Sourav; Mishra, Amartya; Sengupta, Souvik; Roy, Syamal; Majumder, Hemanta K.

2014-01-01

In parasites, ATP-binding cassette (ABC) transporters represent an important family of proteins related to drug resistance and other biological activities. Resistance of leishmanial parasites to therapeutic drugs continues to escalate in developing countries, and in many instances, it is due to overexpressed ABC efflux pumps. Progressively adapted baicalein (BLN)-resistant parasites (pB25R) show overexpression of a novel ABC transporter, which was classified as ABCC2 or Leishmania donovani multidrug resistance protein 2 (LdMRP2). The protein is primarily localized in the flagellar pocket region and in internal vesicles. Overexpressed LdABCC2 confers substantial BLN resistance to the parasites by rapid drug efflux. The BLN-resistant promastigotes when transformed into amastigotes in macrophage cells cannot be cured by treatment of macrophages with BLN. Amastigote resistance is concomitant with the overexpression of macrophage MRP2 transporter. Reporter analysis and site-directed mutagenesis assays demonstrated that antioxidant response element 1 is activated upon infection. The expression of this phase II detoxifying gene is regulated by NFE2-related factor 2 (Nrf2)-mediated antioxidant response element activation. In view of the fact that the signaling pathway of phosphoinositol 3-kinase controls microfilament rearrangement and translocation of actin-associated proteins, the current study correlates with the intricate pathway of phosphoinositol 3-kinase-mediated nuclear translocation of Nrf2, which activates MRP2 expression in macrophages upon infection by the parasites. In contrast, phalloidin, an agent that prevents depolymerization of actin filaments, inhibits Nrf2 translocation and Mrp2 gene activation by pB25R infection. Taken together, these results provide insight into the mechanisms by which resistant clinical isolates of L. donovani induce intracellular events relevant to drug resistance. PMID:24706751

Neuroprotective effects of α-iso-cubebene against glutamate-induced damage in the HT22 hippocampal neuronal cell line.

PubMed

Park, Sun Young; Jung, Won Jung; Kang, Jum Soon; Kim, Cheol-Min; Park, Geuntae; Choi, Young-Whan

2015-02-01

Since oxidative stress is critically involved in excitotoxic damage, we sought to determine whether the activation of the transcription factors, cAMP-responsive element binding protein (CREB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2, also known as NFE2L2), by α-iso-cubebene is involved in its protective effects against glutamate-induced neuronal cell death. Pre-treatment with α-iso-cubebene significantly attenuated glutamate-induced cytotoxicity in mouse hippocampus-derived neuronal cells. α-iso-cubebene also reduced the glutamate-induced generation of reactive oxygen species and calcium influx, thus preventing apoptotic cell death. α-iso-cubebene inhibited glutamate-induced mitochondrial membrane depolarization and, consequently, inhibited the release of the apoptosis-inducing factor from the mitochondria. Immunoblot anlaysis revealed that the phosphorylation of extracellular signal-regulated kinase (ERK) by glutamate was reduced in the presence of α-iso-cubebene. α-iso-cubebene activated protein kinase A (PKA), CREB and Nrf2, which mediate the expression of the antioxidant enzymes, heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1), involved in neuroprotection. In addition, α-iso-cubebene induced the expression of antioxidant responsive element and CRE transcriptional activity, thus conferring neuroprotection against glutamate-induced oxidative injury. α-iso-cubebene also induced the expression of Nrf2-dependent genes encoding HO-1 and NQO1. Furthermore, the knockdown of CREB and Nrf2 by small interfering RNA attenuated the neuroprotective effects of α-iso-cubebene. Taken together, our results indicate that α-iso-cubebene protects HT22 cells from glutamate-induced oxidative damage through the activation of Nrf2/HO-1/NQO-1, as well as through the PKA and CREB signaling pathways.

Mangiferin activates Nrf2-antioxidant response element signaling without reducing the sensitivity to etoposide of human myeloid leukemia cells in vitro

PubMed Central

Zhang, Ben-ping; Zhao, Jie; Li, Shan-shan; Yang, Li-jing; Zeng, Ling-lan; Chen, Yan; Fang, Jun

2014-01-01

Aim: Mangiferin is glucosylxanthone extracted from plants of the Anacardiaceae and Gentianaceae families. The aim of this study was to investigate the effects of mangiferin on Nrf2-antioxidant response element (ARE) signaling and the sensitivity to etoposide of human myeloid leukemia cells in vitro. Methods: Human HL-60 myeloid leukemia cells and mononuclear human umbilical cord blood cells (MNCs) were examined. Nrf2 protein was detected using immunofluorescence staining and Western blotting. Binding of Nrf2 to ARE was examined with electrophoretic mobility shift assay. The level of NQO1 was assessed with real-time RT-PCR and Western blotting. DCFH-DA was used to evaluate intracellular ROS level. Cell proliferation and apoptosis were analyzed using MTT and flow cytometry, respectively. Results: Mangiferin (50 μmol/L) significantly increased Nrf2 protein accumulation in HL-60 cells, particularly in the nucleus. Mangiferin also enhanced the binding of Nrf2 to an ARE, significantly up-regulated NQO1 expression and reduced intracellular ROS in HL60 cells. Mangiferin alone dose-dependently inhibited the proliferation of HL-60 cells. Mangiferin (50 mol/L) did not attenuate etoposide-induced cytotoxicity in HL-60 cells, and combined treatment of mangiferin with low concentration of etoposide (0.8 μg/mL) even increased the cell inhibition rate. Nor did mangiferin change the rate of etoposide-induced apoptosis in HL-60 cells. In MNCs, mangiferin significantly relieved oxidative stress, but attenuated etoposide-induced cytotoxicity. Conclusion: Mangiferin is a novel Nrf2 activator that reduces oxidative stress and protects normal cells without reducing the sensitivity to etoposide of HL-60 leukemia cells in vitro. Mangiferin may be a potential chemotherapy adjuvant. PMID:24374812

Mangiferin activates Nrf2-antioxidant response element signaling without reducing the sensitivity to etoposide of human myeloid leukemia cells in vitro.

PubMed

Zhang, Ben-ping; Zhao, Jie; Li, Shan-shan; Yang, Li-jing; Zeng, Ling-lan; Chen, Yan; Fang, Jun

2014-02-01

Mangiferin is glucosylxanthone extracted from plants of the Anacardiaceae and Gentianaceae families. The aim of this study was to investigate the effects of mangiferin on Nrf2-antioxidant response element (ARE) signaling and the sensitivity to etoposide of human myeloid leukemia cells in vitro. Human HL-60 myeloid leukemia cells and mononuclear human umbilical cord blood cells (MNCs) were examined. Nrf2 protein was detected using immunofluorescence staining and Western blotting. Binding of Nrf2 to ARE was examined with electrophoretic mobility shift assay. The level of NQO1 was assessed with real-time RT-PCR and Western blotting. DCFH-DA was used to evaluate intracellular ROS level. Cell proliferation and apoptosis were analyzed using MTT and flow cytometry, respectively. Mangiferin (50 μmol/L) significantly increased Nrf2 protein accumulation in HL-60 cells, particularly in the nucleus. Mangiferin also enhanced the binding of Nrf2 to an ARE, significantly up-regulated NQO1 expression and reduced intracellular ROS in HL60 cells. Mangiferin alone dose-dependently inhibited the proliferation of HL-60 cells. Mangiferin (50 mol/L) did not attenuate etoposide-induced cytotoxicity in HL-60 cells, and combined treatment of mangiferin with low concentration of etoposide (0.8 μg/mL) even increased the cell inhibition rate. Nor did mangiferin change the rate of etoposide-induced apoptosis in HL-60 cells. In MNCs, mangiferin significantly relieved oxidative stress, but attenuated etoposide-induced cytotoxicity. Mangiferin is a novel Nrf2 activator that reduces oxidative stress and protects normal cells without reducing the sensitivity to etoposide of HL-60 leukemia cells in vitro. Mangiferin may be a potential chemotherapy adjuvant.

Sublethal toxicity of quinalphos on oxidative stress and antioxidant responses in a freshwater fish Cyprinus carpio.

PubMed

Hemalatha, Devan; Amala, Antony; Rangasamy, Basuvannan; Nataraj, Bojan; Ramesh, Mathan

2016-11-01

Extensive use of quinalphos, an organophosphorus pesticide, is likely to reach the aquatic environment and thereby posing a health concern for aquatic organisms. Oxidative stress and antioxidant responses may be good indicators of pesticide contamination in aquatic organisms. The data on quinalphos induced oxidative stress and antioxidant responses in carps are scanty. This study is aimed to assess the two sublethal concentrations of quinalphos (1.09 and 2.18 μL L -1 ) on oxidative stress and antioxidant responses of Cyprinus carpio for a period of 20 days. In liver, the malondialdehyde level was found to be significantly increased in both the concentrations. The results of the antioxidant parameters obtained show a significant increase in superoxide dismutase, catalase, and glutathione-S-transferase activity in liver of fish. These results demonstrate that environmentally relevant levels of the insecticide quinalphos can cause oxidative damage and increase the antioxidant scavenging capacity in C. carpio. This may reflect the potential role of these parameters as useful biomarkers for the assessment of pesticide contamination. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1399-1406, 2016. © 2015 Wiley Periodicals, Inc.

Beta-thalassemia major and female fertility: the role of iron and iron-induced oxidative stress.

PubMed

Roussou, Paraskevi; Tsagarakis, Nikolaos J; Kountouras, Dimitrios; Livadas, Sarantis; Diamanti-Kandarakis, Evanthia

2013-01-01

Endocrine complications due to haemosiderosis are present in a significant number of patients with beta-thalassemia major (BTM) worldwide and often become barriers in their desire for parenthood. Thus, although spontaneous fertility can occur, the majority of females with BTM is infertile due to hypogonadotropic hypogonadism (HH) and need assisted reproductive techniques. Infertility in these women seems to be attributed to iron deposition and iron-induced oxidative stress (OS) in various endocrine organs, such as hypothalamus, pituitary, and female reproductive system, but also through the iron effect on other organs, such as liver and pancreas, contributing to the impaired metabolism of hormones and serum antioxidants. Nevertheless, the gonadal function of these patients is usually intact and fertility is usually retrievable. Meanwhile, a significant prooxidants/antioxidants imbalance with subsequent increased (OS) exists in patients with BTM, which is mainly caused by tissue injury due to overproduction of free radicals by secondary iron overload, but also due to alteration in serum trace elements and antioxidant enzymes. Not only using the appropriate antioxidants, essential trace elements, and minerals, but also regulating the advanced glycation end products, could probably reduce the extent of oxidative damage and related complications and retrieve BTM women's infertility.

p62/Sequestosome-1, Autophagy-related Gene 8, and Autophagy in Drosophila Are Regulated by Nuclear Factor Erythroid 2-related Factor 2 (NRF2), Independent of Transcription Factor TFEB.

PubMed

Jain, Ashish; Rusten, Tor Erik; Katheder, Nadja; Elvenes, Julianne; Bruun, Jack-Ansgar; Sjøttem, Eva; Lamark, Trond; Johansen, Terje

2015-06-12

The selective autophagy receptor p62/sequestosome 1 (SQSTM1) interacts directly with LC3 and is involved in oxidative stress signaling in two ways in mammals. First, p62 is transcriptionally induced upon oxidative stress by the NF-E2-related factor 2 (NRF2) by direct binding to an antioxidant response element in the p62 promoter. Second, p62 accumulation, occurring when autophagy is impaired, leads to increased p62 binding to the NRF2 inhibitor KEAP1, resulting in reduced proteasomal turnover of NRF2. This gives chronic oxidative stress signaling through a feed forward loop. Here, we show that the Drosophila p62/SQSTM1 orthologue, Ref(2)P, interacts directly with DmAtg8a via an LC3-interacting region motif, supporting a role for Ref(2)P in selective autophagy. The ref(2)P promoter also contains a functional antioxidant response element that is directly bound by the NRF2 orthologue, CncC, which can induce ref(2)P expression along with the oxidative stress-associated gene gstD1. However, distinct from the situation in mammals, Ref(2)P does not interact directly with DmKeap1 via a KEAP1-interacting region motif; nor does ectopically expressed Ref(2)P or autophagy deficiency activate the oxidative stress response. Instead, DmAtg8a interacts directly with DmKeap1, and DmKeap1 is removed upon programmed autophagy in Drosophila gut cells. Strikingly, CncC induced increased Atg8a levels and autophagy independent of TFEB/MitF in fat body and larval gut tissues. Thus, these results extend the intimate relationship between oxidative stress-sensing NRF2/CncC transcription factors and autophagy and suggest that NRF2/CncC may regulate autophagic activity in other organisms too. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Addition of mushroom powder to pasta enhances the antioxidant content and modulates the predictive glycaemic response of pasta.

PubMed

Lu, Xikun; Brennan, Margaret A; Serventi, Luca; Liu, Jianfu; Guan, Wenqiang; Brennan, Charles S

2018-10-30

This study reports the effects of addition of mushroom powder on the nutritional properties, predictive in vitro glycaemic response and antioxidant potential of durum wheat pasta. Addition of the mushroom powder enriched the pasta as a source of protein, and soluble and insoluble dietary fibre compared with durum wheat semolina. Incorporation of mushroom powder significantly decreased the extent of starch degradation and the area under the curve (AUC) of reducing sugars released during digestion, while the total phenolic content and antioxidant capacities of samples increased. A mutual inhibition system between the degree of starch gelatinisation and antioxidant capacity of the pasta samples was observed. These results suggest that mushroom powder could be incorporated into fresh semolina pasta, conferring healthier characteristics, namely lowering the potential glycaemic response and improving antioxidant capacity of the pasta. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Mi-Hwi; Kim, Eung-Hwi

Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H{sub 2}O{sub 2}. Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured. The mRNA and protein expression levels of antioxidant genes were examined. The level of nuclear factormore » erythroid 2-related factor 2 (Nrf2), its binding to antioxidant response element (ARE), and its ubiquination in the presence of EX4 were determined. The Nrf2 signaling pathway was determined using rottlerin (protein kinase [PK]Cδ inhibitor), H89 (PKA inhibitor) and LY294002 (phosphatidylinositide 3-kinase [PI3K] inhibitor). EX4 treatment decreased ROS production, recovered cellular glutathione levels and insulin secretion in the presence of oxidative stress in INS-1 cells. The expression levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 were increased by EX4 treatment. EX4 promoted Nrf2 translocation, ARE binding activity and enhanced stabilization of Nrf2 by inhibition of ubiquitination. Knockdown of Nrf2 abolished the effect of EX4 on increased insulin secretion. Inhibition of PKCδ attenuated Nrf2 translocation and antioxidative gene expression by EX4 treatment. We suggest that EX4 activates and stabilizes Nrf2 through PKCδ activation, contributing to the increase of antioxidant gene expression and consequently improving beta cell function in the presence of oxidative stress. - Highlights: • EX4 protects against oxidative stress-induced pancreatic beta cell dysfunction. • EX4 increases antioxidant gene expression. • Antioxidative effect of EX4 is mediated by Nrf2. • EX4 increases Nrf2 level by stabilizing Nrf2 protein. • EX4 stabilizes Nrf2 by activation of PKCδ.« less

The antioxidant effect of derivatives pyroglutamic lactam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rohadi, Atisya; Lazim, Azwani Mat; Hasbullah, Siti Aishah

Diphenylpicrylhydrazyl (DPPH) is widely used for quickly accessing the ability of polyphenols to transfer labile H atoms to radicals. The antioxidant activity of all the synthesized compounds was screened by DPPH method. Compound (4) showed 54% antioxidant potential while all other compounds were found to have moderate to have moderate to mild antioxidant activity ranging from 47–52%. Pyroglutamic lactams have been synthesized stereoselectively in racemic form from levulinic acid as bifunctional adduct using convertible isocyanide in one-pot Ugi 4-center-3-component condensation reaction (U-4C-3CR). The product formed provides biologically interesting products in excellent yields in a short reaction time. The structures ofmore » the synthesized compounds were elucidated using spectroscopic data and elemental analysis.« less

Conservative Nonhormonal Options for the Treatment of Male Infertility: Antibiotics, Anti-Inflammatory Drugs, and Antioxidants

PubMed Central

Condorelli, Rosita A.

2017-01-01

The nonhormonal medical treatment can be divided into empirical, when the cause has not been identified, and nonempirical, if the pathogenic mechanism causing male infertility can be solved or ameliorated. The empirical nonhormonal medical treatment has been proposed for patients with idiopathic or noncurable oligoasthenoteratozoospermia and for normozoospermic infertile patients. Anti-inflammatory, fibrinolytic, and antioxidant compounds, oligo elements, and vitamin supplementation may be prescribed. Infection, inflammation, and/or increased oxidative stress often require a specific treatment with antibiotics, anti-inflammatory drugs, and/or antioxidants. Combined therapies can contribute to improve sperm quality. PMID:28164122

Conservative Nonhormonal Options for the Treatment of Male Infertility: Antibiotics, Anti-Inflammatory Drugs, and Antioxidants.

PubMed

Calogero, Aldo E; Condorelli, Rosita A; Russo, Giorgio Ivan; La Vignera, Sandro

2017-01-01

The nonhormonal medical treatment can be divided into empirical, when the cause has not been identified, and nonempirical, if the pathogenic mechanism causing male infertility can be solved or ameliorated. The empirical nonhormonal medical treatment has been proposed for patients with idiopathic or noncurable oligoasthenoteratozoospermia and for normozoospermic infertile patients. Anti-inflammatory, fibrinolytic, and antioxidant compounds, oligo elements, and vitamin supplementation may be prescribed. Infection, inflammation, and/or increased oxidative stress often require a specific treatment with antibiotics, anti-inflammatory drugs, and/or antioxidants. Combined therapies can contribute to improve sperm quality.

Ozone therapy effects on biomarkers and lung function in asthma.

PubMed

Hernández Rosales, Frank A; Calunga Fernández, José L; Turrent Figueras, José; Menéndez Cepero, Silvia; Montenegro Perdomo, Adonis

2005-01-01

The relationship and behavior of serum immunoglobulin E (IgE) level, peripheral blood mononuclear cell (PBMC) human leukocyte antigen DR (HLA-DR) expression and erythrocyte glutathione antioxidant pathway in asthma patients treated with systemic ozone therapy have not been studied before. Asthma patients were treated about 1 year with three cycles (5 or 6 months each) with three different ozone therapy protocols. Ozone major autohemotherapy (MAHT) was applied at doses of 4 and 8 mg, 15 sessions each cycle; and ozone rectal insufflations (RI) at a dose of 10 mg, 20 sessions each cycle. Serum IgE, HLA-DR expression in PBMC and biomarkers for antioxidant pathway were measured before and at the end of each cycle. Lung function and symptoms test were recorded at the beginning and after the third cycle. IgE and HLA-DR decreased with the three types of treatments, while increments in reduced glutathione, glutathione peroxidase, glutation reductase and glutathione S-transferase were achieved with all treatments. Lung function and symptoms test were markedly improved. However, in all parameters the best response was obtained in the order: MAHT at 8 mg better than MAHT at 4 mg better than RI at 10 mg. Before ozone treatment, glutathione antioxidant parameters were under the normal reference values, suggesting the occurrence of oxidative stress associated with atopic asthma. This study demonstrates the effectiveness of ozone therapy in reducing IgE and inflammatory mediators along with the induction of antioxidant elements. The study raises the role of systemic ozone therapy in atopic asthma by means of its immunomodulatory and oxidative stress regulation properties.

Nrf2-ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice.

PubMed

Miller, Darren M; Singh, Indrapal N; Wang, Juan A; Hall, Edward D

2015-02-01

The importance of free radical-induced oxidative damage after traumatic brain injury (TBI) has been well documented. Despite multiple clinical trials with radical-scavenging antioxidants that are neuroprotective in TBI models, none is approved for acute TBI patients. As an alternative antioxidant target, Nrf2 is a transcription factor that activates expression of antioxidant and cytoprotective genes by binding to antioxidant response elements (AREs) within DNA. Previous research has shown that neuronal mitochondria are susceptible to oxidative damage post-TBI, and thus the current study investigates whether Nrf2-ARE activation protects mitochondrial function when activated post-TBI. It was hypothesized that administration of carnosic acid (CA) would reduce oxidative damage biomarkers in the brain tissue and also preserve cortical mitochondrial respiratory function post-TBI. A mouse controlled cortical impact (CCI) model was employed with a 1.0mm cortical deformation injury. Administration of CA at 15 min post-TBI reduced cortical lipid peroxidation, protein nitration, and cytoskeletal breakdown markers in a dose-dependent manner at 48 h post-injury. Moreover, CA preserved mitochondrial respiratory function compared to vehicle animals. This was accompanied by decreased oxidative damage to mitochondrial proteins, suggesting the mechanistic connection of the two effects. Lastly, delaying the initial administration of CA up to 8h post-TBI was still capable of reducing cytoskeletal breakdown, thereby demonstrating a clinically relevant therapeutic window for this approach. This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of trans-acting factors regulating SamDC expression in Oryza sativa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, Supratim, E-mail: supratim_genetics@yahoo.co.in; Division of Plant Biology, Bose Institute, Kolkata; Roychoudhury, Aryadeep

2014-03-07

Highlights: • Identification of cis elements responsible for SamDC expression by in silico analysis. • qPCR analysis of SamDC expression to abiotic and biotic stress treatments. • Detection of SamDC regulators using identified cis-elements as probe by EMSA. • Southwestern Blot analysis to predict the size of the trans-acting factors. - Abstract: Abiotic stress affects the growth and productivity of crop plants; to cope with the adverse environmental conditions, plants have developed efficient defense machinery comprising of antioxidants like phenolics and flavonoids, and osmolytes like polyamines. SamDC is a key enzyme in the polyamine biosynthesis pathway in plants. In ourmore » present communication we have done in silico analysis of the promoter region of SamDC to look for the presence of different cis-regulatory elements contributing to its expression. Based on the presence of different cis-regulatory elements we completed comparative analysis of SamDC gene expression in rice lamina of IR-29 and Nonabokra by qPCR in response to the abiotic stress treatments of salinity, drought, cold and the biotic stress treatments of ABA and light. Additionally, to explore the role of the cis-regulatory elements in regulating the expression of SamDC gene in plants we comparatively analyzed the binding of rice nuclear proteins prepared from IR-29 and Nonabokra undergoing various stress treatments. The intensity of the complex formed was low and inducible in IR-29 in contrast to Nonabokra. Southwestern blot analysis helped in predicting the size of the trans-acting factors binding to these cis-elements. To our knowledge this is the first report on the comprehensive analysis of SamDC gene expression in rice and identification of the trans-acting factors regulating its expression.« less

Studies on the effects on growth and antioxidant responses of two marine microalgal species to uniconazole

NASA Astrophysics Data System (ADS)

Mei, Xueqiao; Zheng, Kang; Wang, Lingdong; Li, Yantuan

2014-10-01

Uniconazole, as a plant growth retardant, can enhance stress tolerance in plants, possibly because of improved antioxidation defense mechanisms with higher activities of superoxide dismutase (SOD) and peroxidase (POD) enzymes that retard lipid peroxidation and membrane deterioration. These years much attention has been focused on the responses of antioxidant system in plants to uniconazole stress, but such studies on aquatic organism are very few. Moreover, no information is available on growth and antioxidant response in marine microalgae to uniconazole. In this paper, the growth and antioxidant responses of two marine microalgal species, Platymonas helgolandica and Pavlova viridis, at six uniconazole concentrations (0-15 mg L-1) were investigated. The results demonstrated that 3 mg L-1 uniconazole could increase significantly chlorophyll a and carbohydrate contents of P. helgolandica ( P < 0.05). Higher concentrations (≥12 mg L-1) of uniconazole could inhibit significantly the growth, dry weight, chlorophyll-a and carbohydrate contents of P. helgolandica and P. viridis ( P < 0.05). Uniconazole caused a significant increase in lipid peroxidation production (MDA) at higher concentrations (≥ 9 mg L-1). The activities of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) were enhanced remarkably at low concentrations of uniconazole. However, significant reduction of SOD and CAT activities was observed at higher concentrations of uniconazole.

Phenolic content and antioxidant activities of burr parsley (Caucalis platycarpos L.).

PubMed

Plazonić, Ana; Mornar, Ana; Maleš, Željan; Kujundžić, Nikola

2013-07-22

Since C. platycarpos contains a wide variety of antioxidants, in the present study total flavonoid and phenolic acid content as well as antioxidative activity of various C. platycarpos extracts were investigated. The results obtained show a significant polyphenol content and antioxidant activity of the investigated plant. Moreover, a positive correlation between antioxidant activity and content of flavonoids and phenolic acids was found, indicating the responsibility of these compounds for the antioxidant effectiveness of C. platycarpos extracts and making C. platycarpos a good potential source of natural antioxidants.

Synergistic, additive and antagonistic effects of fruit mixtures on total antioxidant capacities and bioactive compounds in tropical fruit juices.

PubMed

Pereira, Ana Carolina da Silva; Wurlitzer, Nedio Jair; Dionisio, Ana Paula; Lacerda Soares, Marcia Valéria; Rocha Bastos, Maria do Socorro; Elesbão Alves, Ricardo; Montenegro Brasil, Isabella

2015-06-01

The objective of this work was investigate the synergistic, additive and antagonistic effects of fruit mixtures on total antioxidant capacities and bioactive compounds in tropical fruit juices, and optimize its formulation by the response surface methodology based on the responses: total polyphenols (TP), total antioxidant capacity (TAC), ascorbic acid content and sensorial acceptance. Camu-camu, acerola and acai were the major factors that influenced the antioxidant potential of the juice; and the yellow mombin showed a positive effect on the acceptance of the tropical juice. It was observed an/antagonistic effect between acerola and camu-camu for the TAC response. The optimum formulation obtained was 20% acerola, 10% camu-camu, 10% yellow mombin, 10% cashew apple and 10% acai, which was responsible for a response of 155.46 mg.100 g(-1) of ascorbic acid, 103.01 mg of GAE.100 g-1 of TP, 10.27 µM Trolox g(-1) of TAC and approximately 6.1 of acceptance.

The level of elements and antioxidant activity of commercial dietary supplement formulations based on edible mushrooms.

PubMed

Stilinović, Nebojša; Škrbić, Biljana; Živančev, Jelena; Mrmoš, Nataša; Pavlović, Nebojša; Vukmirović, Saša

2014-12-01

Commercial preparations of Cordyceps sinensis, Ganoderma lucidum and Coprinus comatus mushroom marketed as healthy food supplements in Serbia were analyzed by atomic absorption spectrometry with a graphite furnace (GFAAS) for their element content. Antioxidant activity potential and total phenolics of the same mushrooms were determined. The element content of mushroom samples was in the range of 0.130-0.360 mg kg(-1) for lead (Pb), <0.03-0.46 mg kg(-1) for arsenic (As), 0.09-0.39 mg kg(-1) for cadmium (Cd), 98.14-989.18 mg kg(-1) for iron (Fe), 0.10-101.32 mg kg(-1) for nickel (Ni), 5.06-26.50 mg kg(-1) for copper (Cu), 0.20-0.70 mg kg(-1) for cobalt (Co), 1.74-136.33 mg kg(-1) for chromium (Cr) and 2.19-21.54 mg kg(-1) for manganese (Mn). In the tests for measuring the antioxidant activity, the methanolic extract of C. sinensis showed the best properties. The same was seen for the analysis of selected phenolic compounds; C. sinensis was found to have the highest content. Commercial preparations of C. sinensis and C. comatus can be considered to be safe and suitable food supplements included in well-balanced diets.

In vitro analysis of the properties of Beiqishen tea.

PubMed

Blázovics, A; Szentmihályi, K; Lugasi, A; Balázs, A; Hagymási, K; Bányai, E; Then, M; Rapavi, E; Héthelyi, E

2003-10-01

Chinese Beiqishen tea was studied in an in vitro test system. Phytochemical screening, trace element analysis, and the analysis of antioxidant properties were carried out. Characteristic constituents were determined by chromatographic (capillary gas chromatography and GCQ Ion Trap mass spectrometry) and spectrometric (ultraviolet and UV-VIS) methods. Element concentrations were determined by inductively coupled plasma optical emission spectrometry. Antioxidant capacity was studied by spectrophotometric and luminometric techniques using a Berthold Lumat 9501 luminometer. Hydrogen-donating activity, reducing power, and total scavenger capacity were measured. Total polyphenol content was 20.77 +/- 0.52 g/100 g of drug; total flavonoid content was 0.485 +/- 0.036 g/100 g of drug; and tannin content was 9.063 +/- 0.782 g/100 g of drug. Caffeine content was 1.08 mg/100 g of drug. Essential oils were identified by gas chromatography: (+)-limonene (21%), p-cymene (1.7%), estragol (3.2%), beta-ocimene (1.4%), and thymol (2.6%). Metallic ion analysis showed significantly high concentrations of Al, As, Ba, Cr, Cu, Fe, Mn, Ni, and Ti in the drug. Antioxidant and scavenger properties were identified as a function of concentration. The tea infusion contained some non-desirable trace elements and caffeine in addition to polyphenols and tannins in high concentrations. Therefore, the consumption of this tea may involve risks.

Limiting immunopathology: Interaction between carotenoids and enzymatic antioxidant defences.

PubMed

Babin, A; Saciat, C; Teixeira, M; Troussard, J-P; Motreuil, S; Moreau, J; Moret, Y

2015-04-01

The release of reactive oxygen and nitrogen species (ROS and RNS) during the inflammatory response generates damages to host tissues, referred to as immunopathology, and is an important factor in ecological immunology. The integrated antioxidant system, comprising endogenous antioxidant enzymes (e.g. superoxide dismutase SOD, and catalase CAT) and dietary antioxidants (e.g. carotenoids), helps to cope with immune-mediated oxidative stress. Crustaceans store large amounts of dietary carotenoids for yet unclear reasons. While being immunostimulants and antioxidants, the interaction of these pigments with antioxidant enzymes remains unclear. Here, we tested the interaction between dietary supplementation with carotenoids and immune challenge on immune defences and the activity of the antioxidant enzymes SOD and CAT, in the amphipod crustacean Gammarus pulex. Dietary supplementation increased the concentrations of circulating carotenoids and haemocytes in the haemolymph, while the immune response induced the consumption of circulating carotenoids and a drop of haemocyte density. Interestingly, supplemented gammarids exhibited down-regulated SOD activity but high CAT activity compared to control ones. Our study reveals specific interactions of dietary carotenoids with endogenous antioxidant enzymes, and further underlines the potential importance of carotenoids in the evolution of immunity and/or of antioxidant mechanisms in crustaceans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ganoderma lucidum ('Lingzhi'); acute and short-term biomarker response to supplementation.

PubMed

Wachtel-Galor, Sissi; Szeto, Yim-Tong; Tomlinson, Brian; Benzie, Iris F F

2004-02-01

Ganoderma lucidum (Lingzhi) is a popular Chinese herb with an impressive array of reputed health benefits, including antioxidant properties. However, these require scientific validation. The aim of this study was to investigate in vitro antioxidant capacity of Lingzhi, absorption and systemic distribution of Lingzhi antioxidants, and effects of short-term (10 days) supplementation on biomarkers of antioxidant status, coronary heart disease (CHD) risk and DNA damage. In this double-blinded, placebo-controlled, cross-over intervention study, blood and urine samples were collected from 10 healthy volunteers at 0 (fasting) and 45, 90, 135 and 180 min post-ingestion of a single dose (1.1g) of Lingzhi. Repeat fasting samples were collected after 10 days' supplementation with 0.72 g/d Lingzhi. The acute response (up to 3 hours) was also investigated with a larger dose (3.3 g) of Lingzhi (n=7). Results showed that the total antioxidant capacity (as the FRAP value) of an aqueous suspension of Lingzhi was 360 micromol/g. Ingestion of Lingzhi caused a significant post-ingestion increase (mean+/-SEM 23+/-3 micromol/L; P<0.05) in plasma antioxidant capacity, with peak response at 90 min. Average increase of 29+/-11% (P<0.05) in urine antioxidant capacity was seen within 3 hours of ingestion. After 10 days' supplementation with 0.72 g per day of Lingzhi, fasting plasma lipid standardised alpha-tocopherol concentration and urine antioxidant capacity increased (P<0.05). Fasting plasma ascorbic acid and total alpha-tocopherol concentrations and erythrocyte SOD and GPx activities increased slightly but non-significantly with supplementation. Plasma lipids and uric acid tended to decrease, but changes were not statistically significant. No discernable differences were seen in other variables measured. Results indicate that Lingzhi intake causes an acute increase in plasma antioxidant capacity. No deleterious effects on measured variables were seen. The pattern of biomarker response after supplementation indicated possible benefit in terms of antioxidant status and CHD risk, but further study is needed to elucidate the nature and longer-term effects of the absorbable antioxidants from Lingzhi.

Flavonoids Derived from Abelmoschus esculentus Attenuates UV-B Induced Cell Damage in Human Dermal Fibroblasts Through Nrf2-ARE Pathway.

PubMed

Patwardhan, Juilee; Bhatt, Purvi

2016-05-01

Ultraviolet-B (UV-B) radiation is a smaller fraction of the total radiation reaching the Earth but leads to extensive damage to the deoxyribonucleic acid (DNA) and other biomolecules through formation of free radicals altering redox homeostasis of the cell. Abelmoschus esculentus (okra) has been known in Ayurveda as antidiabetic, hypolipidemic, demulscent, antispasmodic, diuretic, purgative, etc. The aim of this study is to evaluate the protective effect of flavonoids from A. esculentus against UV-B-induced cell damage in human dermal fibroblasts. UV-B protective activity of ethyl acetate (EA) fraction of okra was studied against UV-B-induced cytotoxicity, antioxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway. Flavonoid-rich EA fraction depicted a significant antioxidant potential also showing presence of rutin. Pretreatment of cells with EA fraction (10-30 μg/ml) prevented UV-B-induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1. Our study demonstrated for the 1(st) time that EA fraction of okra may reduce oxidative stress through Nrf2-ARE pathway as well as through endogenous enzymatic antioxidant system. These results suggested that flavonoids from okra may be considered as potential UV-B protective agents and may also be formulated into herbal sunscreen for topical application. Flavonoid-enriched ethyl acetate (EA) fraction from A. esculentus protected against ultraviolet-B (UV-B)-induced oxidative DNA damageEA fraction prevented UV-B-induced cytotoxicity, depletion of endogenous enzymatic antioxidants, and intracellular reactive oxygen species productionEA fraction could reduce oxidative stress through the Nrf2-ARE PathwayEA fraction was found to be nongenotoxic and prevented apoptotic changes. Flavonoids from Abelmoschus esculentus protected from ultraviolet-B-induced damageThey were capable of reducing oxidative stress through Nrf2-ARE PathwayThey are nongenotoxic and do not possess mutagenic potentialFlavonoids from A. esculentus can be studied and explored further for its topical application as sunscreen. Abbreviations used: ABTS: 2,2'-azino-bis-(3-ethylbenzothiazoline -6-sulphonic acid), AO: Acridine orange, Analysis of variance, ARE: Antioxidant response elements, BSA: Bovine serum albumin, CAPE: Caffeic acid phenethyl ester, CAT: Catalase, DCFH-DA: 2',7'-dichlorofluorescein diacetate, DMEM: Dulbecco's modified eagle's medium, DMSO: dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DPBS: Dulbecco's phosphate-buffered saline, DPPH: 2,2-diphenyl-1-picryl hydrazyl, ECL: Enhanced chemiluminescence, EDTA: Ethylenediaminetetraacetic acid, ELISA: Enzyme-linked immunosorbent assay, EtBr: Ethidium bromide, FBS: Fetal bovine serum, FE Fraction: Flavonoid-enriched fraction, FRAP: Ferric reducing antioxidant power, GPx: Glutathione peroxidase, GR: Glutathione reductase, GST: Glutathione-S-transferase, GSH: Reduced glutathione, GSSG: Oxidized glutathione, HDF: Human dermal fibroblast adult cells, HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid, HRP: Horseradish peroxidase, HO-1: Heme oxygenase-1, HPTLC: High-performance thin layer chromatography, Keap-1: Kelch-like ECH-associated protein-1, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NaCl: sodium chloride, NFDM: nonfat dry milk, Nrf2: Nuclear factor E2-related factor 2, NQO1: NAD (P) H: Quinine oxidoreductase 1, OH: Hydroxyl ions, PBST: Phosphate-buffered saline with 0.1% tween 20, PCR: Polymerase chain reaction, PMSF: Phenylmethanesulfonyl fluoride, Rf: Retention factor, ROS: Reactive oxygen species, rRNA: Ribosomal ribonucleic acid, SDS: Sodium dodecyl sulfate, SOD: Superoxide dismutase, TLC: Thin layer chromatography, TLC-DPPH: Thin layer chromatography-2,2-diphenyl-1-picryl hydrazyl, UV: Ultraviolet, UV-A: Ultraviolet-A, UV-B: Ultraviolet-B, UV-C: Ultraviolet-C, qPCR: Quantitative polymerase chain reaction.

Plant-parasitic nematodes: towards understanding molecular players in stress responses

PubMed Central

Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair

2017-01-01

Background Plant–parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant–nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Scope Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1, which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. Conclusion DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. PMID:28087659

Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption.

PubMed

Bayele, Henry K; Balesaria, Sara; Srai, Surjit K S

2015-12-01

Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Sulforaphane inhibits multiple inflammasomes through an Nrf2-independent mechanism.

PubMed

Greaney, Allison J; Maier, Nolan K; Leppla, Stephen H; Moayeri, Mahtab

2016-01-01

The inflammasomes are intracellular complexes that have an important role in cytosolic innate immune sensing and pathogen defense. Inflammasome sensors detect a diversity of intracellular microbial ligands and endogenous danger signals and activate caspase-1, thus initiating maturation and release of the proinflammatory cytokines interleukin-1β and interleukin-18. These events, although crucial to the innate immune response, have also been linked to the pathology of several inflammatory and autoimmune disorders. The natural isothiocyanate sulforaphane, present in broccoli sprouts and available as a dietary supplement, has gained attention for its antioxidant, anti-inflammatory, and chemopreventive properties. We discovered that sulforaphane inhibits caspase-1 autoproteolytic activation and interleukin-1β maturation and secretion downstream of the nucleotide-binding oligomerization domain-like receptor leucine-rich repeat proteins NLRP1 and NLRP3, NLR family apoptosis inhibitory protein 5/NLR family caspase-1 recruitment domain-containing protein 4 (NAIP5/NLRC4), and absent in melanoma 2 (AIM2) inflammasome receptors. Sulforaphane does not inhibit the inflammasome by direct modification of active caspase-1 and its mechanism is not dependent on protein degradation by the proteasome or de novo protein synthesis. Furthermore, sulforaphane-mediated inhibition of the inflammasomes is independent of the transcription factor nuclear factor erythroid-derived 2-like factor 2 (Nrf2) and the antioxidant response-element pathway, to which many of the antioxidant and anti-inflammatory effects of sulforaphane have been attributed. Sulforaphane was also found to inhibit cell recruitment to the peritoneum and interleukin-1β secretion in an in vivo peritonitis model of acute gout and to reverse NLRP1-mediated murine resistance to Bacillus anthracis spore infection. These findings demonstrate that sulforaphane inhibits the inflammasomes through a novel mechanism and contributes to our understanding of the beneficial effects of sulforaphane. © Society for Leukocyte Biology.

Sulforaphane inhibits multiple inflammasomes through an Nrf2-independent mechanism

PubMed Central

Greaney, Allison J.; Maier, Nolan K.; Leppla, Stephen H.; Moayeri, Mahtab

2016-01-01

The inflammasomes are intracellular complexes that have an important role in cytosolic innate immune sensing and pathogen defense. Inflammasome sensors detect a diversity of intracellular microbial ligands and endogenous danger signals and activate caspase-1, thus initiating maturation and release of the proinflammatory cytokines interleukin-1β and interleukin-18. These events, although crucial to the innate immune response, have also been linked to the pathology of several inflammatory and autoimmune disorders. The natural isothiocyanate sulforaphane, present in broccoli sprouts and available as a dietary supplement, has gained attention for its antioxidant, anti-inflammatory, and chemopreventive properties. We discovered that sulforaphane inhibits caspase-1 autoproteolytic activation and interleukin-1β maturation and secretion downstream of the nucleotide-binding oligomerization domain-like receptor leucine-rich repeat proteins NLRP1 and NLRP3, NLR family apoptosis inhibitory protein 5/NLR family caspase-1 recruitment domain-containing protein 4 (NAIP5/NLRC4), and absent in melanoma 2 (AIM2) inflammasome receptors. Sulforaphane does not inhibit the inflammasome by direct modification of active caspase-1 and its mechanism is not dependent on protein degradation by the proteasome or de novo protein synthesis. Furthermore, sulforaphane-mediated inhibition of the inflammasomes is independent of the transcription factor nuclear factor erythroid-derived 2-like factor 2 (Nrf2) and the antioxidant response-element pathway, to which many of the antioxidant and anti-inflammatory effects of sulforaphane have been attributed. Sulforaphane was also found to inhibit cell recruitment to the peritoneum and interleukin-1β secretion in an in vivo peritonitis model of acute gout and to reverse NLRP1-mediated murine resistance to Bacillus anthracis spore infection. These findings demonstrate that sulforaphane inhibits the inflammasomes through a novel mechanism and contributes to our understanding of the beneficial effects of sulforaphane. PMID:26269198

Nrf2 protects against airway disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, Hye-Youn, E-mail: cho2@niehs.nih.go; Kleeberger, Steven R.

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver,more » gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies.« less

The Effects of Supplementary Mulberry Leaf (Morus alba) Extracts on the Trace Element Status (Fe, Zn and Cu) in Relation to Diabetes Management and Antioxidant Indices in Diabetic Rats.

PubMed

Król, Ewelina; Jeszka-Skowron, Magdalena; Krejpcio, Zbigniew; Flaczyk, Ewa; Wójciak, Rafał W

2016-11-01

Mulberry leaves (Morus alba) have been used in folk medicine to mitigate symptoms of diabetes. The mulberry plant contains phenolic compounds that are able to decrease blood glucose concentration. Since various phenolics have antioxidant and metal binding properties, they can be used to alleviate oxidative stress and chelate trace elements involved in redox reactions. The aim of this study was to evaluate the effects of dietary supplementation with mulberry leaf extracts (acetone-water (AE) and ethanol-water (EE)) on the trace element status (Fe, Zn and Cu) in relation to diabetes management and antioxidant indices in high-fat diet-fed/STZ diabetic rats. The experiment was performed on 38 male Wistar rats with diabetes (induced by high-fat diet (HF) and streptozotocin injection) or the control fed with AIN-93M or high-fat diet. As a result, five experimental groups were used: (1) a healthy control group fed with AIN-93M; (2) an HF control group; (3) a diabetic HF group; (4) a diabetic HF + AE group (6 g/kg diet); (5) a diabetic HF + EE group (6 g/kg diet). The rats were fed with appropriate diets for 4 weeks. The content of trace elements (Fe, Zn and Cu) in the serum and tissues was measured by means of atomic absorption spectrometry (AAS). Biochemical analyses (glucose, TBARS, FRAP) were performed on the blood serum. It was shown that the AE decreased hepatic and renal Fe stores, while the EE increased hepatic Cu levels in diabetic rats and confirmed their ability to regulate the Fe and Cu status in diabetes. The results confirmed a significant hypoglycaemic and antioxidant potential of both mulberry leaf extracts in diabetic rats.

Watermelon consumption improves inflammation and antioxidant capacity in rats fed an atherogenic diet.

PubMed

Hong, Mee Young; Hartig, Nicole; Kaufman, Katy; Hooshmand, Shirin; Figueroa, Arturo; Kern, Mark

2015-03-01

Cardiovascular disease (CVD) is the leading cause of death in the United States. Watermelon, rich in antioxidants and other bioactive components, may be a viable method to improve CVD risk factors through reduced oxidative stress. The purpose of the study was to determine the effects of watermelon powder consumption on lipid profiles, antioxidant capacity, and inflammation in dextran sodium sulfate (DSS)-treated rats fed an atherogenic diet. We hypothesized that watermelon would increase antioxidant capacity and reduce blood lipids and inflammation through modulation of related gene expression. Forty male-weanling (21 days old) Sprague-Dawley rats were divided into 4 groups (10 per group, total N = 40) in a 2 diets (control or 0.33% watermelon) × 2 treatments (with or without DSS) factorial design using an atherogenic diet. Watermelon-fed groups exhibited significantly lower serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol (P< .05). C-reactive protein levels were significantly lower in watermelon-fed rats than the control (P= .001). In addition, oxidative stress as measured by thiobarbituric acid reactive substances was significantly lower in watermelon groups (P= .001). Total antioxidant capacity, superoxide dismutase, and catalase activities were greater in watermelon groups (P< .05). Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase were significantly lower in DSS-treated rats when watermelon was consumed (P< .05). Fatty acid synthase, 3-hydroxy-3methyl-glutaryl-CoA reductase, sterol regulatory element-binding protein 1, sterol regulatory element-binding protein 2, and cyclooxygenase-2 gene expression was significantly downregulated in the watermelon group without DSS (P< .05). These findings indicate that watermelon improves risk factors for CVD in rats through better lipid profiles, lower inflammation, and greater antioxidant capacity by altering gene expression for lipid metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of Experimental Herpes Encephalitis-Associated Neurotoxicity through Sulforaphane Treatment

PubMed Central

Schachtele, Scott J.; Hu, Shuxian; Lokensgard, James R.

2012-01-01

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection. PMID:22558388

Human cell toxicogenomic analysis links reactive oxygen species to the toxicity of monohaloacetic acid drinking water disinfection byproducts

PubMed Central

Pals, Justin; Attene-Ramos, Matias S.; Xia, Menghang; Wagner, Elizabeth D.; Plewa, Michael J.

2014-01-01

Chronic exposure to drinking water disinfection byproducts has been linked to adverse health risks. The monohaloacetic acids (monoHAAs) are generated as byproducts during the disinfection of drinking water and are cytotoxic, genotoxic, mutagenic, and teratogenic. Iodoacetic acid toxicity was mitigated by antioxidants, suggesting the involvement of oxidative stress. Other monoHAAs may share a similar mode of action. Each monoHAA generated a significant concentration-response increase in the expression of a β-lactamase reporter under the control of the Antioxidant Response Element (ARE). The monoHAAs generated oxidative stress with a rank order of IAA > BAA >> CAA; this rank order was observed with other toxicological endpoints. Toxicogenomic analysis was conducted with a non-transformed human intestinal epithelial cell line (FHs 74 Int). Exposure to the monoHAAs altered the transcription levels of multiple oxidative stress responsive genes, indicating that each exposure generated oxidative stress. The transcriptome profiles showed an increase in TXNRD1 and SRXN1, suggesting peroxiredoxin proteins had been oxidized during monoHAA exposures. Three sources of reactive oxygen species were identified, the hypohalous acid generating peroxidase enzymes LPO and MPO, NADPH-dependent oxidase NOX5, and PTGS2 (COX-2) mediated arachidonic acid metabolism. Each monoHAA exposure caused an increase in COX-2 mRNA levels. These data provide a functional association between monoHAA exposure and adverse health outcomes such as oxidative stress, inflammation, and cancer. PMID:24050308

Effect of treatment with geraniol on ovalbumin-induced allergic asthma in mice.

PubMed

Xue, Zheng; Zhang, Xin-Guang; Wu, Jie; Xu, Wan-Chao; Li, Li-Qing; Liu, Fei; Yu, Jian-Er

2016-06-01

Asthma, a complex highly prevalent airway disease, is a major public health problem for which current treatment options are inadequate. To evaluate the antiasthma activity of geraniol and investigate its underlying molecular mechanisms. In a standard experimental asthma model, Balb/c mice were sensitized with ovalbumin, treated with geraniol (100 or 200 mg/kg) or a vehicle control, during ovalbumin challenge. Treatment of ovalbumin-sensitized/challenged mice with geraniol significantly decreased airway hyperresponsiveness to inhaled methacholine. Geraniol treatment reduced eotaxin levels in bronchoalveolar lavage fluid and attenuated infiltration of eosinophils induced by ovalbumin. Geraniol treatment reduced TH2 cytokines (including interleukins 4, 5, and 13), increased TH1 cytokine interferon γ in bronchoalveolar lavage fluid, and reduced ovalbumin-specific IgE in serum. In addition, treatment of ovalbumin-sensitized/challenged mice with geraniol enhanced T-bet (TH1 response) messenger RNA expression and reduced GATA-3 (TH2 response) messenger RNA expression in lungs. Furthermore, treatment of ovalbumin -sensitized/challenged mice with geraniol further enhanced Nrf2 protein expression and activated Nrf2-directed antioxidant pathways, such as glutamate-cysteine ligase, superoxide dismutase, and glutathione S-transferase, and enhanced formation of reduced glutathione and reduced formation of malondialdehyde in lungs. Geraniol attenuated important features of allergic asthma in mice, possibly through the modulation of TH1/TH2 balance and activation the of Nrf2/antioxidant response element pathway. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4

PubMed Central

Huggins, Christopher J.; Mayekar, Manasi K.; Martin, Nancy; Saylor, Karen L.; Gonit, Mesfin; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C.; Quiñones, Octavio A.

2015-01-01

The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPγ:ATF4 heterodimers, but not C/EBPβ:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPγ and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPβ and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg−/− mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg−/− mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPγ-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg−/− mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPγ as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells. PMID:26667036

The role of oxidative, inflammatory and neuroendocrinological systems during exercise stress in athletes: implications of antioxidant supplementation on physiological adaptation during intensified physical training.

PubMed

Slattery, Katie; Bentley, David; Coutts, Aaron J

2015-04-01

During periods of intensified physical training, reactive oxygen species (ROS) release may exceed the protective capacity of the antioxidant system and lead to dysregulation within the inflammatory and neuroendocrinological systems. Consequently, the efficacy of exogenous antioxidant supplementation to maintain the oxidative balance in states of exercise stress has been widely investigated. The aim of this review was to (1) collate the findings of prior research on the effect of intensive physical training on oxidant-antioxidant balance; (2) summarise the influence of antioxidant supplementation on the reduction-oxidation signalling pathways involved in physiological adaptation; and (3) provide a synopsis on the interactions between the oxidative, inflammatory and neuroendocrinological response to exercise stimuli. Based on prior research, it is evident that ROS are an underlying aetiology in the adaptive process; however, the impact of antioxidant supplementation on physiological adaptation remains unclear. Equivocal results have been reported on the impact of antioxidant supplementation on exercise-induced gene expression. Further research is required to establish whether the interference of antioxidant supplementation consistently observed in animal-based and in vivo research extends to a practical sports setting. Moreover, the varied results reported within the literature may be due to the hormetic response of oxidative, inflammatory and neuroendocrinological systems to an exercise stimulus. The collective findings suggest that intensified physical training places substantial stress on the body, which can manifest as an adaptive or maladaptive physiological response. Additional research is required to determine the efficacy of antioxidant supplementation to minimise exercise-stress during intensive training and promote an adaptive state.

Alterations in antioxidant defense system of workers chronically exposed to arsenic, cadmium and mercury from coal flying ash.

PubMed

Zeneli, Lulzim; Sekovanić, Ankica; Ajvazi, Majlinda; Kurti, Leonard; Daci, Nexhat

2016-02-01

Humans are exposed to different stress factors that are responsible for over-production of reactive oxygen species. Exposure to heavy metals is one of these factors. The aim of the study was to analyze the effect of chronic exposure to heavy metals through coal flying ash on the efficiency of antioxidative defensive mechanisms, represented by the activity of superoxide dismutase, glutathione peroxidase and ascorbic acid. Nonessential elements such as arsenic and mercury levels showed a significant increase (p > 0.001) in the power plant workers rather than in the control subjects. There were no significant differences of blood cadmium between power plant workers and control subjects. We found a significant positive correlation (p < 0.05) between BAs/SZn (r = 0.211), BAs/BSe (r = 0.287), BCd/SCu (r = 0.32) and BHg/BSe (r = 0.263) in the plant workers. Red blood cell antioxidant enzymes and plasma ascorbic acid were significantly lower in power plants workers than in the control group (p < 0.002). We can conclude that levels of mercury, arsenic and cadmium in blood, despite their concentration within the reference values, significantly affect plasma ascorbic acid concentration, superoxide dismutase and glutathione peroxidase activity, which are able to increase the risk of oxidative stress.

The importance of the oxidative status of dairy cattle in the periparturient period: revisiting antioxidant supplementation.

PubMed

Abuelo, A; Hernández, J; Benedito, J L; Castillo, C

2015-12-01

Dairy cows are especially vulnerable to health disorders during the transition period, when they shift from late pregnancy to the onset of lactation. Diseases at this stage affect not only the animals' well-being, but also cause a major economic impact in dairy farms, because apart from treatment costs, affected cows will not reach their peak milk-producing capacity. The overproduction of reactive oxygen species (ROS) leads to oxidative stress, which has been identified as an underlying factor of dysfunctional inflammatory responses. Supplementation with vitamins and trace elements attempts to minimize the harmful consequences of excessive ROS production, thereby trying to improve animals' health status and to reduce disease incidence. However, results regarding the effects of supplementing antioxidants on dairy cows' health and performance have been inconsistent, because in most cases, the antioxidant potential of the animals was not assessed beforehand and the nutritional strategy planned accordingly. Therefore, reviewing the physiological and harmful effects of ROS production, along with the different options available for assessing the redox balance in dairy cattle and some of the key findings of different supplementation trials, could bring one step forward the on-farm application of determinations of oxidative status for establishing nutritional strategies early enough in the dry period that could improve transition cow health. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Silymarin: a novel antioxidant with antiglycation and antiinflammatory properties in vitro and in vivo.

PubMed

Wu, Chi-Hao; Huang, Shang-Ming; Yen, Gow-Chin

2011-02-01

The current study was designed to evaluate the effects of silymarin (SM) on advanced glycation endproduct (AGE) formation and monocyte activation induced by S100b, a specific ligand of receptor for AGEs. The in vivo verification of antiglycation, antioxidant, and antiinflammatory capacities was examined by 12 weeks of SM administration in streptozotocin-diabetic rats. In vitro glycation assays demonstrated that SM exerted marked inhibition during the late stages of glycation and subsequent crosslinking. Dual action mechanisms, namely, antioxidant and reactive carbonyl trapping activities, may contribute to its antiglycation effect. SM produced a significant decrease in monocytic interleukin-1β and COX-2 levels and prevented oxidant formation caused by S100b, which appeared to be mediated by inhibition of p47phox membrane translocation. Chromatin immunoprecipitation demonstrated that S100b increased the recruitment of nuclear factor-kappaB transcription factor as well as cAMP response element-binding-binding protein and coactivator-associated arginine methyltransferase-1 cofactors to the interleukin-1β promoter, whereas these changes were inhibited with SM treatment. In vivo, SM reduced tissue AGE accumulation, tail collagen crosslinking, and concentrations of plasma glycated albumin. Levels of oxidative and inflammatory biomarkers were also significantly decreased in SM-treated groups compared with the diabetic group. These data suggest that SM supplementation may reduce the burden of AGEs in diabetics and may prevent resulting complications.

Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng

2013-04-19

Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal andmore » glial cultures, and protects neurons against glutamate-induced excitotoxicity.« less

Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

PubMed

Matsumoto, M; Imagawa, M; Aoki, Y

2000-07-01

Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did not stimulate GPEI-mediated gene expression. On the other hand, the antioxidant reagents butylhydroxyanisole and t-butylhydroquinone, stimulated GPEI-mediated gene expression, but the level of GSTP1 mRNA was not elevated. Our observations suggest that EGF and TGF alpha induce GSTP1 by the same signal transduction pathway as PenCB. Since the sequence of GPEI is similar to that of the antioxidant responsive element (ARE), some factors which bind to ARE might play a role in GPEI-mediated gene expression.

Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

PubMed Central

Matsumoto, M; Imagawa, M; Aoki, Y

2000-01-01

Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did not stimulate GPEI-mediated gene expression. On the other hand, the antioxidant reagents butylhydroxyanisole and t-butylhydroquinone, stimulated GPEI-mediated gene expression, but the level of GSTP1 mRNA was not elevated. Our observations suggest that EGF and TGF alpha induce GSTP1 by the same signal transduction pathway as PenCB. Since the sequence of GPEI is similar to that of the antioxidant responsive element (ARE), some factors which bind to ARE might play a role in GPEI-mediated gene expression. PMID:10861232

Temporal responses to intrinsically coupled calcium and zinc dyshomeostasis in cardiac myocytes and mitochondria during aldosteronism

PubMed Central

Kamalov, German; Ahokas, Robert A.; Zhao, Wenyuan; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Sun, Yao; Gerling, Ivan C.

2010-01-01

Intracellular Ca2+ overloading, coupled to induction of oxidative stress, is present at 4-wk aldosterone/salt treatment (ALDOST). This prooxidant reaction in cardiac myocytes and mitochondria accounts for necrotic cell death and subsequent myocardial scarring. It is intrinsically linked to increased intracellular zinc concentration ([Zn2+]i) serving as an antioxidant. Herein, we addressed the temporal responses in coupled Ca2+ and Zn2+ dyshomeostasis, reflecting the prooxidant-antioxidant equilibrium, by examining preclinical (week 1) and pathological (week 4) stages of ALDOST to determine whether endogenous antioxidant defenses would be ultimately overwhelmed to account for this delay in cardiac remodeling. We compared responses in cardiomyocyte free [Ca2+]i and [Zn2+]i and mitochondrial total [Ca2+]m and [Zn2+]m, together with biomarkers of oxidative stress and antioxidant defenses, during 1- and 4-wk ALDOST. At week 1 and compared with controls, we found: 1) elevations in [Ca2+]i and [Ca2+]m were coupled with [Zn2+]i and [Zn2+]m; 2) increased mitochondrial H2O2 production, cardiomyocyte xanthine oxidase activity, and cardiac and mitochondrial 8-isoprostane levels, counterbalanced by increased activity of antioxidant proteins, enzymes, and the nonenzymatic antioxidants that can be considered as cumulative antioxidant capacity; some of these enzymes and proteins (e.g., metallothionein-1, Cu/Zn-superoxide, glutathione synthase) are regulated by metal-responsive transcription factor-1; and 3) although these augmented antioxidant defenses were sustained at week 4, they fell short in combating the persistent intracellular Ca2+ overloading and marked rise in cardiac tissue 8-isoprostane and mitochondrial transition pore opening. Thus a coupled Ca2+ and Zn2+ dyshomeostasis occurs early during ALDOST in cardiac myocytes and mitochondria that regulate redox equilibrium until week 4 when ongoing intracellular Ca2+ overloading and prooxidants overwhelm antioxidant defenses. PMID:19915175

Antioxidant enzymes stimulation in Aspergillus parasiticus by Lentinula edodes inhibits aflatoxin production.

PubMed

Reverberi, M; Fabbri, A A; Zjalic, S; Ricelli, A; Punelli, F; Fanelli, C

2005-11-01

Biosynthesis of aflatoxins, toxic metabolites produced by Aspergillus parasiticus, is correlated to the fungal oxidative stress and cell ageing. In this paper, the mechanism underlying the aflatoxin-inhibiting effect of the Lentinula edodes culture filtrates was studied by analysing their anti-oxidant activity and beta-glucan content. Mushroom beta-glucans are pharmacologically active compounds stimulating anti-oxidant responses in animal cells. L. edodes lyophilised filtrates stimulate A. parasiticus anti-oxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and aflatoxin inhibition was better correlated with beta-glucan content than with anti-oxidant activity of the filtrates. RT-PCR analyses on treated mycelia showed a delay in the activation of aflR, and norA, genes of aflatoxin cluster and a synchronous activation of hsf2-like, a homologue of a yeast transcription factor involved in oxidative stress responses. The first evidence of hsf2-like in A. parasiticus and its activation during aflatoxin biosynthesis is reported. L. edodes filtrates could play a role as external stimulus affecting the anti-oxidant status in the fungal cell that, in turn, leads to aflatoxin inhibition. In the fungal cell, beta-glucans present in the filtrates could stimulate the activation of transcription factors related to anti-oxidant response and anti-oxidant enzyme activity with a contemporaneous delay of aflatoxin genes transcription, which led to a marked reduction of aflatoxin production. This research suggests new perspectives to set suitable strategies against aflatoxins and L. edodes could be considered a promising tool.

Selenium fertilization on lentil (Lens culinaris Medikus) grain yield, seed selenium concentration, and antioxidant activity

USDA-ARS?s Scientific Manuscript database

Selenium (Se) is an essential element for mammals but has not been considered as an essential element for higher plants. Lentil (Lens culinaris Medik.) is a cool season food legume rich in protein and a range of micronutrients including minerals (iron and zinc), folates, and carotenoids. The objecti...

Oxidative stress damage as a detrimental factor in preterm birth pathology.

PubMed

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal-fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways.

Oxidative Stress Damage as a Detrimental Factor in Preterm Birth Pathology

PubMed Central

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal–fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways. PMID:25429290

Chronic toxicity of arsenic during Rhinella arenarum embryonic and larval development: Potential biomarkers of oxidative stress and antioxidant response.

PubMed

Mardirosian, Mariana Noelia; Lascano, Cecilia Inés; Bongiovanni, Guillermina Azucena; Venturino, Andrés

2017-06-01

The Argentinean autochthonous toad Rhinella arenarum was selected to study the chronic toxicity of arsenic (As) and the biochemical responses elicited by exposure to As in water during embryonic and larval development. Significant decreases in the total reactive antioxidant potential and in catalase activity were observed in individuals exposed chronically to sublethal concentrations of As, which is indicative of an oxidative stress situation. However, an antioxidant response was elicited during chronic exposure to As, as evidenced by the increase in endogenous reduced glutathione content and glutathione-related enzymatic activities such as glutathione S-transferase (GST) and glutathione reductase. This protective response might prevent a deeper decline in the antioxidant system and further oxidative damage. Alternatively, it might be linked to As conjugation with reduced glutathione for its excretion. Considering the sustained increase in GST activity and the decrease in the total antioxidant reactive potential observed, the authors propose them as good candidates to be used as biomarkers during As exposure. Interestingly, glutathione reductase activity was inhibited at a very low concentration of As considered safe for aquatic life. Environ Toxicol Chem 2017;36:1614-1621. © 2016 SETAC. © 2016 SETAC.

Antioxidant responses in soybean and alfalfa plants grown in DDTs contaminated soils: Useful variables for selecting plants for soil phytoremediation?

PubMed

Mitton, Francesca M; Ribas Ferreira, Josencler L; Gonzalez, Mariana; Miglioranza, Karina S B; Monserrat, José M

2016-06-01

Phytoremediation is a low-cost alternative technology based on the use of plants to remove pollutants from the environment. Persistent organic pollutants such as DDTs with a long half-life in soils are attractive candidates for remediation. This study aimed to determine the potential of antioxidant response use in the evaluation of plants' tolerance for selecting species in phytoremediation purposes. Alfalfa and soybean plants were grown in DDT contaminated soils. After 60days, growth, protein content, antioxidant capacity, GST activity, concentration of proteic and non-proteic thiol groups, chlorophyll content and carotenoid content were measured in plant tissues. Results showed no effect on alfalfa or soybean photosynthetic pigments but different responses in the protein content, antioxidant capacity, GST activity and thiol groups on roots, stems and leaves, indicating that DDTs affected both species. Soybean showed higher susceptibility than alfalfa plants due to the lower antioxidant capacity and GST activity in leaves, in spite of having the lowest DDT accumulation. This study provides new insights into the role of oxidative stress as an important component of the plant's response to DDT exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nordgren, Kendra K.S., E-mail: knordgre@d.umn.edu; Wallace, Kendall B., E-mail: kwallace@d.umn.edu

Doxorubicin (DOX) is a widely prescribed treatment for a broad scope of cancers, but clinical utility is limited by the cumulative, dose-dependent cardiomyopathy that occurs with repeated administration. DOX-induced cardiotoxicity is associated with the production of reactive oxygen species (ROS) and oxidation of lipids, DNA and proteins. A major cellular defense mechanism against such oxidative stress is activation of the Keap1/Nrf2-antioxidant response element (ARE) signaling pathway, which transcriptionally regulates expression of antioxidant genes such as Nqo1 and Gstp1. In the present study, we address the hypothesis that an initial event associated with DOX-induced oxidative stress is activation of the Keap1/Nrf2-dependentmore » expression of antioxidant genes and that this is regulated through drug-induced changes in redox status of the Keap1 protein. Incubation of H9c2 rat cardiac myoblasts with DOX resulted in a time- and dose-dependent decrease in non-protein sulfhydryl groups. Associated with this was a near 2-fold increase in Nrf2 protein content and enhanced transcription of several of the Nrf2-regulated down-stream genes, including Gstp1, Ugt1a1, and Nqo1; the expression of Nfe2l2 (Nrf2) itself was unaltered. Furthermore, both the redox status and the total amount of Keap1 protein were significantly decreased by DOX, with the loss of Keap1 being due to both inhibited gene expression and increased autophagic, but not proteasomal, degradation. These findings identify the Keap1/Nrf2 pathway as a potentially important initial response to acute DOX-induced oxidative injury, with the primary regulatory events being the oxidation and autophagic degradation of the redox sensor Keap1 protein. - Highlights: • DOX caused a ∼2-fold increase in Nrf2 protein content. • DOX enhanced transcription of several Nrf2-regulated down-stream genes. • Redox status and total amount of Keap1 protein were significantly decreased by DOX. • Loss of Keap1 protein was due to inhibited gene expression and increased autophagy. • Keap1/Nrf2 pathway is an important initial response to DOX-induced oxidative injury.« less

Polymer Directed Self-Assembly of pH-Responsive Antioxidant Nanoparticles

PubMed Central

Tang, Christina; Amin, Devang; Messersmith, Phillip B.; Anthony, John E.; Prud’homme, Robert K.

2015-01-01

We have developed pH-responsive, multifunctional nanoparticles based on encapsulation of an antioxidant, tannic acid (TA), using Flash NanoPrecipitation, a polymer directed self-assembly method. Formation of insoluble coordination complexes of tannic acid and iron during mixing drives nanoparticle assembly. Tuning the core material to polymer ratio, the size of the nanoparticles can be readily tuned between 50 and 265 nm. The resulting nanoparticle is pH-responsive, i.e. stable at pH 7.4 and soluble under acidic conditions due to the nature of the coordination complex. Further, the coordination complex can be coprecipitated with other hydrophobic materials such as therapeutics or imaging agents. For example, coprecipitation with a hydrophobic fluorescent dye creates fluorescent nanoparticles. In vitro, the nanoparticles have low cytotoxicity show antioxidant activity. Therefore, these particles may facilitate intracellular delivery of antioxidants. PMID:25760226

Supplementing with vitamin C the diet of honeybees (Apis mellifera carnica) parasitized with Varroa destructor: effects on antioxidative status.

PubMed

Farjan, Marek; Łopieńska-Biernat, Elżbieta; Lipiński, Zbigniew; Dmitryjuk, Małgorzata; Żółtowska, Krystyna

2014-05-01

We studied a total of eight developmental stages of capped brood and newly emerged workers of Apis mellifera carnica colonies naturally parasitized with Varroa destructor. During winter and early spring four colonies were fed syrup containing 1.8 mg vitamin C kg(-1) (ascorbic acid group; group AA) while four colonies were fed syrup without the vitamin C (control group C). Selected elements of the antioxidative system were analysed including total antioxidant status (TAS), glutathione content and antioxidative enzyme activities (superoxide dismutase, catalase, peroxidase and glutathione S-transferase). Body weight, protein content and indices of infestation were also determined. The prevalence (8.11%) and intensity (1·15 parasite per bee) of the infestation were lower in group AA compared with group C (11.3% and 1.21, respectively). Changes in the indicators of antioxidative stress were evidence for the strengthening of the antioxidative system in the brood by administration of vitamin C. In freshly emerged worker bees of group AA, despite the infestation, protein content, TAS, and the activity of all antioxidative enzymes had significantly higher values in relation to group C.

Antioxidants reverse depression of the hypoxic ventilatory response by acetazolamide in man.

PubMed

Teppema, Luc J; Bijl, Hans; Romberg, Raymonda R; Dahan, Albert

2006-05-01

The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and stimulatory effects on breathing. In this placebo-controlled double-blind study we measured the effect of an intravenous dose (4 mg kg(-1)) of this agent on the acute isocapnic hypoxic ventilatory response in 16 healthy volunteers (haemoglobin oxygen saturation 83-85%) and examined whether its inhibitory effects on this response could be reversed by antioxidants (1 g ascorbic acid i.v. and 200 mg alpha-tocopherol p.o.). The subjects were randomly divided into an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55% (P < 0.01), respectively, and abolished the O2-CO2 interaction, i.e. the increase in O2 sensitivity with rising Pco2. Antioxidants completely reversed this inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the reversal was partial. In the placebo group, acetazolamide reduced the normo- and hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus control in both cases), and also abolished the O2-CO2 interaction. Placebo failed to reverse these inhibitory effects of acetazolamide in this group. We hypothesize that either an isoform of carbonic anhydrase may be involved in the regulation of the redox state in the carotid bodies or that acetazolamide and antioxidants exert independent effects on oxygen-sensing cells, in which both carbonic anhydrase and potassium channels may be involved. The novel findings of this study may have clinical implications, for example with regard to a combined use of acetazolamide and antioxidants at high altitude.

Antioxidants reverse depression of the hypoxic ventilatory response by acetazolamide in man

PubMed Central

Teppema, Luc J; Bijl, Hans; Romberg, Raymonda R; Dahan, Albert

2006-01-01

The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and stimulatory effects on breathing. In this placebo-controlled double-blind study we measured the effect of an intravenous dose (4 mg kg−1) of this agent on the acute isocapnic hypoxic ventilatory response in 16 healthy volunteers (haemoglobin oxygen saturation 83–85%) and examined whether its inhibitory effects on this response could be reversed by antioxidants (1 g ascorbic acid i.v. and 200 mg α-tocopherol p.o.). The subjects were randomly divided into an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55% (P < 0.01), respectively, and abolished the O2–CO2 interaction, i.e. the increase in O2 sensitivity with rising PCO2. Antioxidants completely reversed this inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the reversal was partial. In the placebo group, acetazolamide reduced the normo- and hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus control in both cases), and also abolished the O2–CO2 interaction. Placebo failed to reverse these inhibitory effects of acetazolamide in this group. We hypothesize that either an isoform of carbonic anhydrase may be involved in the regulation of the redox state in the carotid bodies or that acetazolamide and antioxidants exert independent effects on oxygen-sensing cells, in which both carbonic anhydrase and potassium channels may be involved. The novel findings of this study may have clinical implications, for example with regard to a combined use of acetazolamide and antioxidants at high altitude. PMID:16439432

Soy protein supports cardiovascular health by downregulating hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium sulfate-induced mild systemic inflammation.

PubMed

Marsh, Tanya G; Straub, Rachel K; Villalobos, Fatima; Hong, Mee Young

2011-12-01

Animal and human studies have indicated that the presence of soy in the diet improves cardiovascular health. Inflammation plays a pivotal role in the progression of cardiovascular disease (CVD). However, little is known about how dextran sodium sulfate (DSS)-induced systemic inflammation impacts overall heart health and, correspondingly, how soy protein modulates risk of CVD development in DSS-induced systemic inflammation. We hypothesized that soy protein-fed rats would have a lower risk of CVD by beneficial alteration of gene expression involving lipid metabolism and antioxidant capacity in DSS-induced systemic inflammation. Forty Sprague-Dawley rats were divided into 4 groups: casein, casein + DSS, soy protein, and soy protein + DSS. After 26 days, inflammation was induced in one group from each diet by incorporating 3% DSS in drinking water for 48 hours. Soy protein-fed rats had lower final body weights (P = .010), epididymal fat weights (P = .049), total cholesterol (P < .001), and low-density lipoprotein cholesterol (P < .001). In regard to gene expression, soy protein-fed rats had lower sterol regulatory element-binding protein-2 (P = .032) and hydroxymethylglutaryl-coenzyme A reductase (P = .028) levels and higher low-density lipoprotein receptor levels (P = .036). Antioxidant enzyme activity of superoxide dismutase and catalase was higher among the soy protein groups (P = .037 and P = .002, respectively). These results suggest that soy protein positively influences cardiovascular health by regulating serum lipids through modified expression of sterol regulatory element-binding protein-2 and its downstream genes (ie, hydroxymethylglutaryl-coenzyme A reductase and low-density lipoprotein receptor) and by promoting the antioxidant enzyme activity of superoxide dismutase and catalase. Copyright © 2011 Elsevier Inc. All rights reserved.

Production of antioxidant compounds of grape seed skin by fermentation and its optimization using response surface method

NASA Astrophysics Data System (ADS)

Andayani, D. G. S.; Risdian, C.; Saraswati, V.; Primadona, I.; Mawarda, P. C.

2017-03-01

Skins and seeds of grape are waste generated from food industry. These wastes contain nutrients of which able to be utilized as an important source for antioxidant metabolite production. Through an environmentally friendly process, natural antioxidant material was produced. This study aimed to generate antioxidant compounds by liquid fermentation. Optimization was carried out by using Schizosaccharomyces cerevisiae in Katu leaf substrate. Optimization variables through response surface methodology (RSM) were of sucrose concentration, skins and seeds of grape concentration, and pH. Results showed that the optimum conditions for antioxidant production were of 5 g/L sucrose, 5 g/L skins and seed at pH 5, respectively. The resulted antioxidant activity was of 1.62 mg/mL. Mathematical model of variance analysis using a second order polynomial corresponding to the resulted data for the antioxidant was of 20.70124 - 3.86997 A - 0.65996 B - 1.88367 C + 0.19634 A2 - 0.016638 B2 + 0.28848 C2 + 0.26980 AB - 0.068333 AC - 0.12367 BC. From the gained equation, the optimum yield from all variables was significant. Chemical analysis of the antioxidant was carried out using 2,2-Diphenyl-1-picrylhydrazyl (DPPH).

Reserpine Inhibit the JB6 P+ Cell Transformation Through Epigenetic Reactivation of Nrf2-Mediated Anti-oxidative Stress Pathway.

PubMed

Hong, Bo; Su, Zhengyuan; Zhang, Chengyue; Yang, Yuqing; Guo, Yue; Li, Wenjing; Kong, Ah-Ng Tony

2016-05-01

Nuclear factor erythroid-2 related factor 2 (Nrf2) is a crucial transcription factor that regulates the expression of defensive antioxidants and detoxification enzymes in cells. In a previous study, we showed that expression of the Nrf2 gene is regulated by an epigenetic modification. Rauvolfia verticillata, a traditional Chinese herbal medicine widely used in China, possesses anticancer and antioxidant effects. In this study, we investigated how Nrf2 is epigenetically regulated by reserpine, the main active component in R. verticillata, in mouse skin epidermal JB6 P+ cells. Reserpine induced ARE (antioxidant response element)-luciferase activity in HepG2-C8 cells. Accordingly, in JB6 P+ cells, it upregulated the mRNA and protein levels of Nrf2 and its downstream target genes heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1), while it only increased the protein level of UDP-glucuronosyltransferase 1A1 (UGT1A1). Furthermore, reserpine decreased the TPA (12-O-tetradecanoylphorbol-13-acetate)-induced colony formation of JB6 cells in a dose-dependent manner. DNA sequencing and methylated DNA immunoprecipitation further demonstrated the demethylation effect of reserpine on the first 15 CpGs of the Nrf2 promoter in JB6 P+ cells. Reserpine also reduced the mRNA and protein expression of DNMT1 (DNA methyltransferase 1), DNMT3a (DNA methyltransferases 3a), and DNMT3b (DNA methyltransferases 3b). Moreover, reserpine induced Nrf2 expression via an epigenetic pathway in skin epidermal JB6 P+ cells, enhancing the protective antioxidant activity and decreasing TPA-induced cell transformation. These results suggest that reserpine exhibits a cancer preventive effect by reactivating Nrf2 and inducing the expression of target genes involved in cellular protection, potentially providing new insight into the chemoprevention of skin cancer using reserpine.

Procyanidins from Wild Grape (Vitis amurensis) Seeds Regulate ARE-Mediated Enzyme Expression via Nrf2 Coupled with p38 and PI3K/Akt Pathway in HepG2 Cells

PubMed Central

Bak, Min-Ji; Jun, Mira; Jeong, Woo-Sik

2012-01-01

Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles in inducing phase II detoxifying/antioxidant enzymes as well as in modulating the upstream kinases. Ethanolic extract of V. amurensis seeds was fractionated with a series of organic solvents and finally separated into six fractions, F1–F6. Chemical properties of the procyanidins were analyzed by vanillin assay, BuOH-HCl test, and depolymerization with phloroglucinol followed by LC/MS analysis. The F5 had the highest procyanidin content among all the fractions and strongly induced the reporter activity of antioxidant response element as well as the protein expression of nuclear factor E2-related factor (Nrf2) in HepG2 human hepatocarcinoma cells. The procyanidin-rich F5 also strongly induced the expression of the phase II detoxifying and antioxidant enzymes such as NAD(P)H:quinone oxidoreductase1 and hemeoxygenase1. Phosphorylations of the upstream kinases such as MAPKs and PI3K/Akt were significantly increased by treatment with procyanidin fraction. In addition, the procyanidin-mediated Nrf2 expression was partly attenuated by PI3K inhibitor LY294002, and almost completely by p38 inhibitor SB202190, but neither by JNK inhibitor SP600125 nor by MEK1/2 inhibitor U0126. Taken together, the procyanidins from wild grape seeds could be used as a potential natural chemopreventive agent through Nrf2/ARE-mediated phase II detoxifying/antioxidant enzymes induction via p38 and PI3K/Akt pathway. PMID:22312287

No Evidence of Racial Differences in Endothelial Function and Exercise Blood Flow in Young, Healthy Males Following Acute Antioxidant Supplementation.

PubMed

Kappus, Rebecca M; Bunsawat, Kanokwan; Rosenberg, Alexander J; Fernhall, Bo

2017-03-01

This study investigated the effects of acute antioxidant supplementation on endothelial function, exercise blood flow and oxidative stress biomarkers in 9 young African American compared to 10 Caucasian males (25.7±1.2 years). We hypothesized that African American males would have lower exercise blood flow and endothelial responsiveness compared to Caucasian males, and these responses would be improved following antioxidant supplementation. Ultrasonography was used to measure blood flow during handgrip exercise. Endothelial function was assessed using flow-mediated dilation, and lipid peroxidation was assessed by measuring levels of malondialdehyde-thiobarbituric acid reactive substances. African American males exhibited lower endothelial function than Caucasians at baseline (8.3±1.7 vs. 12.2±1.7%) and the difference was ameliorated with antioxidant supplementation (10.7±1.9% vs. 10.8±1.8%), but the interaction was not significant (p=0.10). There were no significant changes in malondialdehyde-thiobarbituric acid reactive substances following antioxidant supplementation. There was a significant increase in brachial blood flow and forearm vascular conductance with exercise but no differences with antioxidant supplementation. There were no group differences in exercise responses and no differences with antioxidant supplementation, suggesting a lack of influence of oxidative stress during exercise in this cohort. © Georg Thieme Verlag KG Stuttgart · New York.

Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.

PubMed

Muhammad, Faheem; Wang, Aifei; Qi, Wenxiu; Zhang, Shixing; Zhu, Guangshan

2014-01-01

Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums.

A critical point: the problems associated with the variety of criteria to quantify the antioxidant capacity.

PubMed

Prieto, M A; Vázquez, J A; Murado, M A

2014-06-18

The oxidant action implies interfering in an autocatalytic process, in which no less than five chemical species are present (oxygen, oxidizable substrate, radicals, antioxidants, and oxidation products); furthermore, reactions of first and second order can take place, and interactions can occur, at several levels of the process. The common and incorrect practice is to use the single-time dose-response of an established antioxidant as a calibration curve to compute the equivalent antioxidant capacity of a sample, which is only tested at one single time-dose, assuming too many false aspects as true. Its use is unreasonable, given the availability of computational applications and instrumental equipment that, combined, provide the adequate tools to work with different variables in nonlinear models. The evaluation of the dose-time dependency of the response of the β-carotene method as a case study, using the combination of strong quantification procedures and a high amount of results with lower experimental error (applying microplate readers), reveals the lack of meaning of single-time criteria. Also, it demonstrates that, in most of the reactions, the time-dependent response in the oxidation process is inherently nonlinear and should not be standardized at one single time, because it would lead to unreliable results, hiding the real aspects of the response. In food matrices, the application of single-time criteria causes deficiencies in the control of the antioxidant content. Therefore, it is logical that, in the past decade, researchers have claimed consensus to increase the determination and effectiveness of antioxidant responses.

[Benefits of moderate beer consumption at different stages of life of women].

PubMed

Pérez Medina, Tirso; de Argila Fernández-Durán, Nuria; Pereira Sánchez, Augusto; Serrano González, Lucía

2015-07-18

Beer is a natural beverage low calorie, low degree of alcohol, no fats or sugars and a significant amount of carbohydrates, vitamins, and proteins. Beneficial health qualities are based on the presence in the beer of antioxidant compounds (polyphenols), which reduce the presence of free radicals in the organism, and phytoestrogens, elements biosimilars to natural estrogens. In pregnant women, beer, obviously alcohol-free, presents elements in its composition that differ it from other fermented beverages as it is the folic acid, vitamin necessary to prevent defects of the neural tube in the fetus or regulate homocysteine. With regard to breastfeeding, beer alcohol-free supplementation increases the antioxidant activity in breast milk and therefore reduces the oxidative stress of the newborn after birth In menopause, the presence of antioxidants, vitamins, nutrients, and dietetic fiber, as well as phytoestrogens, is highly beneficial in the prevention of pathologies arising from the decline in estrogens. Osteoporosis also is effectively combated by the beer. The intake of beer, favors a greater bone mass in women, irrespective of their gonadal status. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

The association of oxidant-antioxidant status in patients with chronic renal failure.

PubMed

Aziz, Manal A; Majeed, Ghanim H; Diab, Kareem S; Al-Tamimi, Raid J

2016-01-01

Oxidative stress has been linked to disease progression, including chronic renal failure (CRF). The aim of the present study was to determine malondialdehyde (MDA) as a sign of lipid peroxidation, and to investigate the association between antioxidant activities and three trace elements, in 49 patients with CRF. The erythrocyte and plasma trace elements [selenium (Se), zinc (Zn), and copper (Cu)] and antioxidant defense levels were determined: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), vitamins E and C. The obtained values were compared with 42 age- and sex-matched healthy controls. There were significantly lower mean values of plasma Se, GPx, vitamins E and C, erythrocyte Se, SOD and CAT levels in the patient group compared to the control group (p < 0.001). Plasma MDA showed a significant increase in all CRF patients in comparison with controls. No significant difference was found in plasma Cu, Zn, and erythrocyte GPx, Cu and Zn levels between patient and control groups. These findings indicate oxidative stress is present in patients of CRF, and may serve to establish a simple protocol for evaluation of renal function.

Shikonin inhibits oxidized LDL-induced monocyte adhesion by suppressing NFκB activation via up-regulation of PI3K/Akt/Nrf2-dependent antioxidation in EA.hy926 endothelial cells.

PubMed

Huang, Chin-Shiu; Lin, Ai-Hsuan; Yang, Ting-Chun; Liu, Kai-Li; Chen, Haw-Wen; Lii, Chong-Kuei

2015-02-01

Oxidized low-density lipoprotein (oxLDL) is a key contributor to atherogenesis through multiple mechanisms, including the reactive oxygen species (ROS)-mediated nuclear factor-kappaB (NFκB) signaling pathway. Although shikonin, one of the main active components isolated from the Chinese herb Lithospermum erythrorhizon, has been shown to possess cardioprotective, antioxidative, and anti-inflammatory effects, the mechanisms underlying these actions are not well understood. In this study, we used EA.hy926 endothelial-like cells to examine the anti-atherogenic activity of shikonin. Shikonin (0-1 μM) concentration-dependently induced heme oxygenase-1, glutamate cysteine ligase modifier subunit, catalase, superoxide dismutase 1, glutathione peroxidase 1, and glutathione reductase protein and mRNA expression and glutathione content via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/Nrf2 signaling pathway. In the presence of oxLDL (40 μg/ml), shikonin pretreatment reversed oxLDL-induced ROS production, antioxidant response element reporter activity, NFκB nuclear translocation, and intercellular adhesion molecule (ICAM)-1 and E-selectin expression and suppressed the increase of monocyte adhesion to endothelial cells. Nrf2 knockdown by using RNA interference attenuated the ability of shikonin to inhibit oxLDL-induced NFκB DNA binding activity, adhesion molecule expression, and monocyte adhesion. Taken together, these results suggest that shikonin protects against oxLDL-induced endothelial damage by suppressing ROS/NFκB-mediated ICAM-1 and E-selectin expression via up-regulation of PI3K/Akt/Nrf2-dependent antioxidant enzyme expression. Copyright © 2014 Elsevier Inc. All rights reserved.

EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical neurons against in vitro ischemia/reperfusion damages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, Da-min; Lu, Pei-Hua, E-mail: lphty1_1@163.com; Zhang, Ke

In this study, we tested the potential role of astragaloside IV (AS-IV) against oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damages in murine cortical neurons, and studied the associated signaling mechanisms. AS-IV exerted significant neuroprotective effects against OGD/R by reducing reactive oxygen species (ROS) accumulation, thereby attenuating oxidative stress and neuronal cell death. We found that AS-IV treatment in cortical neurons resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by Nrf2 Ser-40 phosphorylation, and its nuclear localization, as well as transcription of antioxidant-responsive element (ARE)-regulated genes: heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1) and sulphiredoxin 1 (SRXN-1). Knockdown of Nrf2 throughmore » lentiviral shRNAs prevented AS-IV-induced ARE genes transcription, and abolished its anti-oxidant and neuroprotective activities. Further, we discovered that AS-IV stimulated heparin-binding-epidermal growth factor (HB-EGF) release to trans-activate epidermal growth factor receptor (EGFR) in cortical neurons. Blockage or silencing EGFR prevented Nrf2 activation by AS-IV, thus inhibiting AS-IV-mediated anti-oxidant and neuroprotective activities against OGD/R. In summary, AS-IV protects cortical neurons against OGD/R damages through activating of EGFR-Nrf2 signaling. - Highlights: • Pre-treatment of astragaloside IV (AS-IV) protects murine cortical neurons from OGD/R. • AS-IV activates Nrf2-ARE signaling in murine cortical neurons. • Nrf2 is required for AS-IV-mediated anti-oxidant and neuroprotective activities. • AS-IV stimulates HB-EGF release to trans-activate EGFR in murine cortical neurons. • EGFR mediates AS-IV-induced Nrf2 activation and neuroprotection against OGD/R.« less

Lycopene inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells.

PubMed

Yang, Po-Min; Wu, Zhi-Zhen; Zhang, Yu-Qi; Wung, Being-Sun

2016-06-15

Age-related macular degeneration (AMD) is one of the most common diseases leading to blindness in elderly people. The progression of AMD may be prevented through anti-inflammation and antioxidation in retinal pigment epithelium (RPE) cells. Lycopene, a carotenoid, has been shown to possess both antioxidative and anti-inflammatory properties. This research was conducted to detail the mechanisms of these effects of lycopene-treated RPE cells. We exposed ARPE-19 cells to TNFα after pretreatment with lycopene, and measured monocyte adhesion, ICAM-1 expression, NF-κB nuclear translocation, and transcriptional activity. Cell viability was assayed with Alamar Blue. The cell redox state was tested by glutathione (GSH) and reactive oxygen species (ROS) levels. The importance of the Nrf2 pathway was tested in nuclear translocation, promoter reporter assay, and siRNA. Lycopene could reduce TNF-α-induced monocyte adhesion and H2O2- induced cell damage in RPE cells. Furthermore, lycopene inhibits ICAM-1 expression and abolishes NF-κB activation for up to 12h in TNFα-treated RPE cells. Lycopene upregulates Nrf2 levels in nuclear extracts and increases the transactivity of antioxidant response elements. The use of Nrf2 siRNA blocks the inhibitory effect of lycopene in TNF-α-induced ICAM-1 expression and NF-κB activation. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the de novo synthesis of GSH. We found that lycopene increases intracellular GSH levels and GCL expression. Following lycopene treatment, TNF-α-induced ROS production was abolished. The Nrf2-regulated antioxidant property plays a pivotal role in the anti-inflammatory mechanism underlying the inhibition of NF-κB activation in lycopene-treated ARPE-19 cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Studies on oxidants and antioxidants with a brief glance at their relevance to the immune system.

PubMed

Amir Aslani, Banafsheh; Ghobadi, Sirous

2016-02-01

Free radical generation occurs continuously within cells as a consequence of common metabolic processes. However, in high concentrations, whether from endogenous or exogenous sources, free radicals can lead to oxidative stress; a harmful process that cause serious damages to all biomolecules in our body hence impairs cell functions and even results in cell death and diseased states. Oxidative injuries accumulate over time and participate in cancer development, cardiovascular and neurodegenerative disorders as well as aging. Nature has bestowed the human body with a complex web of antioxidant defense system including enzymatic antioxidants like glutathione peroxidase and glutathione reductase, catalase and superoxide dismutase as well as non-enzymatic antioxidants such as thiol antioxidants, melatonin, coenzyme Q, and metal chelating proteins, which are efficient enough to fight against excessive free radicals. Also, nutrient antioxidants such as vitamin C, vitamin E, carotenoids, polyphenols, and trace elements are known to have high antioxidant potency to assist in minimizing harmful effects of reactive species. The immune system is also extremely vulnerable to oxidant and antioxidant balance as uncontrolled free radical production can impair its function and defense mechanism. The present paper reviews the ways by which free radicals form in the body and promote tissue damage, as well as the role of the antioxidants defense mechanisms. Finally, we will have a brief glance at oxidants and antioxidants relevance to the immune system. Copyright © 2016 Elsevier Inc. All rights reserved.

Multi-criteria optimization for ultrasonic-assisted extraction of antioxidants from Pericarpium Citri Reticulatae using response surface methodology, an activity-based approach.

PubMed

Zeng, Shanshan; Wang, Lu; Zhang, Lei; Qu, Haibin; Gong, Xingchu

2013-06-01

An activity-based approach to optimize the ultrasonic-assisted extraction of antioxidants from Pericarpium Citri Reticulatae (Chenpi in Chinese) was developed. Response surface optimization based on a quantitative composition-activity relationship model showed the relationships among product chemical composition, antioxidant activity of extract, and parameters of extraction process. Three parameters of ultrasonic-assisted extraction, including the ethanol/water ratio, Chenpi amount, and alkaline amount, were investigated to give optimum extraction conditions for antioxidants of Chenpi: ethanol/water 70:30 v/v, Chenpi amount of 10 g, and alkaline amount of 28 mg. The experimental antioxidant yield under the optimum conditions was found to be 196.5 mg/g Chenpi, and the antioxidant activity was 2023.8 μmol Trolox equivalents/g of the Chenpi powder. The results agreed well with the second-order polynomial regression model. This presented approach promised great application potentials in both food and pharmaceutical industries. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Response of nutrients, minerals, antioxidant leaf pigments, vitamins, polyphenol, flavonoid and antioxidant activity in selected vegetable amaranth under four soil water content.

PubMed

Sarker, Umakanta; Oba, Shinya

2018-06-30

Four selected vegetable amaranths were grown under four soil water content to evaluate their response in nutrients, minerals, antioxidant leaf pigments, vitamins, polyphenol, flavonoid and total antioxidant activity (TAC). Vegetable amaranth was significantly affected by variety, soil water content and variety × soil water content interactions for all the traits studied. Increase in water stress, resulted in significant changes in proximate compositions, minerals (macro and micro), leaf pigments, vitamin, total polyphenol content (TPC), and total flavonoid content (TFC) of vegetable amaranth. Accessions VA14 and VA16 performed better for all the traits studied. Correlation study revealed a strong antioxidant scavenging activity of leaf pigments, ascorbic acid, TPC and TFC. Vegetable amaranth can tolerate soil water stress without compromising the high quality of the final product in terms of nutrients and antioxidant profiles. Therefore, it could be a promising alternative crop in semi-arid and dry areas and also during dry seasons. Copyright © 2018. Published by Elsevier Ltd.

ANTIOXIDANT SUPPLEMENTATION AND NASAL INFLAMMATORY RESPONSES AMONG YOUNG ASTHMATICS EXPOSED TO HIGH LEVELS OF OZONE

EPA Science Inventory

Background: Recent studies examining the inflammatory response in atopic asthma to ozone suggest a release of soluble mediators of inflammation factors that might be related to reactive oxygen species (ROS). Antioxidant could prove useful in subjects exposed to additional oxidati...

Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

PubMed Central

AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T. S.; Janssens, Ivan A.; Asard, Han

2016-01-01

Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including “all” papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity. PMID:27200030

Transport stress-induced cerebrum oxidative stress is not mitigated by activating the Nrf2 antioxidant defense response in newly hatched chicks.

PubMed

Ge, J; Li, H; Sun, F; Li, X-N; Lin, J; Xia, J; Zhang, C; Li, J-L

2017-07-01

Transportation of newly hatched chicks from the hatchery to the farm is inevitable, especially for parent stock and grandsire parent stock chicks. However, the possible effects of transport stress in the newly hatched chicks are poorly understood. The aim of this study was to determine the adaptive responses to transport stress by activing the nuclear factor-erythroid 2-related factor 2 (Nrf2)-induced antioxidant defense. One hundred twenty newly hatched chicks were divided into 3 groups (control group, transport group, and simulation transport group) for 2, 4, and 8 h of real or simulated transportation. Transport stress could cause oxidative stress in the cerebrum of newly hatched chicks by increasing lipid peroxidation and production of free radicals and decreasing the activities of antioxidant enzymes and the glutathione:oxidized glutathione ratio. Transport stress activated the Nrf2 signaling pathway and triggered the transcription of antioxidant parameters. However, transport stress-induced cerebrum oxidative stress was not mitigated by activating the Nrf2 antioxidant defense response in newly hatched chicks.

The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.

PubMed

Arowojolu, Omotayo A; Orlow, Seth J; Elbuluk, Nada; Manga, Prashiela

2017-07-01

Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Crude oil exposure results in oxidative stress-mediated dysfunctional development and reproduction in the copepod Tigriopus japonicus and modulates expression of cytochrome P450 (CYP) genes.

PubMed

Han, Jeonghoon; Won, Eun-Ji; Hwang, Dae-Sik; Shin, Kyung-Hoon; Lee, Yong Sung; Leung, Kenneth Mei-Yee; Lee, Su-Jae; Lee, Jae-Seong

2014-07-01

In this study, we investigated the effects of the water-accommodated fraction (WAF) of crude oil on the development and reproduction of the intertidal copepod Tigriopus japonicus through life-cycle experiments. Furthermore, we investigated the mechanisms underlying the toxic effects of WAF on this benthic organism by studying expression patterns of cytochrome P450 (CYP) genes. Development of T. japonicus was delayed and molting was interrupted in response to WAF exposure. Hatching rate was also significantly reduced in response to WAF exposure. Activities of antioxidant enzymes such as glutathione S-transferase (GST), glutathione reductase (GR), and catalase (CAT) were increased by WAF exposure in a concentration-dependent manner. These results indicated that WAF exposure resulted in oxidative stress, which in turn was associated with dysfunctional development and reproduction. To evaluate the involvement of cytochrome P450 (CYP) genes, we cloned the entire repertoire of CYP genes in T. japonicus (n=52) and found that the CYP genes belonged to five different clans (i.e., Clans 2, 3, 4, mitochondrial, and 20). We then examined expression patterns of these 52 CYP genes in response to WAF exposure. Three TJ-CYP genes (CYP3024A2, CYP3024A3, and CYP3027C2) belonging to CYP clan 3 were significantly induced by WAF exposure in a time- and concentration-dependent manner. We identified aryl hydrocarbon responsive elements (AhRE), xenobiotic responsive elements (XREs), and metal response elements (MRE) in the promoter regions of these three CYP genes, suggesting that these genes are involved in detoxification of toxicants. Overall, our results indicate that WAF can trigger oxidative stress and thus induce dysfunctional development and reproduction in the copepod T. japonicus. Furthermore, we identified three TJ-CYP genes that represent potential biomarkers of oil pollution. Copyright © 2014 Elsevier B.V. All rights reserved.

Natural preservatives for superficial scald reduction and enhancement of protective phenolic-linked antioxidant responses in apple during post-harvest storage.

PubMed

Sarkar, Dipayan; Ankolekar, Chandrakant; Greene, Duane; Shetty, Kalidas

2018-05-01

Superficial scald during post-harvest storage is a serious problem for long-term preservation and shelf-life of some apple and pear cultivars. Development of superficial scald and related physiological disorders such as enzymatic and non-enzymatic browning are associated in part with oxidative breakdown and redox imbalance. Therefore, targeting natural antioxidants from food-grade sources as post-harvest treatment to reduce superficial scald has merit. Such natural antioxidants can potentially counter oxidation-linked damages associated with superficial scald through stimulation of antioxidant enzyme responses and biosynthesis of less-oxidized phenolics involving protective redox-linked pathway such as proline-associated pentose phosphate pathway. Based on this rationale, bioprocessed food-grade oregano extract (OX) and soluble chitosan oligosaccharide (COS) were targeted as post-harvest treatment (2 and 4 g L -1 ) and were compared with diphenylamine (DPA) (1 and 2 g L -1 ) to reduce superficial scald and to improve protective phenolic-linked antioxidant responses in "Cortland" cultivar stored at 4 °C for 15 weeks. Overall, significant reduction of superficial scald and conjugated triene was observed with DPA and OX (2 g L -1 ) post-harvest treatments. Furthermore, stimulation of antioxidant enzyme responses such as increases in superoxide dismutase and guaiacol peroxidase activity was also observed, but was more evident with DPA and COS treatment. Overall, results of this study indicated that critical balance of less-oxidized phenolics and antioxidant enzymes and associated anabolic PPP-linked redox regulation is essential for improving post-harvest preservation and reduction of superficial scald in apple.

Liver δ-Aminolevulinate Dehydratase Activity is Inhibited by Neonicotinoids and Restored by Antioxidant Agents

PubMed Central

Sauer, Elisa; Moro, Angela M.; Brucker, Natália; Nascimento, Sabrina; Gauer, Bruna; Fracasso, Rafael; Gioda, Adriana; Beck, Ruy; Moreira, José C. F.; Eifler-Lima, Vera Lucia; Garcia, Solange Cristina

2014-01-01

Neonicotinoids represent the most used class of insecticides worldwide, and their precursor, imidacloprid, is the most widely marketed. The aim of this study was to evaluate the effect of imidacloprid on the activity of hepatic δ-aminolevulinate dehydratase (δ-ALA-D), protective effect of potential antioxidants against this potential effect and presence of chemical elements in the constitution of this pesticide. We observed that δ-ALA-D activity was significantly inhibited by imidacloprid at all concentrations tested in a dose-dependent manner. The IC50 value was obtained and used to evaluate the restoration of the enzymatic activity. δ-ALA-D inhibition was completely restored by addition of dithiotreitol (DTT) and partly by ZnCl2, demonstrating that the inhibition occurs by oxidation of thiol groups and by displacement of the Zn (II), which can be explained by the presence of chemical elements found in the constitution of pesticides. Reduced glutathione (GSH) had the best antioxidant effect against to δ-ALA-D inhibition caused by imidacloprid, followed by curcumin and resveratrol. It is well known that inhibition of the enzyme δ-ALA-D may result in accumulation of its neurotoxic substrate (δ-ALA), in this line, our results suggest that further studies are needed to investigate the possible neurotoxicity induced by neonicotinoids and the involvement of antioxidants in cases of poisoning by neonicotinoids. PMID:25402564

MOLECULAR MECHANISM OF HUMAN NRF2 ACTIVATION AND DEGRADATION: ROLE OF SEQUENTIAL PHOSPHORYLATION BY PROTEIN KINASE CK2

PubMed Central

Pi, Jingbo; Bai, Yushi; Reece, Jeffrey M.; Williams, Jason; Liu, Dianxin; Freeman, Michael L.; Fahl, William E.; Shugar, David; Liu, Jie; Qu, Wei; Collins, Sheila; Waalkes, Michael P.

2007-01-01

Nrf2 is a key transcription factor in the cellular response to oxidative stress. In this study we first identify two phosphorylated forms of endogenous human Nrf2 after chemically-induced oxidative stress and provide evidence that protein kinase CK2-mediated sequential phosphorylation plays potential role in Nrf2 activation and degradation. Human Nrf2 has a predicted molecular mass of 66 kDa. However, immunoblots showed that two bands at 98 and 118 kDa, which are identified as phosphorylated forms, are increased in response to Nrf2 inducers. In addition, human Nrf2 was found to be a substrate for CK2 which mediated two steps of phosphorylation, resulting in two forms of Nrf2 migrating with differing Mr at 98 kDa (Nrf2–98) and 118 kDa (Nrf2–118). Our results support a role in which calmodulin binding regulates CK2 activity, in that cold (25 °C) in Ca2+-free media (cold/Ca2+-free) decreased both cellular calcium levels and CK2-calmodulin binding and induced Nrf2–118 formation, the latter of which was prevented by CK2 specific inhibitors. Gel-shift assays showed that the Nrf2–118 generated under cold/Ca2+-free conditions does not bind to the antioxidant response element, indicating that Nrf2–98 has transcriptional activity. In contrast, Nrf2–118 is more susceptible to degradation. These results provide evidence for phosphorylation by CK2 as a critical controlling factor in Nrf2-mediated cellular antioxidant response. PMID:17512459

Plant-parasitic nematodes: towards understanding molecular players in stress responses.

PubMed

Gillet, François-Xavier; Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair; Grossi-de-Sa, Maria Fatima

2017-03-01

Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1 , which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

Modulation of antioxidant defense and immune response in zebra fish (Danio rerio) using dietary sodium propionate.

PubMed

Safari, Roghieh; Hoseinifar, Seyed Hossein; Kavandi, Morteza

2016-12-01

The present study explores the effect of dietary sodium propionate on mucosal immune response and expression of antioxidant enzyme genes in zebra fish (Danio rerio). Six hundred healthy zebra fish (0.42 ± 0.06 g) supplied, randomly stocked in 12 aquariums and fed on basal diets supplemented with different levels of sodium propionate [0 (control), 5, 10 and 20 g kg -1 ] for 8 weeks. At the end of the feeding trial, mucosal immune parameters (TNF-α, IL-1β, Lyz), antioxidant enzyme (SOD, CAT) as well as heat shock protein 70 (HSP70) gene expression were measured. The results revealed feeding on sodium propionate significantly up-regulated inflammatory response genes (TNF-α, IL-1β, Lyz) in a dose-dependent manner (P < 0.05). However, antioxidant enzyme genes significantly down-regulated in the treated group compared with control (P < 0.05). Also, HSP70 gene expression was higher in the liver of fish fed the basal diet and deceased with elevation of sodium propionate levels in the diet. These results showed beneficial effects of dietary sodium propionate on mucosal immune response as well as the antioxidant defense of zebra fish.

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound.

PubMed

Pais, Joana M; Barroca, Maria João; Marques, Maria Paula M; Almeida Paz, Filipe A; Braga, Susana S

2017-01-01

Fisetin is a natural antioxidant with a wide range of nutraceutical properties, including antidiabetic, neuroprotecting, and suppression or prevention of tumors. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with gamma-cyclodextrin (γ-CD), a cyclic oligosaccharide approved for human consumption. A detailed physicochemical analysis of the product is carried out using elemental analysis, powder X-ray diffraction (PXRD), Raman, infrared and 13 C{ 1 H} CP-MAS NMR spectroscopies, and thermal analysis (TGA) to verify fisetin inclusion and to present a hypothetical structural arrangement for the host-guest units. The antioxidant activity of the γ-CD·fisetin inclusion compound is evaluated by the DPPH assay.

Identification and quantification of antioxidant components of honeys from various floral sources.

PubMed

Gheldof, Nele; Wang, Xiao-Hong; Engeseth, Nicki J

2002-10-09

Little is known about the individual components of honey that are responsible for its antioxidant activity. The present study was carried out to characterize the phenolics and other antioxidants present in honeys from seven floral sources. Chromatograms of the phenolic nonpolar fraction of the honeys indicated that most honeys have similar but quantitatively different phenolic profiles. Many of the flavonoids and phenolic acids identified have been previously described as potent antioxidants. A linear correlation between phenolic content and ORAC activity was demonstrated (R(2) = 0.963, p < 0.0001). Honeys were separated by solid-phase extraction into four fractions for sugar removal and separation based on solubility to identify the relative contribution of each fraction to the antioxidant activity of honey. Antioxidant analysis of the different honey fractions suggested that the water-soluble fraction contained most of the antioxidant components. Specific water-soluble antioxidant components were quantified, including protein; gluconic acid; ascorbic acid; hydroxymethylfuraldehyde; and the combined activities of the enzymes glucose oxidase, catalase and peroxidase. Of these components, a significant correlation could be established only between protein content and ORAC activity (R(2) = 0.674, p = 0.024). In general, the antioxidant capacity of honey appeared to be a result of the combined activity of a wide range of compounds including phenolics, peptides, organic acids, enzymes, Maillard reaction products, and possibly other minor components. The phenolic compounds contributed significantly to the antioxidant capacity of honey but were not solely responsible for it.

Bioinspired near-infrared-excited sensing platform for in vitro antioxidant capacity assay based on upconversion nanoparticles and a dopamine-melanin hybrid system.

PubMed

Wang, Dong; Chen, Chuan; Ke, Xuebin; Kang, Ning; Shen, Yuqing; Liu, Yongliang; Zhou, Xi; Wang, Hongjun; Chen, Changqing; Ren, Lei

2015-02-11

A novel core-shell structure based on upconversion fluorescent nanoparticles (UCNPs) and dopamine-melanin has been developed for evaluation of the antioxidant capacity of biological fluids. In this approach, dopamine-melanin nanoshells facilely formed on the surface of UCNPs act as ultraefficient quenchers for upconversion fluorescence, contributing to a photoinduced electron-transfer mechanism. This spontaneous oxidative polymerization of the dopamine-induced quenching effect could be effectively prevented by the presence of various antioxidants (typically biothiols, ascorbic acid (Vitamin C), and Trolox). The chemical response of the UCNPs@dopamine-melanin hybrid system exhibited great selectivity and sensitivity toward antioxidants relative to other compounds at 100-fold higher concentration. A satisfactory correlation was established between the ratio of the "anti-quenching" fluorescence intensity and the concentration of antioxidants. Besides the response of the upconversion fluorescence signal, a specific evaluation process for antioxidants could be visualized by the color change from colorless to dark gray accompanied by the spontaneous oxidation of dopamine. The near-infrared (NIR)-excited UCNP-based antioxidant capacity assay platform was further used to evaluate the antioxidant capacity of cell extracts and human plasma, and satisfactory sensitivity, repeatability, and recovery rate were obtained. This approach features easy preparation, fluorescence/visual dual mode detection, high specificity to antioxidants, and enhanced sensitivity with NIR excitation, showing great potential for screening and quantitative evaluation of antioxidants in biological systems.

Development of functional beverages from blends of Hibiscus sabdariffa extract and selected fruit juices for optimal antioxidant properties.

PubMed

Ogundele, Oluwatoyin M A; Awolu, Olugbenga O; Badejo, Adebanjo A; Nwachukwu, Ifeanyi D; Fagbemi, Tayo N

2016-09-01

The demand for functional foods and drinks with health benefit is on the increase. The synergistic effect from mixing two or more of such drinks cannot be overemphasized. This study was carried out to formulate and investigate the effects of blends of two or more of pineapple, orange juices, carrot, and Hibiscus sabdariffa extracts (HSE) on the antioxidant properties of the juice formulations in order to obtain a combination with optimal antioxidant properties. Experimental design was carried out using optimal mixture model of response surface methodology which generated twenty experimental runs with antioxidant properties as the responses. The DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)] radical scavenging abilities, ferric reducing antioxidant potential (FRAP), vitamin C, total phenolics, and total carotenoids contents of the formulations were evaluated as a test of antioxidant property. In all the mixtures, formulations having HSE as part of the mixture showed the highest antioxidant potential. The statistical analyzes, however, showed that the formulations containing pineapple, carrot, orange, and HSE of 40.00, 16.49, 17.20, and 26.30%, respectively, produced optimum antioxidant potential and was shown to be acceptable to a research laboratory guidance panel, thus making them viable ingredients for the production of functional beverages possessing important antioxidant properties with potential health benefits.

Antioxidant activity of different fractions of Spirulina platensis protean extract.

PubMed

Piñero Estrada, J E; Bermejo Bescós, P; Villar del Fresno, A M

2001-01-01

Spirulina platensis, planktonic blue-green algae, is gaining increasing attention because of its nutritional and medicinal properties. This microalgae contains phycobiliproteins (phycocyanin and allophycocyanin). Previous reports from our laboratory have shown that a protean extract of S. platensis is a potent free-radical scavenger (hydroxyl and peroxyl radicals) and inhibits microsomal lipid peroxidation. The aim of this study was to purify and characterize phycocyanin of S. platensis. Besides, we tried to demonstrate that one of the main components responsible for this antioxidant activity is a biliprotein phycocyanin. For this purpose, we studied the antioxidant activity of different fractions obtained during the phycocyanin purification process, through the scavenger activity of hydroxyl radical. We also observed that an increase in phycocyanin content was related to an increase in the antioxidant activity in different fractions, and therefore phycobiliprotein phycocyanin is the component mainly responsible for the antioxidant activity.

Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila

USDA-ARS?s Scientific Manuscript database

Curcumin is an antioxidant extracted from the root of the turmeric plant. We examined the antioxidant effect and lifespan extension of curcumin in Drosophila. To ascertain the antioxidant effects of curcumin with regard to lifespan extension and the response to reactive oxygen species, female and ma...

Short term supplementation of dietary antioxidants selectively regulates the inflammatory responses during early cutaneous wound healing in diabetic mice

PubMed Central

2011-01-01

Background Diabetic foot ulcers are serious complications for diabetic patients, yet the precise mechanism that underlines the treatment of these diabetic complications remains unclear. We hypothesized that dietary antioxidant supplementation with vitamin C, combined either with vitamin E or with vitamin E and NAC, improves delayed wound healing through modulation of blood glucose levels, oxidative stress, and inflammatory response. Methods Diabetes was induced by administration of alloxan monohydrate. Mice were divided into 4 groups; CON (non-diabetic control mice fed AIN 93 G purified rodent diet), DM (diabetic mice fed AIN 93 G purified rodent diet), VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet), and Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E, and 2.5% NAC supplemented diet). After 10 days of dietary antioxidant supplementation, cutaneous full-thickness excisional wounds were performed, and the rate of wound closure was examined. TBARS as lipid peroxidation products and vitamin E levels were measured in the liver. Expression levels of oxidative stress and inflammatory response related proteins were measured in the cutaneous wound site. Results Dietary antioxidant supplementation improved blood glucose levels and wound closure rate and increased liver vitamin E, but not liver TBARS levels in the diabetic mice as compared to those of the CON. In addition, dietary antioxidant supplementation modulated the expression levels of pIκBα, HO-1, CuZnSOD, iNOS and COX-2 proteins in the diabetic mice. Conclusions These findings demonstrated that delayed wound healing is associated with an inflammatory response induced by hyperglycaemia, and suggests that dietary antioxidant supplementation may have beneficial effects on wound healing through selective modulation of blood glucose levels, oxidative stress, and inflammatory response. PMID:22088091

BaP-metals co-exposure induced tissue-specific antioxidant defense in marine mussels Mytilus coruscus.

PubMed

Chen, Siyu; Qu, Mengjie; Ding, Jiawei; Zhang, Yifei; Wang, Yi; Di, Yanan

2018-04-18

Both benzo(α)pyrene (BaP) and metals are frequently found in marine ecosystem and can cause detrimental effects in marine organism, especially the filter feeder-marine mussels. Although the biological responses in mussels have been well-studied upon the single metal or BaP exposure, the information about antioxidant defense, especially in different tissues of mussels, are still limited. Considering the variety of contaminants existing in the actual marine environment, single BaP (56 μg/L) and the co-exposure with Cu, Cd and Pb (50 μg/L, 50 μg/L and 3 mg/L respectively) were applied in a 6 days exposure followed by 6 days depuration experiment. The alterations of superoxide dismutase (SOD), catalase (CAT) activities and total antioxidant capacity (TAC) level were assessed in haemolymph, gills and digestive glands of marine mussels, Mytilus coruscus. An unparalleled change in antioxidant biomarkers was observed in all cells/tissues, with the SOD activity showing higher sensitivity to exposure. A tissue-specific response showing unique alteration in gill was investigated, indicating the different function of tissues during stress responses. Depressed antioxidant effects were induced by BaP-metals co-exposure, indicating the interaction may alter the intact properties of BaP. To our knowledge, this is the first research to explore the antioxidant defense induced by combined exposure of BaP-metals regarding to tissue-specific responses in marine mussels. The results and experimental model will provide valuable information and can be utilized in the investigation of stress response mechanisms, especially in relation to tissue functions in marine organism in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dietary antioxidants and exercise.

PubMed

Powers, Scott K; DeRuisseau, Keith C; Quindry, John; Hamilton, Karyn L

2004-01-01

Muscular exercise promotes the production of radicals and other reactive oxygen species in the working muscle. Growing evidence indicates that reactive oxygen species are responsible for exercise-induced protein oxidation and contribute to muscle fatigue. To protect against exercise-induced oxidative injury, muscle cells contain complex endogenous cellular defence mechanisms (enzymatic and non-enzymatic antioxidants) to eliminate reactive oxygen species. Furthermore, exogenous dietary antioxidants interact with endogenous antioxidants to form a cooperative network of cellular antioxidants. Knowledge that exercise-induced oxidant formation can contribute to muscle fatigue has resulted in numerous investigations examining the effects of antioxidant supplementation on human exercise performance. To date, there is limited evidence that dietary supplementation with antioxidants will improve human performance. Furthermore, it is currently unclear whether regular vigorous exercise increases the need for dietary intake of antioxidants. Clearly, additional research that analyses the antioxidant requirements of individual athletes is needed.

Human cell toxicogenomic analysis linking reactive oxygen species to the toxicity of monohaloacetic acid drinking water disinfection byproducts.

PubMed

Pals, Justin; Attene-Ramos, Matias S; Xia, Menghang; Wagner, Elizabeth D; Plewa, Michael J

2013-01-01

Chronic exposure to drinking water disinfection byproducts has been linked to adverse health risks. The monohaloacetic acids (monoHAAs) are generated as byproducts during the disinfection of drinking water and are cytotoxic, genotoxic, mutagenic, and teratogenic. Iodoacetic acid toxicity was mitigated by antioxidants, suggesting the involvement of oxidative stress. Other monoHAAs may share a similar mode of action. Each monoHAA generated a significant concentration-response increase in the expression of a β-lactamase reporter under the control of the antioxidant response element (ARE). The monoHAAs generated oxidative stress with a rank order of iodoacetic acid (IAA) > bromoacetic acid (BAA) ≫ chloroacetic acid (CAA); this rank order was observed with other toxicological end points. Toxicogenomic analysis was conducted with a nontransformed human intestinal epithelial cell line (FHs 74 Int). Exposure to the monoHAAs altered the transcription levels of multiple oxidative stress responsive genes, indicating that each exposure generated oxidative stress. The transcriptome profiles showed an increase in thioredoxin reductase 1 (TXNRD1) and sulfiredoxin (SRXN1), suggesting peroxiredoxin proteins had been oxidized during monoHAA exposures. Three possible sources of reactive oxygen species were identified, the hypohalous acid generating peroxidase enzymes lactoperoxidase (LPO) and myeloperoxidase (MPO), nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase 5 (NOX5), and PTGS2 (COX-2) mediated arachidonic acid metabolism. Each monoHAA exposure caused an increase in COX-2 mRNA levels. These data provide a functional association between monoHAA exposure and adverse health outcomes such as oxidative stress, inflammation, and cancer.

Sulforaphane Ameliorates 3-Nitropropionic Acid-Induced Striatal Toxicity by Activating the Keap1-Nrf2-ARE Pathway and Inhibiting the MAPKs and NF-κB Pathways.

PubMed

Jang, Minhee; Cho, Ik-Hyun

2016-05-01

The potential neuroprotective value of sulforaphane (SFN) in Huntington's disease (HD) has not been established yet. We investigated whether SFN prevents and improves the neurological impairment and striatal cell death in a 3-nitropropionic acid (3-NP)-induced mouse model of HD. SFN (2.5 and 5.0 mg/kg/day, i.p.) was given daily 30 min before 3-NP treatment (pretreatment) and from onset/progression/peak points of the neurological scores. Pretreatment with SFN (5.0 mg/kg/day) produced the best neuroprotective effect with respect to the neurological scores and lethality among other conditions. The protective effects due to pretreatment with SFN were associated with the following: suppression of the formation of a lesion area, neuronal death, succinate dehydrogenase activity, apoptosis, microglial activation, and mRNA or protein expression of inflammatory mediators, including tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, inducible nitric oxide synthase, and cyclooxygenase-2 in the striatum after 3-NP treatment. Also, pretreatment with SFN activated the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and inhibited the mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) pathways in the striatum after 3-NP treatment. As expected, the pretreatment with activators (dimethyl fumarate and antioxidant response element inducer-3) of the Keap1-Nrf2-ARE pathway decreased the neurological impairment and lethality after 3-NP treatment. Our findings suggest that SFN may effectively attenuate 3-NP-induced striatal toxicity by activating the Keap1-Nrf2-ARE pathway and inhibiting the MAPKs and NF-κB pathways and that SFN has a wide therapeutic time-window for HD-like symptoms.

Synthesis, characterization, antioxidant and brine shrimp cytotoxic activity of novel 3-benzothioyl-1-(3-hydroxy-3-phenyl -3-propyl)-1-methylthiourea.

PubMed

Shoaib, Mohammad; Ullah, Abid; Shah, Syed Wadood Ali; Tahir, Muhammad Nawaz

2017-07-01

In the present research work novel ephedrine based thiourea derivative, 3-benzothioyl-1-(3-hydroxy-3-phenyl -3-propyl)-1-methylthiourea 4is synthesized and then characterized elemental analyzed via various techniques i.e., Proton NMR, carbon13 NMR and fatherly confirmed via X-ray crystallography. Compound 4 was then screened for their possible antioxidant and cytotoxic potentials. Benzoyl chloride was treated with an equimolar potassium thiocyanate in acetone to achieve benzoyl isothiocyantes. It was then treated with an equimolar (1R, 2S)-(-)-Ephedrine to obtain the 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methyl thiourea4. It was then screened for antioxidant and cytotoxic potentials. The compound 4 showed excellent antioxidant activity almost comparable to ascorbic acid (standard) and have significant cytotoxic activity with LC 50 value 05±0.58 ppm.

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

PubMed

Patrick, Lyn

2002-12-01

Mercury exposure is the second-most common cause of toxic metal poisoning. Public health concern over mercury exposure, due to contamination of fish with methylmercury and the elemental mercury content of dental amalgams, has long been a topic of political and medical debate. Although the toxicology of mercury is complex, there is evidence for antioxidant protection in the prevention of neurological and renal damage caused by mercury toxicity. Alpha-lipoic acid, a coenzyme of pyruvate and alpha-ketoglutarate dehydrogenase, has been used in Germany as an antioxidant and approved treatment for diabetic polyneuropathy for 40 years. Research has attempted to identify the role of antioxidants, glutathione and alpha-lipoic acid specifically, in both mitigation of heavy metal toxicity and direct chelation of heavy metals. This review of the literature will assess the role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

Acute phase response and plasma carotenoid concentrations in older women: findings from the nun study.

PubMed

Boosalis, M G; Snowdon, D A; Tully, C L; Gross, M D

1996-01-01

This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.

Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a ‘mitohormesis’ mechanism involving reactive oxygen species and PGC-1

PubMed Central

Bouitbir, Jamal; Charles, Anne-Laure; Echaniz-Laguna, Andoni; Kindo, Michel; Daussin, Frédéric; Auwerx, Johan; Piquard, François; Geny, Bernard; Zoll, Joffrey

2012-01-01

Aims Statins protect against cardiovascular-related mortality but induce skeletal muscle toxicity. To investigate mechanisms of statins, we tested the hypothesis that statins optimized cardiac mitochondrial function but impaired vulnerable skeletal muscle by inducing different level of reactive oxygen species (ROS). Methods and results In atrium of patients treated with statins, ROS production was decreased and oxidative capacities were enhanced together with an extensive augmentation of mRNAs expression of peroxisome proliferator-activated receptor gamma co-activator (PGC-1) family. However, in deltoid biopsies from patients with statin-induced muscular myopathy, oxidative capacities were decreased together with ROS increase and a collapse of PGC-1 mRNA expression. Several animal and cell culture experiments were conducted and showed by using ROS scavengers that ROS production was the triggering factor responsible of atorvastatin-induced activation of mitochondrial biogenesis pathway and improvement of antioxidant capacities in heart. Conversely, in skeletal muscle, the large augmentation of ROS production following treatment induced mitochondrial impairments, and reduced mitochondrial biogenesis mechanisms. Quercetin, an antioxidant molecule, was able to counteract skeletal muscle deleterious effects of atorvastatin in rat. Conclusion Our findings identify statins as a new activating factor of cardiac mitochondrial biogenesis and antioxidant capacities, and suggest the importance of ROS/PGC-1 signalling pathway as a key element in regulation of mitochondrial function in cardiac as well as skeletal muscles. PMID:21775390

Mixture of Peanut Skin Extract and Fish Oil Improves Memory in Mice via Modulation of Anti-Oxidative Stress and Regulation of BDNF/ERK/CREB Signaling Pathways

PubMed Central

Xiang, Lan; Cao, Xue-Li; Xing, Tian-Yan; Mori, Daisuke; Tang, Rui-Qi; Li, Jing; Gao, Li-Juan; Qi, Jian-Hua

2016-01-01

Long-term use of fish oil (FO) is known to induce oxidative stress and increase the risk of Alzheimer’s disease in humans. In the present study, peanut skin extract (PSE), which has strong antioxidant capacity, was mixed with FO to reduce its side effects while maintaining its beneficial properties. Twelve-week Institute of Cancer Research (ICR) mice were used to conduct animal behavior tests in order to evaluate the memory-enhancing ability of the mixture of peanut skin extract and fish oil (MPF). MPF significantly increased alternations in the Y-maze and cognitive index in the novel object recognition test. MPF also improved performance in the water maze test. We further sought to understand the mechanisms underlying these effects. A significant decrease in superoxide dismutase (SOD) activity and an increase in malonyldialdehyde (MDA) in plasma were observed in the FO group. The MPF group showed reduced MDA level and increased SOD activity in the plasma, cortex and hippocampus. Furthermore, the gene expression levels of brain-derived neurotrophic factor (BDNF) and cAMP responsive element-binding protein (CREB) in the hippocampus were increased in the MPF group, while phosphorylation of protein kinase B (AKT), extracellular signal-regulated kinase (ERK) and CREB in the hippocampus were enhanced. MPF improves memory in mice via modulation of anti-oxidative stress and activation of BDNF/ERK/CREB signaling pathways. PMID:27136583

Evaluation of antioxidant and anticancer activity of copper oxide nanoparticles synthesized using medicinally important plant extracts.

PubMed

Rehana, Dilaveez; Mahendiran, D; Kumar, R Senthil; Rahiman, A Kalilur

2017-05-01

Copper oxide (CuO) nanoparticles were synthesized by green chemistry approach using different plant extracts obtained from the leaves of Azadirachta indica, Hibiscus rosa-sinensis, Murraya koenigii, Moringa oleifera and Tamarindus indica. In order to compare their efficiency, the same copper oxide nanoparticles was also synthesized by chemical method. Phytochemical screening of the leaf extracts showed the presence of carbohydrates, flavonoids, glycosides, phenolic compounds, saponins, tannins, proteins and amino acids. FT IR spectra confirmed the possible biomolecules responsible for the formation of copper oxide nanoparticles. The surface plasmon resonance absorption band at 220-235nm in the UV-vis spectra also supports the formation of copper oxide nanoparticles. XRD patterns revealed the monoclinic phase of the synthesized copper oxide nanoparticles. The average size, shape and the crystalline nature of the nanoparticles were determined by SEM, TEM and SAED analysis. EDX analysis confirmed the presence of elements in the synthesized nanoparticles. The antioxidant activity was evaluated by three different free radical scavenging assays. The cytotoxicity of copper oxide nanoparticles was evaluated against four cancer cell lines such as human breast (MCF-7), cervical (HeLa), epithelioma (Hep-2) and lung (A549), and one normal human dermal fibroblast (NHDF) cell line. The morphological changes were evaluated using Hoechst 33258 staining assay. Copper oxide nanoparticles synthesized by green method exhibited high antioxidant and cytotoxicity than that synthesized by chemical method. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications

PubMed Central

Kuang, Haixue; Tang, Zhenqiu; Zhang, Chengyue; Wang, Zhibin; Li, Wenji; Yang, Chunjuan; Wang, Qiuhong; Yang, Bingyou; Kong, Ah-Ng

2017-01-01

Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells. TAX induced antioxidant response element (ARE)-luciferase activity in HepG2-C8 cells and up-regulated mRNA and protein levels of Nrf2 and its downstream genes heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), in JB6 P+ cells. Furthermore, bisulfite genomic sequencing revealed that TAX treatment reduces the methylation level of the first 15 CpGs sites in the Nrf2 promoter. Western blotting showed that TAX inhibits the expression levels of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) proteins. In summary, our results revealed that TAX can induce expression of Nrf2 and its downstream target genes in JB6 P+ cells by CpG demethylation. These finding suggest that TAX may exhibit a skin cancer preventive effect by activating Nrf2 via an epigenetic pathway. PMID:28714938

Threonine modulates immune response, antioxidant status and gene expressions of antioxidant enzymes and antioxidant-immune-cytokine-related signaling molecules in juvenile blunt snout bream (Megalobrama amblycephala).

PubMed

Habte-Tsion, Habte-Michael; Ren, Mingchun; Liu, Bo; Ge, Xianping; Xie, Jun; Chen, Ruli

2016-04-01

A 9-week feeding trial was conducted to investigate the effects of graded dietary threonine (Thr) levels (0.58-2.58%) on the hematological parameters, immune response, antioxidant status and hepatopancreatic gene expression of antioxidant enzymes and antioxidant-immune-cytokine-related signaling molecules in juvenile blunt snout bream. For this purpose, 3 tanks were randomly arranged and assigned to each experimental diet. Fish were fed with their respective diet to apparent satiation 4 times daily. The results indicated that white blood cell, red blood cell and haemoglobin significantly responded to graded dietary Thr levels, while hematocrit didn't. Complement components (C3 and C4), total iron-binding capacity (TIBC), immunoglobulin M (IgM), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) increased with increasing dietary Thr levels up to 1.58-2.08% and thereafter tended to decrease. Dietary Thr regulated the gene expressions of Cu/Zn-SOD, Mn-SOD and CAT, GPx1, glutathione S-transferase mu (GST), nuclear factor erythroid 2-related factor 2 (Nrf2), heat shock protein-70 (Hsp70), tumor necrosis factor-alpha (TNF-α), apolipoprotein A-I (ApoA1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and fructose-bisphosphate aldolase B (ALDOB); while the gene expression of peroxiredoxin II (PrxII) was not significantly modified by graded Thr levels. These genes are involved in different functions including antioxidant, immune, and defense responses, energy metabolism and protein synthesis. Therefore, this study could provide a new molecular tool for studies in fish immunonutrition and shed light on the regulatory mechanisms that dietary Thr improved the antioxidant and immune capacities of fish. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative effects of dietary flavanols on antioxidant defences and their response to oxidant-induced stress on Caco2 cells.

PubMed

Rodríguez-Ramiro, Ildefonso; Martín, María Angeles; Ramos, Sonia; Bravo, Laura; Goya, Luis

2011-08-01

Flavanols are an important fraction of our diet both for their antioxidant capacity and because they are constituents of greatly accepted foodstuffs such as tea, wine and cocoa. In addition to their antioxidant activity by directly scavenging intracellular reactive oxygen species (ROS), flavanols have been recently shown to enhance protective enzymes. The objective was to evaluate the antioxidant response of colon-derived Caco2 cells to dietary flavanols. Four representative flavanols were selected: epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin-3-gallate (EGCG) and procyanidin B2 (PB2). Cell viability, concentration of ROS and reduced glutathione (GSH), and activity of antioxidant/detoxification enzymes and caspase 3 were determined. Treatment of Caco2 cells with flavanols decreased ROS production but did not affect GSH content. ECG induced glutathione peroxidase (GPx), whereas PB2 evoked a dose-dependent increase in GPx, glutathione reductase and glutathione-S-transferase. Enhancement of the antioxidant defences implies an improved cell response to an oxidative challenge. Hence, Caco2 cells treated 20 h with the flavanols, especially PB2, and then submitted to an oxidative stress induced by a pro-oxidant, tert-butyl-hydroperoxide, showed a reduced ROS production, restricted activation of caspase 3 and higher viability than cells plainly submitted to the stressor. Flavanols protect Caco2 cells against an induced oxidative stress and subsequent cellular death by reducing ROS production and preventing caspase-3 activation. In particular, PB2 increases the activity of antioxidant/detoxification enzymes and thus protects Caco2 cells by directly counteracting free radicals and also by activating the antioxidant defence system.

LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPS) IN RATS

EPA Science Inventory

2003 AAR PM Meeting
Particulate Matter: Atmospheric Sciences,
Exposure and the Fourth Colloquium on PM and Human Health

LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPs) IN RATS. JA Dye, LC Walsh, C...

Mineral Elements Bio-Accessibility and Antioxidant Indices of Blanched Basella rubra at Different Phases of in vitro Gastrointestinal Digestion

PubMed Central

Olukemi, Bukola Eugenia; Asikhia, Ikuosho Charity; Akindahunsi, Akintunde Afolabi

2018-01-01

The present investigation was designed to evaluate the mineral element bio-accessibility and antioxidant indices of blanched Basella rubra at different phases of simulated in vitro digestion (oral, gastric, and intestinal). The phenolic composition of processed vegetable was determined using high-performance liquid chromatography (HPLC)-diode-array detection method. Mineral composition, total phenolic content (TPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), and total antioxidant activity (TAA) of the in vitro digested blanched and raw vegetable were also determined. HPLC analysis revealed the presence of some phenolic compounds, with higher levels (mg/g) of polyphenols in raw B. rubra (catechin, 1.12; p-coumaric acid, 6.17; caffeic acid, 2.05) compared with the blanched counterpart, with exeption of chlorogenic acid (2.84), that was higher in blanched vegetable. The mineral content (mg/100 g) showed a higher value in enzyme treated raw vegetable compared to their blanched counterparts, with few exceptions. The results revealed a higher level of some of the evaluated minerals at the intestinal phase of digestion (Zn, 6.36/5.31; Mg, 5.29/8.97; Ca, 2,307.69/1,565.38; Na, 5,128/4,128.21) for raw and blanched respectively, with the exception of Fe, K, and P. The results of the antioxidant indices of in vitro digested B. rubra revealed a higher value at the intestinal phase of in vitro digestion, with raw vegetal matter ranking higher (TPC, 553.56 mg/g; TFC, 518.88 mg/g; FRAP, 8.15 mg/g; TAA, 5,043.16 μM Trolox equivalent/g) than the blanched counterpart. The studied vegetable contains important minerals and antioxidant molecules that would be readily available after passing through the gastrointestinal tract and could be harnessed as functional foods. PMID:29662844

Caffeine and sleep-deprivation mediated changes in open-field behaviours, stress response and antioxidant status in mice.

PubMed

Onaolapo, J Olakunle; Onaolapo, Y Adejoke; Akanmu, A Moses; Olayiwola, Gbola

2016-01-01

Effects of daily caffeine consumption on open-field behaviours, serum corticosterone and brain antioxidant levels were investigated after six hours of total sleep-deprivation in prepubertal mice. We tested the hypothesis that daily caffeine consumption may significantly alter behaviour, stress and antioxidative response of prepubertal mice to an acute episode of total sleep-deprivation. Prepubertal Swiss mice of both sexes were assigned to two main groups of 120 each (subdivided into 6 groups of 10 each, based on sex), and administered vehicle or graded oral doses of caffeine (10, 20, 40, 80 and 120 mg/kg/day) for 14 days. On day 14, a main group was subjected to 6 h of total sleep-deprivation by 'gentle-handling'. Open-field behaviours were then assessed in both groups, after which animals were euthanized, and levels of corticosterone, superoxide dismutase and glutathione peroxidase assayed. Horizontal locomotion, rearing and grooming increased significantly, compared to control, with sleep-deprived (SD) mice showing stronger caffeine-driven responses at higher doses; and SD female mice showing sustained response to caffeine, compared to respective males. Plasma corticosterone increased with increasing doses of caffeine in both non sleep-deprived (NSD) and SD mice; although SD mice had higher corticosterone levels. Sleep-deprivation and/or higher doses of caffeine were associated with derangements in brain antioxidant levels. Repeated caffeine consumption and/or acute sleep-deprivation led to significant changes in pattern of open-field behaviour and stress/antioxidant response in mice. Responses seen in the study are probably due to modulatory effects of caffeine on the total body response to stressful stimuli.

Transcriptional and catalytic responses of antioxidant and biotransformation pathways in mussels, Mytilus galloprovincialis, exposed to chemical mixtures.

PubMed

Giuliani, Maria Elisa; Benedetti, Maura; Arukwe, Augustine; Regoli, Francesco

2013-06-15

Antioxidant and biotransformation pathways are widely studied in marine organisms exposed to environmental stressors. However, mechanisms of responses and links between different intracellular levels are not always easy to elucidate and conflicting results are frequently observed between molecular and enzymatic data. In this study, transcriptional and catalytic responses of antioxidant and biotransformation parameters were analyzed after a 4-week exposure of a marine invertebrate, Mytilus galloprovincialis, to chemical mixtures from low polluted and highly polluted sediments. A significant, dose-dependent bioaccumulation was observed for polycyclic aromatic hydrocarbons, especially low molecular weight compounds. Among antioxidant defences, catalase and glutathione peroxidases did not exhibit variations in enzymatic activity, while the corresponding gene transcriptions were up- and down-regulated, respectively; unchanged mRNA levels of superoxide dismutase confirmed the non-synchronous pathways of variations for such antioxidants. Biotransformation responses also revealed inconsistent trends between transcriptional and catalytic variations of glutathione S-transferases, and a significant increase in mRNA levels for cytochrome P450 3A1. The overall results indicated that transcriptional responses might be sensitive but do not necessarily correspond to functional changes, being more useful as "exposure" rather than "effect" biomarkers. Data on gene transcription and catalytic activities should be carefully interpreted when assessing the impact of chemical pollutants and additional studies are needed on modulation of post-transcriptional mechanisms by environmental stressors. Copyright © 2013 Elsevier B.V. All rights reserved.

Elemental selenium at nano size (Nano-Se) as a potential chemopreventive agent with reduced risk of selenium toxicity: comparison with se-methylselenocysteine in mice.

PubMed

Zhang, Jinsong; Wang, Xufang; Xu, Tongwen

2008-01-01

Selenium (Se) is an essential trace element with a narrow margin between beneficial and toxic effects. As a promising chemopreventive agent, its use requires consumption over the long term, so the toxicity of Se is always a crucial concern. Based on clinical findings and recent studies in selenoprotein gene-modified mice, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect of Se. Furthermore, upregulation of phase 2 enzymes by Se has been implicated as a possible chemopreventive mechanism at supranutritional dietary levels. Se-methylselenocysteine (SeMSC), a naturally occurring organic Se product, is considered as one of the most effective chemopreventive selenocompounds. The present study revealed that, as compared with SeMSC, elemental Se at nano size (Nano-Se) possessed equal efficacy in increasing the activities of glutathione peroxidase, thioredoxin reductase, and glutathione S-transferase, but had much lower toxicity as indicated by median lethal dose, acute liver injury, survival rate, and short-term toxicity. Our results suggest that Nano-Se can serve as a potential chemopreventive agent with reduced risk of Se toxicity.

Antioxidant activity of hybrid grape pomace extracts derived from Midwestern grapes in bulk oil and oil-in-water emulsions

USDA-ARS?s Scientific Manuscript database

Natural antioxidants to inhibit oxidation in edible oils are in high demand. Grape (Vitis vinifera) pomace is an abundant and inexpensive source of polyphenolic antioxidants, which are responsible for numerous health benefits. We examined pomace from eight varieties of Midwestern hybrid grapes for p...

Application of response surface methodology to optimize pressurized liquid extraction of antioxidant compounds from sage (Salvia officinalis L.), basil (Ocimum basilicum L.) and thyme (Thymus vulgaris L.).

PubMed

Hossain, M B; Brunton, N P; Martin-Diana, A B; Barry-Ryan, C

2010-12-01

The present study optimized pressurized liquid extraction (PLE) conditions using Dionex ASE® 200, USA to maximize the antioxidant activity [Ferric ion Reducing Antioxidant Power (FRAP)] and total polyphenol content (TP) of the extracts from three spices of Lamiaceae family (sage, basil and thyme). Optimal conditions with regard to extraction temperature (66-129 °C) and solvent concentration (32-88% methanol) were identified using response surface methodology (RSM). For all three spices, results showed that 129 °C was the optimum temperature with regard to antioxidant activity. Optimal methanol concentrations with respect to the antioxidant activity of sage and basil extracts were 58% and 60% respectively. Thyme showed a different trend with regard to methanol concentration and was optimally extracted at 33%. Antioxidant activity yields of the optimal PLE were significantly (p < 0.05) higher than solid/liquid extracts. Predicted models were highly significant (p < 0.05) for both total phenol (TP) and FRAP values in all the spices with high regression coefficients (R(2)) ranging from 0.651 to 0.999.

Protein hydrolysate from turkey meat and optimization of its antioxidant potential by response surface methodology.

PubMed

Wang, Daoying; Shahidi, Fereidoon

2018-05-01

The objective of this research was to optimize antioxidant potential of hydrolyzed protein using Flavourzyme assisted hydrolysis of turkey meat and compare the antioxidant activity of hydrolysates from turkey meat, chicken, and beef. Response surface methodology (RSM) was used to determine the optimal Flavourzyme hydrolysis conditions for preparation of hydrolysate from turkey meat, which were at a temperature of 50.09°C, pH of 5.42, and processing time of 1.08 hours. For comparison, antioxidant activities of the hydrolysate from turkey meat, chicken, and beef under the optimum conditions were determined using reducing power, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation, hydroxyl radical, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. The antioxidant activity of turkey meat and chicken meat was significantly higher than that of beef (P < 0.05). Therefore Flavourzyme could be regarded as an effective hydrolytic enzyme for preparation of antioxidant hydrolysate from turkey meat, indicating the potential use of it as a functional food ingredient with shelf-life extension purposes.

Antioxidants as Potential Therapeutics for Lung Fibrosis

PubMed Central

DAY, BRIAN J.

2009-01-01

Interstitial lung disease encompasses a large group of chronic lung disorders associated with excessive tissue remodeling, scarring, and fibrosis. The evidence of a redox imbalance in lung fibrosis is substantial, and the rationale for testing antioxidants as potential new therapeutics for lung fibrosis is appealing. Current animal models of lung fibrosis have clear involvement of ROS in their pathogenesis. New classes of antioxidant agents divided into catalytic antioxidant mimetics and antioxidant scavengers are being developed. The catalytic antioxidant class is based on endogenous antioxidant enzymes and includes the manganese-containing macrocyclics, porphyrins, salens, and the non–metal-containing nitroxides. The antioxidant scavenging class is based on endogenous antioxidant molecules and includes the vitamin E analogues, thiols, lazaroids, and polyphenolic agents. Numerous studies have shown oxidative stress to be associated with many interstitial lung diseases and that these agents are effective in attenuating fibroproliferative responses in the lung of animals and humans. PMID:17999627

Analysis of the effects of iron and vitamin C co-supplementation on oxidative damage, antioxidant response and inflammation in THP-1 macrophages.

PubMed

Marcil, V; Lavoie, J C; Emonnot, L; Seidman, E; Levy, E

2011-07-01

The aims of the study were to test the susceptibility of THP-1 macrophages to develop oxidative stress and to deploy antioxidant defense mechanisms that insure the balance between the pro- and antioxidant molecules. Differentiated THP-1 were incubated in the presence or absence of iron-ascorbate (Fe/As) (100/1000μM) and the antioxidants Trolox, BHT, α-Tocopherol and NAC. Fe/As promoted the production of lipid peroxidation as reflected by the formation of malondialdehyde and H(2)O(2) along with reduced PUFA levels and elevated glutathione disulfide/total glutathione ratio, a reliable index of cellular redox status. THP-1 macrophages developed an increase in cytoplasmic SOD activity due in part to high cytoplasmic SOD1. On the other hand, a decline was noted in mRNA and protein of extra-cellular SOD3, as well as the activity of GSH-peroxidase, GSH-transferase and ATOX-1 expression. Macrophages activated under conditions of oxidative stress do not adequately deploy a powerful endogenous antioxidant response, a situation that can lead to an enhanced inflammatory response. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Short term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior

PubMed Central

Ramanathan, Lalini; Hu, Shuxin; Frautschy, Sally A.; Siegel, Jerome M.

2009-01-01

Total sleep deprivation (TSD) induces a broad spectrum of cognitive, behavioral and cellular changes. We previously reported that long term (5–11 days) TSD in the rat, by the disk-over-water method, decreases the activity of the antioxidant enzyme superoxide dismutase (SOD) in the brainstem and hippocampus. To gain insight into the mechanisms causing cognitive impairment, here we explore the early associations between metabolic activity, antioxidant responses and working memory (one form of cognitive impairment). Specifically we investigated the impact of short term (6 h) TSD, by gentle handling, on the levels of the endogenous antioxidant, total glutathione (GSHt), and the activities of the antioxidative enzymes, SOD and glutathione peroxidase (GPx). Short term TSD had no significant impact on SOD activity, but increased GSHt levels in the rat cortex, brainstem and basal forebrain, and GPx activity in the rat hippocampus and cerebellum. We also observed increased activity of hexokinase, (HK), the rate limiting enzyme of glucose metabolism, in the rat cortex and hypothalamus. We further showed that 6h of TSD leads to increased exploratory behavior to a new environment, without impairing spontaneous alternation behavior (SAB) in the Y maze. We conclude that acute (6h) sleep loss may trigger compensatory mechanisms (like increased antioxidant responses) that prevent initial deterioration in working memory. PMID:19850085

Lipidomic and Antioxidant Response to Grape Seed, Corn and Coconut Oils in Healthy Wistar Rats

PubMed Central

Wall-Medrano, Abraham; de la Rosa, Laura A.; Vázquez-Flores, Alma A.; Mercado-Mercado, Gilberto; González-Arellanes, Rogelio; López-Díaz, José A.; González-Córdova, Aarón F.; González-Aguilar, Gustavo A.; Vallejo-Cordoba, Belinda; Molina-Corral, Francisco J.

2017-01-01

Specialty oils differ in fatty acid, phytosterol and antioxidant content, impacting their benefits for cardiovascular health. The lipid (fatty acid, phytosterol) and antioxidant (total phenolics, radical scavenging capacity) profiles of grapeseed (GSO), corn (CO) and coconut (CNO) oils and their physiological (triacylglycerides, total and HDL-cholesterol and antioxidant capacity (FRAP) in serum and fatty acid and phytosterol hepatic deposition) and genomic (HL, LCAT, ApoA-1 and SR-BP1 mRNA hepatic levels) responses after their sub-chronic intake (10% diet for 28 days) was examined in healthy albino rats. Fatty acid, phytosterol and antioxidant profiles differed between oils (p ≤ 0.01). Serum and hepatic triacylglycerides and total cholesterol increased (p ≤ 0.01); serum HDL-Cholesterol decreased (p < 0.05); but serum FRAP did not differ (p > 0.05) in CNO-fed rats as compared to CO or GSO groups. Hepatic phytosterol deposition was higher (+2.2 mg/g; p ≤ 0.001) in CO- than GSO-fed rats, but their fatty acid deposition was similar. All but ApoA-1 mRNA level increased in GSO-fed rats as compared to other groups (p ≤ 0.01). Hepatic fatty acid handling, but not antioxidant response, nor hepatic phytosterol deposition, could be related to a more efficient reverse-cholesterol transport in GSO-fed rats as compared to CO or CNO. PMID:28117688

Antioxidant-based topical formulations influence on the inflammatory response of Japanese skin: A clinical study using non-invasive techniques.

PubMed

Wagemaker, Tais A L; Maia Campos, Patrícia M B G; Shimizu, Kenji; Kyotani, Daiki; Yoshida, Daisuke

2017-08-01

Cutaneous irritants exposure induces an excess of ROS in the skin and can ensue an inflammatory response. Topical antioxidant-based formulations can help to counteract ROS generation. This study evaluated the influence of antioxidant-based topical formulations on the inflammatory response of skin, using a combination of in vivo real-time non-invasive techniques. Nine test areas were defined on each volar forearm of the 25 Japanese volunteers. Measurements were performed before and after treatment with 15μL of a 5% sodium dodecyl sulfate solution and 15μL of the same based formulation or the vehicle with 1% of the antioxidants. Volunteers without antioxidant treatment showed more pronounced erythematous areas. Transepidermal water loss of areas treated with green tea polyphenol (GTP)-based formulation showed fully recovered skin. Skin barrier damage caused by repeated applications of SDS showed characteristic alterations, detectable by in vivo confocal microscopy such as desquamation, spongiosis and inflammatory infiltrates. The majority of confocal microscopy inflammation signs were found in skin without treatment followed by the vehicle. Ascorbyl tetraisopalmitate, Coenzyme Q 10 , GTP- and Resveratrol-based formulations reduced the anti-inflammatory cytokines release and attenuated inflammatory signs. The combination of techniques provides results that highlight the importance of antioxidant-based formulations for rapid skin recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

Phenolic compounds, antioxidant potential and antiproliferative potential of 10 common edible flowers from China assessed using a simulated in vitro digestion-dialysis process combined with cellular assays.

PubMed

Huang, Weisu; Mao, Shuqin; Zhang, Liuquan; Lu, Baiyi; Zheng, Lufei; Zhou, Fei; Zhao, Yajing; Li, Maiquan

2017-11-01

Phenolic compounds could be sensitive to digestive conditions, thus a simulated in vitro digestion-dialysis process and cellular assays was used to determine phenolic compounds and antioxidant and antiproliferative potentials of 10 common edible flowers from China and their functional components. Gallic acid, ferulic acid, and rutin were widely present in these flowers, which demonstrated various antioxidant capacities (DPPH, ABTS, FRAP and CAA values) and antiproliferative potentials measured by the MTT method. Rosa rugosa, Paeonia suffruticosa and Osmanthus fragrans exhibited the best antioxidant and antiproliferative potentials against HepG2, A549 and SGC-7901 cell lines, except that Osmanthus fragrans was not the best against SGC-7901 cells. The in vitro digestion-dialysis process decreased the antioxidant potential by 33.95-90.72% and the antiproliferative potential by 13.22-87.15%. Following the in vitro digestion-dialysis process, phenolics were probably responsible for antioxidant (R 2 = 0.794-0.924, P < 0.01) and antiproliferative (R 2 = 0.408-0.623, P < 0.05) potential. Moreover, gallic acid may be responsible for the antioxidant potential of seven flowers rich in edible flowers. The antioxidant and antiproliferative potential of 10 edible flowers revealed a clear decrease after digestion and dialysis along with the reduction of phenolics. Nevertheless, they still had considerable antioxidant and antiproliferative potential, which merited further investigation in in vivo studies. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Renoprotective effect of the antioxidant curcumin: Recent findings☆

PubMed Central

Trujillo, Joyce; Chirino, Yolanda Irasema; Molina-Jijón, Eduardo; Andérica-Romero, Ana Cristina; Tapia, Edilia; Pedraza-Chaverrí, José

2013-01-01

For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury. PMID:24191240

Effects of Weather Conditions on Oxidative Stress, Oxidative Damage, and Antioxidant Capacity in a Wild-Living Mammal, the European Badger (Meles meles).

PubMed

Bilham, Kirstin; Newman, Chris; Buesching, Christina D; Noonan, Michael J; Boyd, Amy; Smith, Adrian L; Macdonald, David W

Wild-living animals are subject to weather variability that may cause the generation of reactive oxygen species, resulting in oxidative stress and tissue damage, potentially driving demographic responses. Our 3-yr field study investigated the effects of seasonal weather conditions on biomarkers for oxidative stress, oxidative damage, and antioxidant defense in the European badger (Meles meles). We found age class effects: cubs were more susceptible to oxidative stress and oxidative damage than adults, especially very young cubs in the spring, when they also exhibited lower antioxidant biomarkers than adults. Although previous studies have found that intermediate spring and summer rainfall and warmer temperatures favor cub survival, counterintuitively these conditions were associated with more severe oxidative damage. Oxidative damage was high in cubs even when antioxidant biomarkers were high. In contrast, adult responses accorded with previous survival analyses. Wetter spring and summer conditions were associated with higher oxidative damage, but they were also associated with higher antioxidant biomarkers. Autumnal weather did not vary substantially from normative values, and thus effects were muted. Winter carryover effects were partially evident, with drier and milder conditions associated with greater oxidative damage in the following spring but also with higher antioxidant capacity. Plausibly, warmer conditions promoted more badger activity, with associated metabolic costs at a time of year when food supply is limited. Modeling biomarkers against projected climate change scenarios predicted greater future risks of oxidative damage, although not necessarily exceeding antioxidant capacity. This interdisciplinary approach demonstrates that individual adaptive physiological responses are associated with variation in natural environmental conditions.

Measurement of the total antioxidant response in preeclampsia with a novel automated method.

PubMed

Harma, Mehmet; Harma, Muge; Erel, Ozcan

2005-01-10

Preeclampsia is one of the most serious complications of pregnancy. Free radical damage has been implicated in the pathophysiology of this condition. In this study, we aimed to measure the antioxidant capacity in plasma samples from normotensive and preeclamptic pregnant women to evaluate their antioxidant status using a more recently developed automated measurement method. Our study group contained 42 women, 24 of whom had preeclampsia, while 18 had normotensive pregnancies. We measured the total plasma antioxidant capacity for all patients, as well as the levels of four major individual plasma antioxidant components; albumin, uric acid, ascorbic acid and bilirubin, and as a reciprocal measure, their total plasma peroxide levels. Statistically significant differences (determined using Student's t-test) were noted between the normotensive and the preeclamptic groups for their total antioxidant responses and their vitamin C levels (1.31 +/- 0.12 mmol versus 1.06 +/- 0.41 mmol Trolox eq./L; 30.2 +/- 17.83 micromol/L versus 18.1 +/- 11.37 micromol/L, respectively), which were both considerably reduced in the preeclamptic patients. In contrast, the total plasma peroxide levels were significantly elevated in this group (49.8 +/- 14.3 micromol/L versus 38.8 +/- 9.6 micromol/L). We found a decreased total antioxidant response in preeclamptic patients using a simple, rapid and reliable automated colorimetric assay, which may suitable for use in any routine clinical biochemistry laboratory, and considerably facilitates the assessment of this useful clinical parameter. We suggest that this novel method may be used as a routine test to evaluate and follow up of the levels of oxidative stress in preeclampsia.

Interplay between Selenium Levels, Selenoprotein Expression, and Replicative Senescence in WI-38 Human Fibroblasts*

PubMed Central

Legrain, Yona; Touat-Hamici, Zahia; Chavatte, Laurent

2014-01-01

Selenium is an essential trace element, which is incorporated as selenocysteine into at least 25 selenoproteins using a unique translational UGA-recoding mechanism. Selenoproteins are important enzymes involved in antioxidant defense, redox homeostasis, and redox signaling pathways. Selenium levels decline during aging, and its deficiency is associated with a marked increase in mortality for people over 60 years of age. Here, we investigate the relationship between selenium levels in the culture medium, selenoprotein expression, and replicative life span of human embryonic lung fibroblast WI-38 cells. Selenium levels regulate the entry into replicative senescence and modify the cellular markers characteristic for senescent cells. Whereas selenium supplementation extends the number of population doublings, its deficiency impairs the proliferative capacity of WI-38 cells. We observe that the expression of several selenoproteins involved in antioxidant defense is specifically affected in response to cellular senescence. Their expression is selectively controlled by the modulation of mRNA levels and translational recoding efficiencies. Our data provide novel mechanistic insights into how selenium impacts the replicative life span of mammalian cells by identifying several selenoproteins as new targets of senescence. PMID:24425862

Epigallocatechin activates haem oxygenase-1 expression via protein kinase Cδ and Nrf2

PubMed Central

Ogborne, Richard M.; Rushworth, Stuart A.; O’Connell, Maria A.

2008-01-01

The Nrf2/anti-oxidant response element (ARE) pathway plays an important role in regulating cellular anti-oxidants, including haem oxygenase-1 (HO-1). Various kinases have been implicated in the pathways leading to Nrf2 activation. Here, we investigated the effect of epigallocatechin (EGC) on ARE-mediated gene expression in human monocytic cells. EGC time and dose dependently increased HO-1 mRNA and protein expression but had minimal effect on expression of other ARE-regulated genes, including NAD(P)H:quinone oxidoreductase 1, glutathione cysteine ligase and ferritin. siRNA knock down of Nrf2 significantly inhibited EGC-induced HO-1 expression. Furthermore, inhibition of PKC by Ro-31-8220 dose dependently decreased EGC-induced HO-1 mRNA expression, whereas MAP kinase and phosphatidylinositol-3-kinase pathway inhibitors had no significant effect. EGC stimulated phosphorylation of PKCαβ and δ in THP-1 cells. PKCδ inhibition significantly decreased EGC-induced HO-1 mRNA expression, whereas PKCα- and β-specific inhibitors had no significant effect. These results demonstrate for the first time that EGC-induced HO-1 expression occurs via PKCδ and Nrf2. PMID:18586007

Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes.

PubMed

Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

2014-11-01

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes

PubMed Central

Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

2014-01-01

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes. PMID:25489416

Synthesis, characterization, spectroscopic and antioxidation studies of Cu(II)-morin complex

NASA Astrophysics Data System (ADS)

Panhwar, Qadeer Khan; Memon, Shahabuddin; Bhanger, M. I.

2010-04-01

Complex formation between copper (II) sulfate and morin (3,5,7,2',4'-pentahydroxyflavone) have been studied in methanol. Structure of the complex was determined through various analytical techniques including UV-vis, IR, 1H NMR, thermal, gravimetric and elemental analyses. The stoichiometric ratio for the reaction between the flavonoid and the metal ion in methanol has been determined by Job's method and elemental analysis for metal content of complex by titration with EDTA, which confirm that morin forms a 1:1 metal:ligand complex. 1H NMR study reveals that, 3OH and 4CO groups of morin take part in complexation with a copper ion. Individual stress was given to the site of central ion and composition of the complex. Antioxidant activity of the complex was evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method, which showed that the antioxidant activity of complexed morin has higher value as compared to the free morin. Moreover, it was observed that the metal complex is sufficiently stable as well as the data indicates the spontaneous formation of complex (-Δ G) that is exothermic in nature (-Δ H) and entropically unfavourable (-Δ S).

Human semen as an early, sensitive biomarker of highly polluted living environment in healthy men: A pilot biomonitoring study on trace elements in blood and semen and their relationship with sperm quality and RedOx status.

PubMed

Bergamo, Paolo; Volpe, Maria Grazia; Lorenzetti, Stefano; Mantovani, Alberto; Notari, Tiziana; Cocca, Ennio; Cerullo, Stefano; Di Stasio, Michele; Cerino, Pellegrino; Montano, Luigi

2016-12-01

The Campania region in Italy is facing an environmental crisis due to the illegal disposal of toxic waste. Herein, a pilot study (EcoFoodFertility initiative) was conducted to investigate the use of human semen as an early biomarker of pollution on 110 healthy males living in various areas of Campania with either high or low environmental impact. The semen from the "high impact" group showed higher zinc, copper, chromium and reduced iron levels, as well as reduced sperm motility and higher sperm DNA Fragmentation Index (DFI). Redox biomarkers (total antioxidant capacity, TAC, and glutathione, GSH) and the activity of antioxidant enzymes in semen were lower in the "high impact" group. The percentage of immotile spermatozoa showed a significant inverse correlation with TAC and GSH. Overall, several semen parameters (reduced sperm quality and antioxidant defenses, altered chemical element pattern), which were associated with residence in a high polluted environment, could be used in a further larger scale study, as early biomarkers of environmental pollution. Copyright © 2016 Elsevier Inc. All rights reserved.

The Ascorbate-glutathione-α-tocopherol Triad in Abiotic Stress Response

PubMed Central

Szarka, András; Tomasskovics, Bálint; Bánhegyi, Gábor

2012-01-01

The life of any living organism can be defined as a hurdle due to different kind of stresses. As with all living organisms, plants are exposed to various abiotic stresses, such as drought, salinity, extreme temperatures and chemical toxicity. These primary stresses are often interconnected, and lead to the overproduction of reactive oxygen species (ROS) in plants, which are highly reactive and toxic and cause damage to proteins, lipids, carbohydrates and DNA, which ultimately results in oxidative stress. Stress-induced ROS accumulation is counteracted by enzymatic antioxidant systems and non-enzymatic low molecular weight metabolites, such as ascorbate, glutathione and α-tocopherol. The above mentioned low molecular weight antioxidants are also capable of chelating metal ions, reducing thus their catalytic activity to form ROS and also scavenge them. Hence, in plant cells, this triad of low molecular weight antioxidants (ascorbate, glutathione and α-tocopherol) form an important part of abiotic stress response. In this work we are presenting a review of abiotic stress responses connected to these antioxidants. PMID:22605990

Response of Saccharomyces cerevisiae to D-limonene-induced oxidative stress.

PubMed

Liu, Jidong; Zhu, Yibo; Du, Guocheng; Zhou, Jingwen; Chen, Jian

2013-07-01

In the present study, we investigated the mode of cell response induced by D-limonene in Saccharomyces cerevisiae. D-limonene treatment was found to be accompanied by intracellular accumulation of reactive oxygen species (ROS). Since ROS impair cell membranes, an engineered strain with enhanced membrane biosynthesis exhibited a higher tolerance to D-limonene. Subsequent addition of an ROS scavenger significantly reduced the ROS level and alleviated cell growth inhibition. Thus, D-limonene-induced ROS accumulation plays an important role in cell death in S. cerevisiae. In D-limonene-treated S. cerevisiae strains, higher levels of antioxidants, antioxidant enzymes, and nicotinamide adenine dinucleotide phosphate (NADPH) were synthesized. Quantitative real-time PCR results also verified that D-limonene treatment triggered upregulation of genes involved in the antioxidant system and the regeneration of NADPH at the transcription level in S. cerevisiae. These data indicate that D-limonene treatment results in intracellular ROS accumulation, an important factor in cell death, and several antioxidant mechanisms in S. cerevisiae were enhanced in response to D-limonene treatment.

Reciprocal effects of caulerpenyne and intense herbivorism on the antioxidant response of Bittium reticulatum and Caulerpa taxifolia.

PubMed

Sureda, Antoni; Box, Antonio; Deudero, Salud; Pons, Antoni

2009-03-01

We studied the antioxidant enzyme response of the gastropoda Bittium reticulatum feeding the toxic alga Caulerpa taxifolia, and also the effects of intense herbivorism on caulerpenyne production and on the antioxidant response of C. taxifolia. B. reticulatum were maintained in two separated aquariums containing Posidonia oceanica or C. taxifolia. Glutathione peroxidase, glutathione reductase and glutathione S-transferase activities were significantly higher in B. reticulatum living in presence of C. taxifolia with respect to animals living in P. oceanica aquarium. Malondialdehyde levels in B. reticulatum showed similar values in both environments. Caulerpenyne levels were significantly higher in C. taxifolia fronds after herbivore exposure. C. taxifolia activities of catalase and glutathione reductase significantly increased in presence of B. reticulatum. B. reticulatum exposed to caulerpenyne evidenced antioxidant enzyme adaptations to prevent oxidative damage. The presence of B. reticulatum in the aquarium induces a protective adaptation in C. taxifolia in order to reduce the herbivorism.

[Vitamins and oxidative stress].

PubMed

Kodentsova, V M; Vrzhesinskaia, O A; Mazo, V K

2013-01-01

The central and local stress limiting systems, including the antioxidant defense system involved in defending the organism at the cellular and systemic levels from excess activation response to stress influence, leading to damaging effects. The development of stress, regardless of its nature [cold, increased physical activity, aging, the development of many pathologies (cardiovascular, neurodegenerative diseases, diseases of the gastrointestinal tract, ischemia, the effects of burns), immobilization, hypobaric hypoxia, hyperoxia, radiation effects etc.] leads to a deterioration of the vitamin status (vitamins E, A, C). Damaging effect on the antioxidant defense system is more pronounced compared to the stress response in animals with an isolated deficiency of vitamins C, A, E, B1 or B6 and the combined vitamins deficiency in the diet. Addition missing vitamin or vitamins restores the performance of antioxidant system. Thus, the role of vitamins in adaptation to stressors is evident. However, vitamins C, E and beta-carotene in high doses, significantly higher than the physiological needs of the organism, may be not only antioxidants, but may have also prooxidant properties. Perhaps this explains the lack of positive effects of antioxidant vitamins used in extreme doses for a long time described in some publications. There is no doubt that to justify the current optimal doses of antioxidant vitamins and other dietary antioxidants specially-designed studies, including biochemical testing of initial vitamin and antioxidant status of the organism, as well as monitoring their change over time are required.

Rice proteins, extracted by alkali and α-amylase, differently affect in vitro antioxidant activity.

PubMed

Wang, Zhengxuan; Liu, Ye; Li, Hui; Yang, Lin

2016-09-01

Alkali treatment and α-amylase degradation are different processes for rice protein (RP) isolation. The major aim of this study was to determine the influence of two different extraction methods on the antioxidant capacities of RPA, extracted by alkaline (0.2% NaOH), and RPE, extracted by α-amylase, during in vitro digestion for 2h with pepsin and for 3h with pancreatin. Upon pepsin-pancreatin digestion, the protein hydrolysates (RPA-S, RPE-S), which were the supernatants in the absence of undigested residue, and the whole protein digests (RPA, RPE), in which undigested residue remained, were measured. RPE exhibited the stronger antioxidant responses to free radical scavenging activity, metal chelating activity, and reducing power, whereas the weakest antioxidant capacities were produced by RPE-S. In contrast, no significant differences in antioxidant activity were observed between RPA and RPA-S. The present study demonstrated that the in vitro antioxidant responses induced by the hydrolysates and the protein digests of RPs could be affected differently by alkali treatment and α-amylase degradation, suggesting that the extraction is a vital processing step to modify the antioxidant capacities of RPs. The results of the current study indicated that the protein digests, in which undigested residues remained, could exhibit more efficacious antioxidant activity compared to the hydrolysates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of lemongrass water extract supplementation on atherogenic index and antioxidant status in rats.

PubMed

Somparn, Nuntiya; Saenthaweeuk, Suphaket; Naowaboot, Jarinyaporn; Thaeomor, Atcharaporn; Kukongviriyapan, Veerapol

2018-06-01

Cymbopogon citratus (DC) Stapf., commonly known as lemongrass, possesses strong antioxidant and cardiotonic properties. Lemongrass water extract contains several polyphenolic compounds including gallic acid, isoquercetin, quercetin, rutin, catechin and tannic acid. Rutin, isoquercetin catechin and quercetin are the flavonoids most abundantly found in the extract. The extract significantly decreased total cholesterol, low-density lipoprotein and atherogenic index in rats after treatment (p < 0.05). Expression of genes and protein of sterol regulatory element binding protein-1c (SREBP1c) and HMG-CoA reductase (HMGR) was also lowered significantly in treated groups (p < 0.05). Moreover, serum antioxidant capacity increased in treated rats in comparison with untreated ones (p < 0.05) and was associated with decreased serum lipid peroxidation.

Report: antioxidant and nutraceutical value of wild medicinal Rubus berries.

PubMed

Ahmad, Mushtaq; Masood, Saima; Sultana, Shazia; Hadda, Taibi Ben; Bader, Ammar; Zafar, Muhammad

2015-01-01

Nutritional quality and antioxidant capacity of three edible wild berries (Rubus ellipticus Smith, Rubus niveus Thunb, Rubus ulmifolius L.) from Lesser Himalayan Range (LHR) were evaluated. Their edible portion was assayed for moisture, fats, ash, carbohydrates, proteins, fibers, essential minerals (Ca, P, Mg, K, Na, Cl, S, Mn, Zn, Fe, Cu, Se, Co, Ni) and DPPH free radical scavenging activity was applied to determine the antioxidant potential. The fruit of Rubus ulmifolius L. (blackberry) possessed the highest values of energy (403.29 Kcal), total protein (6.56g/100 g), Nitrogen (N) content (1500mg/100g), K (860.17mg/100g), Ca (620.56mg/100g), Zn (17.509mg/100g) and the strongest antioxidant activity (98.89% inhibition). While the raspberries (Rubus ellipticus Smith, Rubus niveus Thunb.) exhibited more significant contents of dietary fiber (5.90g/100g), carbohydrates (86.4 g/100 g) and Fe (4.249mg/100g). Significant variation was observed among the tested samples in all the investigated features. The combination of bio elements and active antioxidants clearly showed the applicability of these berries as a nutraceutical supplement.

Identification, quantification of bioactive constituents, evaluation of antioxidant and in vivo acute toxicity property from the methanol extract of Vernonia cinerea leaf extract.

PubMed

Rajamurugan, R; Selvaganabathy, N; Kumaravel, S; Ramamurthy, Ch; Sujatha, V; Suresh Kumar, M; Thirunavukkarasu, C

2011-12-01

Vernonia cinerea (L.) Less [Compositae (Asteraceae)] is used traditionally for several medical purposes such as inflammation, pain, fever, and cancer. The present study identified the bioactive constituents in the methanol extract of Vernonia cinerea leaf and evaluated its antioxidant activity and acute toxicity. The identification of phytochemicals was accomplished by GC-MS and the major antioxidant phenolic compounds in the extract were quantified by HPTLC analysis. To quantify the essential elements, atomic absorption spectrophotometeric analysis was carried out. Total phenol and flavonoid content was measured by Folin-Ciocalteau reagent and 2% aluminium chloride, respectively. GC-MS analysis identified the presence of 27 phytoconstituents. The predominant phenolic compound in the extract as quantified by HPTLC was gallic acid (1.92 mg/g) followed by rutin (0.705 mg/g), quercetin (0.173 mg/g), caffeic acid (0.082 mg/g) and ferulic acid (0.033 mg/g). The following elements were quantified: Fe (0.050 ppm), Mn (0.022 ppm), Co (0.0180 ppm), Pb (0.029 ppm), Hg (3.885 ppm) and Se (4.5240 ppm). The antioxidant activity of the extract increased with increasing concentration and the correlation (r²) for all in vitro assays were satisfactory. V. cinerea extract has significant (p < 0.05) antiradical activity. Hence, V. cinerea may have potential medicinal value and can be used in the formulation of pharmacological products for degenerative diseases.

Synchrotron radiation induced X-ray emission studies of the antioxidant mechanism of the organoselenium drug ebselen.

PubMed

Aitken, Jade B; Lay, Peter A; Duong, T T Hong; Aran, Roshanak; Witting, Paul K; Harris, Hugh H; Lai, Barry; Vogt, Stefan; Giles, Gregory I

2012-04-01

Synchrotron radiation induced X-ray emission (SRIXE) spectroscopy was used to map the cellular uptake of the organoselenium-based antioxidant drug ebselen using differentiated ND15 cells as a neuronal model. The cellular SRIXE spectra, acquired using a hard X-ray microprobe beam (12.8-keV), showed a large enhancement of fluorescence at the K(α) line for Se (11.2-keV) following treatment with ebselen (10 μM) at time periods from 60 to 240 min. Drug uptake was quantified and ebselen was shown to induce time-dependent changes in cellular elemental content that were characteristic of oxidative stress with the efflux of K, Cl, and Ca species. The SRIXE cellular Se distribution map revealed that ebselen was predominantly localized to a discreet region of the cell which, by comparison with the K and P elemental maps, is postulated to correspond to the endoplasmic reticulum. On the basis of these findings, it is hypothesized that a major outcome of ebselen redox catalysis is the induction of cellular stress. A mechanism of action of ebselen is proposed that involves the cell responding to drug-induced stress by increasing the expression of antioxidant genes. This hypothesis is supported by the observation that ebselen also regulated the homeostasis of the transition metals Mn, Cu, Fe, and Zn, with increases in transition metal uptake paralleling known induction times for the expression of antioxidant metalloenzymes. © SBIC 2012

Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes

PubMed Central

Marchitti, Satori A.; Chen, Ying; Thompson, David C.; Vasiliou, Vasilis

2011-01-01

Solar ultraviolet radiation (UVR) exposes the human eye to near constant oxidative stress. Evidence suggests that UVR is the most important environmental insult leading to the development of a variety of ophthalmoheliosis disorders. UVR-induced reactive oxygen species are highly reactive with DNA, proteins and cellular membranes, resulting in cellular and tissue damage. Antioxidant defense systems present in ocular tissues function to combat reactive oxygen species and protect the eye from oxidative damage. Important enzymatic antioxidants are the superoxide dismutases, catalase, glutathione peroxidases, glutathione reductase and members of the aldehyde dehydrogenase (ALDH) superfamily. Glutathione, ascorbic and uric acids, α-tocopherol, NADPH and ferritin serve as small molecule, nonenzymatic antioxidants. Ocular tissues have high levels of these antioxidants which are essential for the maintenance of redox homeostasis in the eye and protection against oxidative damage. ALDH1A1 and ALDH3A1, present abundantly in the cornea and lens, have been shown to have unique roles in the defense against UVR and the downstream effects of oxidative stress. This review presents the properties and functions of ocular antioxidants that play critical roles in the cellular response to UVR exposure, including a focused discussion of the unique roles that the ALDH1A1 and ALDH3A1 enzymes have as multi-functional ocular antioxidants. PMID:21670692

Supra-optimal expression of the cold-regulated OsMyb4 transcription factor in transgenic rice changes the complexity of transcriptional network with major effects on stress tolerance and panicle development.

PubMed

Park, Myoung-Ryoul; Yun, Kil-Young; Mohanty, Bijayalaxmi; Herath, Venura; Xu, Fuyu; Wijaya, Edward; Bajic, Vladimir B; Yun, Song-Joong; De Los Reyes, Benildo G

2010-12-01

The R2R3-type OsMyb4 transcription factor of rice has been shown to play a role in the regulation of osmotic adjustment in heterologous overexpression studies. However, the exact composition and organization of its underlying transcriptional network has not been established to be a robust tool for stress tolerance enhancement by regulon engineering. OsMyb4 network was dissected based on commonalities between the global chilling stress transcriptome and the transcriptome configured by OsMyb4 overexpression. OsMyb4 controls a hierarchical network comprised of several regulatory sub-clusters associated with cellular defense and rescue, metabolism and development. It regulates target genes either directly or indirectly through intermediary MYB, ERF, bZIP, NAC, ARF and CCAAT-HAP transcription factors. Regulatory sub-clusters have different combinations of MYB-like, GCC-box-like, ERD1-box-like, ABRE-like, G-box-like, as1/ocs/TGA-like, AuxRE-like, gibberellic acid response element (GARE)-like and JAre-like cis-elements. Cold-dependent network activity enhanced cellular antioxidant capacity through radical scavenging mechanisms and increased activities of phenylpropanoid and isoprenoid metabolic processes involving various abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), ethylene and reactive oxygen species (ROS) responsive genes. OsMyb4 network is independent of drought response element binding protein/C-repeat binding factor (DREB/CBF) and its sub-regulons operate with possible co-regulators including nuclear factor-Y. Because of its upstream position in the network hierarchy, OsMyb4 functions quantitatively and pleiotrophically. Supra-optimal expression causes misexpression of alternative targets with costly trade-offs to panicle development. © 2010 Blackwell Publishing Ltd.

Transcriptional regulation of human paraoxonase 1 by PXR and GR in human hepatoma cells.

PubMed

Ponce-Ruiz, N; Rojas-García, A E; Barrón-Vivanco, B S; Elizondo, G; Bernal-Hernández, Y Y; Mejía-García, A; Medina-Díaz, I M

2015-12-25

Human paraoxonase 1 (PON1) is A-esterase synthesized in the liver and secreted into the plasma, where it associates with HDL. PON1 acts as an antioxidant preventing lipid oxidation and detoxifies a wide range of substrates, including organophosphate compounds. The variability of PON1 (enzyme activity/serum levels) has been attributed to internal and external factors. However, the molecular mechanisms involved in the transcriptional regulation of PON1 have not been well-studied. The aim of this study was to evaluate and characterize the transcriptional activation of PON1 by nuclear receptors (NR) in human hepatoma cells. In silico analysis was performed on the promoter region of PON1 to determine the response elements of NR. Real-time PCR was used to evaluate the effect of specific NR ligands on the mRNA levels of genes regulated by NR and PON1. The results indicated that NR response elements had 95% homology to pregnenolone (PXR), glucocorticoids (GR), retinoic acid (RXR) and peroxisomes proliferator-activated receptor alpha (PPARα). Treatments with Dexamethasone (GR ligand), Rifampicin (PXR ligand) and TCDD (AhR ligand) increased the mRNA levels of PON1 at 24 and 48 h. We showed that the activation of GR by Dexamethasone results in PON1 gene induction accompanied by an increase in activity levels. In conclusion, these results demonstrate that GR regulates PON1 gene transcription through directly binding to NR response elements at -95 to -628 bp of the PON1 promoter. This study suggests new molecular mechanisms for the transcriptional regulation of PON1 through a process involving the activation of PXR. Copyright © 2015 Elsevier B.V. All rights reserved.

Selection of quantum chemical descriptors by chemometric methods in the study of antioxidant activity of flavonoid compounds

NASA Astrophysics Data System (ADS)

Weber, K. C.; Honório, K. M.; da Silva, S. L.; Mercadante, R.; da Silva, A. B. F.

In the present study, the aim was to select electronic properties responsible for free radical scavenging ability of a set of 25 flavonoid compounds employing chemometric methods. Electronic parameters were calculated using the AM1 semiempirical method, and chemometric methods (principal component analysis, hierarchical cluster analysis, and k-nearest neighbor) were used with the aim to build models able to find relationships between electronic features and the antioxidant activity presented by the compounds studied. According to these models, four electronic variables can be considered important to discriminate more and less antioxidant flavonoid compounds: polarizability (α), charge at carbon 3 (QC3), total charge at substituent 5 (QS5), and total charge at substituent 3' (QS3'). The features found as being responsible for the antioxidant activity of the flavonoid compounds studied are consistent with previous results found in the literature. The results obtained can also bring improvements in the search for better antioxidant flavonoid compounds.

Enzymatic synthesis of eugenol benzoate by immobilized Staphylococcus aureus lipase: optimization using response surface methodology and determination of antioxidant activity.

PubMed

Horchani, Habib; Ben Salem, Nadia; Zarai, Zied; Sayari, Adel; Gargouri, Youssef; Chaâbouni, Moncef

2010-04-01

The ability of a non-commercial immobilized Staphylococcus aureus lipase to catalyze the esterification of eugenol with benzoic acid was checked and the antioxidant power of the ester formed was evaluated. Response surface methodology based on four variables (the reaction temperature, the amount of lipase, the benzoic acid/eugenol molar ratio and the volume of solvent) was used to optimize the experimental conditions of eugenol benzoate synthesis. The maximum conversion yield (75%) was obtained using 240 IU of immobilized lipase, a benzoic acid/eugenol molar ratio of 1.22 dissolved in 4.6 ml chloroform at 41 degrees Celsius. The antioxidant activities of eugenol and its ester were evaluated. Compared to BHT, used as a model synthetic antioxidant, the eugenol benzoate showed a higher antioxidative activity. The IC(50) value for 1,1-diphenyl-2-picrylhydrazyl was found to be 18.2 microg/ml versus 20.2 microg/ml for eugenol and eugenol benzoate. Copyright 2009 Elsevier Ltd. All rights reserved.

Antioxidant Compound Extraction from Maqui (Aristotelia chilensis [Mol] Stuntz) Berries: Optimization by Response Surface Methodology

PubMed Central

Quispe-Fuentes, Issis; Vega-Gálvez, Antonio; Campos-Requena, Víctor H.

2017-01-01

The optimum conditions for the antioxidant extraction from maqui berry were determined using a response surface methodology. A three level D-optimal design was used to investigate the effects of three independent variables namely, solvent type (methanol, acetone and ethanol), solvent concentration and extraction time over total antioxidant capacity by using the oxygen radical absorbance capacity (ORAC) method. The D-optimal design considered 42 experiments including 10 central point replicates. A second-order polynomial model showed that more than 89% of the variation is explained with a satisfactory prediction (78%). ORAC values are higher when acetone was used as a solvent at lower concentrations, and the extraction time range studied showed no significant influence on ORAC values. The optimal conditions for antioxidant extraction obtained were 29% of acetone for 159 min under agitation. From the results obtained it can be concluded that the given predictive model describes an antioxidant extraction process from maqui berry.

Trace elements profile is associated with insulin resistance syndrome and oxidative damage in thyroid disorders: Manganese and selenium interest in Algerian participants with dysthyroidism.

PubMed

Maouche, Naima; Meskine, Djamila; Alamir, Barkahoum; Koceir, Elhadj-Ahmed

2015-10-01

The relationship between dysthyroidism and antioxidant trace elements (ATE) status is very subtle during oxidative stress (OS). This relationship is mediated by thyroid hormone (TH) disorder, insulin resistance syndrome (IRS) and inflammation. The aim of this study was to investigate ATE such as selenium (Se), manganese (Mn), zinc (Zn) and copper (Cu) status on thyroid dysfunction, and their interaction with antioxidant enzyme activities, mainly, superoxide dismutase (SOD) and glutathione peroxidase (GPx), TH profile (TSH, T(3), T(4)) and IRS clusters. The study was undertaken on 220 Algerian adults (30-50 years), including 157 women and 63 men who were divided to 4 groups: subclinical hypothyroidism (n = 50), overt hypothyroidism (n = 60), Graves's disease hyperthyroidism (n = 60) and euthyroid controls (n = 50). The IRS was confirmed according to NCEP (National Cholesterol Education Program). Insulin resistance was evaluated by HOMA-IR model. Trace elements were determined by the Flame Atomic Absorption Spectrometry (Flame-AAS) technique. The antioxidant enzymes activity and metabolic parameters were determined by biochemical methods. The TH profile and anti-Thyroperoxidase Antibodies (anti-TPO-Ab) were evaluated by radioimmunoassay. Results showed that the plasma manganese levels were significantly increased in all dysthyroidism groups (p ≤ 0.01). However, the plasma copper and zinc concentrations were maintained normal or not very disturbed vs control group. In contrast, the plasma selenium levels were highly decreased (p ≤ 0.001) and positively correlated with depletion of glutathione peroxidase activity; and associated both with anti-TPO-Ab overexpression and fulminant HS-CRP levels. This study confirms the oxidative stress-inflammation relationship in the dysthyroidism. The thyroid follicles antioxidant protection appears preserved in the cytosol (Cu/Zn-SOD), while it is altered in the mitochondria (Mn-SOD), which gives this cell organelle, a status of real target therapy in thyroid dysfunction. The publisher would like to apologise for any inconvenience caused. [corrected].

Antioxidant responses to heat and light stress differ with habitat in a common reef coral

NASA Astrophysics Data System (ADS)

Hawkins, Thomas D.; Krueger, Thomas; Wilkinson, Shaun P.; Fisher, Paul L.; Davy, Simon K.

2015-12-01

Coral bleaching—the stress-induced collapse of the coral- Symbiodinium symbiosis—is a significant driver of worldwide coral reef degradation. Yet, not all corals are equally susceptible to bleaching, and we lack a clear understanding of the mechanisms underpinning their differential susceptibilities. Here, we focus on cellular redox regulation as a potential determinant of bleaching susceptibility in the reef coral Stylophora pistillata. Using slow heating (1 °C d-1) and altered irradiance, we induced bleaching in S. pistillata colonies sampled from two depths [5-8 m (shallow) and 15-18 m (deep)]. There was significant depth-dependent variability in the timing and extent of bleaching (loss of symbiont cells), as well as in host enzymatic antioxidant activity [specifically, superoxide dismutase and catalase (CAT)]. However, among the coral fragments that bleached, most did so without displaying any evidence of a host enzymatic antioxidant response. For example, both deep and shallow corals suffered significant symbiont loss at elevated temperature, but only deep colonies exposed to high temperature and high light displayed any up-regulation of host antioxidant enzyme activity (CAT). Surprisingly, this preceded the equivalent antioxidant responses of the symbiont, which raises questions about the source(s) of hydrogen peroxide in the symbiosis. Overall, changes in enzymatic antioxidant activity in the symbionts were driven primarily by irradiance rather than temperature, and responses were similar across depth groups. Taken together, our results suggest that in the absence of light stress, heating of 1 °C d-1 to 4 °C above ambient is not sufficient to induce a substantial oxidative challenge in S. pistillata. We provide some of the first evidence that regulation of coral enzymatic antioxidants can vary significantly depending on habitat, and, in terms of determining bleaching susceptibility, our results suggest a significant role for the host's differential regulation of cellular redox status.

Influence of vitamin C and vitamin E on redox signaling: Implications for exercise adaptations.

PubMed

Cobley, James N; McHardy, Helen; Morton, James P; Nikolaidis, Michalis G; Close, Graeme L

2015-07-01

The exogenous antioxidants vitamin C (ascorbate) and vitamin E (α-tocopherol) often blunt favorable cell signaling responses to exercise, suggesting that redox signaling contributes to exercise adaptations. Current theories posit that this antioxidant paradigm interferes with redox signaling by attenuating exercise-induced reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. The well-documented in vitro antioxidant actions of ascorbate and α-tocopherol and characterization of the type and source of the ROS/RNS produced during exercise theoretically enable identification of redox-dependent mechanisms responsible for the blunting of favorable cell signaling responses to exercise. This review aimed to apply this reasoning to determine how the aforementioned antioxidants might attenuate exercise-induced ROS/RNS production. The principal outcomes of this analysis are (1) neither antioxidant is likely to attenuate nitric oxide signaling either directly (reaction with nitric oxide) or indirectly (reaction with derivatives, e.g., peroxynitrite); (2) neither antioxidant reacts appreciably with hydrogen peroxide, a key effector of redox signaling; (3) ascorbate but not α-tocopherol has the capacity to attenuate exercise-induced superoxide generation; and (4) alternate mechanisms, namely pro-oxidant side reactions and/or reduction of bioactive oxidized macromolecule adducts, are unlikely to interfere with exercise-induced redox signaling. Out of all the possibilities considered, ascorbate-mediated suppression of superoxide generation with attendant implications for hydrogen peroxide signaling is arguably the most cogent explanation for blunting of favorable cell signaling responses to exercise. However, this mechanism is dependent on ascorbate accumulating at sites rich in NADPH oxidases, principal contributors to contraction-mediated superoxide generation, and outcompeting nitric oxide and superoxide dismutase isoforms. The major conclusions of this review are: (1) direct evidence for interference of ascorbate and α-tocopherol with exercise-induced ROS/RNS production is lacking; (2) theoretical analysis reveals that both antioxidants are unlikely to have a major impact on exercise-induced redox signaling; and (3) it is worth considering alternate redox-independent mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Dongxu; Wang, Yijun; Wan, Xiaochun

(−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1more » (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG at lethal dose substantially suppresses hepatic Nrf2 pathway.« less

Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia.

PubMed

Ungvari, Zoltan; Bailey-Downs, Lora; Gautam, Tripti; Jimenez, Rosario; Losonczy, Gyorgy; Zhang, Cuihua; Ballabh, Praveen; Recchia, Fabio A; Wilkerson, Donald C; Sonntag, William E; Pearson, Kevin; de Cabo, Rafael; Csiszar, Anna

2011-04-01

Hyperglycemia in diabetes mellitus promotes oxidative stress in endothelial cells, which contributes to development of cardiovascular diseases. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor activated by oxidative stress that regulates expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes. This study was designed to elucidate the homeostatic role of adaptive induction of Nrf2-driven free radical detoxification mechanisms in endothelial protection under diabetic conditions. Using a Nrf2/antioxidant response element (ARE)-driven luciferase reporter gene assay we found that in a cultured coronary arterial endothelial cell model hyperglycemia (10-30 mmol/l glucose) significantly increases transcriptional activity of Nrf2 and upregulates the expression of the Nrf2 target genes NQO1, GCLC, and HMOX1. These effects of high glucose were significantly attenuated by small interfering RNA (siRNA) downregulation of Nrf2 or overexpression of Keap-1, which inactivates Nrf2. High-glucose-induced upregulation of NQO1, GCLC, and HMOX1 was also prevented by pretreatment with polyethylene glycol (PEG)-catalase or N-acetylcysteine, whereas administration of H(2)O(2) mimicked the effect of high glucose. To test the effects of metabolic stress in vivo, Nrf2(+/+) and Nrf2(-/-) mice were fed a high-fat diet (HFD). HFD elicited significant increases in mRNA expression of Gclc and Hmox1 in aortas of Nrf2(+/+) mice, but not Nrf2(-/-) mice, compared with respective standard diet-fed control mice. Additionally, HFD-induced increases in vascular ROS levels were significantly greater in Nrf2(-/-) than Nrf2(+/+) mice. HFD-induced endothelial dysfunction was more severe in Nrf2(-/-) mice, as shown by the significantly diminished acetylcholine-induced relaxation of aorta of these animals compared with HFD-fed Nrf2(+/+) mice. Our results suggest that adaptive activation of the Nrf2/ARE pathway confers endothelial protection under diabetic conditions.

Nuclear factor erythroid 2-related factor 2-antioxidant activation through the action of ataxia telangiectasia-mutated serine/threonine kinase is essential to counteract oxidative stress in bovine mammary epithelial cells.

PubMed

Ma, Y F; Wu, Z H; Gao, M; Loor, J J

2018-06-01

Nuclear factor (erythroid-derived 2)-like factor 2 (NFE2L2, formerly Nrf2) is a transcription factor that binds to the antioxidant response element (ARE) in the upstream promoter region of various antioxidant-responsive genes. Hence, at least in nonruminants, the NFE2L2-ARE signaling pathway plays an important role in the cellular antioxidant defense system. Whether oxidative stress in bovine mammary epithelial cells alters NFE2L2 or the NFE2L2-ARE pathway is unclear. Therefore, the objective of this study was to examine the response in NFE2L2- and NFE2L2-ARE-related components in bovine mammary epithelial cells (BMEC) under oxidative stress. An in silico analysis to identify potential phosphorylation sites on NFE2L2 and the protein kinases was performed with Netphos 3.1 (http://www.cbs.dtu.dk/services/NetPhos/) and Scansite (http://scansite.mit.edu) software. Isolated BMEC were exposed to H 2 O 2 (600 μM) for 6 h to induce oxidative stress. In silico analysis revealed ataxia telangiectasia-mutated (ATM) serine/threonine kinase as a key kinase responsible for the phosphorylation of NFE2L2. Thus, after the 6 h incubation with H 2 O 2 , BMEC were transiently transfected with ATM-small interfering RNA (siRNA) 1, 2, or 3. Compared with the control, transfection with ATM-siRNA3 resulted in proliferation rates that were 60.7 and 36.2% lower with or without H 2 O 2 . In addition, production of reactive oxygen species and malondialdehyde increased markedly, but activities of superoxide dismutase, glutathione peroxidase, catalase, and glutathione-S-transferase decreased markedly in transfected cells without or with H 2 O 2 compared with the control. Transfected cells had markedly lower protein and mRNA expression of NFE2L2 without or with H 2 O 2 compared with the control. In addition, fluorescent activity of the ARE in transfected BMEC indicated that NFE2L2-driven transcriptional activation decreased under oxidative stress. Overall, results indicate that ATM is a physiologically relevant NFE2L2 kinase. Furthermore, inhibition of ATM activity can cause marked alterations in oxidative stress leading to cell death as a result of diminished capacity of BMEC to cope with H 2 O 2 -induced cytotoxicity. The relevance of this kinase in vivo merits further study. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The relationship between metal composition, phenolic acid and flavonoid content in Imleria badia from non-polluted and polluted areas.

PubMed

Gąsecka, Monika; Rzymski, Piotr; Mleczek, Mirosław; Siwulski, Marek; Budzyńska, Sylwia; Magdziak, Zuzanna; Niedzielski, Przemysław; Sobieralski, Krzysztof

2017-03-04

The aim of this study was to determine the elemental composition, phenolic content and composition and antioxidant properties of Imleria badia (Fr.) Vizzini (former names Boletus badius (Fr.) Fr., and Xerocomus badius (Fr.) E.-J. Gilbert) fruiting bodies collected from sites with different levels of pollution. Imleria badia was relatively tolerant to soil contamination with toxic elements and was able to grow in As, Cd, Hg and Pb concentrations exceeding 15, 2.9, 0.4 and 77 mg kg -1 , respectively. The concentration of elements in soil was reflected in the element content in I. badia. The fruiting bodies from polluted sites exhibited significantly higher content of all the analyzed elements. Among 21 individual phenolic compounds only protocatechiuc and caffeic acids, and quercetin were determined in fruiting bodies of I. badia. The differences between the concentration of the quantified phenolic compounds and the total flavonoid content in fruiting bodies of I. badia from unpolluted and polluted sites were not significant. However, the greatest total phenolic content was found in fruiting bodies from the polluted areas. The antioxidative capacity of mushrooms collected from heavily polluted sites was lower than those growing in unpolluted areas. The concentrations of some metals in soil and fruiting soil were positively correlated with phenolic content and IC 50 .

Carvedilol, a third-generation β-blocker prevents oxidative stress-induced neuronal death and activates Nrf2/ARE pathway in HT22 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouyang, Ying; Chen, Ziwei; Tan, Min

Highlights: •Carvedilol significantly prevented oxidative stress-induced cell death. •Carvedilol significantly decreased the production of ROS. •Carvedilol activated Nrf2/ARE pathway. •Carvedilol increased the protein levels of HO-1 and NQO-1. -- Abstract: Carvedilol, a nonselective β-adrenoreceptor blocker with pleiotropic activities has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. Here we investigated the effect of carvedilol on oxidative stress-induced cell death (glutamate 2 mM and H{sub 2}O{sub 2}more » 600 μM) and the activity of Nrf2/ARE pathway in HT22 hippocampal cells. Carvedilol significantly increased cell viability and decreased ROS in HT22 cells exposed to glutamate or H{sub 2}O{sub 2}. Furthermore, carvedilol activated the Nrf2/ARE pathway in a concentration-dependent manner, and increased the protein levels of heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1(NQO-1), two downstream factors of the Nrf2/ARE pathway. Collectively, our results indicate that carvedilol protects neuronal cell against glutamate- and H{sub 2}O{sub 2}-induced neurotoxicity possibly through activating the Nrf2/ARE signaling pathway.« less

miR398 and miR395 are involved in response to SO2 stress in Arabidopsis thaliana.

PubMed

Li, Lihong; Yi, Huilan; Xue, Meizhao; Yi, Min

2017-11-01

Sulfur dioxide (SO 2 ) is a common air pollutant that has adverse effects on plants. MicroRNAs (miRNAs) are small noncoding RNA that play critical roles in plant development and stress response. In this study, we found that two miRNAs, miR398 and miR395, were differentially expressed in Arabidopsis shoots under SO 2 stress. The expression of miR398 was down-regulated, and the transcript levels of its target genes, Cu/Zn superoxide dismutases (CSD1 and CSD2), were increased during SO 2 exposure. The activity of superoxide dismutase (SOD), one of the major antioxidant enzymes, was enhanced with the increase in the CSD transcript level, suggesting an important role of miR398 in response to SO 2 -induced oxidative stress. Meanwhile, the expression of miR395 was increased, and the transcript levels of its target genes, ATP sulfurylases (APS3 and APS4) and a low-affinity sulfate transporter (SULTR2;1), were decreased in Arabidopsis shoots, showing that miR395 played important roles in the regulation of sulfate assimilation and translocation during SO 2 exposure. The content of glutathione (GSH), an important sulfur-containing antioxidant, was enhanced with the changes in sulfur metabolism in Arabidopsis shoots under SO 2 stress. These results showed that both miR398 and miR395 were involved in protecting plants from oxidative damage during SO 2 exposure. Many stress-responsive cis-elements were found in the promoter regions of MIR398 and MIR395, suggesting that these miRNAs might respond to various environmental conditions, including SO 2 stress. Overall, our study provides an insight into the regulatory roles of miRNAs in response to SO 2 stress in plants, and highlights the molecular mechanisms of plant adaptation to environmental stress.

In vitro antioxidant and antimalarial activities of leaves, pods and bark extracts of Acacia nilotica (L.) Del.

PubMed

Sadiq, Muhammad Bilal; Tharaphan, Pattamon; Chotivanich, Kesinee; Tarning, Joel; Anal, Anil Kumar

2017-07-18

The emergence of drug resistant malaria is threatening our ability to treat and control malaria in the Southeast Asian region. There is an urgent need to develop novel and chemically diverse antimalarial drugs. This study aimed at evaluating the antimalarial and antioxidant potentials of Acacia nilotica plant extracts. The antioxidant activities of leaves, pods and bark extracts were determined by standard antioxidant assays; reducing power capacity, % lipid peroxidation inhibition and ferric reducing antioxidant power assay. The antimalarial activities of plant extracts against Plasmodium falciparum parasites were determined by the 48 h schizont maturation inhibition assay. Further confirmation of schizonticide activity of extracts was made by extending the incubation period up to 96 h after removing the plant extract residues from parasites culture. Inhibition assays were analyzed by dose-response modelling. In all antioxidant assays, leaves of A. nilotica showed higher antioxidant activity than pods and bark. Antimalarial IC 50 values of leaves, pods and bark extracts were 1.29, 4.16 and 4.28 μg/ml respectively, in the 48 h maturation assay. The IC 50 values determined for leaves, pods and bark extracts were 3.72, 5.41 and 5.32 μg/ml respectively, after 96 h of incubation. All extracts inhibited the development of mature schizont, indicating schizonticide activity against P. falciparum. A. nilotica extracts showed promising antimalarial and antioxidant effects. However, further investigation is needed to isolate and identify the active components responsible for the antimalarial and antioxidant effects.

An essential role of Nrf2 in American ginseng-mediated anti-oxidative actions in cardiomyocytes.

PubMed

Li, Jinqing; Ichikawa, Tomonaga; Jin, Yu; Hofseth, Lorne J; Nagarkatti, Prakash; Nagarkatti, Mitzi; Windust, Anthony; Cui, Taixing

2010-07-20

Ginseng has been used as a folk medicine for thousands of years in Asia, and has become a popular herbal medicine world-wide. Recent studies have revealed that ginseng, including American ginseng, exerts antioxidant effects in the cardiovascular system; however, the underlying mechanisms are not fully understood. Thus, we investigated role of Nrf2, a master transcription factor of endogenous anti-oxidative defense systems, in the regulation of American ginseng-mediated anti-oxidative actions in cardiomyocytes. A standardized crude extract of American ginseng was supplied by the National Research Council of Canada, Institute for National Measurement Standards. H9C2 cells, a rat cardiomyocyte cell line, were exposed to angiotensin II (Ang II) or tumor necrosis factor alpha (TNFalpha) to induce oxidative stress that was examined by measuring formation of reactive oxygen and nitrogen species. Oxidative stress-induced cell death was induced by exogenous addition of hydrogen peroxide (H(2)O(2)). Proteins were measured by Western blot and mRNA expression was determined by quantitative real time PCR. Nrf2-driven transcriptional activity was assessed by antioxidant response element (ARE)-luciferase reporter assay. Direct Nrf2 binding to its target gene promoters was determined by chromatin immunoprecipitation assay. Adenoviral over-expression of Nrf2 shRNA was utilized to knock down Nrf2 in H9C2 cells. Immunochemical staining was applied for Nrf2 expression in the heart. American ginseng induced dramatic increases in Nrf2 protein expression, Nrf2 nuclear translocation, Nrf2 transcriptional activity, direct Nrf2 binding to its target gene promoters, and expression of a group of anti-oxidative genes driven by Nrf2 in H9C2 cells. In addition, American ginseng inhibited Ang II- or TNFalpha-induced free radical formation and H(2)O(2)-induced cell death in H9C2 cells over-expressed with control shRNA but not in the cells over-expressed with Nrf2 shRNA. Finally, oral administration of American ginseng markedly increased Nrf2 activity in murine hearts. These results demonstrate that American ginseng suppresses oxidative stress and oxidative stress-induced cell death in cardiomyocytes through activating the Nrf2 pathway, thereby providing cardioprotection against pathological cardiac remodeling. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Short-term UV-B radiation affects photosynthetic performance and antioxidant gene expression in highbush blueberry leaves.

PubMed

Inostroza-Blancheteau, Claudio; Acevedo, Patricio; Loyola, Rodrigo; Arce-Johnson, Patricio; Alberdi, Miren; Reyes-Díaz, Marjorie

2016-10-01

The impact of increased artificial UV-B radiation on photosynthetic performance, antioxidant and SOD activities and molecular antioxidant metabolism responses in leaves of two highbush blueberry (Vaccinium corymbosum L. cv. Brigitta and Bluegold) genotypes was studied. Plants were grown in a solid substrate and exposed to 0, 0.07, 0.12 and 0.19 W m(-2) of biologically-effective UV-B irradiance for 0-72 h. Our findings show that net photosynthesis (Pn) decreased significantly in Bluegold, accompanied by a reduction in the effective quantum yield (ФPSII) and electron transport rate (ETR), especially at the highest UV-B irradiation. On the other hand, Brigitta showed a better photosynthetic performance, as well as a clear increment in the antioxidant activity response that could be associated with increased superoxide dismutase activity (SOD) in the early hours of induced UV-B stress in all treatments. At the molecular level, the expression of the three antioxidant genes evaluated in both genotypes had a similar tendency. However, ascorbate peroxidase (APX) expression was significantly increased (6-fold) in Bluegold compared to Brigitta. Thus, the reduction of Pn concomitant with a lower photochemical performance and a reduced response of antioxidant metabolism suggest that the Bluegold genotype is more sensitive to UV-B radiation, while Brigitta appears to tolerate better moderate UV-B irradiance in a short-term experiment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Early response of wheat antioxidant system with special reference to Fusarium head blight stress.

PubMed

Spanic, Valentina; Viljevac Vuletic, Marija; Abicic, Ivan; Marcek, Tihana

2017-06-01

Fusarium head blight (FHB) is a destructive fungal disease of wheat (Triticum aestivum L.) that causes significant grain yield losses and end-use quality reduction associated with contamination by the mycotoxin deoxynivalenol (DON). Three winter wheat varieties ('Vulkan', 'Kraljica' and 'Golubica') were screened for FHB resistance using artificial inoculation technique under field conditions. The aim of this study was to examine a relationship between FHB resistance and the effectiveness of enzyme antioxidant system of wheat varieties under different sampling times (3, 15, 24, 48, 96, 120 and 336 hai). In the time-course experiments FHB-resistant variety 'Vulkan' showed rapid induction of ascorbate peroxidase (APX) and polyphenol oxidase (PPO) activity in the early stages after infection (3 hai) and it seems that in 'Vulkan' FHB-resistance is associated with antioxidative enzymes activity. Moderately FHB resistant variety 'Kraljica' showed the higher guaiacol peroxidase (POD) activity and higher H 2 O 2 content after 24 hai, increased malondialdehyde (MDA) content at the beginning of infection (3, 15 hai) while induction of catalase (CAT), APX and PPO was delayed. FHB-susceptible variety 'Golubica' involved antioxidant enzymes in defense response much later. Based on our results the activity of antioxidant enzymes (APX and PPO) was more pronounced in 'Vulkan' than in FHB-medium resistant variety 'Kraljica' and FHB-susceptible 'Golubica'. The differences in antioxidant response of wheat varieties under Fusarium infestation could be the result of genetic properties. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cocoa and Chocolate in Human Health and Disease

PubMed Central

Doughty, Kim; Ali, Ather

2011-01-01

Abstract Cocoa contains more phenolic antioxidants than most foods. Flavonoids, including catechin, epicatechin, and procyanidins predominate in antioxidant activity. The tricyclic structure of the flavonoids determines antioxidant effects that scavenge reactive oxygen species, chelate Fe2+ and Cu+, inhibit enzymes, and upregulate antioxidant defenses. The epicatechin content of cocoa is primarily responsible for its favorable impact on vascular endothelium via its effect on both acute and chronic upregulation of nitric oxide production. Other cardiovascular effects are mediated through anti-inflammatory effects of cocoa polyphenols, and modulated through the activity of NF-κB. Antioxidant effects of cocoa may directly influence insulin resistance and, in turn, reduce risk for diabetes. Further, cocoa consumption may stimulate changes in redox-sensitive signaling pathways involved in gene expression and the immune response. Cocoa can protect nerves from injury and inflammation, protect the skin from oxidative damage from UV radiation in topical preparations, and have beneficial effects on satiety, cognitive function, and mood. As cocoa is predominantly consumed as energy-dense chocolate, potential detrimental effects of overconsumption exist, including increased risk of weight gain. Overall, research to date suggests that the benefits of moderate cocoa or dark chocolate consumption likely outweigh the risks. Antioxid. Redox Signal. 15, 2779–2811. PMID:21470061

Polydatin promotes Nrf2-ARE anti-oxidative pathway through activating Sirt1 to resist AGEs-induced upregulation of fibronetin and transforming growth factor-β1 in rat glomerular messangial cells.

PubMed

Huang, Kaipeng; Chen, Cheng; Hao, Jie; Huang, Junying; Wang, Shaogui; Liu, Peiqing; Huang, Heqing

2015-01-05

Sirt1 and nuclear factor-E2 related factor 2 (Nrf2)-anti-oxidant response element (ARE) anti-oxidative pathway play important regulatory roles in the pathological progression of diabetic nephropathy (DN) induced by advanced glycation-end products (AGEs). Polydatin (PD), a glucoside of resveratrol, has been shown to possess strong anti-oxidative bioactivity. Our previous study demonstrated that PD markedly resists the progression of diabetic renal fibrosis and thus, inhibits the development of DN. Whereas, whether PD could resist DN through regulating Sirt1 and consequently promoting Nrf2-ARE pathway needs further investigation. Here, we found that concomitant with decreasing RAGE (the specific receptor for AGEs) expression, PD significantly reversed the downregulation of Sirt1 in terms of protein expression and deacetylase activity and attenuated FN and TGF-β1 expression in GMCs exposed to AGEs. Under AGEs-treatment condition, PD could decrease Keap1 expression and promote the nuclear content, ARE-binding ability, and transcriptional activity of Nrf2. In addition, PD increased the protein levels of heme oxygenase 1 (HO-1) and superoxide dismutase 1 (SOD1), two target genes of Nrf2. The activation of Nrf2-ARE pathway by PD eventually led to the quenching of ROS overproduction sharply boosted by AGEs. Depletion of Sirt1 blocked Nrf2-ARE pathway activation and reversed FN and TGF-β1 downregulation induced by PD in GMCs challenged with AGEs. Along with reducing HO-1 and SOD1 expression, silencing of Nrf2 increased FN and TGF-β1 levels. PD treatment elevated Sirt1 and Nrf2 levels in the kidney tissues of diabetic rats, then improved the anti-oxidative capacity and renal dysfunction of diabetic models, and finally reversed the upregulation of FN and TGF-β1. Taken together, the resistance of PD on upregulated FN and TGF-β1 induced by AGEs via oxidative stress in GMCs is closely associated with its activation of Sirt1-Nrf2-ARE pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Selenium in bone health: roles in antioxidant protection and cell proliferation.

PubMed

Zeng, Huawei; Cao, Jay J; Combs, Gerald F

2013-01-10

Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health.

Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation

PubMed Central

Zeng, Huawei; Cao, Jay J.; Combs, Gerald F.

2013-01-01

Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health. PMID:23306191

Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic exercise.

PubMed

Funes, Lorena; Carrera-Quintanar, Lucrecia; Cerdán-Calero, Manuela; Ferrer, Miguel D; Drobnic, Franchek; Pons, Antoni; Roche, Enrique; Micol, Vicente

2011-04-01

Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.

Development of Phaleria macrocarpa (Scheff.) Boerl Fruits Using Response Surface Methodology Focused on Phenolics, Flavonoids and Antioxidant Properties.

PubMed

Mohamed Mahzir, Khurul Ain; Abd Gani, Siti Salwa; Hasanah Zaidan, Uswatun; Halmi, Mohd Izuan Effendi

2018-03-22

In this study, the optimal conditions for the extraction of antioxidants from the Buah Mahkota Dewa fruit ( Phaleria macrocarpa) was determined by using Response Surface Methodology (RSM). The optimisation was applied using a Central Composite Design (CCD) to investigate the effect of three independent variables, namely extraction temperature (°C), extraction time (minutes) and extraction solvent to-feed ratio (% v / v ) on four responses: free radical scavenging activity (DPPH), ferric ion reducing power assay (FRAP), total phenolic content (TPC) and total flavonoid content (TFC). The optimal conditions for the antioxidants extraction were found to be 64 °C extraction temperature, 66 min extraction time and 75% v / v solvent to-feed ratio giving the highest percentage yields of DPPH, FRAP, TPC and TFC of 86.85%, 7.47%, 292.86 mg/g and 3.22 mg/g, respectively. Moreover, the data were subjected to Response Surface Methodology (RSM) and the results showed that the polynomial equations for all models were significant, did not show lack of fit, and presented adjusted determination coefficients ( R ²) above 99%, proving that the yield of phenolic, flavonoid and antioxidants activities obtained experimentally were close to the predicted values and the suitability of the model employed in RSM to optimise the extraction conditions. Hence, in this study, the fruit from P. macrocarpa could be considered to have strong antioxidant ability and can be used in various cosmeceutical or medicinal applications.

[Alteration mechanisms of oxidative stress at periodontal tissues of rats in a simulated periodontitis and elaborate methods of their correction].

PubMed

Хмиль, Елена В; Ляшенко, Лилия И; Янко, Наталия В; Хмиль, Дмитрий А; Каськова, Людмила Ф

2016-01-01

one of the peroxidation stress mechanisms is inducible NO synthase (iNOS) expression involved in the pathogenesis of periodontitis. to access the influence of isoform NO synthase (NOS) on alteration mechanisms of oxidative stress at periodontal tissues of 50 mature rats in a simulated periodontitis (SP). a SP at rats was induced by a high-carbohydrate, high-fat (HCHF) diet. Тreated SP rat groups were intragastrically administered with selective neuronal NOS (nNOS) inhibitor 7-nitroindazole, selective inducible NOS (iNOS) inhibitor aminoguanidine, and nitric oxide synthase substrate L-arginine. Oxidative stress level in the homogenated soft periodontal tissues was evaluated by TBARS (thiobarbituric acid reactive substances) level before and after 1,5 hours of incubation. Antioxidant response was evaluated by the increase in concentration of TBARS for incubation, аnd by antioxidant enzyme activity - superoxide dismutase and catalase. nNOS activity increase in a SP considerably limits oxidative stress activation at periodontal tissues, decreases antioxidant response, but heightens catalase activity. iNOS functional activity stimulates oxidative stress at periodontal tissues of rats, decreases antioxidant response. L-arginine in a MS effectively repaired antioxidant response at periodontal tissues that probably will give positive result at complex treatment of periodontitis and MS generally. in the near future, the appropriate regulation of NO activity by using NOS-active agents may provide a novel strategy for the periodontal disease prevention and correction in a MS.

[Alteration mechanisms of oxidative stress at periodontal tissues of rats in a simulated periodontitis and elaborate methods of their correction].

PubMed

Хмиль, Елена В; Ляшенко, Лилия И; Янко, Наталия В; Хмиль, Дмитрий А; Каськова, Людмила Ф

one of the peroxidation stress mechanisms is inducible NO synthase (iNOS) expression involved in the pathogenesis of periodontitis. to access the influence of isoform NO synthase (NOS) on alteration mechanisms of oxidative stress at periodontal tissues of 50 mature rats in a simulated periodontitis (SP). a SP at rats was induced by a high-carbohydrate, high-fat (HCHF) diet. Тreated SP rat groups were intragastrically administered with selective neuronal NOS (nNOS) inhibitor 7-nitroindazole, selective inducible NOS (iNOS) inhibitor aminoguanidine, and nitric oxide synthase substrate L-arginine. Oxidative stress level in the homogenated soft periodontal tissues was evaluated by TBARS (thiobarbituric acid reactive substances) level before and after 1,5 hours of incubation. Antioxidant response was evaluated by the increase in concentration of TBARS for incubation, аnd by antioxidant enzyme activity - superoxide dismutase and catalase. nNOS activity increase in a SP considerably limits oxidative stress activation at periodontal tissues, decreases antioxidant response, but heightens catalase activity. iNOS functional activity stimulates oxidative stress at periodontal tissues of rats, decreases antioxidant response. L-arginine in a MS effectively repaired antioxidant response at periodontal tissues that probably will give positive result at complex treatment of periodontitis and MS generally. in the near future, the appropriate regulation of NO activity by using NOS-active agents may provide a novel strategy for the periodontal disease prevention and correction in a MS.

An eco-benign synthesis of AgNPs using aqueous extract of Longan fruit peel: Antiproliferative response against human breast cancer cell line MCF-7, antioxidant and photocatalytic deprivation of methylene blue.

PubMed

Khan, Arif Ullah; Yuan, Qipeng; Khan, Zia Ul Haq; Ahmad, Aftab; Khan, Faheem Ullah; Tahir, Kamran; Shakeel, Muhammad; Ullah, Sadeeq

2018-05-07

Plants mediated synthesis of noble metal nanoparticles is encountered as a clean, environment friendly, lucrative and benign loom. The current study consists of clean and green synthesis of Silver nanoparticles (AgNPs). Phytoconstituents from Longan (Euphorbia longana Lam.) fruit peel were used to reduce Ag + into AgNPs. Different analytical techniques i.e. UV-vis Spectroscopy, X-ray diffraction spectroscopy (XRD), electron dispersive X-ray (EDX), High-resolution transmission electron microscopy (HRTEM) and Fourier transform infrared spectroscopy (FTIR) were used to analyze the synthesized AgNPs. AgNPs have localized surface plasmon resonance (LSPR) peak at 445 nm which is confirmed by UV-vis spectroscopy. HRTEM showed that the prepared AgNPs are spheroid in shape and well dispersed while XRD results showed that the AgNPs are face centered cubic crystalline. EDX confirmed the elemental composition of AgNPs. The antiproliferative response of AgNPs was assayed by an exhaustive MTT assay. AgNPs showed potent anticancer activity (88%) against breast cancer cells MCF-7. Moreover, the green produced AgNPs effectively scavenged 91% of the stable and harmful 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical which confirms its' efficient antioxidant nature. AgNPs have profound photocatalytic degradation (99%) of methylene blue in a short period of time (7 min). The noteworthy biological and photocatalytic responses of the green and cleanly produced AgNPs are encountered to their well dispersion, petite volume and round shaped structure. Copyright © 2018 Elsevier B.V. All rights reserved.

Airborne nitro-PAHs induce Nrf2/ARE defense system against oxidative stress and promote inflammatory process by activating PI3K/Akt pathway in A549 cells.

PubMed

Shang, Yu; Zhou, Qian; Wang, Tiantian; Jiang, Yuting; Zhong, Yufang; Qian, Guangren; Zhu, Tong; Qiu, Xinghua; An, Jing

2017-10-01

Ambient particulate matter (PM) is a worldwide health issue of concern. However, limited information is available regarding the toxic contributions of the nitro-derivatives of polycyclic aromatic hydrocarbons (nitro-PAHs). This study intend to examine whether 1-nitropyrene (1-NP) and 3-nitrofluoranthene (3-NF) could activate the nuclear factor-erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) antioxidant defense system, and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway participates in regulating pro-inflammatory responses in A549 cells. Firstly, 1-NP and 3-NF concentration-dependently induced cellular apoptosis, reactive oxygen species (ROS) generation, DNA damage, S phase cell cycle arrest and differential expression of related cytokine genes. Secondly, 1-NP and 3-NF activated the Nrf2/ARE defense system, as evidenced by increased protein expression levels and nuclear translocation of transcription factor Nrf2, elevated Nrf2/ARE binding activity, up-regulated expression of the target gene heme oxygenase-1 (HO-1). Significantly increased protein expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and phosphorylation level of Akt indicated that the PI3K/Akt pathway was activated during pro-inflammatory process. Further, both PI3K inhibitor (LY294002) and Akt inhibitor (MK-2206) reversed the elevated TNF-α expression to control level. Our results suggested that Nrf2/ARE pathway activation might cause an initiation step in cellular protection against oxidative stress caused by nitro-PAHs, and the PI3K/Akt pathway participated in regulating inflammatory responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-inflammatory and antioxidative effects of Camellia oleifera Abel components.

PubMed

Xiao, Xiaomei; He, Liangmei; Chen, Yayun; Wu, Longhuo; Wang, Lin; Liu, Zhiping

2017-11-01

Camellia oleifera Abel is a member of Camellia, and its seeds are used to extract Camellia oil, which is generally used as cooking oil in the south of China. Camellia oil consists of unsaturated fatty acids, tea polyphenol, squalene, saponin, carrot element and vitamins, etc. The seed remains after oil extraction of C. oleifera Abel are by-products of oil production, named as Camellia oil cake. Its extracts contain bioactive compounds including sasanquasaponin, flavonoid and tannin. Major components from Camellia oil and its cake have been shown to have anti-inflammatory, antioxidative, antimicrobial and antitumor activities. In this review, we will summarize the latest advance in the studies on anti-inflammatory or antioxidative effects of C. oleifera products, thus providing valuable reference for the future research and development of C. oleifera Abel.

Research into the functional components and antioxidant activities of North China rice wine (Ji Mo Lao Jiu).

PubMed

He, Shuai; Mao, Xiangzhao; Liu, Pei; Lin, Hong; Du, Zuyuan; Lv, Ning; Han, Jichen; Qiu, Cuifang

2013-07-01

Over the last decade, considerable experimental evidence has supported the view that grape wine and South China rice wine are rich in diverse nutrients and have powerful antioxidant activity. However, little research has been carried out for North China rice wine, of which Ji Mo Lao Jiu (JMLJ) is the outstanding representative. In this study, the functional components and antioxidant activity of JMLJ were investigated. Twenty-eight free amino acids were found in JMLJ, much more than that previously reported in other Chinese rice wines (16-21). Functional oligosaccharides (5290.222 mg/L), total phenols (722.431 ± 10.970 mg/L), and mineral elements (9) were rich in JMLJ. When compared with synthetic antioxidants, such as butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), JMLJ showed effective 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging and reducing capacity. The results of this study lay the foundation for promoting the utilization of JMLJ and the development of North China rice wine in the food industry.

Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity.

PubMed

Pereira, Regina M S; Andrades, Norma E D; Paulino, Niraldo; Sawaya, Alexandra C H F; Eberlin, Marcos N; Marcucci, Maria C; Favero, Giovani Marino; Novak, Estela Maria; Bydlowski, Sérgio Paulo

2007-07-09

The antioxidant activity of flavonoids is believed to increase when they are coordinated with transition metal ions. However, the literature on this subject is contradictory and the outcome seems to largely depend on the experimental conditions. In order to understand the contribution of the metal coordination and the type of interaction between a flavonoid and the metal ion, in this study a new metal complex of Cu (II) with naringin was synthesized and characterized by FT-IR, UV-VIS, mass spectrometry (ESI-MS/MS), elemental analysis and 1H-NMR. The results of these analyses indicate that the complex has a Cu (II) ion coordinated via positions 4 and 5 of the flavonoid. The antioxidant, anti-inflammatory and antimicrobial activities of this complex were studied and compared with the activity of free naringin. The Naringin-Cu (II) complex 1 showed higher antioxidant, anti-inflammatory and tumor cell cytotoxicity activities than free naringin without reducing cell viability.

Influence of Sulfur Fertilization on the Antioxidant Activities of Onion Juices Prepared by Thermal Treatment

PubMed Central

Koh, Eunmi; Surh, Jeonghee

2016-01-01

Two onions (Sulfur-1 and Sulfur-4) cultivated with different sulfur applications were thermally processed to elucidate the effects of heat treatment on browning index and antioxidant activity. Sulfur-4 onion had higher sulfur content compared with the Sulfur-1 onion. After thermal processing, browning intensity was different between the two onions juices, with lower values observed for Sulfur-4 onion juice. This suggests that sulfur inhibits the Maillard browning reaction. The total reducing capacity of the juices increased at higher thermal processing temperatures; however, it was also lower in the Sulfur-4 onion juice. This suggests that the heat treatment of onions enhanced their antioxidant activity, but the effect was offset in the Sulfur-4 onion juice presumably due to higher sulfur content. This study indicates that sulfur, a core element for the functionality of onions, can decrease the antioxidant activity of thermally processed onions because of its potential as a Maillard reaction inhibitor. PMID:27390734

Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells.

PubMed Central

Marui, N; Offermann, M K; Swerlick, R; Kunsch, C; Rosen, C A; Ahmad, M; Alexander, R W; Medford, R M

1993-01-01

Oxidative stress and expression of the vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells are early features in the pathogenesis of atherosclerosis and other inflammatory diseases. Regulation of VCAM-1 gene expression may be coupled to oxidative stress through specific reduction-oxidation (redox) sensitive transcriptional or posttranscriptional regulatory factors. In cultured human umbilical vein endothelial (HUVE) cells, the cytokine interleukin 1 beta (IL-1 beta) activated VCAM-1 gene expression through a mechanism that was repressed approximately 90% by the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC). Furthermore, PDTC selectively inhibited the induction of VCAM-1, but not intercellular adhesion molecule-1 (ICAM-1), mRNA and protein accumulation by the cytokine tumor necrosis factor-alpha (TNF alpha) as well as the noncytokines bacterial endotoxin lipopolysaccharide (LPS) and double-stranded RNA, poly(I:C) (PIC). PDTC also markedly attenuated TNF alpha induction of VCAM-1-mediated cellular adhesion. In a distinct pattern, PDTC partially inhibited E-selectin gene expression in response to TNF alpha but not to LPS, IL-1 beta, or PIC. TNF alpha and LPS-mediated transcriptional activation of the human VCAM-1 promoter through NF-kappa B-like DNA enhancer elements and associated NF-kappa B-like DNA binding proteins was inhibited by PDTC. These studies suggest a molecular linkage between an antioxidant sensitive transcriptional regulatory mechanism and VCAM-1 gene expression that expands on the notion of oxidative stress as an important regulatory signal in the pathogenesis of atherosclerosis. Images PMID:7691889

Hawthorn (Crataegus oxyacantha L.) bark extract regulates antioxidant response element (ARE)-mediated enzyme expression via Nrf2 pathway activation in normal hepatocyte cell line.

PubMed

Krajka-Kuźniak, Violetta; Paluszczak, Jarosław; Oszmiański, Jan; Baer-Dubowska, Wanda

2014-04-01

Hawthorn (Crataegus oxyacantha L.), a plant used in traditional medicine, is a rich source of procyanidins which have been reported to exhibit antioxidant and anti-carcinogenic activity. In this study, we assessed the effect of hawthorn bark extract (HBE) on Nrf2 pathway activation in THLE-2 and HepG2 cells. Treatment with 1.1 µg/mL, 5.5 µg/mL and 11 µg/mL of HBE resulted in the translocation of Nrf2 from the cytosol to the nucleus in both cell lines; however, the accumulation of phosphorylated Nrf2 was observed only in THLE-2. Accordingly, treatment of cells with HBE was associated with an increase in the mRNA and protein level of such Nrf2-dependent genes as glutathione S-transferases (GSTA, GSTP, GSTM, GSTT), NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) (0.2-1.1-fold change, p < 0.05), however, only in normal THLE-2 hepatocytes. The induction of NQO1 correlated with an increased level of p53 (0.21-0.42-fold change, p < 0.05). These effects may be related to induction of phosphorylation of upstream ERK and JNK kinases. Collectively, the results suggest that the Nrf2/ARE pathway may play an important role in the regulation of procyanidin-mediated antioxidant/detoxifying effects in hepatocytes, and this may explain the hepatoprotective and chemopreventive properties of these phytochemicals. Copyright © 2013 John Wiley & Sons, Ltd.

Pterostilbene protects against UVB-induced photo-damage through a phosphatidylinositol-3-kinase-dependent Nrf2/ARE pathway in human keratinocytes.

PubMed

Li, Huaping; Jiang, Na; Liang, Bihua; Liu, Qing; Zhang, Erting; Peng, Liqian; Deng, Huiyan; Li, Runxiang; Li, Zhenjie; Zhu, Huilan

2017-11-01

Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes. Human keratinocytes were pretreated with Pter (5 and 10 μM) for 24 h prior to UVB irradiation (300 mJ/cm 2 ). Harvested cells were analyzed by MTT, DCFH-DA, comet, western blotting, luciferase promoter, small interference RNA transfection, and quantitative real-time polymerase chain reaction assay. Pter significantly attenuated UVB-induced cell death and reactive oxygen species (ROS) generation, and effectively increased nuclear translocation of NF-E2-related factor-2 (Nrf2), expression of Nrf2-dependent antioxidant enzymes, and DNA repair activity. Moreover, the protective effects of Pter were abolished by small interference RNA-mediated Nrf2 silencing. Furthermore, Pter was also found to induce the phosphorylation of Nrf2 and the known phosphatidylinositol-3-kinase (PI3K) phosphorylated kinase, Akt. The specific inhibitor of PI3K, LY294002, successfully abrogated Pter-induced Nrf2 phosphorylation, activation of Nrf2-antioxidant response element pathway, ROS scavenging ability, and DNA repair activity. The present study indicated that Pter effectively protected against UVB-induced photodamage by increasing endogenous defense mechanisms, scavenging UVB-induced ROS, and aiding in damaged DNA repair through a PI3K-dependent activation of Nrf2/ARE pathway.

Antioxidant responses in estuarine invertebrates exposed to repeated oil spills: Effects of frequency and dosage in a field manipulative experiment.

PubMed

Sandrini-Neto, Leonardo; Pereira, Letícia; Martins, César C; Silva de Assis, Helena C; Camus, Lionel; Lana, Paulo C

2016-08-01

We have experimentally investigated the effects of repeated diesel spills on the bivalve Anomalocardia brasiliana, the gastropod Neritina virginea and the polychaete Laeonereis culveri, by monitoring the responses of oxidative stress biomarkers in a subtropical estuary. Three frequencies of exposure events were compared against two dosages of oil in a factorial experiment with asymmetrical controls. Hypotheses were tested to distinguish between (i) the overall effect of oil spills, (ii) the effect of diesel dosage via different exposure regimes, and (iii) the effect of time since last spill. Antioxidant defense responses and oxidative damage in the bivalve A. brasiliana and the polychaete L. culveri were overall significantly affected by frequent oil spills compared to undisturbed controls. The main effects of diesel spills on both species were the induction of SOD and GST activities, a significant increase in LPO levels and a decrease in GSH concentration. N. virginea was particularly tolerant to oil exposure, with the exception of a significant GSH depletion. Overall, enzymatic activities and oxidative damage in A. brasiliana and L. culveri were induced by frequent low-dosage spills compared to infrequent high-dosage spills, although the opposite pattern was observed for N. virginea antioxidant responses. Antioxidant responses in A. brasiliana and L. culveri were not affected by timing of exposure events. However, our results revealed that N. virginea might have a delayed response to acute high-dosage exposure. Experimental in situ simulations of oil exposure events with varying frequencies and intensities provide a useful tool for detecting and quantifying environmental impacts. In general, antioxidant biomarkers were induced by frequent low-dosage exposures compared to infrequent high-dosage ones. The bivalve A. brasiliana and the polychaete L. culveri are more suitable sentinels due to their greater responsiveness to oil and also to their wider geographical distribution. Copyright © 2016 Elsevier B.V. All rights reserved.

Spectrophotometric Determination of Phenolic Antioxidants in the Presence of Thiols and Proteins.

PubMed

Avan, Aslı Neslihan; Demirci Çekiç, Sema; Uzunboy, Seda; Apak, Reşat

2016-08-12

Development of easy, practical, and low-cost spectrophotometric methods is required for the selective determination of phenolic antioxidants in the presence of other similar substances. As electron transfer (ET)-based total antioxidant capacity (TAC) assays generally measure the reducing ability of antioxidant compounds, thiols and phenols cannot be differentiated since they are both responsive to the probe reagent. In this study, three of the most common TAC determination methods, namely cupric ion reducing antioxidant capacity (CUPRAC), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt/trolox equivalent antioxidant capacity (ABTS/TEAC), and ferric reducing antioxidant power (FRAP), were tested for the assay of phenolics in the presence of selected thiol and protein compounds. Although the FRAP method is almost non-responsive to thiol compounds individually, surprising overoxidations with large positive deviations from additivity were observed when using this method for (phenols + thiols) mixtures. Among the tested TAC methods, CUPRAC gave the most additive results for all studied (phenol + thiol) and (phenol + protein) mixtures with minimal relative error. As ABTS/TEAC and FRAP methods gave small and large deviations, respectively, from additivity of absorbances arising from these components in mixtures, mercury(II) compounds were added to stabilize the thiol components in the form of Hg(II)-thiol complexes so as to enable selective spectrophotometric determination of phenolic components. This error compensation was most efficient for the FRAP method in testing (thiols + phenols) mixtures.

Differential effects of ozone on photosynthesis of winter wheat among cultivars depend on antioxidative enzymes rather than stomatal conductance.

PubMed

Feng, Zhaozhong; Wang, Liang; Pleijel, Håkan; Zhu, Jianguo; Kobayashi, Kazuhiko

2016-12-01

Five modern cultivars of winter wheat (Triticum aestivum L.): Yangmai16 (Y16), Yangmai 15 (Y15), Yangfumai 2 (Y2), Yannong 19 (Y19) and Jiaxing 002 (J2) were investigated to determine the impacts of elevated ozone concentration (E-O 3 ) on photosynthesis-related parameters and the antioxidant system under fully open-air field conditions in China. The plants were exposed to E-O 3 at 1.5 times the ambient ozone concentration (A-O 3 ) from the initiation of tillering to final harvest. Pigments, gas exchange rates, chlorophyll a fluorescence, antioxidants contents, antioxidative enzyme activity and lipid oxidation were measured in three replicated plots throughout flag leaf development. Results showed that significant O 3 effects on most variables were only found during the mid-grain filling stage. Across five cultivars, E-O 3 significantly accelerated leaf senescence, as indicated by increased lipid oxidation as well as faster declines in pigment amounts and photosynthetic rates. The lower photosynthetic rates were mainly due to non-stomatal factors, e.g. lower maximum carboxylation capacity and electron transport rates. There were strong interactions between O 3 and cultivar in photosynthetic pigments, light-saturated photosynthesis rate and chlorophyll a fluorescence with O 3 -sensitive (Y19, Y2 and Y15) and O 3 -tolerant (J2, Y16) cultivars being clearly differentiated in their responses to E-O 3 . E-O 3 significantly influenced the antioxidative enzymes but not antioxidant contents. Significant interactions between O 3 and cultivar were found in antioxidative enzymes, such as SOD and CAT, but not in stomatal conductance (g s ). Therefore, it can be concluded that antioxidative enzymes rather than g s or antioxidants are responsible for the differential responses to E-O 3 among cultivars. These findings provide important information for the development of accurate modeling O 3 effects on crops, especially with respect to the developmental stage when O 3 damage to photosynthesis becomes manifest. Copyright © 2016 Elsevier B.V. All rights reserved.

Stress cross-response of the antioxidative system promoted by superimposed drought and cold conditions in Coffea spp.

PubMed Central

Rodrigues, Ana P.; Lidon, Fernando C.; Marques, Luís M. C.; Leitão, A. Eduardo; Fortunato, Ana S.; Pais, Isabel P.; Silva, Maria J.; Scotti-Campos, Paula; Lopes, António; Reboredo, F. H.; Ribeiro-Barros, Ana I.

2018-01-01

The understanding of acclimation strategies to low temperature and water availability is decisive to ensure coffee crop sustainability, since these environmental conditions determine the suitability of cultivation areas. In this context, the impacts of single and combined exposure to drought and cold were evaluated in three genotypes of the two major cropped species, Coffea arabica cv. Icatu, Coffea canephora cv. Apoatã, and the hybrid Obatã. Crucial traits of plant resilience to environmental stresses have been examined: photosynthesis, lipoperoxidation and the antioxidant response. Drought and/or cold promoted leaf dehydration, which was accompanied by stomatal and mesophyll limitations that impaired leaf C-assimilation in all genotypes. However, Icatu showed a lower impact upon stress exposure and a faster and complete photosynthetic recovery. Although lipoperoxidation was increased by drought (Icatu) and cold (all genotypes), it was greatly reduced by stress interaction, especially in Icatu. In fact, although the antioxidative system was reinforced under single drought and cold exposure (e.g., activity of enzymes as Cu,Zn-superoxide dismutase, ascorbate peroxidase, APX, glutathione reductase and catalase, CAT), the stronger increases were observed upon the simultaneous exposure to both stresses, which was accompanied with a transcriptional response of some genes, namely related to APX. Complementary, non-enzyme antioxidant molecules were promoted mostly by cold and the stress interaction, including α-tocopherol (in C. arabica plants), ascorbate (ASC), zeaxanthin, and phenolic compounds (all genotypes). In general, drought promoted antioxidant enzymes activity, whereas cold enhanced the synthesis of both enzyme and non-enzyme antioxidants, the latter likely related to a higher need of antioxidative capability when enzyme reactions were probably quite repressed by low temperature. Icatu showed the wider antioxidative capability, with the triggering of all studied antioxidative molecules by drought (except CAT), cold, and, particularly, stress interaction (except ASC), revealing a clear stress cross-tolerance. This justified the lower impacts on membrane lipoperoxidation and photosynthetic capacity under stress interaction conditions, related to a better ROS control. These findings are also relevant to coffee water management, showing that watering in the cold season should be largely avoided. PMID:29870563

Stress cross-response of the antioxidative system promoted by superimposed drought and cold conditions in Coffea spp.

PubMed

Ramalho, José C; Rodrigues, Ana P; Lidon, Fernando C; Marques, Luís M C; Leitão, A Eduardo; Fortunato, Ana S; Pais, Isabel P; Silva, Maria J; Scotti-Campos, Paula; Lopes, António; Reboredo, F H; Ribeiro-Barros, Ana I

2018-01-01

The understanding of acclimation strategies to low temperature and water availability is decisive to ensure coffee crop sustainability, since these environmental conditions determine the suitability of cultivation areas. In this context, the impacts of single and combined exposure to drought and cold were evaluated in three genotypes of the two major cropped species, Coffea arabica cv. Icatu, Coffea canephora cv. Apoatã, and the hybrid Obatã. Crucial traits of plant resilience to environmental stresses have been examined: photosynthesis, lipoperoxidation and the antioxidant response. Drought and/or cold promoted leaf dehydration, which was accompanied by stomatal and mesophyll limitations that impaired leaf C-assimilation in all genotypes. However, Icatu showed a lower impact upon stress exposure and a faster and complete photosynthetic recovery. Although lipoperoxidation was increased by drought (Icatu) and cold (all genotypes), it was greatly reduced by stress interaction, especially in Icatu. In fact, although the antioxidative system was reinforced under single drought and cold exposure (e.g., activity of enzymes as Cu,Zn-superoxide dismutase, ascorbate peroxidase, APX, glutathione reductase and catalase, CAT), the stronger increases were observed upon the simultaneous exposure to both stresses, which was accompanied with a transcriptional response of some genes, namely related to APX. Complementary, non-enzyme antioxidant molecules were promoted mostly by cold and the stress interaction, including α-tocopherol (in C. arabica plants), ascorbate (ASC), zeaxanthin, and phenolic compounds (all genotypes). In general, drought promoted antioxidant enzymes activity, whereas cold enhanced the synthesis of both enzyme and non-enzyme antioxidants, the latter likely related to a higher need of antioxidative capability when enzyme reactions were probably quite repressed by low temperature. Icatu showed the wider antioxidative capability, with the triggering of all studied antioxidative molecules by drought (except CAT), cold, and, particularly, stress interaction (except ASC), revealing a clear stress cross-tolerance. This justified the lower impacts on membrane lipoperoxidation and photosynthetic capacity under stress interaction conditions, related to a better ROS control. These findings are also relevant to coffee water management, showing that watering in the cold season should be largely avoided.

Muscle redox signalling pathways in exercise. Role of antioxidants.

PubMed

Mason, Shaun A; Morrison, Dale; McConell, Glenn K; Wadley, Glenn D

2016-09-01

Recent research highlights the importance of redox signalling pathway activation by contraction-induced reactive oxygen species (ROS) and nitric oxide (NO) in normal exercise-related cellular and molecular adaptations in skeletal muscle. In this review, we discuss some potentially important redox signalling pathways in skeletal muscle that are involved in acute and chronic responses to contraction and exercise. Specifically, we discuss redox signalling implicated in skeletal muscle contraction force, mitochondrial biogenesis and antioxidant enzyme induction, glucose uptake and muscle hypertrophy. Furthermore, we review evidence investigating the impact of major exogenous antioxidants on these acute and chronic responses to exercise. Redox signalling pathways involved in adaptive responses in skeletal muscle to exercise are not clearly elucidated at present, and further research is required to better define important signalling pathways involved. Evidence of beneficial or detrimental effects of specific antioxidant compounds on exercise adaptations in muscle is similarly limited, particularly in human subjects. Future research is required to not only investigate effects of specific antioxidant compounds on skeletal muscle exercise adaptations, but also to better establish mechanisms of action of specific antioxidants in vivo. Although we feel it remains somewhat premature to make clear recommendations in relation to application of specific antioxidant compounds in different exercise settings, a bulk of evidence suggests that N-acetylcysteine (NAC) is ergogenic through its effects on maintenance of muscle force production during sustained fatiguing events. Nevertheless, a current lack of evidence from studies using performance tests representative of athletic competition and a potential for adverse effects with high doses (>70mg/kg body mass) warrants caution in its use for performance enhancement. In addition, evidence implicates high dose vitamin C (1g/day) and E (≥260 IU/day) supplementation in impairments to some skeletal muscle cellular adaptations to chronic exercise training. Thus, determining the utility of antioxidant supplementation in athletes likely requires a consideration of training and competition periodization cycles of athletes in addition to type, dose and duration of antioxidant supplementation. Copyright © 2016 Elsevier Inc. All rights reserved.

Red Star Ruby (Sunrise) and blond qualities of Jaffa grapefruits and their influence on plasma lipid levels and plasma antioxidant activity in rats fed with cholesterol-containing and cholesterol-free diets.

PubMed

Gorinstein, Shela; Leontowicz, Hanna; Leontowicz, Maria; Drzewiecki, Jerzy; Jastrzebski, Zenon; Tapia, María S; Katrich, Elena; Trakhtenberg, Simon

2005-09-23

Bioactive compounds of peels and peeled red Star Ruby (Sunrise) and blond qualities of Jaffa grapefruits were analyzed and their antioxidant potential was assessed. The dietary fibers were determined according to Prosky et al., the total polyphenol content by Folin-Ciocalteu method and measured at 765 nm, minerals and trace elements by atomic absorption spectrometer, phenolic and ascorbic acids by HPLC and the antioxidant potential by two different antioxidant assays (DPPH and beta-carotene linoleate model system). It was found that the contents of most studied bioactive compounds in both qualities are comparable. Only the contents of total polyphenols and flavonoids were higher in red grapefruits, but not significant. The antioxidant potentials of red peeled grapefruits and their peels were significantly higher than of blond peeled grapefruits and their peels (P<0.05 in both cases). Diets supplemented with peeled red and blond qualities of Jaffa grapefruits and their peels have increased the plasma antioxidant capacity and improved plasma lipid levels, especially in rats fed with cholesterol added diet. In conclusion, both qualities of Jaffa grapefruits contain high quantities of bioactive compounds, but the antioxidant potential of red grapefruits is significantly higher. Diets supplemented with both qualities of Jaffa grapefruits improve the plasma lipid levels and increase the plasma antioxidant activity, especially in rats fed with cholesterol added diets. Jaffa grapefruits, especially their red Star Ruby quality, could be a valuable supplementation for diseases-preventing diets.

Nrf2/p62 signaling in apoptosis resistance and its role in cadmium-induced carcinogenesis.

PubMed

Son, Young-Ok; Pratheeshkumar, Poyil; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei; Zhang, Zhuo; Shi, Xianglin

2014-10-10

The cadmium-transformed human lung bronchial epithelial BEAS-2B cells exhibit a property of apoptosis resistance as compared with normal non-transformed BEAS-2B cells. The level of basal reactive oxygen species (ROS) is extremely low in transformed cells in correlation with elevated expressions of both antioxidant enzymes (catalase, SOD1, and SOD2) and antiapoptotic proteins (Bcl-2/Bcl-xL). Moreover, Nrf2 and p62 are highly expressed in these transformed cells. The knockdown of Nrf2 or p62 by siRNA enhances ROS levels and cadmium-induced apoptosis. The binding activities of Nrf2 on the antioxidant response element promoter regions of p62/Bcl-2/Bcl-xL were dramatically increased in the cadmium-exposed transformed cells. Cadmium exposure increased the formation of LC3-II and the frequency of GFP-LC3 punctal cells in non-transformed BEAS-2B cells, whereas these increases are not shown in transformed cells, an indication of autophagy deficiency of transformed cells. Furthermore, the expression levels of Nrf2 and p62 are dramatically increased during chronic long term exposure to cadmium in the BEAS-2B cells as well as antiapoptotic proteins and antioxidant enzymes. These proteins are overexpressed in the tumor tissues derived from xenograft mouse models. Moreover, the colony growth is significantly attenuated in the transformed cells by siRNA transfection specific for Nrf2 or p62. Taken together, this study demonstrates that cadmium-transformed cells have acquired autophagy deficiency, leading to constitutive p62 and Nrf2 overexpression. These overexpressions up-regulate the antioxidant proteins catalase and SOD and the antiapoptotic proteins Bcl-2 and Bcl-xL. The final consequences are decrease in ROS generation, apoptotic resistance, and increased cell survival, proliferation, and tumorigenesis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Nrf2/p62 Signaling in Apoptosis Resistance and Its Role in Cadmium-induced Carcinogenesis*

PubMed Central

Son, Young-Ok; Pratheeshkumar, Poyil; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei; Zhang, Zhuo; Shi, Xianglin

2014-01-01

The cadmium-transformed human lung bronchial epithelial BEAS-2B cells exhibit a property of apoptosis resistance as compared with normal non-transformed BEAS-2B cells. The level of basal reactive oxygen species (ROS) is extremely low in transformed cells in correlation with elevated expressions of both antioxidant enzymes (catalase, SOD1, and SOD2) and antiapoptotic proteins (Bcl-2/Bcl-xL). Moreover, Nrf2 and p62 are highly expressed in these transformed cells. The knockdown of Nrf2 or p62 by siRNA enhances ROS levels and cadmium-induced apoptosis. The binding activities of Nrf2 on the antioxidant response element promoter regions of p62/Bcl-2/Bcl-xL were dramatically increased in the cadmium-exposed transformed cells. Cadmium exposure increased the formation of LC3-II and the frequency of GFP-LC3 punctal cells in non-transformed BEAS-2B cells, whereas these increases are not shown in transformed cells, an indication of autophagy deficiency of transformed cells. Furthermore, the expression levels of Nrf2 and p62 are dramatically increased during chronic long term exposure to cadmium in the BEAS-2B cells as well as antiapoptotic proteins and antioxidant enzymes. These proteins are overexpressed in the tumor tissues derived from xenograft mouse models. Moreover, the colony growth is significantly attenuated in the transformed cells by siRNA transfection specific for Nrf2 or p62. Taken together, this study demonstrates that cadmium-transformed cells have acquired autophagy deficiency, leading to constitutive p62 and Nrf2 overexpression. These overexpressions up-regulate the antioxidant proteins catalase and SOD and the antiapoptotic proteins Bcl-2 and Bcl-xL. The final consequences are decrease in ROS generation, apoptotic resistance, and increased cell survival, proliferation, and tumorigenesis. PMID:25157103

Melatonin successfully rescues hippocampal bioenergetics and improves cognitive function following drug intoxication by promoting Nrf2-ARE signaling activity.

PubMed

Chen, Li-You; Renn, Ting-Yi; Liao, Wen-Chieh; Mai, Fu-Der; Ho, Ying-Jui; Hsiao, George; Lee, Ai-Wei; Chang, Hung-Ming

2017-09-01

Prolonged exposure to gamma-hydroxybutyric acid (GHB) would cause drug intoxication in which impaired cognitive function results from enhanced hippocampal oxidative stress may serve as a major symptom in this deficiency. Considering melatonin possesses significant anti-oxidative efficacy, this study aimed to determine whether melatonin would successfully promote the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling, depress oxidative stress, and rescue hippocampal bioenergetics and cognitive function following drug intoxication injury. Adolescent rats subjected to 10 days of GHB were received melatonin at doses of either 10 or 100 mg/kg. Time-of-flight secondary ion mass spectrometry, biochemical assay, quantitative histochemistry, [ 14 C]-2-deoxyglucose analysis, together with Morris water maze were employed to detect the molecular signaling, oxidative status, bioenergetic level, as well as the cognitive performances, respectively. Results indicated that in GHB-intoxicated rats, enhanced oxidative stress, increased cholesterol level, and decreased anti-oxidative enzymes activities were detected in hippocampal regions. Intense oxidative stress paralleled well with reduced bioenergetics and poor performance in behavioral testing. However, in rats treated with melatonin following GHB intoxication, all above parameters and cognitive function were gradually returned to nearly normal levels. Melatonin also remarkably promoted the translocation of Nrf2 from cytoplasm to nucleus in a dose-dependent manner, thereby increased the Nrf2-ARE signaling-related downstream anti-oxidative enzymes activities. As melatonin effectively rescues hippocampal bioenergetics through depressing the oxidative stress by promoting Nrf2-ARE molecular machinery, this study thus highlights for the first time that clinical use of melatonin may serve as a therapeutic strategy to improve the cognitive function in unsuspecting victims suffered from GHB intoxication injury. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

6-shogaol-rich extract from ginger up-regulates the antioxidant defense systems in cells and mice.

PubMed

Bak, Min-Ji; Ok, Seon; Jun, Mira; Jeong, Woo-Sik

2012-07-04

The rhizome of ginger (Zingiber officinale Roscoe) is known to have several bioactive compounds including gingerols and shogaols which possess beneficial health properties such as anti-inflammatory and chemopreventive effects. Based on recent observations that 6-shogaol may have more potent bioactivity than 6-gingerol, we obtained a 6-shogaol-rich extract from ginger and examined its effects on the nuclear factor E2-related factor2 (Nrf2)/antioxidant response element (ARE) pathway in vitro and in vivo. 6-Shogaol-rich extract was produced by extracting ginger powder with 95% ethanol at 80 °C after drying at 80 °C (GEE8080). GEE8080 contained over 6-fold more 6-shogaol compared to the room temperature extract (GEE80RT). In HepG2 cells, GEE8080 displayed much stronger inductions of ARE-reporter gene activity and Nrf2 expression than GEE80RT. GEE8080 stimulated phosphorylations of mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. Moreover, the GEE8080-induced expressions of Nrf2 and HO-1 were attenuated by treatments of SB202190 (a p38 specific inhibitor) and LY294002 (an Akt specific inhibitor). In a mouse model, the GEE8080 decreased the diethylnitrosamine (DEN)-mediated elevations of serum aspartate transaminase and alanine transaminase as well as the DEN-induced hepatic lipid peroxidation. Inductions of Nrf2 and HO-1 by GEE8080 were also confirmed in the mice. In addition, the administration of GEE8080 to the mice also restored the DEN-reduced activity and protein expression of hepatic antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase. In conclusion, GEE8080, a 6-shogaol-rich ginger extract, may enhance antioxidant defense mechanism through the induction of Nrf2 and HO-1 regulated by p38 MAPK and PI3k/Akt pathway in vitro and in vivo.

Effect of diesel exhaust inhalation on antioxidant and oxidative stress responses in adults with metabolic syndrome

PubMed Central

Allen, Jason; Trenga, Carol A.; Peretz, Alon; Sullivan, Jeffrey H.; Carlsten, Christopher C.; Kaufman, Joel D.

2011-01-01

Background Traffic-related air pollution is associated with cardiovascular morbidity and mortality. Although the biological mechanisms are not well understood, oxidative stress may be a primary pathway. Subpopulations, such as individuals with metabolic syndrome (MeS), may be at increased risk of adverse effects associated with air pollution. Our aim was to assess the relationship between exposure to diesel exhaust (DE) and indicators of systemic antioxidant and oxidative responses in adults with MeS. We hypothesized that DE exposure would result in greater oxidative stress and antioxidant responses compared with filtered air (FA). Methods Ten adult subjects with MeS were exposed on separate days for two hours to FA or DE (at 200μg/m3), in a double blind, crossover experiment. Urinary 8-isoPGF2α (F2-isoprostanes), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were assessed as markers of oxidative stress at 3 hrs and 22 hrs, respectively, after exposure initiation. To assess the short-term antioxidant response we analyzed plasma ascorbic acid (AA) 90 minutes after exposure initiation. All outcomes were compared to pre-exposure levels, and mean changes were compared between FA and DE exposures. Results Mean changes in urinary F2-isoprostanes (ng/mg creatinine), (-0.05 [95% CI = −0.29, 0.15]), and 8-OHdG (μg/g creatinine) (-0.09 [-0.13, 0.31]), were not statistically significant. Mean changes in plasma AA (mg/dl) were also not significant (-0.02 [-0.78, 0.04]). Conclusions In this carefully controlled experiment, we did not detect significant changes in oxidative stress or systemic antioxidant responses in subjects with MeS exposed to 200μg/m3 DE. PMID:19852547

The effect of acute pre-exercise dark chocolate consumption on plasma antioxidant status, oxidative stress and immunoendocrine responses to prolonged exercise.

PubMed

Davison, Glen; Callister, Robin; Williamson, Gary; Cooper, Karen A; Gleeson, Michael

2012-02-01

Acute antioxidant supplementation may modulate oxidative stress and some immune perturbations that typically occur following prolonged exercise. The aims of the present study were to examine the effects of acutely consuming dark chocolate (high polyphenol content) on plasma antioxidant capacity, markers of oxidative stress and immunoendocrine responses to prolonged exercise. Fourteen healthy men cycled for 2.5 h at ~60% maximal oxygen uptake 2 h after consuming 100 g dark chocolate (DC), an isomacronutrient control bar (CC) or neither (BL) in a randomised-counterbalanced design. DC enhanced pre-exercise antioxidant status (P = 0.003) and reduced by trend (P = 0.088) 1 h post-exercise plasma free [F₂-isoprostane] compared with CC (also, [F₂-isoprostane] increased post-exercise in CC and BL but not DC trials). Plasma insulin concentration was significantly higher pre-exercise (P = 0.012) and 1 h post-exercise (P = 0.026) in the DC compared with the CC trial. There was a better maintenance of plasma glucose concentration on the DC trial (2-way ANOVA trial × time interaction P = 0.001), which decreased post-exercise in all trials but was significantly higher 1 h post-exercise (P = 0.039) in the DC trial. There were no between trial differences in the temporal responses (trial × time interactions all P > 0.05) of hypothalamic-pituitary-adrenal axis stress hormones, plasma interleukin-6, the magnitude of leukocytosis and neutrophilia and changes in neutrophil function. Acute DC consumption may affect insulin, glucose, antioxidant status and oxidative stress responses, but has minimal effects on immunoendocrine responses, to prolonged exercise.

Responses of the rotifer Brachionus plicatilis to flame retardant (BDE-47) stress.

PubMed

Jian, Xiaoyang; Tang, Xuexi; Xu, Ningning; Sha, Jingjing; Wang, You

2017-03-15

A series of short-term toxicological tests were conducted on the rotifer Brachionus plicatilis to assess the toxicity of the flame retardant 2,2',4,4'-tetrabrominated biphenyl ether (BDE-47). BDE-47 increased mortality, morphological damage, and altered population dynamics and fecundity of rotifer. Antioxidant enzymes were differentially changed to maintain the balance between antioxidant and pro-oxidant activity. However, with increases in the concentration of BDE-47, the metabolic and antioxidant activity decreased. Moreover, the reactive oxygen species (ROS) and malondialdehyde contents increased and the ratio between glutathione and glutathione-SH decreased, indicating oxidative stress. The addition of the ROS-inhibitor N-acetylcysteine alleviated the degree of damage and stimulated the activity of xenobiotic-metabolizing and antioxidant system, which suggested that ROS were the most important loop in the stress response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimization of ultrasonic-assisted extraction of antioxidant compounds from Guava (Psidium guajava L.) leaves using response surface methodology

PubMed Central

Kong, Fansheng; Yu, Shujuan; Feng, Zeng; Wu, Xinlan

2015-01-01

Objective: To optimization of extraction of antioxidant compounds from guava (Psidium guajava L.) leaves and showed that the guava leaves are the potential source of antioxidant compounds. Materials and Methods: The bioactive polysaccharide compounds of guava leaves (P. guajava L.) were obtained using ultrasonic-assisted extraction. Extraction was carried out according to Box-Behnken central composite design, and independent variables were temperature (20–60°C), time (20–40 min) and power (200–350 W). The extraction process was optimized by using response surface methodology for the highest crude extraction yield of bioactive polysaccharide compounds. Results: The optimal conditions were identified as 55°C, 30 min, and 240 W. 1,1-diphenyl-2-picryl-hydrazyl and hydroxyl free radical scavenging were conducted. Conclusion: The results of quantification showed that the guava leaves are the potential source of antioxidant compounds. PMID:26246720

Optimization of ultrasonic-assisted extraction of antioxidant compounds from Guava (Psidium guajava L.) leaves using response surface methodology.

PubMed

Kong, Fansheng; Yu, Shujuan; Feng, Zeng; Wu, Xinlan

2015-01-01

To optimization of extraction of antioxidant compounds from guava (Psidium guajava L.) leaves and showed that the guava leaves are the potential source of antioxidant compounds. The bioactive polysaccharide compounds of guava leaves (P. guajava L.) were obtained using ultrasonic-assisted extraction. Extraction was carried out according to Box-Behnken central composite design, and independent variables were temperature (20-60°C), time (20-40 min) and power (200-350 W). The extraction process was optimized by using response surface methodology for the highest crude extraction yield of bioactive polysaccharide compounds. The optimal conditions were identified as 55°C, 30 min, and 240 W. 1,1-diphenyl-2-picryl-hydrazyl and hydroxyl free radical scavenging were conducted. The results of quantification showed that the guava leaves are the potential source of antioxidant compounds.

Combined Effects of Lanthanum (III) and Acid Rain on Antioxidant Enzyme System in Soybean Roots.

PubMed

Zhang, Xuanbo; Du, Yuping; Wang, Lihong; Zhou, Qing; Huang, Xiaohua; Sun, Zhaoguo

2015-01-01

Rare earth element pollution (REEs) and acid rain (AR) pollution simultaneously occur in many regions, which resulted in a new environmental issue, the combined pollution of REEs and AR. The effects of the combined pollution on the antioxidant enzyme system of plant roots have not been reported. Here, the combined effects of lanthanum ion (La3+), one type of REE, and AR on the antioxidant enzyme system of soybean roots were investigated. In the combined treatment of La3+ (0.08 mM) and AR, the cell membrane permeability and the peroxidation of cell membrane lipid of soybean roots increased, and the superoxide dismutase, catalase, peroxidase and reduced ascorbic acid served as scavengers of reactive oxygen species. In other combined treatments of La3+ (0.40 mM, 1.20 mM) and AR, the membrane permeability, malonyldialdehyde content, superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content increased, while the catalase activity decreased. The increased superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content were inadequate to scavenge the excess hydrogen peroxide and superoxide, leading to the damage of the cell membrane, which was aggravated with the increase in the concentration of La3+ and the level of AR. The deleterious effects of the combined treatment of La3+ and AR were stronger than those of the single treatment of La3+ or AR. Moreover, the activity of antioxidant enzyme system in the combined treatment group was affected directly and indirectly by mineral element content in soybean plants.

Quorum Quenching and Microbial Control through Phenolic Extract of Eugenia Uniflora Fruits.

PubMed

Rodrigues, Adeline Conceição; Zola, Flávia Guimarães; Ávila Oliveira, Brígida D'; Sacramento, Nayara Thais Barbosa; da Silva, Elis Regina; Bertoldi, Michele Corrêa; Taylor, Jason Guy; Pinto, Uelinton Manoel

2016-10-01

We describe the characterization of the centesimal composition, mineral and phenolic content of Eugenia uniflora fruit and the determination of the antioxidant, antimicrobial and quorum quenching activities of the pulp phenolic extract. Centesimal composition was determined according to standard methods; trace elements were measured by total reflection X-ray fluorescence spectroscopy. The phenolic compounds were extracted by solid-phase chromatography and quantified by spectrophotometry. Antioxidant activity was determined by using 3 different methods. Antimicrobial activity was evaluated against a panel of foodborne microorganisms and antiquorum sensing activity in Chromobacterium violaceum was performed by measuring inhibition of quorum sensing dependent violacein production. The centesimal composition (per 100 g of pulp) was as follows: protein 3.68 ± 0.21 g, lipids 0.02 ± 0.03 g, carbohydrates 10.31 g and fiber 2.06 g. Trace elements (mg/g of pulp) were determined as: K 0.90, Ca 3.36, Fe 0.60, Zn 0.17, Cl 0.56, Cr 0.06, Ni 0.04, and Cu 0.07. The pulp is a source of phenolic compounds and presents antioxidant activity similar to other berries. The fruit phenolic extract inhibited all tested bacteria. We also found that the fruit phenolic extract at low subinhibitory concentrations inhibited up to 96% of violacein production in C. violaceum, likely due to the fruit's phenolic content. This study shows the contribution of E. uniflora phenolic compounds to the antioxidant, antimicrobial and the newly discovered quorum quenching activity, all of which could be used by the food and pharmaceutical industries to develop new functional products. © 2016 Institute of Food Technologists®.

Combined Effects of Lanthanum (III) and Acid Rain on Antioxidant Enzyme System in Soybean Roots

PubMed Central

Zhang, Xuanbo; Du, Yuping; Wang, Lihong; Zhou, Qing; Huang, Xiaohua; Sun, Zhaoguo

2015-01-01

Rare earth element pollution (REEs) and acid rain (AR) pollution simultaneously occur in many regions, which resulted in a new environmental issue, the combined pollution of REEs and AR. The effects of the combined pollution on the antioxidant enzyme system of plant roots have not been reported. Here, the combined effects of lanthanum ion (La3+), one type of REE, and AR on the antioxidant enzyme system of soybean roots were investigated. In the combined treatment of La3+ (0.08 mM) and AR, the cell membrane permeability and the peroxidation of cell membrane lipid of soybean roots increased, and the superoxide dismutase, catalase, peroxidase and reduced ascorbic acid served as scavengers of reactive oxygen species. In other combined treatments of La3+ (0.40 mM, 1.20 mM) and AR, the membrane permeability, malonyldialdehyde content, superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content increased, while the catalase activity decreased. The increased superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content were inadequate to scavenge the excess hydrogen peroxide and superoxide, leading to the damage of the cell membrane, which was aggravated with the increase in the concentration of La3+ and the level of AR. The deleterious effects of the combined treatment of La3+ and AR were stronger than those of the single treatment of La3+ or AR. Moreover, the activity of antioxidant enzyme system in the combined treatment group was affected directly and indirectly by mineral element content in soybean plants. PMID:26230263

Regulation of Manganese Antioxidants by Nutrient Sensing Pathways in Saccharomyces cerevisiae

PubMed Central

Reddi, Amit R.; Culotta, Valeria C.

2011-01-01

In aerobic organisms, protection from oxidative damage involves the combined action of enzymatic and nonproteinaceous cellular factors that collectively remove harmful reactive oxygen species. One class of nonproteinaceous antioxidants includes small molecule complexes of manganese (Mn) that can scavenge superoxide anion radicals and provide a backup for superoxide dismutase enzymes. Such Mn antioxidants have been identified in diverse organisms; however, nothing regarding their physiology in the context of cellular adaptation to stress was known. Using a molecular genetic approach in Bakers’ yeast, Saccharomyces cerevisiae, we report that the Mn antioxidants can fall under control of the same pathways used for nutrient sensing and stress responses. Specifically, a serine/threonine PAS-kinase, Rim15p, that is known to integrate phosphate, nitrogen, and carbon sensing, can also control Mn antioxidant activity in yeast. Rim15p is negatively regulated by the phosphate-sensing kinase complex Pho80p/Pho85p and by the nitrogen-sensing Akt/S6 kinase homolog, Sch9p. We observed that loss of either of these upstream kinase sensors dramatically inhibited the potency of Mn as an antioxidant. Downstream of Rim15p are transcription factors Gis1p and the redundant Msn2/Msn4p pair that typically respond to nutrient and stress signals. Both transcription factors were found to modulate the potency of the Mn antioxidant but in opposing fashions: loss of Gis1p was seen to enhance Mn antioxidant activity whereas loss of Msn2/4p greatly suppressed it. Our observed roles for nutrient and stress response kinases and transcription factors in regulating the Mn antioxidant underscore its physiological importance in aerobic fitness. PMID:21926297

The radical induced cell death protein 1 (RCD1) supports transcriptional activation of genes for chloroplast antioxidant enzymes

PubMed Central

Hiltscher, Heiko; Rudnik, Radoslaw; Shaikhali, Jehad; Heiber, Isabelle; Mellenthin, Marina; Meirelles Duarte, Iuri; Schuster, Günter; Kahmann, Uwe; Baier, Margarete

2014-01-01

The rimb1 (redox imbalanced 1) mutation was mapped to the RCD1 locus (radical-induced cell death 1; At1g32230) demonstrating that a major factor involved in redox-regulation genes for chloroplast antioxidant enzymes and protection against photooxidative stress, RIMB1, is identical to the regulator of disease response reactions and cell death, RCD1. Discovering this link let to our investigation of its regulatory mechanism. We show in yeast that RCD1 can physically interact with the transcription factor Rap2.4a which provides redox-sensitivity to nuclear expression of genes for chloroplast antioxidant enzymes. In the rimb1 (rcd1-6) mutant, a single nucleotide exchange results in a truncated RCD1 protein lacking the transcription factor binding site. Protein-protein interaction between full-length RCD1 and Rap2.4a is supported by H2O2, but not sensitive to the antioxidants dithiotreitol and ascorbate. In combination with transcript abundance analysis in Arabidopsis, it is concluded that RCD1 stabilizes the Rap2.4-dependent redox-regulation of the genes encoding chloroplast antioxidant enzymes in a widely redox-independent manner. Over the years, rcd1-mutant alleles have been described to develop symptoms like chlorosis, lesions along the leaf rims and in the mesophyll and (secondary) induction of extra- and intra-plastidic antioxidant defense mechanisms. All these rcd1 mutant characteristics were observed in rcd1-6 to succeed low activation of the chloroplast antioxidant system and glutathione biosynthesis. We conclude that RCD1 protects plant cells from running into reactive oxygen species (ROS)-triggered programs, such as cell death and activation of pathogen-responsive genes (PR genes) and extra-plastidic antioxidant enzymes, by supporting the induction of the chloroplast antioxidant system. PMID:25295044

Antimicrobial and antioxidant properties of the flavonoid extract from Raphanus sativus L.

NASA Astrophysics Data System (ADS)

Ngoc, Pham Thi Kim; Nguyet, Nguyen Thi Minh; Dao, Dong Thi Anh

2017-09-01

This study was conducted to evaluate the in vitro antimicrobial and antioxidant activities of flavonoid extract from white radish roots (Raphanus sativus L.). Antimicrobial activity was determined by agar diffusion method against 4 strains: Bacillus cereus, Staphylococus aureus, Pseudomonas aeruginosa and Salmonella typhi. Antioxidant activity was determined by ABTS* radical scavenging activity and total antioxidant capacity (TAC). The constituent elements of flavonoid extract were identified by LC-MS. Results showed that the flavonoid extract from Raphanus sativus L. had antibacterial activity against to all four tested bacteria strains with antibacterial ring diameters in the range 8 - 20 mm in the test concentrations from 100 to 1600 mg/ml. Minimum concentration to inhibit (MIC) in the range 20 - 40 mg/ml. In addition, the extract also has the ability to eliminate ABTS* free radical with IC50 = 7.074 µg/ml. The total antioxidant capacity of extract at concentration of 100 µg/ml was 3.424 ± 0.043 mg ascorbic acid/mg. In the extract, there are three flavonoids were found: rutin, quercetin and narigenin. This is the first time narigenin was found in Raphanus sativus L. extract.

In vitro antioxidant and antihemolytic effects of the essential oil and methanolic extract of Allium rotundum L.

PubMed

Assadpour, S; Nabavi, S M; Nabavi, S F; Dehpour, A A; Ebrahimzadeh, M A

2016-12-01

A plethora of scientific evidence showed that several plant species from the genus Allium (Alliaceae) possess multiple therapeutic effects. Present paper aimed to examine the antioxidant and antihemolytic activities of the essential oil and methanol extract Allium rotundum L. through different in vitro assays. 1,1-diphenyl-2-picryl hydroxyl radical (DPPH), nitric oxide as well as hydrogen peroxide scavenging, Fe2+ chelating, reducing power and also hemoglobin-induced linoleic acid peroxidation assay systems have been utilized to examine antioxidant effects of these samples. Total amounts of phenolic and flavonoid contents were calculated. The antihemolytic effect was investigated against hemolysis induced by hydrogen peroxide in rat erythrocytes. Also, mineral contents of plant were evaluated by atomic absorption spectroscopy. IC50 for DPPH radical-scavenging activity were 284 ± 11.64 for methanol extract and 1264 ± 45.60 µg ml-1 for essential oil, respectively. The extract has shown better reducing effects versus essential oil. The extract also demonstrated better activity in nitric oxide-scavenging activity. IC50 were 464 ± 19.68 for extract and 1093 ± 38.25 µg ml-1 for essential oil. The extract shows better activity than essential oil in Fe2+ chelating system. IC50 were 100 ± 3.75 for extract and 1223 ± 36.25 µg ml-1 for essential oil. The A. rotundum extract and essential oil showed significant H2O2 scavenging effects at dose-dependent manners. IC50 was 786 ± 29.08 mg ml-1 for essential oil. The amounts of eight elements were determined. The concentrations of elements were in the order: Mn> Fe> Zn> Cu> Ni> Cd. The extract showed a higher antioxidant effect in all tested models including DPPH, nitric oxide, reducing power as well as iron chelating and antihemolytic activities than essential oil. The latter showed more potent antioxidant activity in scavenging H2O2 and lipid peroxidation model. Antioxidant activities of extract may be attributed at least in part, due to its phenolic and flavonoid contents.

The antioxidant activity of allylpyrocatechol is mediated via decreased generation of free radicals along with escalation of antioxidant mechanisms.

PubMed

Sarkar, Debjani; Kundu, Sunanda; De, Soumita; Hariharan, Chellaram; Saha, Piu; Manna, Alak; Chattopadhyay, Subrata; Chatterjee, Mitali

2013-03-01

Allylpyrocatechol (APC) is responsible for the antiinflammatory activity exhibited by the methanolic extract of leaves of Piper betle. As antiinflammatory compounds may display antioxidant properties and vice versa, we investigated the antioxidant effect of APC. APC effectively reduced phorbol-myristate-acetate-induced generation of reactive oxygen species and superoxide in murine peritoneal macrophages as well as inhibited Escherichia-coli-induced phagocytic activity of macrophages. Furthermore, pBluescript SK(+) plasmid DNA damage induced by addition of sodium ascorbate was attenuated by APC as it inhibited transformation of the supercoiled form to a relaxed form. In addition, APC increased the enzymatic (catalase) and nonenzymatic (GSH) antioxidant components of murine macrophages. Taken together, APC exhibited an antioxidant activity which was mediated both via decreased generation of free radicals along with increase in cellular antioxidants. Copyright © 2012 John Wiley & Sons, Ltd.

Blood antioxidant and oxidative stress biomarkers acute responses to a 1000-m kayak sprint in elite male kayakers.

PubMed

Teixeira, V H; Valente, H F; Casal, S I; Marques, F P; Moreira, P A

2013-02-01

This study aimed to investigate the response of blood antioxidants and biomarkers of lipid peroxidation, muscle damage and inflammation to a 1000m kayak trial in elite male kayakers. Enzymatic (superoxide dismutase [SOD], glutathione reductase [Gr] and glutathione peroxidase [GPx] activities) and non-enzymatic (total antioxidant status [TAS], uric acid, α-tocopherol, α-carotene, β-carotene, lycopene and lutein and zeaxanthin) antioxidants, thiobarbituric acid reactive substances (TBARS), creatine kinase (CK), interleukin-6 (IL-6) and cortisol were determined in 15 elite male kayakers before and 15 min after a 1000-m kayak simulated race. Both enzymatic and non-enzymatic antioxidants were unaffected by exercise, with the exception of α-carotene which decreased (P=0.013). Uric acid levels were incremented following exercise (P=0.016). The acute exercise resulted in a significant decrease in TAS (P=0.001) and in an increase in CK (P=0.023), TBARS (P<0.001) and IL-6 (P=0.028). Our study suggests that a 1000-m kayak simulated race induces oxidative stress and damage in highly-trained kayakers.

Serum biomarkers of oxidative stress in dogs with idiopathic inflammatory bowel disease.

PubMed

Rubio, C P; Martínez-Subiela, S; Hernández-Ruiz, J; Tvarijonaviciute, A; Cerón, J J; Allenspach, K

2017-03-01

The objective of this work was to study and compare a panel of various serum biomarkers evaluating both the antioxidant response and oxidative damage in dogs with idiopathic inflammatory bowel disease (IBD). Eighteen dogs with IBD and 20 healthy dogs were enrolled in the study. Trolox equivalent antioxidant capacity (TEAC), cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of the plasma (FRAP), total thiol concentrations, and paraoxonase 1 (PON1) activity were evaluated in serum to determine antioxidant response. To evaluate oxidative status, ferrous oxidation-xylenol orange (FOX), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species production (ROS) concentrations in serum were determined. Mean concentrations of all antioxidant biomarkers analyzed, with exception of FRAP, were significantly lower (P < 0.0001) in the sera of dogs with IBD than in healthy dogs. The oxidant markers studied were significantly higher (P < 0.0001) in sera of dogs with IBD than in healthy dogs. These findings support the hypothesis that oxidative stress could play an important role in the pathogenesis of canine IBD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidative Stress and Antioxidant System in Periodontitis

PubMed Central

Wang, Yue; Andrukhov, Oleh; Rausch-Fan, Xiaohui

2017-01-01

Periodontitis is a common inflammatory disease, which is initiated by bacterial infection and subsequently progressed by aberrant host response. It can result in the destruction of teeth supporting tissues and have an influence on systemic health. When periodontitis occurs, reactive oxygen species, which are overproduced mostly by hyperactive neutrophils, could not be balanced by antioxidant defense system and cause tissues damage. This is characterized by increased metabolites of lipid peroxidation, DNA damage and protein damage. Local and systemic activities of antioxidants can also be influenced by periodontitis. Total antioxidant capacity, total oxidant status and oxidative stress index have been used to evaluate the oxidative stress associated with periodontitis. Studies have confirmed that inflammatory response in periodontitis is associated with an increased local and systemic oxidative stress and compromised antioxidant capacity. Our review focuses on increased oxidative stress in periodontal disease, specifically, on the relationship between the local and systemic biomarkers of oxidative stress and periodontitis and their association with the pathogenesis of periodontitis. Also, the relationship between periodontitis and systemic inflammation, and the effects of periodontal therapy on oxidative stress parameters will be discussed. PMID:29180965

Comparative study of spasmolytic properties, antioxidant activity and phenolic content of Arbutus unedo from Montenegro and Greece.

PubMed

Pavlović, Dragana R; Branković, Suzana; Kovačević, Nada; Kitić, Dušanka; Veljković, Slavimir

2011-05-01

Arbutus unedo leaf is used traditionally for gastrointestinal complaints. Ethanol extracts from Arbutus unedo collected in both Montenegro (AuM) and Greece (AuG) were found to decrease the ileal basal tonus, with AuG producing a significantly higher (p < 0.05) reduction in contractile response to acetylcholine. AuM and AuG relaxed 80 mM K(+) induced contractions and shifted the Ca(++) concentration-response curves to the right, similar to that caused by verapamil, suggesting that the spasmolytic effect was induced through calcium channel inhibition. The antioxidant activity of AuM and AuG and the phenolic content of the extracts and dry plant material were studied, and both extracts were found to possess considerable antioxidant properties. AuG showed a stronger in vitro antioxidative activity in the DPPH assay and in the TBA test. Polyphenol, tannin and flavonoid levels were higher in AuG, supporting the more potent spasmolytic and antioxidative effects, whereas the arbutin content was higher in dry plant material collected in Montenegro. Copyright © 2011 John Wiley & Sons, Ltd.

Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases.

PubMed

Zhang, Yu-Jie; Gan, Ren-You; Li, Sha; Zhou, Yue; Li, An-Na; Xu, Dong-Ping; Li, Hua-Bin

2015-11-27

Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.

Extraction, characterization and antioxidant activities of Se-enriched tea polysaccharides.

PubMed

Wang, Yuanfeng; Li, Yongfu; Liu, Yangyang; Chen, Xueqing; Wei, Xinlin

2015-01-01

Se-polysaccharides from Se-enriched tea leaves were purified by DEAE-sepharose fast flow gel column (2.5×60cm) and three polysaccharide fractions (Se-TPS1, Se-TPS2, and Se-TPS3) were isolated and purified with yields of 6.5, 37.14, and 8.57%, respectively. The average sizes of Se-TPS1 and Se-TPS2 were determined by HPGPC system, with molecular weights of 1.1×10(5) and 2.4×10(5)Da, respectively. Se-TPS3 was a polysaccharide polymer with two peaks with molecular weights of 9.2×10(5) and 2.5×10(5)Da. Monosaccharide components analysis by ion chromatography revealed Se-polysaccharides were acidic polysaccharoses and different from each other in monosaccharide kinds and molar ratio. Elements of Se, C, H, N, S, and 14 kinds of mineral elements were analyzed by AFS, EA, and ICP-AES, respectively. Spectral analysis (IR and UV) indicated Se-polysaccharides were typical glycoproteins. Morphological analyses of the samples were determined by SEM and AFM. In addition, the DPPH and superoxide radicals scavenging activities were also discussed to assess antioxidant activities of the samples, and Se-polysaccharides showed higher antioxidant activities compared to the ordinary polysaccharides. Copyright © 2015 Elsevier B.V. All rights reserved.

Selenium, zinc, copper, Cu/Zn ratio and total antioxidant status in the serum of vitiligo patients treated by narrow-band ultraviolet-B phototherapy.

PubMed

Wacewicz, Marta; Socha, Katarzyna; Soroczyńska, Jolanta; Niczyporuk, Marek; Aleksiejczuk, Piotr; Ostrowska, Jolanta; Borawska, Maria H

2018-03-01

Vitiligo is a chronic, depigmenting skin disorder, whose pathogenesis is still unknown. Narrow band ultraviolet-B (NB-UVB) is now one of the most widely used treatment of vitiligo. It was suggested that trace elements may play a role in pathogenesis of vitiligo. The aim of this study was to estimate the concentration of selenium (Se), zinc (Zn), copper (Cu) and Cu/Zn ratio as well as total antioxidant status (TAS) in the serum of patients with vitiligo. We assessed 50 patients with vitiligo and 58 healthy controls. Serum levels of Se, Zn and Cu were determined by the atomic absorption spectrometry method, and the Cu/Zn ratio was also calculated. TAS in serum was measured spectrophotometrically. Serum concentration of Se in patients with vitiligo before and after phototherapy was significantly lower as compared to the control group. Zn level in the serum of patients decreased significantly after phototherapy. We observed higher Cu/Zn ratio (p < .05) in examined patients than in the control group and after NB-UVB. We have found decrease in TAS in the serum of vitiligo patients after NB-UVB. The current study showed some disturbances in the serum levels of trace elements and total antioxidant status in vitiligo patients.

Paper-based assay of antioxidant activity using analyte-mediated on-paper nucleation of gold nanoparticles as colorimetric probes.

PubMed

Choleva, Tatiana G; Kappi, Foteini A; Giokas, Dimosthenis L; Vlessidis, Athanasios G

2015-02-20

With the increasing interest in the health benefits arising from the consumption of dietary products rich in antioxidants, there exists a clear demand for easy-to-use and cost-effective tests that can be used for the identification of the antioxidant power of food products. Paper-based analytical devices constitute a remarkable platform for such expedient and low-cost assays with minimal external resources but efforts in this direction are still scarce. In this work we introduce a new paper-based device in the form of a sensor patch that enables the determination of antioxidant activity through analyte-driven on-paper formation of gold nanoparticles. The principle of detection capitalizes, for the first time, on the on-paper nucleation of gold ions to its respective nanoparticles, upon reduction by antioxidant compounds present in an aqueous sample. The ensuing chromatic transitions, induced on the paper surface, are used as an optical "signature" of the antioxidant strength of the solution. The response of the paper-based sensor was evaluated against a large variety of antioxidant species and the respective dose response curves were constructed. On the basis of these data, the contribution of each species according to its chemical structure was elucidated. For the analysis of real samples, a concentration-dependent colorimetric response was established against Gallic acid equivalents over a linear range of 10 μM-1.0 mM, with detection limits at the low and ultra-low μM levels (i.e. <1.0 μM) and satisfactory precision (RSD=3.6-12.6%). The sensor has been tested for the assessment of antioxidant activity in real samples (teas and wines) and the results correlated well with commonly used antioxidant detection methods. Importantly, the sensor performed favorably for long periods of time when stored at moisture-free and low temperature conditions without losing its activity thus posing as an attractive alternative to the assessment of antioxidant activity without specialized equipment. The use of the sensor by non-experts for a rapid assessment of natural products in field testing is envisioned. Importantly, we demonstrate for the first time that analyte-mediated growth of nanomaterials directly on the paper surface could open new opportunities in paper-based analytical devices. Copyright © 2014 Elsevier B.V. All rights reserved.

[Lymphocyte metabolism in children with extensive burns].

PubMed

Artem'ev, S A; Nazarov, I P; Kamzalakova, N I; Bulygin, G V

2009-01-01

The results of the study lead to the conclusion that the development of burn disease in children is accompanied by significant lymphocytic structural metabolic changes that determine the functional capabilities of cells and the immune system as a whole. There is an evident activation of the glutathione antioxidant system, a drastic activation of enzymes that ensure Krebs cycle reactions, as well as activation of anaerobic processes. The above changes are mainly caused by the activated sympathoadrenal system that is characteristic of stresses. The knowledge about the metabolic mechanisms responsible for the development of cellular reactions to burn shock and burn disease permits specification of the elements of the pathogenesis of these severe conditions and substantiation of the possibility of using metabolic correction in the complex treatment of children with the above pathology.

Correlations between plasma noradrenaline concentrations, antioxidants, and neutrophil counts after submaximal resistance exercise in men

PubMed Central

Ramel, A; Wagner, K; Elmadfa, I

2004-01-01

Objectives: To investigate noradrenaline concentrations, neutrophil counts, plasma antioxidants, and lipid oxidation products before and after acute resistance exercise. Methods: 17 male participants undertook a submaximal resistance exercise circuit (10 exercises; 75% of the one repetition maximum; mean (SD) exercise time, 18.6 (1.1) minutes). Blood samples were taken before and immediately after exercise and analysed for plasma antioxidants, noradrenaline, neutrophils, and lipid oxidation products. Wilcoxon's signed-rank test and Pearson's correlation coefficient were used for calculations. Results: Neutrophils, noradrenaline, fat soluble antioxidants, and lipid oxidation products increased after exercise. Noradrenaline concentrations were associated with higher antioxidant concentrations. Neutrophils were related to higher concentrations of conjugated dienes. Conclusions: Submaximal resistance exercise increases plasma antioxidants. This might reflect enhanced antioxidant defence in response to the oxidative stress of exercise, though this is not efficient for inhibiting lipid oxidation. The correlation between noradrenaline concentrations and plasma antioxidants suggests a modulating role of the stress hormone. Neutrophils are a possible source of oxidative stress after resistance exercise. PMID:15388566

Antioxidant activity of amino acids in soybean oil at frying temperature: Structural effects and synergism with tocopherols.

PubMed

Hwang, Hong-Sik; Winkler-Moser, Jill K

2017-04-15

The purpose of this study was to evaluate amino acids as natural antioxidants for frying. Twenty amino acids were added to soybean oil heated to 180°C, and the effects of amino acid structure on the antioxidant activity were investigated. Amino acids containing a thiol, a thioether, or an extra amine group such as arginine, cysteine, lysine, methionine, and tryptophan had the strongest antioxidant activities. At 5.5mM, these amino acids had stronger antioxidant activities than 0.02% (1.1mM) tert-butylhydroquinone (TBHQ). A functional group such as an amide, carboxylic acid, imidazole, or phenol appeared to negatively affect amino acid antioxidant activity. Synergism between amino acids and tocopherols was demonstrated, and we found that this synergistic interaction may be mostly responsible for the antioxidant activity that was observed. In a frying study with potato cubes, 5.5mM l-methionine had significantly stronger antioxidant activity than 0.02% TBHQ. Published by Elsevier Ltd.

Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases

PubMed Central

Zhang, Zhong-Wei; Xu, Xiao-Chao; Liu, Ting

2016-01-01

Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC) was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid) to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders. PMID:26649144

Constituents and Antioxidant Activity of Bleeding Sap from Various Xinjiang Grapes.

PubMed

Le, Lv; Umar, Anwar; Iburaim, Arkin; Moore, Nicholas

2017-10-01

Wine grape sap or bleeding sap of grapes (GBS) is commonly used in Xinjiang (China) for therapeutic aims. Do variations in composition related to region and variety affect its properties? GBS samples originating in various parts of Xinjiang (Turpan, Hotan, Kashgar, and Atush) were tested for phenols and polyphenols, polysaccharides, saponin, proteins, individual amino acids, and minerals. Their antioxidant activity was measured using ascorbic acid as reference. Polyphenol content varied from 2.6 to 6.6 mg/L, polysaccharides 18.3-816 mg/L, saponin 6.25-106 mg/L, and protein 3.0-22.4 mg/L. Mineral elements and amino acids ranged from 6.20 to 201.2 mg/L and 0.06-118.7 mg/L, respectively. ·OH scavenging ability varied from 70% to over 90%, higher than Vitamin C. Grapes from Turpan had lower antioxidant activity than other grapes even though the polyphenol content was generally higher. Bleeding sap of Xinjiang grape is rich in amino acids, polysaccharides, polyphenols, and protein. The contents are different according to the origin, related possibly to species, climate, and environment. Antioxidant effects were not correlated with polyphenol content. Antioxidant activity of plants or plant extracts is often associated with polyphenolsBleeding sap of grapes has strong antioxidant propertiesBleeding sap from different grape varieties from different parts of Xinjiang (China) had different polyphenol concentrationsThere was no correlation of polyphenol concentrations with antioxidant activity. Abbreviations used: GBS: Bleeding sap of grapes; PITC: phenyl isothiocyanate.

Albumin Antioxidant Response to Stress in Diabetic Nephropathy Progression

PubMed Central

Medina-Navarro, Rafael; Corona-Candelas, Itzia; Barajas-González, Saúl; Díaz-Flores, Margarita; Durán-Reyes, Genoveva

2014-01-01

Background A new component of the protein antioxidant capacity, designated Response Surplus (RS), was recently described. A major feature of this component is the close relationship between protein antioxidant capacity and molecular structure. Oxidative stress is associated with renal dysfunction in patients with renal failure, and plasma albumin is the target of massive oxidation in nephrotic syndrome and diabetic nephropathy. The aim of the present study was to explore the albumin redox state and the RS component of human albumin isolated from diabetic patients with progressive renal damage. Methods/Principal Findings Serum aliquots were collected and albumin isolated from 125 diabetic patients divided into 5 groups according to their estimated glomerular filtration rate (GFR). In addition to clinical and biochemical variables, the albumin redox state, including antioxidant capacity, thiol group content, and RS component, were evaluated. The albumin antioxidant capacity and thiol group content were reciprocally related to the RS component in association with GFR reduction. The GFR decline and RS component were significantly negatively correlated (R = –0.83, p<0.0001). Age, creatinine, thiol groups, and antioxidant capacity were also significantly related to the GFR decline (R = –0.47, p<0.001; R = –0.68, p<0.0001; R = 0.44, p<0.001; and R = 0.72, p<0.0001). Conclusion/Significance The response of human albumin to stress in relation to the progression of diabetic renal disease was evaluated. The findings confirm that the albumin molecular structure is closely related to its redox state, and is a key factor in the progression of diabetes nephropathy. PMID:25187963

Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced by single-walled carbon nanotubes in C57BL/6 mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shvedova, Anna A.; Kisin, Elena R.; Murray, Ashley R.

2007-06-15

Exposure of mice to single-walled carbon nanotubes (SWCNTs) induces an unusually robust pulmonary inflammatory response with an early onset of fibrosis, which is accompanied by oxidative stress and antioxidant depletion. The role of specific components of the antioxidant protective system, specifically vitamin E, the major lipid-soluble antioxidant, in the SWCNT-induced reactions has not been characterized. We used C57BL/6 mice, maintained on vitamin E-sufficient or vitamin E-deficient diets, to explore and compare the pulmonary inflammatory reactions to aspired SWCNTs. The vitamin E-deficient diet caused a 90-fold depletion of {alpha}-tocopherol in the lung tissue and resulted in a significant decline of othermore » antioxidants (GSH, ascorbate) as well as accumulation of lipid peroxidation products. A greater decrease of pulmonary antioxidants was detected in SWCNT-treated vitamin E-deficient mice as compared to controls. Lowered levels of antioxidants in vitamin E-deficient mice were associated with a higher sensitivity to SWCNT-induced acute inflammation (total number of inflammatory cells, number of polymorphonuclear leukocytes, released LDH, total protein content and levels of pro-inflammatory cytokines, TNF-{alpha} and IL-6) and enhanced profibrotic responses (elevation of TGF-{beta} and collagen deposition). Exposure to SWCNTs markedly shifted the ratio of cleaved to full-length extracellular superoxide dismutase (EC-SOD). Given that pulmonary levels of vitamin E can be manipulated through diet, its effects on SWCNT-induced inflammation may be of practical importance in optimizing protective strategies.« less

Induction of Antioxidant and Heat Shock Protein Responses During Torpor in the Gray Mouse Lemur, Microcebus murinus.

PubMed

Wu, Cheng-Wei; Biggar, Kyle K; Zhang, Jing; Tessier, Shannon N; Pifferi, Fabien; Perret, Martine; Storey, Kenneth B

2015-04-01

A natural tolerance of various environmental stresses is typically supported by various cytoprotective mechanisms that protect macromolecules and promote extended viability. Among these are antioxidant defenses that help to limit damage from reactive oxygen species and chaperones that help to minimize protein misfolding or unfolding under stress conditions. To understand the molecular mechanisms that act to protect cells during primate torpor, the present study characterizes antioxidant and heat shock protein (HSP) responses in various organs of control (aroused) and torpid gray mouse lemurs, Microcebus murinus. Protein expression of HSP70 and HSP90α was elevated to 1.26 and 1.49 fold, respectively, in brown adipose tissue during torpor as compared with control animals, whereas HSP60 in liver of torpid animals was 1.15 fold of that in control (P<0.05). Among antioxidant enzymes, protein levels of thioredoxin 1 were elevated to 2.19 fold in white adipose tissue during torpor, whereas Cu-Zn superoxide dismutase 1 levels rose to 1.1 fold in skeletal muscle (P<0.05). Additionally, total antioxidant capacity was increased to 1.6 fold in liver during torpor (P<0.05), while remaining unchanged in the five other tissues. Overall, our data suggest that antioxidant and HSP responses are modified in a tissue-specific manner during daily torpor in gray mouse lemurs. Furthermore, our data also show that cytoprotective strategies employed during primate torpor are distinct from the strategies in rodent hibernation as reported in previous studies. Copyright © 2015. Production and hosting by Elsevier Ltd.

Antitrypanosomal and antioxidant properties of 4-hydroxycoumarins derivatives.

PubMed

Pérez-Cruz, Fernanda; Serra, Silvia; Delogu, Giovanna; Lapier, Michel; Maya, Juan Diego; Olea-Azar, Claudio; Santana, Lourdes; Uriarte, Eugenio

2012-09-01

In the present communication we prepared a series of six 4-hydroxycoumarin derivatives, isosters of quercetin, recognized as an antioxidant natural compound, with the aim of evaluating the antitrypanosomal activity against Trypanosoma cruzi, the parasite responsible for Chagas disease, and the antioxidant properties. We have used the 4-hydroxycoumarin moiety (compound 1) as the molecular template for the synthesis of compounds 2-7. These derivates have shown moderate trypanocidal activity. However they have been proved to be good antioxidants. In particular compound 7 is the most active antioxidant and it is, therefore, a potential candidate for a successful employment in conditions characterized by free radicals overproduction. Copyright © 2012 Elsevier Ltd. All rights reserved.

A synthetic chalcone as a potent inducer of glutathione biosynthesis.

PubMed

Kachadourian, Remy; Day, Brian J; Pugazhenti, Subbiah; Franklin, Christopher C; Genoux-Bastide, Estelle; Mahaffey, Gregory; Gauthier, Charlotte; Di Pietro, Attilio; Boumendjel, Ahcène

2012-02-09

Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2',5'-dihydroxychalcone (2',5'-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure-activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F and Cl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4',6'-dimethoxy-2'-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements.

A Synthetic Chalcone as a Potent Inducer of Glutathione Biosynthesis

PubMed Central

Kachadourian, Remy; Day, Brian J.; Pugazhenti, Subbiah; Franklin, Christopher C.; Genoux-Bastide, Estelle; Mahaffey, Gregory; Gauthier, Charlotte; Di Pietro, Attilio; Boumendjel, Ahcène

2014-01-01

Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2′,5′-dihydroxychalcone (2′,5′-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure–activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F and Cl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4′,6′-dimethoxy-2′-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements. PMID:22239485

Transcriptional regulation of nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase in murine hepatoma cells by 6-(methylsufinyl)hexyl isothiocyanate, an active principle of wasabi (Eutrema wasabi Maxim).

PubMed

Hou, D X; Fukuda, M; Fujii, M; Fuke, Y

2000-12-20

Wasabi is a very popular pungent spice in Japan. This study examined the ability of 6-(methylsufinyl)hexyl isothiocyanate (6-MITC), an active principle of wasabi, to induce the cellular expression of nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase (QR) in Hepa 1c1c7 cells. The cells were treated with various concentrations of 6-MITC, and were then assessed for cell growth, QR activity and QR mRNA expression. The induction of QR activity and QR mRNA expression was time- and dose-responsive over a narrow range of 0.1-5 microM, with declining induction at higher concentrations due to cell toxicity. Furthermore, transfection studies demonstrated that the induction of transcription of the QR gene by 6-MITC involved an antioxidant/electrophile-responsive element (ARE/EpRE) activation. Our results suggest a novel mechanism by which dietary wasabi 6-MITC may be implicated in cancer chemoprevention.

Responses of Noccaea caerulescens and Lupinus albus in trace elements-contaminated soils.

PubMed

Martínez-Alcalá, Isabel; Hernández, Luis E; Esteban, Elvira; Walker, David J; Bernal, M Pilar

2013-05-01

Plants exposed to trace elements can suffer from oxidative stress, which is characterised by the accumulation of reactive oxygen species, alteration in the cellular antioxidant defence system and ultimately lipid peroxidation. We assessed the most-appropriate stress indexes to describe the response of two plant species, with different strategies for coping with trace elements (TEs), to particular contaminants. Noccaea caerulescens, a hyperaccumulator, and Lupinus albus, an excluder, were grown in three soils of differing pH: an acidic soil, a neutral soil (both contaminated mainly by Cu, Zn and As) and a control soil. Then, plant stress indicators were measured. As expected, N. caerulescens accumulated higher levels of Zn and Cd in shoots than L. albus, this effect being stronger in the acid soil, reflecting greater TE solubility in this soil. However, the shoot concentrations of Mn were higher in L. albus than in N. caerulescens, while the As concentration was similar in the two species. In L. albus, the phenolic content and lipid peroxidation were related with the Cu concentration, whereas the Zn and Cd concentrations in N. caerulescens were more closely related to glutathione content and lipid peroxidation. Interestingly, phytochelatins were only found in L. albus grown in polluted soils. Hence, the two species differed with respect to the TEs which provoked stress and the biochemical indicators of the stress, there being a close relationship between the accumulation of TEs and their associated stress indicators in the different plant organs. Crown Copyright © 2013. Published by Elsevier Masson SAS. All rights reserved.

Anti-inflammatory and wound healing potential of cashew apple juice (Anacardium occidentale L.) in mice

PubMed Central

da Silveira Vasconcelos, Mirele; Gomes-Rochette, Neuza F; de Oliveira, Maria Liduína M; Nunes-Pinheiro, Diana Célia S; Tomé, Adriana R; Maia de Sousa, Francisco Yuri; Pinheiro, Francisco Geraldo M; Moura, Carlos Farley H; Miranda, Maria Raquel A; Mota, Erika Freitas

2015-01-01

Cashew apple is a tropical pseudofruit consumed as juice due to its excellent nutritional and sensory properties. In spite of being well known for its important antioxidant properties, the cashew apple has not been thoroughly investigated for its therapeutic potential. Thereby, this study evaluated the antioxidant capacity, anti-inflammatory, and wound-healing activities of cashew apple juice. Juices from ripe and immature cashew apples were analyzed for antioxidant, anti-inflammatory, and wound-healing properties. Those were evaluated in murine models of xylene-induced ear edema and wound excision. Swiss mice were treated with cashew juice by gavage. Edema thickness was measured and skin lesions were analyzed by planimetry and histology. Both antioxidant content and total antioxidant activity were higher in ripe cashew apple juice (RCAJ) than in unripe cashew apple juice (UNCAJ). The UNCAJ presented the main anti-inflammatory activity by a significant inhibition of ear edema (66.5%) when compared to RCAJ (10%). Moreover, UNCAJ also showed the best result for wound contraction (86.31%) compared to RCAJ (67.54%). Despite of higher antioxidant capacity, RCAJ did not promote better anti-inflammatory, and healing responses, which may be explained by the fact that treatment increased antioxidants level leading to a redox “imbalance” turning down the inflammatory response modulation exerted by reactive oxygen species (ROS). The results suggest that UNCAJ presents a greater therapeutic activity due to a synergistic effect of its phytochemical components, which improve the immunological mechanisms as well as an optimal balance between ROS and antioxidants leading to a better wound healing process. PMID:25819683

Antioxidant Generation during Coffee Roasting: A Comparison and Interpretation from Three Complementary Assays

PubMed Central

Opitz, Sebastian E. W.; Smrke, Samo; Goodman, Bernard A.; Keller, Marco; Schenker, Stefan; Yeretzian, Chahan

2014-01-01

Coffee is a major source of dietary antioxidants; some are present in the green bean, whereas others are generated during roasting. However, there is no single accepted analytical method for their routine determination. This paper describes the adaption of three complementary assays (Folin-Ciocalteu (FC), ABTS and ORAC) for the routine assessment of antioxidant capacity of beverages, their validation, and use for determining the antioxidant capacities of extracts from coffee beans at different stages in the roasting process. All assays showed a progressive increase in antioxidant capacity during roasting to a light roast state, consistent with the production of melanoidins having a higher antioxidant effect than the degradation of CGAs. However, the three assays gave different numbers for the total antioxidant capacity of green beans relative to gallic acid (GA), although the range of values was much smaller when chlorogenic acid (CGA) was used as reference. Therefore, although all three assays indicated that there was an increase in antioxidant activity during coffee roasting, and the large differences in responses to GA and CGA illustrate their different sensitivities to different types of antioxidant molecule. PMID:28234339

Treatment of oxidative stress in brain of ovariectomized rats with omega-3 and lipoic acid.

PubMed

Behling, Camile S; Andrade, Alexey S; Putti, Jordana S; Mahl, Camila D; Hackenhaar, Fernanda S; da Silva, Ana Carolina A; e Silva, Mélany Natuane C; Salomon, Tiago B; Dos Santos, Carla E I; Dias, Johnny F; Benfato, Mara S

2015-12-01

Postmenopausal women are often affected by a group of metabolic disorders related to oxidative stress. Alternative treatments that can improve the quality of life of these women have been the subject of recent studies. The objective of this study was to evaluate the response to oxidative stress in the brains of rats following ovariectomy, and to determine enzymatic and nonenzymatic antioxidant responses when the animals received 3 months of dietary supplementation. Ovariectomy produced changes in antioxidant profiles characterized by reductions in glutathione S-transferase activity, H2 O2 consumption, superoxide dismutase activity, and vitamin C levels and increases in protein carbonylation. Docosahexaenoic fatty acid (DHA) supplementation restored these parameters to normal values and increased values of other antioxidants (glutathione peroxidase and total glutathione). However, DHA supplementation also increased protein carbonylation and lipid peroxidation. Eicosapentaenoic acid supplementation produced no changes in antioxidants, but decreased lipid peroxidation. Lipoic acid supplementation increased consumption of H2 O2 and decreased protein carbonylation and lipid peroxidation. These results suggest that the antioxidant response to omega-3 varies in different tissues, and in this study DHA treatment had a prooxidant effect in the brain. Lipoic acid treatment, on the other hand, had a protective effect, reducing markers of oxidative damage. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simultaneous optimization of the ultrasound-assisted extraction for phenolic compounds content and antioxidant activity of Lycium ruthenicum Murr. fruit using response surface methodology.

PubMed

Chen, Shasha; Zeng, Zhi; Hu, Na; Bai, Bo; Wang, Honglun; Suo, Yourui

2018-03-01

Lycium ruthenicum Murr. (LR) is a functional food that plays an important role in anti-oxidation due to its high level of phenolic compounds. This study aims to optimize ultrasound-assisted extraction (UAE) of phenolic compounds and antioxidant activities of obtained extracts from LR using response surface methodology (RSM). A four-factor-three-level Box-Behnken design (BBD) was employed to discuss the following extracting parameters: extraction time (X 1 ), ultrasonic power (X 2 ), solvent to sample ratio (X 3 ) and solvent concentration (X 4 ). The analysis of variance (ANOVA) results revealed that the solvent to sample ratio had a significant influence on all responses, while the extraction time had no statistically significant effect on phenolic compounds. The optimum values of the combination of phenolic compounds and antioxidant activities were obtained for X 1 =30min, X 2 =100W, X 3 =40mL/g, and X 4 =33% (v/v). Five phenolic acids, including chlorogenic acid, caffeic acid, syringic acid, p-coumaric acid and ferulic acid, were analyzed by HPLC. Our results indicated that optimization extraction is vital for the quantification of phenolic compounds and antioxidant activity in LR, which may be contributed to large-scale industrial applications and future pharmacological activities research. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Protective Roles of the Antioxidant Enzymes Superoxide Dismutase and Catalase in the Green Photosynthetic Bacterium Chloroflexus Aurantiacus

NASA Technical Reports Server (NTRS)

Blankenship, Robert E.; Rothschild, Lynn (Technical Monitor)

2004-01-01

The purpose of this study was to examine the biochemical response of the green thermophilic photosynthetic bacterium Chloroflexus aurantiacus to oxidative stress. Lab experiments focused primarily on characterizing the antioxidant enzyme superoxide dismutase and the response of this organism to oxidative stress. Experiments in the field at the hotsprings in Yellowstone National Park focused on the changes in the level of these enzymes during the day in response to oxidants and to the different types of ultraviolet radiation.

Antioxidant Activities of Basella alba Aqueous Leave Extract In Blood, Pancreas, and Gonadal Tissues of Diabetic Male Wistar Rats.

PubMed

Arokoyo, Dennis Seyi; Oyeyipo, Ibukun Peter; Du Plessis, Stefan Simon; Aboua, Yapo Guillaume

2018-01-01

Oxidative stress is frequently identified as a key element in the pathophysiology of many complications of diabetes mellitus, including reproductive complications. The antioxidant potential of medicinal plants have been suggested for therapeutic focus of diseases in recent reports. To investigate the effect of Basella alba (Ba) aqueous leave extract on diabetes-induced oxidative stress. Forty male Wistar rats (8-10 weeks) were randomly divided into four groups ( n = 10) and treated as follows; Control (C + Ns) and Diabetic (D + Ns) animals received oral normal saline 0.5 ml/100 g body weight daily, while Healthy Treatment (H + Ba) and Diabetic Treatment (D + Ba) rats were given Ba extract at an oral dose of 200 mg/kg body weight daily. Treatment was by gavage and lasted 4 weeks in all groups. Diabetes was induced in D + Ns and D + Ba rats by single intraperitoneal injection of streptozotocin (55 mg/kg) and fasting blood sugar (FBS) recorded weekly in all rats afterwards. Animals were euthanized at the end of the experiment and blood samples, pancreas, testes, and epididymis were preserved for analysis of oxidative stress biomarkers. Oral administration of aqueous leave extract of Ba significantly ( P < 0.0001) lowered FBS in D + Ba rats. There was significantly higher blood superoxide dismutase activity and serum ferric reducing antioxidant power, but lower serum concentration of conjugated dienes and thiobarbituric acid reactive substances in D + Ba compared to D + Ns rats ( P < 0.05). Ba exerts antioxidant effects in the gonads by enhancing antioxidant parameters in circulating blood, but not necessarily in the gonadal tissues. Oral treatment of diabetic rats with aqueous leave extract of Basella alba exerts antioxidant effects in the gonads by enhancing antioxidant parameters in circulating blood, but not necessarily in the gonadal tissues. Abbreviations Used: AP - Antioxidant parameters, Ba - Basella alba , CAT - Catalase, CDs - Conjugated dienes, DM - Diabetes mellitus, FBS - Fasting blood sugar, FRAP - Ferric reducing antioxidant power, GSH - reduced glutathione, Ns - Normal saline, ORAC - oxygen radical antioxidant capacity, RNS - reactive nitrogen species, ROS - reactive oxygen species, SOD - superoxide dismutase, TAC - Total antioxidant capacity, TBARS - thiobarbituric acid reactive substances, TEAC - trolox equivalent antioxidant capacity.

Nrf2 Is an Attractive Therapeutic Target for Retinal Diseases

PubMed Central

2016-01-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of Nrf2 functions is one of the critical defensive mechanisms against oxidative stress in many species. The retina is constantly exposed to reactive oxygen species, and oxidative stress is a major contributor to age-related macular diseases. Moreover, the resulting inflammation and neuronal degeneration are also related to other retinal diseases. The well-known Nrf2 activators, bardoxolone methyl and its derivatives, have been the subject of a number of clinical trials, including those aimed at treating chronic kidney disease, pulmonary arterial hypertension, and mitochondrial myopathies. Recent studies suggest that Nrf2 activation protects the retina from retinal diseases. In particular, this is supported by the finding that Nrf2 knockout mice display age-related retinal degeneration. Moreover, the concept has been validated by the efficacy of Nrf2 activators in a number of retinal pathological models. We have also recently succeeded in generating a novel Nrf2 activator, RS9, using a biotransformation technique. This review discusses current links between retinal diseases and Nrf2 and the possibility of treating retinal diseases by activating the Nrf2 signaling pathway. PMID:27818722

DNA Microarray Profiling Highlights Nrf2-Mediated Chemoprevention Targeted by Wasabi-Derived Isothiocyanates in HepG2 Cells.

PubMed

Trio, Phoebe Zapanta; Kawahara, Atsuyoshi; Tanigawa, Shunsuke; Sakao, Kozue; Hou, De-Xing

2017-01-01

6-MSITC and 6-MTITC are sulforaphane (SFN) analogs found in Japanese Wasabi. As we reported previously, Wasabi isothiocyanates (ITCs) are activators of Nrf2-antioxidant response element pathway, and also inhibitors of pro-inflammatory cyclooxygenase-2. This study is the first to assess the global changes in transcript levels by Wasabi ITCs, comparing with SFN, in HepG2 cells. We performed comparative gene expression profiling by treating HepG2 cells with ITCs, followed by DNA microarray analyses using HG-U133 plus 2.0 oligonucleotide array. Partial array data on selected gene products were confirmed by RT-PCR and Western blotting. Ingenuity Pathway Analysis (IPA) was used to identify functional subsets of genes and biologically significant network pathways. 6-MTITC showed the highest number of differentially altered (≥2 folds) gene expression, of which 114 genes were upregulated and 75 were downregulated. IPA revealed that Nrf2-mediated pathway, together with glutamate metabolism, is the common significantly modulated pathway across treatments. Interestingly, 6-MSITC exhibited the most potent effect toward Nrf2-mediated pathway. Our data suggest that 6-MSITC could exert chemopreventive role against cancer through its underlying antioxidant activity via the activation of Nrf2-mediated subsequent induction of cytoprotective genes.

Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis

PubMed Central

Pak, Wing; Takayama, Fusako; Mine, Manaka; Nakamoto, Kazuo; Kodo, Yasumasa; Mankura, Mitsumasa; Egashira, Toru; Kawasaki, Hiromu; Mori, Akitane

2012-01-01

The pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, but accumulating data suggest oxidative stress and the relationship between inflammation and immunity plays a crucial role. The aim of this study is to investigate the spirulina, which is a blue-green algae rich in proteins and other nutritional elements, and its component-phycocyanin effect on a rat model of NASH. NASH model rats were established by feeding male Wistar rats with choline-deficient high-fat diet (CDHF) and intermittent hypoxemia by sodium nitrite challenge after 5 weeks of CDHF. After experimental period of 10 weeks, blood and liver were collected to determine oxidative stress injuries and efficacies of spirulina or phycocyanin on NASH model rats. In the NASH model rats, increase in plasma liver enzymes and liver fibrosis, increases in productions of reactive oxygen species from liver mitochondria and from leukocytes, the activation of nuclear factor-kappa B, and the change in the lymphocyte surface antigen ratio (CD4+/CD8+) were observed. The spirulina and phycocyanin administration significantly abated these changes. The spirulina or phycocyanin administration to model rats of NASH might lessen the inflammatory response through anti-oxidative and anti-inflammatory mechanisms, breaking the crosstalk between oxidative stress and inflammation, and effectively inhibit NASH progression. PMID:23170052

Induction of hepatic antioxidants in freshwater catfish (Channa punctatus Bloch) is a biomarker of paper mill effluent exposure.

PubMed

Ahmad, I; Hamid, T; Fatima, M; Chand, H S; Jain, S K; Athar, M; Raisuddin, S

2000-09-01

Enzymatic and non-enzymatic antioxidants serve as an important biological defense against environmental oxidative stress. Information on antioxidant defense in fish is meager despite that fish are constantly exposed to a myriad of environmental stress including the oxidants. This study, therefore, assesses the activities of antioxidant enzymes viz., glutathione peroxidase, catalase and glutathione S-transferase and the non-enzymatic antioxidants viz., glutathione and metallothionein in various tissues of freshwater fish Channa punctatus (Bloch), in response to short-term and long-term exposures to paper mill effluent. The fish were exposed to the effluent at a concentration of 1.0% (v/v) for 15, 30, 60 and 90 days. The exposure caused a time-dependent increase in glutathione level (P < 0.001), activities of glutathione peroxidase (P < 0.05 to P < 0.001), glutathione S-transferase (P < 0.001) and a marginal initial decrease in catalase activity in the liver (P < 0.01 to P < 0.001). Metallothionein was induced in liver after 60 days of exposure. Two isoforms of metallothionein were detected. Catalase activity also increased 60 days afterwards. Antioxidant pattern was different in gill and kidney showing that liver was more resistant to oxidative damage as compared to gills and kidney. Our results demonstrate a pollutant-induced adaptive response in fish. In addition, levels of enzymatic and non-enzymatic tissue antioxidants may serve as surrogate markers of exposure to oxidant pollutants in fish.

Spectrophotometric Determination of Phenolic Antioxidants in the Presence of Thiols and Proteins

PubMed Central

Avan, Aslı Neslihan; Demirci Çekiç, Sema; Uzunboy, Seda; Apak, Reşat

2016-01-01

Development of easy, practical, and low-cost spectrophotometric methods is required for the selective determination of phenolic antioxidants in the presence of other similar substances. As electron transfer (ET)-based total antioxidant capacity (TAC) assays generally measure the reducing ability of antioxidant compounds, thiols and phenols cannot be differentiated since they are both responsive to the probe reagent. In this study, three of the most common TAC determination methods, namely cupric ion reducing antioxidant capacity (CUPRAC), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt/trolox equivalent antioxidant capacity (ABTS/TEAC), and ferric reducing antioxidant power (FRAP), were tested for the assay of phenolics in the presence of selected thiol and protein compounds. Although the FRAP method is almost non-responsive to thiol compounds individually, surprising overoxidations with large positive deviations from additivity were observed when using this method for (phenols + thiols) mixtures. Among the tested TAC methods, CUPRAC gave the most additive results for all studied (phenol + thiol) and (phenol + protein) mixtures with minimal relative error. As ABTS/TEAC and FRAP methods gave small and large deviations, respectively, from additivity of absorbances arising from these components in mixtures, mercury(II) compounds were added to stabilize the thiol components in the form of Hg(II)-thiol complexes so as to enable selective spectrophotometric determination of phenolic components. This error compensation was most efficient for the FRAP method in testing (thiols + phenols) mixtures. PMID:27529232

Anti-Oxidative Defences Are Modulated Differentially in Three Freshwater Teleosts in Response to Ammonia-Induced Oxidative Stress

PubMed Central

Giblen, Terri; Zinta, Gaurav; De Rop, Michelle; Asard, Han; Blust, Ronny; De Boeck, Gudrun

2014-01-01

Oxidative stress and the antioxidant response induced by high environmental ammonia (HEA) were investigated in the liver and gills of three freshwater teleosts differing in their sensitivities to ammonia. The highly ammonia-sensitive salmonid Oncorhynchus mykiss (rainbow trout), the less ammonia sensitive cyprinid Cyprinus carpio (common carp) and the highly ammonia-resistant cyprinid Carassius auratus (goldfish) were exposed to 1 mM ammonia (as NH4HCO3) for 0 h (control), 3 h, 12 h, 24 h, 48 h, 84 h and 180 h. Results show that HEA exposure increased ammonia accumulation significantly in the liver of all the three fish species from 24 h–48 h onwards which was associated with an increment in oxidative stress, evidenced by elevation of xanthine oxidase activity and levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA). Unlike in trout, H2O2 and MDA accumulation in carp and goldfish liver was restored to control levels (84 h–180 h); which was accompanied by a concomitant increase in superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase activity and reduced ascorbate content. Many of these defence parameters remained unaffected in trout liver, while components of the glutathione redox cycle (reduced glutathione, glutathione peroxidase and glutathione reductase) enhanced to a greater extent. The present findings suggest that trout rely mainly on glutathione dependent defensive mechanism while carp utilize SOD, CAT and ascorbate as anti-oxidative sentinels. Hepatic cells of goldfish appear to utilize each of these protective systems, and showed more effective anti-oxidative compensatory responses towards HEA than carp, while trout were least effective. The present work also indicates that HEA exposure resulted in a relatively mild oxidative stress in the gills of all three species. This probably explains the almost complete lack of anti-oxidative responses in branchial tissue. This research suggests that oxidative stress, as well as the antioxidant potential clearly differ between salmonid and cyprinid species. PMID:24740135

Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus

PubMed Central

Dal Bosco, Lidiane; Weber, Gisele E.; Parfitt, Gustavo M.; Cordeiro, Arthur P.; Sahoo, Sangram K.; Fantini, Cristiano; Klosterhoff, Marta C.; Romano, Luis Alberto; Furtado, Clascídia A.; Santos, Adelina P.; Monserrat, José M.; Barros, Daniela M.

2015-01-01

Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the hippocampus. PMID:26075787

Effect of brewing conditions on antioxidant properties of rosehip tea beverage: study by response surface methodology.

PubMed

İlyasoğlu, Huri; Arpa, Tuba Eda

2017-10-01

The aim of this study was to investigate the effects of brewing conditions (infusion time and temperature) on the antioxidant properties of rosehip tea beverage. The ascorbic acid content, total phenolic content (TPC), and ferric reducing antioxidant power (FRAP) of rosehip tea beverage were analysed. A two-factor and three-level central composite design was applied to evaluate the effects of the variables on the responses. The best quadratic models were obtained for all responses. The generated models were validated under the optimal conditions. At the optimal conditions, the rosehip tea beverage had 3.15 mg 100 mL -1 of ascorbic acid, 61.44 mg 100 mL -1 of TPC, and 2591 µmol of FRAP. The best brewing conditions for the rosehip tea beverage were found to be an infusion time of 6-8 min at temperatures of 84-86 °C.

Adipose triglyceride lipase decrement affects skeletal muscle homeostasis during aging through FAs-PPARα-PGC-1α antioxidant response.

PubMed

Aquilano, Katia; Baldelli, Sara; La Barbera, Livia; Lettieri Barbato, Daniele; Tatulli, Giuseppe; Ciriolo, Maria Rosa

2016-04-26

During aging skeletal muscle shows an accumulation of oxidative damage as well as intramyocellular lipid droplets (IMLDs). However, although the impact of these modifications on muscle tissue physiology is well established, the direct effectors critical for their occurrence are poorly understood. Here we show that during aging the main lipase of triacylglycerols, ATGL, significantly declines in gastrocnemius and its downregulation in C2C12 myoblast leads to the accumulation of lipid droplets. Indeed, we observed an increase of oxidative damage to proteins in terms of carbonylation, S-nitrosylation and ubiquitination that is dependent on a defective antioxidant cell response mediated by ATGL-PPARα-PGC-1α. Overall our findings describe a pivotal role for ATGL in the antioxidant/anti-inflammatory response of muscle cells highlighting this lipase as a therapeutic target for fighting the progressive decline in skeletal muscle mass and strength.

Extremophilic Enzymatic Response for Protection against UV-Radiation Damage

DTIC Science & Technology

2012-09-17

superoxide dismutase from the thermophile E1 is a very active enzyme and extremely efficient in its function as antioxidant by capturing superoxide radicals...Ollivet-Besson, Papić, L., Blamey J.M. “Optimization of the antioxidant activity of the enzyme superoxide dismutase from the thermophile E1 induced by...antioxidant enzymes , superoxide dismutase and catalase, from selected microorganisms and the contribution of these enzymes to the resistance to extreme and

Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells.

PubMed

Akide-Ndunge, Oscar Bate; Tambini, Elisa; Giribaldi, Giuliana; McMillan, Paul J; Müller, Sylke; Arese, Paolo; Turrini, Francesco

2009-05-29

Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70-2/70-3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of antioxidant enzymes was also increased in oxidatively-stressed trophozoites. Results indicated that mRNA expression of parasite antioxidant enzymes and HSPs was co-ordinated and stage-dependent. Secondly, both systems were redox-responsive and showed remarkably increased and co-ordinated expression in oxidatively-stressed parasites and in parasites growing in antioxidant blunted G6PD-deficient RBCs. Lastly, as important anti-malarials either increase oxidant stress or impair antioxidant defense, results may encourage the inclusion of anti-HSP molecules in anti-malarial combined drugs.

Antioxidant vitamins and their influence in diabetes mellitus.

PubMed

Hasanain, Bibi; Mooradian, Arshag D

2002-10-01

Diabetes mellitus is a chronic disease associated with serious complications. A number of studies have suggested that enhanced oxidation is the underlying abnormality responsible for some of the complications of diabetes. It is not known whether the ingestion of antioxidant vitamins could retard or perhaps reverse the oxidative damage. The information regarding the benefit of antioxidant vitamin supplementation is conflicting some trials have demonstrated adverse effects of excessive consumption of vitamin supplements. In this article, we review the available literature on the association of cardiovascular events and ingestion of vitamins with antioxidant properties. Given the lack of data to substantiate the benefit and safety of ingestion of antioxidant vitamins in excess of the recommended dietary allowance, physicians should avoid the recommendation of vitamin supplementation to their patients.

ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

PubMed Central

Pi, Jingbo; Zhang, Qiang; Fu, Jingqi; Woods, Courtney G.; Hou, Yongyong; Corkey, Barbara E; Collins, Sheila; Andersen, Melvin E.

2009-01-01

This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H2O2, act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function. PMID:19501608

The influence of curcumin and manganese complex of curcumin on cadmium-induced oxidative damage and trace elements status in tissues of mice.

PubMed

Eybl, Vladislav; Kotyzová, Dana; Lesetický, Ladislav; Bludovská, Monika; Koutenský, Jaroslav

2006-01-01

Curcumin (diferuoyl methane) from turmeric is a well-known biologically active compound. It has been shown to ameliorate oxidative stress and it is considered to be a potent cancer chemopreventive agent. In our previous study the antioxidative effects of curcumin in cadmium exposed animals were demonstrated. Also manganese exerts protective effects in experimental cadmium intoxication. The present study examined the ability of the manganese complex of curcumin (Mn-curcumin) and curcumin to protect against oxidative damage and changes in trace element status in cadmium-intoxicated male mice. Curcumin or Mn-curcumin were administered at equimolar doses (0.14 mmol/kg b.w.) for 3 days, by gastric gavages, dispersed in methylcellulose. One hour after the last dose of antioxidants, cadmium chloride (33 micromol/kg) was administered subcutaneously. Both curcumin and Mn-curcumin prevented the increase of hepatic lipid peroxidation -- expressed as MDA level, induced by cadmium intoxication and attenuated the Cd-induced decrease of hepatic GSH level. No change in hepatic glutathione peroxidase or catalase activities was found in Cd-exposed mice. A decreased GSH-Px activity was measured in curcumin and Mn-curcumin alone treated mice. Neither curcumin nor Mn-curcumin treatment influenced cadmium distribution in the tissues and did not correct the changes in the balance of essential elements caused by Cd-treatment. The treatment with Mn-curcumin increased the Fe and Mn content in the kidneys of both control and Cd-treated mice and Fe and Cu content in the brain of control mice. In conclusion, regarding the antioxidative action, introducing manganese into the curcumin molecule does not potentiate the studied effects of curcumin. Copyright 2006 John Wiley & Sons, Ltd.

Coping with Iron Limitation: A Metabolomic Study of Synechocystis sp. PCC 6803.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivas-Ubach, Albert; Poret-Peterson, A. T.; Penuel

2018-02-28

Iron (Fe) is a key element for all living systems, especially for photosynthetic organisms because of its important role in the photosynthetic electron transport chain. Fe limitation in cyanobacteria leads to several physiological and morphological changes. However, the overall metabolic responses to Fe limitation are still poorly understood. In this study, we integrated elemental, stoichiometric, macromolecular, and metabolomic data to shed light on the responses of Synechocystis sp. PCC 6803, a non-N2-fixing freshwater cyanobacterium, to Fe limitation. Compared to Synechocystis growing at nutrient replete conditions, Fe-limited cultures had lower growth rates and amounts of chlorophyll a, RNA, RNA:DNA, C, N,more » and P and higher ratios of Protein:RNA, C:N, C:P and N:P, in accordance with the growth rate hypothesis which predicts faster growing organisms will have decreased biomass RNA contents and C:P and N:P ratios. Fe-limited Synechocystis had lower amounts Fe, Mn and Mo, and higher amount of Cu. Several changes in amino acids of cultures growing under Fe limitation suggest nitrogen limitation. Additionally, we found substantial increases in stress-related metabolites in Fe-limited cyanobacteria such antioxidants. This study represents an advance in understanding the stoichiometric, macromolecular and metabolic strategies that cyanobacteria use to cope with Fe limitation. This information, moreover, may further understanding of changes in cyanobacterial functions under scenarios of Fe limitation in aquatic ecosystems.« less

Effects of water turbidity and different temperatures on oxidative stress in caddisfly (Stenopsyche marmorata) larvae.

PubMed

Suzuki, Jumpei; Imamura, Masahiro; Nakano, Daisuke; Yamamoto, Ryosuke; Fujita, Masafumi

2018-07-15

Anthropogenic water turbidity derived from suspended solids (SS) is caused by reservoir sediment management practices such as drawdown flushing. Turbid water induces stress in many aquatic organisms, but the effects of turbidity on oxidative stress responses in aquatic insects have not yet been demonstrated. Here, we examined antioxidant responses, oxidative damage, and energy reserves in caddisfly (Stenopsyche marmorata) larvae exposed to turbid water (0 mg SS L -1 , 500 mg SS L -1 , and 2000 mg SS L -1 ) at different temperatures. We evaluated the combined effects of turbid water and temperature by measuring oxidative stress and using metabolic biomarkers. No turbidity level was significantly lethal to S. marmorata larvae. Moreover, there were no significant differences in antioxidant response or oxidative damage between the control and turbid water treatments at a low temperature (10 °C). However, at a high temperature (25 °C), turbid water modulated the activity of the antioxidant enzymes superoxide dismutase and catalase and the oxygen radical absorbance capacity as an indicator of the redox state of the insect larvae. Antioxidant defenses require energy, and high temperature was associated with low energy reserves, which might limit the capability of organisms to counteract reactive oxygen species. Moreover, co-exposure to turbid water and high temperature caused fluctuation of antioxidant defenses and increased the oxidative damage caused by the production of reactive oxygen species. Furthermore, the combined effect of high temperature and turbid water on antioxidant defenses and oxidative damage was larger than the individual effects. Therefore, our results demonstrate that exposure to both turbid water and high temperature generates additive and synergistic interactions causing oxidative stress in this aquatic insect species. Copyright © 2018. Published by Elsevier B.V.

Biochemical response of hybrid black poplar tissue culture (Populus × canadensis) on water stress.

PubMed

Popović, B M; Štajner, D; Ždero-Pavlović, R; Tari, I; Csiszár, J; Gallé, Á; Poór, P; Galović, V; Trudić, B; Orlović, S

2017-05-01

In this study, poplar tissue culture (hybrid black poplar, M1 genotype) was subjected to water stress influenced by polyethyleneglycol 6000 (100 and 200 mOsm PEG 6000). The aim of the research was to investigate the biochemical response of poplar tissue culture on water deficit regime. Antioxidant status was analyzed including antioxidant enzymes, superoxide-dismutase (SOD), catalase (CAT), guiacol-peroxidase (GPx), glutathione-peroxidase (GSH-Px), glutathione-reductase, reduced glutathione, total phenol content, Ferric reducing antioxidant power and DPPH radical antioxidant power. Polyphenol oxidase and phenylalanine-ammonium-lyase were determined as enzymatic markers of polyphenol metabolism. Among oxidative stress parameters lipid peroxidation, carbonyl-proteins, hydrogen-peroxide, reactive oxygen species, nitric-oxide and peroxynitrite were determined. Proline, proline-dehydrogenase and glycinebetaine were measured also as parameters of water stress. Cell viability is finally determined as a biological indicator of osmotic stress. It was found that water stress induced reactive oxygen and nitrogen species and lipid peroxidation in leaves of hybrid black poplar and reduced cell viability. Antioxidant enzymes including SOD, GPx, CAT and GSH-Px were induced but total phenol content and antioxidant capacity were reduced by PEG 6000 mediated osmotic stress. The highest biochemical response and adaptive reaction was the increase of proline and GB especially by 200 mOsm PEG. While long term molecular analysis will be necessary to fully address the poplar potentials for water stress adaptation, our results on hybrid black poplar suggest that glycine-betaine, proline and PDH enzyme might be the most important markers of poplar on water stress and that future efforts should be focused on these markers and strategies to enhance their concentration in poplar.

Anti-inflammatory and wound healing potential of cashew apple juice (Anacardium occidentale L.) in mice.

PubMed

da Silveira Vasconcelos, Mirele; Gomes-Rochette, Neuza F; de Oliveira, Maria Liduína M; Nunes-Pinheiro, Diana Célia S; Tomé, Adriana R; Maia de Sousa, Francisco Yuri; Pinheiro, Francisco Geraldo M; Moura, Carlos Farley H; Miranda, Maria Raquel A; Mota, Erika Freitas; de Melo, Dirce Fernandes

2015-12-01

Cashew apple is a tropical pseudofruit consumed as juice due to its excellent nutritional and sensory properties. In spite of being well known for its important antioxidant properties, the cashew apple has not been thoroughly investigated for its therapeutic potential. Thereby, this study evaluated the antioxidant capacity, anti-inflammatory, and wound-healing activities of cashew apple juice. Juices from ripe and immature cashew apples were analyzed for antioxidant, anti-inflammatory, and wound-healing properties. Those were evaluated in murine models of xylene-induced ear edema and wound excision. Swiss mice were treated with cashew juice by gavage. Edema thickness was measured and skin lesions were analyzed by planimetry and histology. Both antioxidant content and total antioxidant activity were higher in ripe cashew apple juice (RCAJ) than in unripe cashew apple juice (UNCAJ). The UNCAJ presented the main anti-inflammatory activity by a significant inhibition of ear edema (66.5%) when compared to RCAJ (10%). Moreover, UNCAJ also showed the best result for wound contraction (86.31%) compared to RCAJ (67.54%). Despite of higher antioxidant capacity, RCAJ did not promote better anti-inflammatory, and healing responses, which may be explained by the fact that treatment increased antioxidants level leading to a redox "imbalance" turning down the inflammatory response modulation exerted by reactive oxygen species (ROS). The results suggest that UNCAJ presents a greater therapeutic activity due to a synergistic effect of its phytochemical components, which improve the immunological mechanisms as well as an optimal balance between ROS and antioxidants leading to a better wound healing process. © 2015 by the Society for Experimental Biology and Medicine.

[Role of trace elements and vitamins in peri-operative nutrition].

PubMed

Berger, M M

1995-01-01

The micronutriment requirements, whether trace elements (inorganic) or vitamins (organic), are tightly linked to the carbohydrate, lipid and protein metabolism, since they are involved in all metabolic pathways as cofactors. The micronutriments also have major immunological, endocrinological and antioxydant functions. Especially in the surgical patient, individual requirements may vary considerably and will be particularly increased in case of prior deficiency, anabolic states, or increased losses (burns, diarrhoea, gastric aspiration, intestinal fistulae, alcoholism, use of renal replacement techniques). In some of these settings, the micronutriment requirements will be independent from the macronutriments: this has been demonstrated for burns and intestinal fistulae. In the case of depletion prior to surgery, an isolated supplementation may be required without starting a proper nutrition. In general, micronutriment supplements will have to be started upon initiation of any artificial nutrition. After elective surgery and in absence of specific losses, the micronutriment requirements will be linked to the metabolic state of the patient and to the energy-protein intakes. This is most striking for the vitamin B group, where the requirements are indicated in mg per 1000 kcal. Vitamins A and E are also at risk in the surgical patient. Recommended micronutriment supplements have been revised in 1994. Some trace element deficiencies (Se, Cr, Mo) can initiate very serious complications and will require special caution in the perioperative period. Other deficiencies (Cu, Zn) result in more slowly evolving clinical pictures, with lesser life-threatening potential, resulting in infections and prolonged wound healing. In such cases, multi-elementary supplements are inadequate, and single element solutions supplements are required. All the micronutriments are characterized by a dose-response curve. The quantity avoiding biochemical dysfunctioning in human pathological situations has not yet been established, and it is unsatisfactory to merely compensate for the losses. This notion of biochemical dysfunctioning phase preceeding the clinical deficiency syndrome is in investigation for many nutriments, especially as the importance of some micronutriments, such as Se and vitamin E, in maintaining antioxidant defences is clearly established. The potential for preventing free radical induced overproduction of cytokines by means of nutritional strategy and enhanced antioxidant defences clearly exists, and is only at an early phase of investigation in patients. The future will be marked by the development of nutritional pharmacology based on pathology-specific micronutriment supplements.

Activity of Selected Antioxidant Enzymes, Selenium Content and Fatty Acid Composition in the Liver of the Brown Hare (Lepus europaeus L.) in Relation to the Season of the Year.

PubMed

Drozd, Radosław; Pilarczyk, Renata; Pilarczyk, Bogumiła; Drozd, Arleta; Tomza-Marciniak, Agnieszka; Bombik, Teresa; Bąkowska, Małgorzata; Bombik, Elżbieta; Jankowiak, Dorota; Wasak, Agata

2015-12-01

The aim of the study was to evaluate the effect of low concentrations of selenium in the environment on the activity of selected antioxidant enzymes: Se-GSHPx, total GSHPx, SOD, CAT, and GST as well as fatty acid profile in the livers of brown hares during winter and spring. Liver tissues obtained from 20 brown hares collected in the north-eastern Poland in the winter and spring season were analyzed. In the tissue analyzed, a significantly lower level of selenium was noticeable in the spring compared to winter; however, values measured in both seasons indicated a deficiency of this element in the analyzed population of brown hares. There were no differences found that could indicate the influence of Se deficiency on the activity of antioxidant enzymes. The determined activity of antioxidant enzymes and fatty acid composition suggest a negligible impact of the low concentration of Se on the analyzed biochemical parameters of brown hare livers.

Antiinflammatory and antioxidant activities of gum mastic.

PubMed

Mahmoudi, M; Ebrahimzadeh, M A; Nabavi, S F; Hafezi, S; Nabavi, S M; Eslami, Sh

2010-09-01

Pistacia lentiscus has traditionally been used in the treatment of many diseases. Its resin was investigated for its mineral contents, anti-inflammatory and antioxidant activities in rats. Inhibition of carrageenan induced edema was used to evaluate anti-inflammatory activity. Fe2+ chelating ability, 1,1-diphenyl-2-picryl hydrazyl radical (DPPH) and nitric oxide scavenging activities were used to evaluate antioxidant activities and mineral contents were determined by atomic absorption spectroscopy. Gallic acid content was determined by HPLC. Resin produced statistically significant inhibition of edema at all doses when compared to the control groups. A 100% inhibition of inflammation was observed at 800 mg/kg i.p. Resin exhibit no toxicity up to 3 g/kg body weights i.p. in mice. Weak DPPH and nitric oxide scavenging activities were observed but showed good Fe2+ chelating ability (IC50 = 162 microg ml(-1)). The amount of elements was decreased in the order: Cu > Fe, Zn > Mn > Ni, Cd. Gallic acid content was 0.1 mg/g resin. These experimental data support the use of Pistacia lentiscus resin as an antiinflammatory and antioxidant agent.

Research into the functional components and antioxidant activities of North China rice wine (Ji Mo Lao Jiu)

PubMed Central

He, Shuai; Mao, Xiangzhao; Liu, Pei; Lin, Hong; Du, Zuyuan; Lv, Ning; Han, Jichen; Qiu, Cuifang

2013-01-01

Over the last decade, considerable experimental evidence has supported the view that grape wine and South China rice wine are rich in diverse nutrients and have powerful antioxidant activity. However, little research has been carried out for North China rice wine, of which Ji Mo Lao Jiu (JMLJ) is the outstanding representative. In this study, the functional components and antioxidant activity of JMLJ were investigated. Twenty-eight free amino acids were found in JMLJ, much more than that previously reported in other Chinese rice wines (16–21). Functional oligosaccharides (5290.222 mg/L), total phenols (722.431 ± 10.970 mg/L), and mineral elements (9) were rich in JMLJ. When compared with synthetic antioxidants, such as butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), JMLJ showed effective 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging and reducing capacity. The results of this study lay the foundation for promoting the utilization of JMLJ and the development of North China rice wine in the food industry. PMID:24804035

Optimization of β-cyclodextrin-based extraction of antioxidant and anti-browning activities from thyme leaves by response surface methodology.

PubMed

Favre, Leonardo Cristian; Dos Santos, Cristina; López-Fernández, María Paula; Mazzobre, María Florencia; Buera, María Del Pilar

2018-11-01

Thyme (Thymus vulgaris) has been demonstrated to extend the shelf-life of food products, being also a potential source of bioactive compounds. The aim of this research was to optimize the ultrasound assisted extraction employing β-cyclodextrin aqueous solutions as no-contaminant technology and Response Surface Methodology to obtain thyme extracts with the maximum antioxidant capacity. The optimal extraction conditions were: a solution of β-ciclodextrin 15 mM, an ultrasonic treatment time of 5.9 min at a temperature of 36.6 °C. They resulted in an extract with a polyphenolic content of 189.3 mg GAE/mL, an antioxidant activity (DPPH) of 14.8 mg GAE/mL, and ferric reducing/antioxidant power (FRAP) of 3.3 mg GAE/mL. Interestingly, the extract demonstrated to inhibit the production of Maillard browning products and can be considered a potential antiglycant agent. The obtained data is important for developing eco-friendly technologies in order to obtain natural antioxidant extracts with a potential inhibitory capacity of Maillard glycation reaction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Oxidant-Induced Cell Death and Nrf2-Dependent Antioxidative Response Are Controlled by Fra-1/AP-1

PubMed Central

Vaz, Michelle; Machireddy, Narsa; Irving, Ashley; Potteti, Haranatha R.; Chevalier, Karinne; Kalvakolanu, Dhananjaya

2012-01-01

AP-1 (Jun/Fos) transcription factors play key roles in various biological processes, including cell death. Here we report a novel role for Fra-1 in oxidant-induced cell death controlled by modulating antioxidant gene expression. Fra-1-deficient (Fra-1Δ/Δ) mouse embryonic fibroblasts (MEFs) and primary lung fibroblasts (PLFs) were remarkably resistant to H2O2- and diquat-induced cell death, compared to their wild-type (Fra-1+/+) counterparts. Fra-1 deficiency ablated oxidant-induced mitochondrion-dependent apoptosis. Fra-1Δ/Δ cells had elevated basal levels of antioxidant enzymes and intracellular glutathione (GSH), which were further stimulated by oxidants. Loss of Fra-1 led to an increased half-life of transcription factor Nrf2 and increased recruitment of this protein to the promoters of antioxidant genes and increased their expression. Depletion of intracellular GSH or RNA interference (RNAi)-mediated knockdown of Nqo1, Hmox1, and Nrf2 restored oxidant-induced cell death in Fra-1Δ/Δ cells. Thus, Fra-1 appears to increase susceptibility to oxidants and promotes cell death by attenuating Nrf2-driven antioxidant responses. PMID:22393254

Cocoa and chocolate in human health and disease.

PubMed

Katz, David L; Doughty, Kim; Ali, Ather

2011-11-15

Cocoa contains more phenolic antioxidants than most foods. Flavonoids, including catechin, epicatechin, and procyanidins predominate in antioxidant activity. The tricyclic structure of the flavonoids determines antioxidant effects that scavenge reactive oxygen species, chelate Fe2+ and Cu+, inhibit enzymes, and upregulate antioxidant defenses. The epicatechin content of cocoa is primarily responsible for its favorable impact on vascular endothelium via its effect on both acute and chronic upregulation of nitric oxide production. Other cardiovascular effects are mediated through anti-inflammatory effects of cocoa polyphenols, and modulated through the activity of NF-κB. Antioxidant effects of cocoa may directly influence insulin resistance and, in turn, reduce risk for diabetes. Further, cocoa consumption may stimulate changes in redox-sensitive signaling pathways involved in gene expression and the immune response. Cocoa can protect nerves from injury and inflammation, protect the skin from oxidative damage from UV radiation in topical preparations, and have beneficial effects on satiety, cognitive function, and mood. As cocoa is predominantly consumed as energy-dense chocolate, potential detrimental effects of overconsumption exist, including increased risk of weight gain. Overall, research to date suggests that the benefits of moderate cocoa or dark chocolate consumption likely outweigh the risks.

Synthesis, spectroscopic characterization, crystal structure, DNA interaction study and invitro biological screenings of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid

NASA Astrophysics Data System (ADS)

Sirajuddin, Muhammad; Nooruddin; Ali, Saqib; McKee, Vickie; Khan, Shahan Zeb; Malook, Khan

2015-01-01

The titled compound, 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid was synthesized and characterized by various techniques like elemental analyses, FT-IR, NMR (1H, and 13C) and single crystal X-ray structural analysis. The appearance of the OH peak of the carboxylic acid in the FT-IR and NMR spectra conform the formation of the compound. A good agreement was found between the calculated values of C, H, N and found values in elemental analysis that show the purity of the compound. Protons H2 and H3 are in cis conformation with each other as conformed both from 1H NMR as well as from single crystal X-ray analysis. The molecular structure of the title compound, C10H10NO3Cl, is stabilized by short intramolecular Osbnd H- - -O hydrogen bonds within the molecule. In the crystal structure, intermolecular Nsbnd H- - -O hydrogen bonds link molecules into zigzag chains resulting in a dendrimer like structure. The title compound was screened for biological activities like interaction with DNA, cytotoxicity, antitumor and antioxidant activities. DNA interaction study reveals that the binding mode of interaction of the compound with SS-DNA is intercalative as it results in hypochromism along with significant red shift of 5 nm. It was also found to be effective antioxidant of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and show almost comparable antioxidant activity to that of the standard and known antioxidant, ascorbic acid, at higher concentration. The antitumor activity data of the compound shows that it can be used as potent antitumor agent.

Effect of some light rare earth elements on seed germination, seedling growth and antioxidant metabolism in Triticum durum.

PubMed

d'Aquino, Luigi; de Pinto, Maria Concetta; Nardi, Luca; Morgana, Massimo; Tommasi, Franca

2009-05-01

Rare earth elements (REEs) enriched fertilizers have been commonly used in China since the 1980s, thus inducing a growing concern about their environmental impact in agriculture. In this work, the effect of some light REEs nitrate mixture and La(3+) nitrate on seed germination, seedling growth and antioxidant metabolism in Triticum durum was investigated with the aim of clarifying the potential benefits or damages of REEs on plants. Seed pre-soaking for 8 h with La(3+) and REEs nitrate inhibited seed germination at low concentrations (0.01 mM and 0.1 mM), while pre-soaking for 2 and 4 h already inhibited seed germination when higher concentrations (1 mM and 10 mM) of La(3+) and REEs nitrate were used. La(3+) and REEs nitrate treatment also affected seedling growth. Root growth was enhanced and inhibited at low and high concentrations, respectively. Shoot growth was inhibited by La(3+) and REEs nitrate at all tested concentrations after 12 d of treatments. Enzymatic and non enzymatic antioxidants were differently affected by La(3+) and REEs nitrate and their behaviour changed also depending on the plant organ. In roots La(3+) and REEs nitrate treatments induced an increase in ascorbate (ASC) and glutathione (GSH) contents. In shoots only La(3+) nitrate induced an increase in the ASC content whereas GSH decreased following both La(3+) and REEs nitrate treatments. An increase in ASC peroxidase activity was observed in shoots and roots, while catalase did not change in roots and slightly decreased in shoots. The possible role of the increase in some antioxidants as indicators of stress caused by lanthanide treatments is discussed.

Bio-antioxidants - a chemical base of their antioxidant activity and beneficial effect on human health.

PubMed

Kancheva, V D; Kasaikina, O T

2013-01-01

The paradox of aerobic life is that higher eukaryotic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. Autoxidation of organic substances frequently occurs via free radical mechanism which generates different active radicals and peroxides OH(•), O2 (•-), LO2 (•), HOOH, LOOH, so called reactive oxygen species (ROS), which appear to be responsible for oxygen toxicity. To survive in such an unfriendly oxygen environment, living organisms generate - or obtain from food - a variety of water- and lipid-soluble antioxidant compounds. Biologically active compounds with antioxidant potential, i.e. bio-antioxidants (natural and their synthetic analogues) have a wide range of applications. They are important drugs, antibiotics, agrochemical substitutes, and food preservatives. Many of the drugs today are synthetic modifications of naturally obtained substances. This review presents information about the chemical base of antioxidant activities and beneficial effects on human health of known and new bio-antioxidants. There is abundant literature on the phenolic antioxidants and tocopherols in particular. In this review the following bio-antioxidants are considered: A) Carotenoids, B) Cathecholamines, C) Phospholipids, D) Chalcones, E) Coumarins, F) Phenolic acids, G) Flavonoids, H) Lignans, and I) Tannins.

Effect of dietary mannanoligosaccharide supplementation on nutrient digestibility, hindgut fermentation, immune response and antioxidant indices in dogs.

PubMed

Pawar, Mahesh M; Pattanaik, Ashok K; Sinha, Dharmendra K; Goswami, Tapas K; Sharma, Kusumakar

2017-01-01

Use of prebiotics in companion animal nutrition is often considered advantageous over probiotics because of the ease of handling, ability to withstand processing and storage etc. While most of the studies on prebiotic use in dogs have been done with processed food as basal diet, the response in relation to homemade diet feeding is not very well explored. The study was conducted to evaluate the effects of dietary mannanoligosaccharide (MOS) supplementation on nutrient digestibility, hindgut fermentation, immune response and antioxidant indices in dogs. Ten Spitz pups were divided into two groups: control (CON) with no supplementation, and experimental (MOS) wherein the basal diet was supplemented with MOS at 15 g/kg diet. All dogs were fed on a home-prepared diet for a period of 150 days. The study protocol included a digestion trial, periodic blood collection and analysis for lipid profile and erythrocytic antioxidants. Immune response of the animals was assessed towards the end of the feeding period. Results revealed no significant ( P > 0.05 ) variations in palatability score, intake and apparent digestibility of nutrients between the groups. Faecal score, faeces voided, faecal pH, concentrations of ammonia, lactate and short-chain fatty acids were comparable ( P > 0.05 ) between the two groups. Cell-mediated immune response, assessed as delayed-type of hypersensitivity response, was significantly higher ( P < 0.05 ) in the MOS group. The percent of lymphocyte sub-populations CD4+ and ratio of CD4+:CD8+ were also significantly ( P < 0.05 ) higher in MOS group. The serum IgG levels were similar ( P > 0.05 ) in both the groups. Supplementation of MOS lowered ( P < 0.05 ) serum total- and LDL- cholesterol levels, when compared with the control group. The erythrocytic antioxidant indices were similar ( P > 0.05 ) between the two groups. The results indicated that supplementation of MOS at the rate of 15 g/kg in the diet of dog augmented the cell-mediated immune response and serum lipid profile without any influences on digestibility of nutrients, hindgut fermentation and antioxidants indices.

THE RELATIONSHIP BETWEEN OZONE-INDUCED LUNG INJURY, ANTIOXIDANT COMPENSATION AND UNDERLYING CARDIOVASCULAR DISEASE (CVD).

EPA Science Inventory

Increased levels of oxidants and compromised compensatory response are associated with CVD susceptibility. We hypothesized that rat strains demonstrating genetic CVD will have lower levels of antioxidants and greater ozone-induced pulmonary injury relative to healthy strains. Mal...

Comparison of physiological and antioxidant responses of Anoda cristata and cotton to progressive drought

USDA-ARS?s Scientific Manuscript database

Simultaneous investigation of variables related to gas exchange, photochemistry and antioxidant defenses during water stress is crucial for understanding stress tolerance mechanisms and consequent success of both economically important plant species and their interfering counterparts. This study ev...

Antioxidant effect of green tea on polymer gel dosimeter

NASA Astrophysics Data System (ADS)

Samuel, E. J. J.; Sathiyaraj, P.; Deena, T.; Kumar, D. S.

2015-01-01

Extract from Green Tea (GTE) acts as an antioxidant in acrylamide based polymer gel dosimeter. In this work, PAGAT gel was used for investigation of antioxidant effect of GTE.PAGAT was called PAGTEG (Polyacrylamide green tea extract gel dosimeter) after adding GTE. Free radicals in water cause pre polymerization of polymer gel before irradiation. Polyphenols from GTE are highly effective to absorb the free radicals in water. THPC is used as an antioxidant in polymer gel dosimeter but here we were replaced it by GTE and investigated its effect by spectrophotometer. GTE added PAGAT samples response was lower compared to THPC added sample. To increase the sensitivity of the PAGTEG, sugar was added. This study confirmed that THPC was a good antioxidant for polymer gel dosimeter. However, GTE also can be used as an antioxidant in polymer gel if use less quantity (GTE) and add sugar as sensitivity enhancer.

Antioxidant response to metal pollution in Phragmites australis from Anzali wetland.

PubMed

Esmaeilzadeh, Marjan; Karbassi, Abdolreza; Bastami, Kazem Darvish

2017-06-15

This research was conducted to examine variations of antioxidant enzyme activity in Phragmites australis as a biomarker for metals such as As, Pb, Cu, and Cd. Samples of sediment and plants were collected from 7 stations located in Anzali wetland. Biochemical parameters including Catalase, Peroxidase and Ascorbate Peroxidase activity were analyzed in the roots, stems and leaves of P. australis. The obtained results indicated that there were significant differences among activities of antioxidant enzymes in three organs (p<0.05). Antioxidant enzyme activities in the organs for all studied stations were as the following order: stem

Role of the flavonoid-rich fraction in the antioxidant and cytotoxic activities of Bauhinia forficata Link. (Fabaceae) leaves extract.

PubMed

Miceli, Natalizia; Buongiorno, Luigina Pasqualina; Celi, Maria Grazia; Cacciola, Francesco; Dugo, Paola; Donato, Paola; Mondello, Luigi; Bonaccorsi, Irene; Taviano, Maria Fernanda

2016-06-01

Bauhinia forficata Link. is utilised as an antidiabetic in Brazilian folk-medicine; furthermore, its antioxidant properties suggest a potential usefulness in the prevention of diabetes complications associated with oxidative stress. The contribution of a flavonoid-rich fraction (FRF), HPLC-PDA-ESI-MS characterised, to the antioxidant and cytotoxic properties of B. forficata hydro-alcoholic leaves extract was evaluated for the first time. Both extract and FRF showed radical-scavenging activity and reducing power with a strong relationship with the flavonoid content found; hence, flavonoids are mainly responsible for the primary antioxidant activity of B. forficata extract. The extract significantly decreased FO-1 cell viability at the higher concentrations. FRF did not exert any effect; thus, flavonoids do not appear to be responsible for the cytotoxicity of the extract. The extract resulted virtually non-toxic against both Artemia salina and normal human lymphocytes, demonstrating potential selectivity in inhibiting cancer cell growth. Finally, no antimicrobial activity was observed against the bacteria and yeasts tested.

Nrf2: A Novel Biomarker of Disease Severity and Target for Therapeutic Intervention in Multiple Sclerosis

DTIC Science & Technology

2013-10-01

transcription factor that controls expression of genes encoding important antioxidant and stress response proteins through binding to the antioxidant response...abundant in many species from the Cucurbita family such as cucumber, watermelon , melon root, culture from radicle. To facilitate further studies of the...via Griess assay in LPS- activated cells treated with BA for 24 h. (B) viability was measured by the MTT assay. (C) iNOS protein levels were

Herbicidal and antioxidant responses of transgenic rice overexpressing Myxococcus xanthus protoporphyrinogen oxidase.

PubMed

Jung, Sunyo; Back, Kyoungwhan

2005-05-01

We analyzed the herbicidal and antioxidant defense responses of transgenic rice plants that overexpressed the Myxococcus xanthus protoporphyrinogen oxidase gene. Leaf squares of the wild-type incubated with oxyfluorfen were characterized by necrotic leaf lesions and increases in conductivity and malonyldialdehyde levels, whereas transgenic lines M4 and M7 did not show any change with up to 100 microM oxyfluorfen. The wild-type had decreased F(v)/F(m) and produced a high level of H(2)O(2) at 18 h after foliar application of oxyfluorfen, whereas transgenic lines M4 and M7 were unaffected. In response to oxyfluorfen, violaxanthin, beta-carotene, and chlorophylls (Chls) decreased in wild-type plants, whereas antheraxanthin and zeaxanthin increased. Only a slight decline in Chls was observed in transgenic lines at 48 h after oxyfluorfen treatment. Noticeable increases of cytosolic Cu/Zn-superoxide dismutase, peroxidase isozymes 1 and 2, and catalase were observed after at 48 h of oxyfluorfen treatment in the wild-type. Non-enzymatic antioxidants appeared to respond faster to oxyfluorfen-induced photodynamic stress than did enzymatic antioxidants. Protective responses for the detoxification of active oxygen species were induced to counteract photodynamic stress in oxyfluorfen-treated, wild-type plants. However, oxyfluorfen-treated, transgenic plants suffered less oxidative stress, confirming increased herbicidal resistance resulted from dual expression of M. xanthus Protox in chloroplasts and mitochondria.

Antioxidant defense response induced by Trichoderma viride against Aspergillus niger Van Tieghem causing collar rot in groundnut (Arachis hypogaea L.).

PubMed

Gajera, H P; Katakpara, Zinkal A; Patel, S V; Golakiya, B A

2016-02-01

The study was conducted to examine the antioxidant enzymes induced by Trichoderma viride JAU60 as initial defense response during invasion of rot pathogen Aspergillus niger Van Tieghem in five groundnut varieties under pot culture. Seed treatment of T. viride JAU60 reduced 51-58% collar rot disease incidence in different groundnut varieties under pathogen infected soil culture. The activities of the antioxidant enzymes, viz., superoxide dismutase (SOD, EC 1.15.1.1), guaiacol peroxidase (GPX, EC 1.11.1.7) and ascorbate peroxidase (APX, EC 1.11.1.11), elevated in response to pathogen infection, in higher rate by tolerant varieties (J-11 and GG-2) compared with susceptible (GAUG-10, GG-13, GG-20) and further induced by T. viride treatment. Trichoderma treatment remarkably increased the 2.3 fold SOD, 5 fold GPX and 2.5 fold APX activities during disease development in tolerant varieties and the same was found about 1.2, 1.5 and 2.0 folds, respectively, in susceptible varieties. Overall, T. viride JAU60 treated seedlings (T3) witnessed higher activities of SOD (1.5 fold), GPX (3.25 fold) and APX (1.25 fold) than pathogen treatment (T2) possibly suggest the induction of antioxidant defense response by Trichoderma bio-controller to combat oxidative burst produced by invading pathogen. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Selenium: the physiopathological and clinical implications].

PubMed

Tato Rocha, R E; Cárdenas Viedma, E; Herrero Huerta, E

1994-09-01

Selenium is an ultra-trace element widely distributed in the environment, although its consumption varies significantly depending on the region. Its daily requirements range between 50 and 200 micrograms/day (or a minimum of 1 microgram/kg/day), which are supplied by animal and vegetal foods. Its essentiality in human nutrition is derived from its antioxidative action, being a part of the glutation-peroxidase system (GPx). Thus, it is a protective agent against the harmful action of free radicals. Determination of the selenium-dependent GPx activity seems to be the best index for the assessment of nutritional status. A deficit of selenium will result in a decrease of the GPx activity and, therefore, in a increase of cell damage which cannot be counter-balanced by other antioxidative systems. Diet has a relevant role for the maintenance of selenium status. Deficiency conditions may appear in different population groups when the selenium content in the diet is inadequate. Toxicity states are rare, but some diseases are sensitive to this element, which is mainly involved in cancer prevention.

A comparative study on oxidative stress response in the hepatopancreas and midgut of the white shrimp Litopenaeus vannamei under gradual changes to low or high pH environment.

PubMed

Han, Si-Yin; Wang, Meng-Qiang; Wang, Bao-Jie; Liu, Mei; Jiang, Ke-Yong; Wang, Lei

2018-05-01

White shrimp Litopenaeus vannamei were reared under conditions of gradual changes to a low pH (gradual-low pH, 6.65-8.20) or a high pH (gradual-high pH, 8.20-9.81) versus a normal pH environment (8.14-8.31) during a 28-day period. Survival of shrimp, and ROS production, antioxidant responses and oxidative damage in the hepatopancreas and midgut were investigated. Consequently, shrimp enhanced MnSOD, GPx, and Hsp70 transcripts as early defense mechanism in the hepatopancreas and midgut to scavenge excessive ROS during short-term (≤ 7 days) gradual-low and high pH stress. Meanwhile, the hepatopancreas was more sensitive to ROS than midgut because of earlier ROS production increase, antioxidant response and oxidative damage. Then, suppressed antioxidant response in the hepatopancreas and midgut of shrimp suggested a loss of antioxidant regulatory capacity caused by aggravated oxidative damage after long-term (≥ 14 days) gradual-high pH stress, leading to continuous death. However, enhanced GPx, GST, and Hsp70 transcripts in the hepatopancreas and midgut might be long-term(≥ 14 days) antioxidant adaptation mechanism of shrimp to gradual-low pH stress, which could prevent further ROS perturbation and weaken oxidative damage to achieve a new immune homeostasis, contributing to stable survival rate. Therefore, we have a few insights that it is necessary to protect hepatopancreas for controlling shrimp death under gradual-high pH stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection.

PubMed

Bolukbas, Cengiz; Bolukbas, Fusun Filiz; Horoz, Mehmet; Aslan, Mehmet; Celik, Hakim; Erel, Ozcan

2005-10-31

Oxidative stress can be defined as an increase in oxidants and/or a decrease in antioxidant capacity. There is limited information about the oxidative status in subjects with hepatitis B virus infection. We aimed to evaluate the oxidative status in patients with various clinical forms of chronic hepatitis B infection. Seventy-six patients with hepatitis B virus infection, in whom 33 with chronic hepatitis, 31 inactive carriers and 12 with cirrhosis, and 16 healthy subjects were enrolled. Total antioxidant response and total peroxide level measurement, and calculation of oxidative stress index were performed in all participants. Total antioxidant response was significantly lower in cirrhotics than inactive HbsAg carriers and controls (p = 0.008 and p = 0.008, respectively). Total peroxide level and oxidative stress index was significantly higher in cirrhotic (p < 0.001, both) and chronic hepatitis B subjects (p < 0.001, both) than inactive HbsAg carriers and controls. Total antioxidant response was comparable in chronic hepatitis B subjects, inactive HbsAg carriers and controls (both, p > 0.05/6). Total peroxide level and oxidative stress index were also comparable in inactive HBsAg carriers and controls (both, p > 0.05/6). Serum alanine amino transferase level was positively correlated with total peroxide level and oxidative stress index only in chronic hepatitis B subjects (p = 0.002, r = 0.519 and p = 0.008, r = 0.453, respectively). Oxidative stress occurs secondarily to increased total lipid peroxidation and inadequate total antioxidant response and is related to severity of the disease and replication status of virus in hepatitis B infection.

Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection

PubMed Central

Bolukbas, Cengiz; Bolukbas, Fusun Filiz; Horoz, Mehmet; Aslan, Mehmet; Celik, Hakim; Erel, Ozcan

2005-01-01

Background Oxidative stress can be defined as an increase in oxidants and/or a decrease in antioxidant capacity. There is limited information about the oxidative status in subjects with hepatitis B virus infection. We aimed to evaluate the oxidative status in patients with various clinical forms of chronic hepatitis B infection. Methods Seventy-six patients with hepatitis B virus infection, in whom 33 with chronic hepatitis, 31 inactive carriers and 12 with cirrhosis, and 16 healthy subjects were enrolled. Total antioxidant response and total peroxide level measurement, and calculation of oxidative stress index were performed in all participants. Results Total antioxidant response was significantly lower in cirrhotics than inactive HbsAg carriers and controls (p = 0.008 and p = 0.008, respectively). Total peroxide level and oxidative stress index was significantly higher in cirrhotic (p < 0.001, both) and chronic hepatitis B subjects (p < 0.001, both) than inactive HbsAg carriers and controls. Total antioxidant response was comparable in chronic hepatitis B subjects, inactive HbsAg carriers and controls (both, p > 0.05/6). Total peroxide level and oxidative stress index were also comparable in inactive HBsAg carriers and controls (both, p > 0.05/6). Serum alanine amino transferase level was positively correlated with total peroxide level and oxidative stress index only in chronic hepatitis B subjects (p = 0.002, r = 0.519 and p = 0.008, r = 0.453, respectively). Conclusion Oxidative stress occurs secondarily to increased total lipid peroxidation and inadequate total antioxidant response and is related to severity of the disease and replication status of virus in hepatitis B infection. PMID:16262897

Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention

PubMed Central

Liu, Hua; Talalay, Paul

2013-01-01

Exemestane (6-methyleneandrosta-1,4-diene-3,17-dione) is a synthetic steroidal inhibitor of the aromatase reaction that catalyzes the terminal and rate-limiting step of the biosynthesis of estrogens. It is active clinically in preventing, delaying progression of, and treating mammary cancers, many of which are estrogen receptor-positive. A striking feature of the structure of exemestane is an extended system of conjugated Michael reaction functions, which is also characteristic of inducers of a broad network of chemoprotective genes regulated by the Keap1 (Kelch-like ECA-associated protein)/Nrf2 (nuclear factor E2-related factor 2)/ARE (antioxidant response element) signaling system. These genes are largely involved in xenobiotic metabolism and antioxidative and anti-inflammatory protection, as well as the synthesis and reduction of glutathione. We show here that exemestane transcriptionally activates NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1), typical chemoprotective gene products, in a wide variety of mouse, rat, and human cells. It protects several cell lines against oxidative toxicity of tert-butyl hydroperoxide and 4-hydroxynonenal, against free radical damage arising from hypoxia–reoxygenation, and against UVA radiation damage. Exemestane also inhibits the inflammatory increases in inducible nitric oxide synthase (iNOS) in mouse macrophages exposed to LPS (lipopolysaccharide), thereby resembling the isothiocyanate sulforaphane derived from broccoli. Remarkably, combinations of exemestane and sulforaphane act highly synergistically, and this property is also displayed by several other phytochemicals. Thus, exemestane has a wide range of previously unrecognized protective activities, probably unrelated to aromatase inhibition. Its potential for reducing the risk, not only of breast cancer, but also of other chronic diseases that arise from inflammation, oxidative stress, and DNA-damaging electrophiles, requires exploration, particularly in view of the synergism with other phytochemicals. PMID:24191056

Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention.

PubMed

Liu, Hua; Talalay, Paul

2013-11-19

Exemestane (6-methyleneandrosta-1,4-diene-3,17-dione) is a synthetic steroidal inhibitor of the aromatase reaction that catalyzes the terminal and rate-limiting step of the biosynthesis of estrogens. It is active clinically in preventing, delaying progression of, and treating mammary cancers, many of which are estrogen receptor-positive. A striking feature of the structure of exemestane is an extended system of conjugated Michael reaction functions, which is also characteristic of inducers of a broad network of chemoprotective genes regulated by the Keap1 (Kelch-like ECA-associated protein)/Nrf2 (nuclear factor E2-related factor 2)/ARE (antioxidant response element) signaling system. These genes are largely involved in xenobiotic metabolism and antioxidative and anti-inflammatory protection, as well as the synthesis and reduction of glutathione. We show here that exemestane transcriptionally activates NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1), typical chemoprotective gene products, in a wide variety of mouse, rat, and human cells. It protects several cell lines against oxidative toxicity of tert-butyl hydroperoxide and 4-hydroxynonenal, against free radical damage arising from hypoxia-reoxygenation, and against UVA radiation damage. Exemestane also inhibits the inflammatory increases in inducible nitric oxide synthase (iNOS) in mouse macrophages exposed to LPS (lipopolysaccharide), thereby resembling the isothiocyanate sulforaphane derived from broccoli. Remarkably, combinations of exemestane and sulforaphane act highly synergistically, and this property is also displayed by several other phytochemicals. Thus, exemestane has a wide range of previously unrecognized protective activities, probably unrelated to aromatase inhibition. Its potential for reducing the risk, not only of breast cancer, but also of other chronic diseases that arise from inflammation, oxidative stress, and DNA-damaging electrophiles, requires exploration, particularly in view of the synergism with other phytochemicals.

Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-beta1 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Hoo-Kyun; Pokharel, Yuba Raj; Lim, Sung Chul

2009-11-01

Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibitedmore » increases in the transforming growth factor-beta1 (TGF-beta1) mRNA and alpha-smooth muscle actin (alpha-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of alpha-SMA and TGF-beta1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of alpha-SMA and TGF-beta1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-beta1 expression via Nrf2/ARE activation.« less

Effects of dietary lipid, vitamins and minerals on total amounts and redox status of glutathione and ubiquinone in tissues of Atlantic salmon (Salmo salar): a multivariate approach.

PubMed

Hamre, Kristin; Torstensen, Bente E; Maage, Amund; Waagbø, Rune; Berge, Rolf K; Albrektsen, Sissel

2010-10-01

The hypothesis of the present study was that Atlantic salmon (Salmo salar) would respond to large variations in supplementation of dietary pro- and antioxidants, and marine lipid, with adjustment of the endogenously synthesised antioxidants, glutathione (GSH) and ubiquinone (UQ). An experiment with 2(7-3) reduced factorial design (the number of cases reduced systematically from 2(7) (full design) to 2(4) (reduced design)) was conducted, where vitamins, minerals and lipid were supplemented in the diet at high and low levels. For the vitamins and minerals the high levels were chosen to be just below anticipated toxic levels and the low levels were just above the requirement (vitamin C, 30 and 1000 mg/kg; vitamin E, 70 and 430 mg/kg; Fe, 70 and 1200 mg/kg; Cu, 8 and 110 mg/kg; Mn, 12 and 200 mg/kg). For astaxanthin, the dietary levels were 10 and 50 mg/kg and for lipid, 150 and 330 g/kg. The experiment was started with post-smolts (148 (sd 17 g)) and lasted for 5 months. The only effect on GSH was a minor increase ( < 10 %) in total concentration in the liver in response to high dietary lipid. GSH redox state was not affected. UQ responded to dietary lipid, astaxanthin and vitamin E, both with regard to total concentration and redox state. Except for an effect of Fe on plasma GSH, the trace elements and vitamin C had no effect on tissue levels and oxidation state of GSH and UQ. This shows that the endogenous redox state is quite robust with regard to variation of dietary pro- and antioxidants in Atlantic salmon.

Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

PubMed

Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R; Masliah, Eliezer; Lipton, Stuart A

2015-06-01

Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2). © 2015 International Society for Neurochemistry.

Protective effects of blueberries (Vaccinium corymbosum L.) extract against cadmium-induced hepatotoxicity in mice.

PubMed

Gong, Pin; Chen, Fu-xin; Wang, Lan; Wang, Jing; Jin, Sai; Ma, Yang-min

2014-05-01

The oxidative status and morphological changes of mouse liver exposed to cadmium chloride (Cd(II)) and therapeutic potential of blueberry (Vaccinium corymbosum L.) extract against Cd(II)-induced hepatic injury were investigated. A variety of parameters were evaluated, including lipid peroxidation (LPO), protein carbonyl (PCO) level, DNA fragment, as well as antioxidative defense system (i.e., superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH)). Elemental analysis and evaluation of morphological changes and NO levels were also performed. Exposure to Cd(II) led to increased LPO and PCO as well as DNA fragment and a reduction of SOD and CAT activities, however, the content of GSH elevated probably due to biological adaptive-response. In contrast, co-treatment of anthocyanin (Ay) inhibited the increased oxidative parameters as well as restored the activities of antioxidative defense system in a dose-dependent manner. Ay administration regained these morphological changes caused by intoxication of Cd(II) to nearly normal levels. Moreover, the accumulation of Cd(II) in liver may be one of the reasons for Cd(II) toxicity and Ay can chelate with Cd(II) to reduce Cd(II) burden. The influence of Cd(II) on the Zn and Ca levels can also be adjusted by the co-administration of Ay. Exposure to Cd(II) led to an increase of NO and Ay reduced NO contents probably by directly scavenging. Potential mechanisms for the protective effect of Ay have been proposed, including its anti-oxidative and anti-inflammatory effect along with the metal-chelating capacity. These results suggest that blueberry extract may be valuable as a therapeutic agent in combating Cd(II)-induced tissue injury. Copyright © 2014 Elsevier B.V. All rights reserved.

The role of Nrf2 in oxidative stress-induced endothelial injuries.

PubMed

Chen, Bo; Lu, Yanrong; Chen, Younan; Cheng, Jingqiu

2015-06-01

Endothelial dysfunction is an important risk factor for cardiovascular disease, and it represents the initial step in the pathogenesis of atherosclerosis. Failure to protect against oxidative stress-induced cellular damage accounts for endothelial dysfunction in the majority of pathophysiological conditions. Numerous antioxidant pathways are involved in cellular redox homeostasis, among which the nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is perhaps the most prominent. Nrf2, a transcription factor with a high sensitivity to oxidative stress, binds to AREs in the nucleus and promotes the transcription of a wide variety of antioxidant genes. Nrf2 is located in the cytoskeleton, adjacent to Keap1. Keap1 acts as an adapter for cullin 3/ring-box 1-mediated ubiquitination and degradation of Nrf2, which decreases the activity of Nrf2 under physiological conditions. Oxidative stress causes Nrf2 to dissociate from Keap1 and to subsequently translocate into the nucleus, which results in its binding to ARE and the transcription of downstream target genes. Experimental evidence has established that Nrf2-driven free radical detoxification pathways are important endogenous homeostatic mechanisms that are associated with vasoprotection in the setting of aging, atherosclerosis, hypertension, ischemia, and cardiovascular diseases. The aim of the present review is to briefly summarize the mechanisms that regulate the Nrf2/Keap1-ARE signaling pathway and the latest advances in understanding how Nrf2 protects against oxidative stress-induced endothelial injuries. Further studies regarding the precise mechanisms by which Nrf2-regulated endothelial protection occurs are necessary for determining whether Nrf2 can serve as a therapeutic target in the treatment of cardiovascular diseases. © 2015 Society for Endocrinology.

Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity

PubMed Central

Stack, Cliona; Jainuddin, Shari; Elipenahli, Ceyhan; Gerges, Meri; Starkova, Natalia; Starkov, Anatoly A.; Jové, Mariona; Portero-Otin, Manuel; Launay, Nathalie; Pujol, Aurora; Kaidery, Navneet Ammal; Thomas, Bobby; Tampellini, Davide; Beal, M. Flint; Dumont, Magali

2014-01-01

Methylene blue (MB, methylthioninium chloride) is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Among its beneficial properties are its abilities to act as an antioxidant, to reduce tau protein aggregation and to improve energy metabolism. These actions are of particular interest for the treatment of neurodegenerative diseases with tau protein aggregates known as tauopathies. The present study examined the effects of MB in the P301S mouse model of tauopathy. Both 4 mg/kg MB (low dose) and 40 mg/kg MB (high dose) were administered in the diet ad libitum from 1 to 10 months of age. We assessed behavior, tau pathology, oxidative damage, inflammation and numbers of mitochondria. MB improved the behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice. These beneficial effects were associated with increased expression of genes regulated by NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE), which play an important role in antioxidant defenses, preventing protein aggregation, and reducing inflammation. The activation of Nrf2/ARE genes is neuroprotective in other transgenic mouse models of neurodegenerative diseases and it appears to be an important mediator of the neuroprotective effects of MB in P301S mice. Moreover, we used Nrf2 knock out fibroblasts to show that the upregulation of Nrf2/ARE genes by MB is Nrf2 dependent and not due to secondary effects of the compound. These findings provide further evidence that MB has important neuroprotective effects that may be beneficial in the treatment of human neurodegenerative diseases with tau pathology. PMID:24556215

Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity.

PubMed

Stack, Cliona; Jainuddin, Shari; Elipenahli, Ceyhan; Gerges, Meri; Starkova, Natalia; Starkov, Anatoly A; Jové, Mariona; Portero-Otin, Manuel; Launay, Nathalie; Pujol, Aurora; Kaidery, Navneet Ammal; Thomas, Bobby; Tampellini, Davide; Beal, M Flint; Dumont, Magali

2014-07-15

Methylene blue (MB, methylthioninium chloride) is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Among its beneficial properties are its abilities to act as an antioxidant, to reduce tau protein aggregation and to improve energy metabolism. These actions are of particular interest for the treatment of neurodegenerative diseases with tau protein aggregates known as tauopathies. The present study examined the effects of MB in the P301S mouse model of tauopathy. Both 4 mg/kg MB (low dose) and 40 mg/kg MB (high dose) were administered in the diet ad libitum from 1 to 10 months of age. We assessed behavior, tau pathology, oxidative damage, inflammation and numbers of mitochondria. MB improved the behavioral abnormalities and reduced tau pathology, inflammation and oxidative damage in the P301S mice. These beneficial effects were associated with increased expression of genes regulated by NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE), which play an important role in antioxidant defenses, preventing protein aggregation, and reducing inflammation. The activation of Nrf2/ARE genes is neuroprotective in other transgenic mouse models of neurodegenerative diseases and it appears to be an important mediator of the neuroprotective effects of MB in P301S mice. Moreover, we used Nrf2 knock out fibroblasts to show that the upregulation of Nrf2/ARE genes by MB is Nrf2 dependent and not due to secondary effects of the compound. These findings provide further evidence that MB has important neuroprotective effects that may be beneficial in the treatment of human neurodegenerative diseases with tau pathology. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In vitro antioxidant profiling of seabuckthorn varieties and their adaptogenic response to high altitude-induced stress

NASA Astrophysics Data System (ADS)

Sharma, Priyanka; Suryakumar, Geetha; Singh, Virendra; Misra, Kshipra; Singh, Shashi Bala

2015-08-01

In the past few years, seabuckthorn plants have gained special attention due to their ability to grow in the harshest of the environment. This adaptability may be contributed by various antioxidants present in the plants besides other morphological adaptation. As in vivo studies cannot be justified without in vitro studies, the present investigation carried out evaluation of both in vitro and in vivo antioxidant potentials of aqueous and alcoholic extracts of the leaves of Hippophae salicifolia (HS) and Hippophae rhamnoides mongolica (HRM) in comparison with Hippophae rhamnoides turkestanica (HRT). The results had clearly depicted that in vitro antioxidant potential of the extracts was responsible for the in vivo adaptogenic performance in animals during cold and hypoxia exposure under restraint stress. Total phenolic content (TPC), total flavonoid content (TFC), total protein content, and antioxidant potential were determined. For adaptogenic studies, rats with oral drug supplementation were exposed to Cold-hypoxia-restraint (C-H-R) stresses-induced hypothermia, as a measure of endurance. Aqueous extracts of HS showed maximum (99 %) resistance compared to HRT (81 %) and HRM (29 %). The levels of biochemical parameters such as malondialdehyde (MDA), reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione (GSH/GSSG), and catalase (CAT) in blood samples also revealed that the aqueous leaf extract of HS has better antioxidant and adaptogenic potential compared to HRM.

Bauhinia variegata leaf extracts exhibit considerable antibacterial, antioxidant, and anticancer activities.

PubMed

Mishra, Amita; Sharma, Amit Kumar; Kumar, Shashank; Saxena, Ajit K; Pandey, Abhay K

2013-01-01

The present study reports the phytochemical profiling, antimicrobial, antioxidant, and anticancer activities of Bauhinia variegata leaf extracts. The reducing sugar, anthraquinone, and saponins were observed in polar extracts, while terpenoids and alkaloids were present in nonpolar and ethanol extracts. Total flavonoid contents in various extracts were found in the range of 11-222.67 mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions exhibited considerable inhibition against Klebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains of E. coli, Proteus spp. and Pseudomonas spp. Minimum bactericidal concentration (MBC) values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest MBC (3.5 mg/mL) was recorded for ethanol extract against Pseudomonas spp. The antioxidant activity of the extracts was compared with standard antioxidants. Dose dependent response was observed in reducing power of extracts. Polar extracts demonstrated appreciable metal ion chelating activity at lower concentrations (10-40 μg/mL). Many extracts showed significant antioxidant response in beta carotene bleaching assay. AQ fraction of B. variegata showed pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1 human cancer cell lines with 90-99% cell growth inhibitory activity. Ethyl acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1 cell lines. The study demonstrates notable antibacterial, antioxidant, and anticancer activities in B. variegata leaf extracts.

Functional genomic responses to cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR(delta508) in the lung.

PubMed

Xu, Yan; Liu, Cong; Clark, Jean C; Whitsett, Jeffrey A

2006-04-21

Cystic fibrosis (CF), a common lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) that disturbs fluid homeostasis and host defense in target organs. The effects of CFTR and delta508-CFTR were assessed in transgenic mice that 1) lack CFTR expression (Cftr-/-); 2) express the human delta508 CFTR (CFTR(delta508)); 3) overexpress the normal human CFTR (CFTR(tg)) in respiratory epithelial cells. Genes were selected from Affymetrix Murine Gene-Chips analysis and subjected to functional classification, k-means clustering, promoter cis-elements/modules searching, literature mining, and pathway exploring. Genomic responses to Cftr-/- were not corrected by expression of CFTR(delta508). Genes regulating host defense, inflammation, fluid and electrolyte transport were similarly altered in Cftr-/- and CFTR(delta508) mice. CFTR(delta508) induced a primary disturbance in expression of genes regulating redox and antioxidant systems. Genomic responses to CFTR(tg) were modest and were not associated with lung pathology. CFTR(tg) and CFTR(delta508) induced genes encoding heat shock proteins and other chaperones but did not activate the endoplasmic reticulum-associated degradation pathway. RNAs encoding proteins that directly interact with CFTR were identified in each of the CFTR mouse models, supporting the hypothesis that CFTR functions within a multiprotein complex whose members interact at the level of protein-protein interactions and gene expression. Promoters of genes influenced by CFTR shared common regulatory elements, suggesting that their co-expression may be mediated by shared regulatory mechanisms. Genes and pathways involved in the response to CFTR may be of interest as modifiers of CF.

Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats.

PubMed

Liu, Wen-Jun; Tang, Hong-Tai; Jia, Yi-Tao; Ma, Bing; Fu, Jin-Feng; Wang, Yu; Lv, Kai-Yang; Xia, Zhao-Fan

2010-09-01

Ischemia-reperfusion (I/R) injury of the kidney is a complex pathophysiological process and a major cause of acute renal failure. It has been shown that I/R injury is related to inflammatory responses and activation of apoptotic pathways. Inhibition of certain elements of inflammatory responses and apoptotic pathway seemed to ameliorate renal I/R injury. As an effective element of Panax notoginseng, NR1 has antioxidant, anti-inflammatory, antiapoptotic, and immune-stimulatory activities. Therefore, we speculate that NR1 can attenuate renal I/R injury. Ischemia-reperfusion injury was induced by renal pedicle ligation followed by reperfusion along with a contralateral nephrectomy. Male Sprague-Dawley rats were randomized to four groups: sham group, I/R control group, NR1-1 group (rats treated with NR1, 20 mg.kg.d) and NR1-2 group (rats treated with NR1, 40 mg.kg.d). All animals were killed 72 h after I/R induction. Blood and renal tissues were collected. Renal dysfunction was observed by the level of serum creatinine and histological evaluation. Apoptosis and inflammatory response in the tissue of kidney were detected mainly with molecular biological methods. NR1 attenuated I/R-induced renal dysfunction as indicated by the level of serum creatinine and histological evaluation. It prevented the I/R-induced increases in the levels of proinflammatory cytokine TNF-alpha, myeloperoxidase activity, phosphorylation of p38, and activation of nuclear factor kappaB with cell apoptosis in the kidney and enhanced expression of antiapoptosis cytokine bcl-2. Treatment with NR1 improves renal function after I/R associated with a significant reduction in cell apoptosis and inflammatory responses, which may be related to p38 and nuclear factor kappaB inhibition.

Glutathione Fine-Tunes the Innate Immune Response toward Antiviral Pathways in a Macrophage Cell Line Independently of Its Antioxidant Properties

PubMed Central

Diotallevi, Marina; Checconi, Paola; Palamara, Anna Teresa; Celestino, Ignacio; Coppo, Lucia; Holmgren, Arne; Abbas, Kahina; Peyrot, Fabienne; Mengozzi, Manuela; Ghezzi, Pietro

2017-01-01

Glutathione (GSH), a major cellular antioxidant, is considered an inhibitor of the inflammatory response involving reactive oxygen species (ROS). However, evidence is largely based on experiments with exogenously added antioxidants/reducing agents or pro-oxidants. We show that depleting macrophages of 99% of GSH does not exacerbate the inflammatory gene expression profile in the RAW264 macrophage cell line or increase expression of inflammatory cytokines in response to the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS); only two small patterns of LPS-induced genes were sensitive to GSH depletion. One group, mapping to innate immunity and antiviral responses (Oas2, Oas3, Mx2, Irf7, Irf9, STAT1, il1b), required GSH for optimal induction. Consequently, GSH depletion prevented the LPS-induced activation of antiviral response and its inhibition of influenza virus infection. LPS induction of a second group of genes (Prdx1, Srxn1, Hmox1, GSH synthase, cysteine transporters), mapping to nrf2 and the oxidative stress response, was increased by GSH depletion. We conclude that the main function of endogenous GSH is not to limit inflammation but to fine-tune the innate immune response to infection. PMID:29033950

Development of a low-cost optical sensor for cupric reducing antioxidant capacity measurement of food extracts.

PubMed

Bener, Mustafa; Ozyürek, Mustafa; Güçlü, Kubilay; Apak, Reşat

2010-05-15

A low-cost optical sensor using an immobilized chromogenic redox reagent was devised for measuring the total antioxidant level in a liquid sample without requiring sample pretreatment. The reagent, copper(II)-neocuproine (Cu(II)-Nc) complex, was immobilized onto a cation-exchanger film of Nafion, and the absorbance changes associated with the formation of the highly colored Cu(I)-Nc chelate as a result of reaction with antioxidants was measured at 450 nm. The sensor gave a linear response over a wide concentration range of standard antioxidant compounds. The trolox equivalent antioxidant capacity (TEAC) values of various antioxidants reported in this work using the optical sensor-based "cupric reducing antioxidant capacity" (CUPRAC) assay were comparable to those of the standard solution-based CUPRAC assay, showing that the immobilized Cu(II)-Nc reagent retained its reactivity toward antioxidants. Common food ingredients like oxalate, citrate, fruit acids, and reducing sugars did not interfere with the proposed sensing method. This assay was validated through linearity, additivity, precision, and recovery, demonstrating that the assay is reliable and robust. The developed optical sensor was used to screen total antioxidant capacity (TAC) of some commercial fruit juices without preliminary treatment and showed a promising potential for the preparation of antioxidant inventories of a wide range of food plants.

The role of ZmWRKY4 in regulating maize antioxidant defense under cadmium stress.

PubMed

Hong, Changyong; Cheng, Dan; Zhang, Guoqiang; Zhu, Dandan; Chen, Yahua; Tan, Mingpu

2017-01-22

WRKY transcription factors act as positive regulators in abiotic stress responses by activation of the cellular antioxidant systems. However, there are few reports on the response of WRKY genes to cadmium (Cd) stress. In this study, the role of maize ZmWRKY4 in regulating antioxidant enzymes in Cd stress was investigated. The results indicated that Cd induced up-regulation of the expression and the activities of ZmWRKY4 and superoxide dismutase (SOD) and ascorbate peroxidase (APX). Transient expression and RNA interference (RNAi) silencing of ZmWRKY4 in maize mesophyll protoplasts further revealed that ZmWRKY4 was required for the abscisic acid (ABA)-induced increase in expression and activity of SOD and APX. Overexpression of ZmWRKY4 in protoplasts upregulated the expression and the activities of antioxidant enzymes, whereas ABA induced increases in the expression and the activities of antioxidant enzymes were blocked by the RNAi silencing of ZmWRKY4. Bioinformatic analysis indicated that ZmSOD4 and ZmcAPX both harbored two W-boxes, binding motif for WRKY transcription factors, in their promoter region. Intriguingly, ZmWRKY4 belongs to group I WRKYs with two WRKY domains. Moreover, the synchronized expression patterns indicate that ZmWRKY4 might play a critical role in either regulating the ZmSOD4 and ZmcAPX expression or cooperating with them in response to stress and phytohormone. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of some metallophthalocyanines with dimethyl 5-(phenoxy)-isophthalate substituents and evaluation of their antioxidant-antibacterial activities

NASA Astrophysics Data System (ADS)

Salih Ağırtaş, M.; Karataş, Ceyhun; Özdemir, Sadin

2015-01-01

The synthesis, characterization, spectral, antioxidant and antibacterial properties of dimethyl 5-(phenoxy)-isophthalate substituted Zinc, Cobalt, Copper, and Nickel phthalocyanines are reported. The novel compounds have been characterized by using electronic absorption, nuclear magnetic resonance spectroscopy, infrared, elemental analysis and mass spectrometry. The antioxidant and antibacterial activities of newly synthesized phthalocyanines and its starting material are tested. The DPPH free radical scavenging ability of phthalocyanine Co(II) and Zn(II) complexes on DPPH are 44.8% and 40.1% at 100 mg/L concentration, respectively. The phthalocyanine Co(II) and Cu(II) complexes show very strong ferrous ion chelating activity of 91.2% and 89.3% at concentration of 100 mg/L, respectively. Compound 3 displays strong reducing power like α-tocopherol. Antibacterial activities of phthalocyanine Co(II) and Amikacin (30 μg/disk) against Micrococcus luteus (ATCC 9341) are 16 mm in diameter.

Effect of short-term treatment with levosimendan on oxidative stress in renal tissues of rats.

PubMed

Gecit, Ilhan; Kavak, Servet; Yüksel, Mehmet Bilgehan; Basel, Halil; Bektas, Hava; Gümrükçüoglu, Hasan Ali; Meral, Ismail; Demir, Halit

2014-02-01

The aim of this study is to evaluate the influences of short-term treatment with levosimendan (chemical formula: C14H12N6O) on oxidative stress and some trace element levels in renal tissues of healthy rats. A total of 20 male Wistar-albino rats were randomly divided into two groups, each consisting of 10 rats. Animals in the first group were not treated with levosimendan and served as control. Animals in the second group were injected intraperitoneally with 12 µg/kg levosimendan and served as levosimendan group. Animals in both the groups were killed 3 days after the treatment, and their kidneys were harvested for the determination of tissue oxidant/antioxidant statues and trace element levels in renal tissues. The tissue malondialdehyde level was significantly (p < 0.001) lower in levosimendan group than in controls. The protective enzyme activities such as superoxide dismutase, catalase, and glutathione peroxidase and antioxidant glutathione level were significantly (p < 0.001) higher in levosimendan group than in controls. It was concluded that levosimendan reduced oxidative stress by avoiding lipid peroxidation and production of reactive oxygen species, and overactivating and/or increasing the protective antioxidant enzyme levels in renal tissues of rats. It is supposed that this experimental study provides beneficial data for clinicians in the management of renal tissue damage related to obstruction and/or ischemia.

Phytochemicals, Monosaccharides and Elemental Composition of the Non-Pomace Constituent of Organic and Conventional Grape Juices (Vitis labrusca L.): Effect of Drying on the Bioactive Content.

PubMed

Haas, Isabel Cristina da Silva; Toaldo, Isabela Maia; de Gois, Jefferson Santos; Borges, Daniel L G; Petkowicz, Carmen Lúcia de Oliveira; Bordignon-Luiz, Marilde T

2016-12-01

Grape and grape derivatives contain a variety of antioxidants that have gain increasing interest for functional foods applications. The chemical composition of grapes is mainly related to grape variety and cultivation factors, and each grape constituent exhib its unique characteristics regarding its bioactive properties. This study investigated the chemical composition and the effect of drying on the bioactive content of the non-pomace constituent obtained in the processing of organic and conventional grape juices from V. labrusca L. The non-pomace samples were analyzed for polyphenols, monosaccharides, antioxidant activity and elemental composition and the effect of drying on the bioactive composition was evaluated in samples subjected to lyophilization and drying with air circulation. The analyses revealed high concentrations of proanthocyanidins, flavanols and anthocyanins, and high antioxidant capacity of the organic and conventional samples. The drying processes reduced significantly (P < 0.05) the total phenolic content that ranged from 13.23 to 36.36 g/kg. Glucose, xylose, and mannose were the predominant monosaccharides, whereas K, Ca and Mg were the most abundant minerals. Variations in the chemical composition of organic and conventional samples were associated with cultivation factors. Nevertheless, this non-pomace constituent is a promising source of nutrients and polyphenols with bioactive potential.

N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viquez, Olga M.; Lai, Barry; Ahn, Jae Hee

2009-08-15

Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas. Firstly, although total copper levels have been shown to increase within the nerve it has not been determined whether copper is increased within the myelin compartment, the primary site of lesion development. Therefore, the distribution of copper in sciatic nerve was characterized using synchrotron X-ray fluorescence microscopy to determine whether the neurotoxic dithiocarbamate, N,N-diethyldithiocarbamate, increases coppermore » levels in myelin. Secondly, because lipid peroxidation is an ongoing process in normal nerve and the levels of lipid peroxidation products produced by dithiocarbamate exposure demonstrated an unusual cumulative dose response in previous studies the biological impact of dithiocarbamate-mediated lipid peroxidation was evaluated. Experiments were performed to determine whether dithiocarbamate-mediated lipid peroxidation products elicit an antioxidant response through measuring the protein expression levels of three enzymes, superoxide dismutase 1, heme oxygenase 1, and glutathione transferase {alpha}, that are linked to the antioxidant response element promoter. To establish the potential of oxidative injury to contribute to myelin injury the temporal relationship of the antioxidant response to myelin injury was determined. Myelin structure in peripheral nerve was assessed using multi-exponential transverse relaxation measurements (MET{sub 2}) as a function of exposure duration, and the temporal relationship of protein expression changes relative to the onset of changes in myelin integrity were determined. Initial assessments were also performed to explore the potential contribution of dithiocarbamate-mediated inhibition of proteasome function and inhibition of cuproenzyme activity to neurotoxicity, and also to assess the potential of dithiocarbamates to promote oxidative stress and injury within the central nervous system. These evaluations were performed using an established model for dithiocarbamate-mediated demyelination in the rat utilizing sciatic nerve, spinal cord and brain samples obtained from rats exposed to N,N-diethyldithiocarbamate (DEDC) by intra-abdominal pumps for periods of 2, 4, and 8 weeks and from non exposed controls. The data supported the ability of DEDC to increase copper within myelin and to enhance oxidative stress prior to structural changes detectable by MET{sub 2}. Evidence was also obtained that the excess copper produced by DEDC in the central nervous system is redox active and promotes oxidative injury.« less

Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?

PubMed Central

Ristow, Michael

2016-01-01

Abstract A popular belief is that reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced during exercise by the mitochondria and other subcellular compartments ubiquitously cause skeletal muscle damage, fatigue and impair recovery. However, the importance of ROS and RNS as signals in the cellular adaptation process to stress is now evident. In an effort to combat the perceived deleterious effects of ROS and RNS it has become common practice for active individuals to ingest supplements with antioxidant properties, but interfering with ROS/RNS signalling in skeletal muscle during acute exercise may blunt favourable adaptation. There is building evidence that antioxidant supplementation can attenuate endurance training‐induced and ROS/RNS‐mediated enhancements in antioxidant capacity, mitochondrial biogenesis, cellular defence mechanisms and insulin sensitivity. However, this is not a universal finding, potentially indicating that there is redundancy in the mechanisms controlling skeletal muscle adaptation to exercise, meaning that in some circumstances the negative impact of antioxidants on acute exercise response can be overcome by training. Antioxidant supplementation has been more consistently reported to have deleterious effects on the response to overload stress and high‐intensity training, suggesting that remodelling of skeletal muscle following resistance and high‐intensity exercise is more dependent on ROS/RNS signalling. Importantly there is no convincing evidence to suggest that antioxidant supplementation enhances exercise‐training adaptions. Overall, ROS/RNS are likely to exhibit a non‐linear (hormetic) pattern on exercise adaptations, where physiological doses are beneficial and high exposure (which would seldom be achieved during normal exercise training) may be detrimental. PMID:26638792

Antioxidant and vascular protective activities of Cratoxylum formosum, Syzygium gratum and Limnophila aromatica.

PubMed

Kukongviriyapan, Upa; Luangaram, Saowanee; Leekhaosoong, Krissadarut; Kukongviriyapan, Veerapol; Preeprame, Srisomporn

2007-04-01

Phytochemicals contained in dietary plants provide a variety of health benefits and may reduce the risk of cardiovascular diseases. The aqueous extracts from three popular Thai dietary and herbal plants, Cratoxylum formosum, Syzygium gratum, and Limnophila aromatica, were investigated for the antioxidant and vascular protective activities in the in vitro and in vivo models. The free radical scavenging and antioxidant activities of plant extracts were evaluated in vitro by the 1,1-diphenyl-2-picrylhydrazyl assay, the ferric reducing antioxidant power assay, the intracellular antioxidant activity in rat peritoneal macrophages by dihydrofluorescein assay, and the inhibition of nitric oxide (NO) production in RAW 264.7 macrophages. In an animal model of oxidative stress and vascular dysfunction, male Sprague-Dawley rats were orally administered with aqueous plant extracts (1 g/kg/d) or N-acetylcysteine (NAC; 300 mg/kg/d) as a control for 6 d. On day four, all animals except the normal control group, were administered with phenylhydrazine (PHZ) intraperitoneally. It was demonstrated that the plant extracts possessed high free radical scavenging and antioxidant activities. PHZ induced severe hemolysis and hemodynamic disturbances and treatment with the extracts and NAC significantly improved the hemodynamic status. Vascular responsiveness to bradykinin, acetylcholine, and phenylephrine in PHZ-control rats was markedly impaired, and the plant extracts or NAC largely restored the vascular responses. Moreover, the plant extracts prevented loss of blood reduced glutathione and suppressed formation of plasma malondialdehyde, plasma NO metabolites and blood superoxide anion. It was concluded that the plant extracts possess antioxidants and have potential roles in protection of vascular dysfunction.

Strain Differences in Antioxidants in Rat Models of Cardiovascular Disease Exposed to Ozone

EPA Science Inventory

We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to 03 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH ...

Antioxidant defense system, immune response and erythron profile modulation in gold fish, Carassius auratus, after acute manganese treatment.

PubMed

Aliko, Valbona; Qirjo, Mihallaq; Sula, Eldores; Morina, Valon; Faggio, Caterina

2018-05-01

The manganese contamination has become a global problem, recently, because it is perceived as a real threat to the human health and the environment. It is well-known that overexposure to Mn 2+ may have negative physiological effects on fish and other organisms inhabiting heavy metal polluted waters. To the best of our knowledge, studies relating with manganese effects on fish antioxidant enzyme response in the blood, immunocompetence and erythron profile alteration, are scarce. In this study, the acute sub-lethal effects of manganese on blood antioxidant response, immune status and erythron profile were determined by exposing the freshwater model organism, Carassius auratus, to two doses of this metal (3.88 ± 0.193 mg/L and 7.52 ± 0.234 mg/L Mn 2+ ) for 96 h. Significant increases in blood antioxidant enzyme activity like superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST), were observed in fish exposed to manganese. Furthermore, plasmatic glucose and cortisol levels increased, while total protein decreased significantly. White blood cell differential count revealed a significant increase in monocyte and neutrophil number and a significant decrease of lymphocyte's number in fish exposed to manganese compared with those of control group. That can be considered as a clear evidence of altered immune system. Measured of erythron profile revealed a significant increasing of cellular and nuclear alteration of red blood cells, with karryorhectic, dividing and micronucleated erythrocytes in exposed fish, indicating the cytotoxic and genotoxic effects Mn 2+ ions. Our data shown also that manganese could trigger antioxidant response, modulate immune response and induce erythron profile modification leading to eryptosis, compromising the blood oxygen carrying capacity, and overall health status in fish. This may suggest those parameters consider as useful biomarkers for monitoring effects of sub-lethal metal exposure on fish. Copyright © 2018 Elsevier Ltd. All rights reserved.

High Antioxidant Activity Facilitates Maintenance of Cell Division in Leaves of Drought Tolerant Maize Hybrids

PubMed Central

Avramova, Viktoriya; AbdElgawad, Hamada; Vasileva, Ivanina; Petrova, Alexandra S.; Holek, Anna; Mariën, Joachim; Asard, Han; Beemster, Gerrit T. S.

2017-01-01

We studied the impact of drought on growth regulation in leaves of 13 maize varieties with different drought sensitivity and geographic origins (Western Europe, Egypt, South Africa) and the inbred line B73. Combining kinematic analysis of the maize leaf growth zone with biochemical measurements at a high spatial resolution allowed us to examine the correlation between the regulation of the cellular processes cell division and elongation, and the molecular redox-regulation in response to drought. Moreover, we demonstrated differences in the response of the maize lines to mild and severe levels of water deficit. Kinematic analysis indicated that drought tolerant lines experienced less impact on leaf elongation rate due to a smaller reduction of cell production, which, in turn, was due to a smaller decrease of meristem size and number of cells in the leaf meristem. Clear differences in growth responses between the groups of lines with different geographic origin were observed in response to drought. The difference in drought tolerance between the Egyptian hybrids was significantly larger than between the European and South-African hybrids. Through biochemical analyses, we investigated whether antioxidant activity in the growth zone, contributes to the drought sensitivity differences. We used a hierarchical clustering to visualize the patterns of lipid peroxidation, H2O2 and antioxidant concentrations, and enzyme activities throughout the growth zone, in response to stress. The results showed that the lines with different geographic region used different molecular strategies to cope with the stress, with the Egyptian hybrids responding more at the metabolite level and African and the European hybrids at the enzyme level. However, drought tolerance correlated with both, higher antioxidant levels throughout the growth zone and higher activities of the redox-regulating enzymes CAT, POX, APX, and GR specifically in leaf meristems. These findings provide evidence for a link between antioxidant regulation in the leaf meristem, cell division, and drought tolerance. PMID:28210264

Formation, characterization, aggregation, fluorescence and antioxidant properties of novel tetrasubstituted metal-free and metallophthalocyanines bearing (4-(methylthio)phenoxy) moieties

NASA Astrophysics Data System (ADS)

Yıldırım, Nurdan; Bilgiçli, Ahmet T.; Alici, Esma Hande; Arabacı, Gulnur; Yarasir, M. Nilüfer

2017-09-01

The synthesis and characterization of peripherally tetra 4-(methylthio)phenoxy substituted metal-free(2), Zn(II) (3) and Co(II) (4) phthalocyanine derivatives were reported. These newly synthesized phthalocyanine derivatives showed the enhanced solubility in organic solvents and they were characterized by a combination of elemental analysis, FTIR, 1H NMR, 13C NMR, UV-vis and MALDI-TOF/MS spectral data. Their aggregation properties were investigated in THF by UV-vis and fluorescence. These metal-free and metallophthalocyanine compounds were also evaluated for their total antioxidant abilities by using three different antioxidant methods such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, ferrous ion chelating and reducing power activity. All tested compounds showed radical scavenging activity. The highest radical scavenging activity was found from cobalt phthalocyanine (4) compound respectively. IC50 values of the compounds and standards (BHT and Trolox) were also determined. The results showed that the compound 4 had the highest antioxidant activity among all tested compounds including standards. The tested phthalocyanine compounds had ferrous ion chelating activity. In addition, they showed very high reducing power. All tested compounds had higher reducing power than the standards such as ascorbic acid and BHT. The present study shows that the synthesized tetra phthalocyanine [M: 2H(2), Zn(II)(3), Co(II)(4)] with four peripheral 4-(methylthio) phenoxy compounds have the effective antioxidant properties that can be used as antioxidant agents.

The toxic effects of ammonia exposure on antioxidant and immune responses in Rockfish, Sebastes schlegelii during thermal stress.

PubMed

Kim, Shin-Hu; Kim, Jun-Hwan; Park, Myoung-Ae; Hwang, Seong Don; Kang, Ju-Chan

2015-11-01

Rockfish, Sebastes schlegelii (mean weight 14.53 ± 1.14 cm, and mean weight 38.36 ± 3.45 g) were exposed for 4 weeks (2 weeks and 4 weeks) with the different levels of ammonia in the concentrations of 0, 0.1, 0.5, 1.0mg/L at 19 and 24°C. The ammonia exposure induced significant alterations in antioxidant responses. The activities of SOD, CAT, and GST were considerably increased by the ammonia exposure depending on water temperature, whereas the GSH level was notably decreased after 2 and 4 weeks. In the stress indicators, the cortisol and HSP 70 were significantly elevated by the exposure to ammonia depending on water temperature. In innate immune responses, the phagocytosis and lysozyme activity were notably decreased by ammonia exposure depending on water temperature after 2 and 4 weeks. The results suggest that ammonia exposure depending on water temperature can induce the considerable alterations in antioxidant responses, stress, and immune inhibition. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis and Antioxidant Activity of 2-Amino-5-methylthiazol Derivatives Containing 1,3,4-Oxadiazole-2-thiol Moiety

PubMed Central

Mohana, Kikkeri N.; Kumar, Chikkur B. Pradeep

2013-01-01

A series of new 5-(2-amino-5-methylthiazol-4-yl)-1,3,4-oxadiazole-2-thiol derivatives 6(a–j) were designed and synthesized with various substituted aldehydes. The chemical structures were confirmed by elemental analyses, FT-IR, 1H NMR, and mass spectral studies. The antioxidant activity of the synthesized compounds was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, nitric oxide, and superoxide radical scavenging assay methods. Compounds 6a, 6e, and 6c showed significant radical scavenging potential due to the presence of electron donating substituent on substituted aldehydes. PMID:24052865

Synthesis and Antioxidant Activity of 2-Amino-5-methylthiazol Derivatives Containing 1,3,4-Oxadiazole-2-thiol Moiety.

PubMed

Mohana, Kikkeri N; Kumar, Chikkur B Pradeep

2013-01-01

A series of new 5-(2-amino-5-methylthiazol-4-yl)-1,3,4-oxadiazole-2-thiol derivatives 6(a-j) were designed and synthesized with various substituted aldehydes. The chemical structures were confirmed by elemental analyses, FT-IR, (1)H NMR, and mass spectral studies. The antioxidant activity of the synthesized compounds was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, nitric oxide, and superoxide radical scavenging assay methods. Compounds 6a, 6e, and 6c showed significant radical scavenging potential due to the presence of electron donating substituent on substituted aldehydes.

Ebselen attenuates cisplatin-induced ROS generation through Nrf2 activation in auditory cells.

PubMed

Kim, Se-Jin; Park, Channy; Han, A Lum; Youn, Myung-Ja; Lee, Jeong-Han; Kim, Yunha; Kim, Eun-Sook; Kim, Hyung-Jin; Kim, Jin-Kyung; Lee, Ho-Kyun; Chung, Sang-Young; So, Hongseob; Park, Raekil

2009-05-01

Ebselen, an organoselenium compound that acts as a glutathione peroxidase mimetic, has been demonstrated to possess antioxidant and anti-inflammatory activities. However, the molecular mechanism underlying this effect is not fully understood in auditory cells. The purpose of the present study is to investigate the protective effect of ebselen against cisplatin-induced toxicity in HEI-OC1 auditory cells, organotypic cultures of cochlear explants from two-day postnatal rats (P(2)) and adult Balb/C mice. Pretreatment with ebselen ameliorated apoptotic death induced by cisplatin in HEI-OC1 cells and organotypic cultures of Corti's organ. Ebselen pretreatment also significantly suppressed cisplatin-induced increases in intracellular reactive oxygen species (ROS), intracellular reactive nitrogen species (RNS) and lipid peroxidation levels. Ebselen dose-dependently increased the expression level of an antioxidant response element (ARE)-luciferase reporter in HEI-OC1 cells through the translocation of Nrf2 into the nucleus. Furthermore, we found that pretreatment with ebselen significantly restored Nrf2 function, whereas it ameliorated the cytotoxicity of cisplatin in cells transfectants with either a pcDNA3.1 (control) or a DN-Nrf2 (dominant-negative) plasmid. We also observed that Nrf2 activation by ebselen increased the expression of phase II antioxidant genes, including heme oxygenase (HO-1), NAD(P)H:quinine oxidoreductase, and gamma-glutamylcysteine synthetase (gamma-GCS). Treatment with ebselen resulted in an increased expression of HO-1 and intranuclear Nrf2 in hair cells of organotypic cultured cochlea. After intraperitoneal injection with cisplatin, auditory brainstem responses (ABRs) threshold was measured on 8th day in Balb/C mice. ABR threshold shift was marked occurred in mice injected with cisplatin (16 mg/kg, n=5; Click and 8-kHz stimuli, p<0.05; 4, 16 and 32 kHz, p<0.01), whereas that of animal group which was treated with cisplatin and ebselen was not significantly changed. These results suggest that ebselen activates the Nrf2-ARE signaling pathway, which ultimately prevents free radical stresses from cisplatin and further contributes to protect auditory sensory hair cells from free radicals produced by cisplatin.

Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Changfang; Zou, Yu; Liu, Yuzhang

Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation ofmore » NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2. • RA-mediated down-regulation of MMP-2 was ROS-dependent.« less

Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jin-Sun; Kim, Hee-Sun, E-mail: hskimp@ewha.ac.kr

2014-05-16

Highlights: • tBHQ increased HO-1 mRNA and protein levels in rat primary astrocytes. • tBHQ enhanced HO-1 gene transcription in an ARE-dependent manner. • tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. • Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. • Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction. - Abstract: Hemeoxygenase-1 (HO-1) is a phase II antioxidant enzyme that is primarily involved in detoxification and cytoprotection in a variety of tissues. However, the mechanism underlying HO-1 gene expression remains unclear. In the present study, we investigatedmore » the regulation of HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone (tBHQ). We found that tBHQ increased HO-1 mRNA and protein levels. Promoter analysis revealed that tBHQ enhanced HO-1 gene transcription in an antioxidant response element (ARE)-dependent manner. In addition, tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. Small interfering RNA (siRNA) experiments demonstrated that Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. Thus, Nrf2 knockdown reduced the basal level of HO-1 expression but did not affect the fold induction by tBHQ. On the other hand, knockdown of c-Jun diminished tBHQ-mediated induction of HO-1 without affecting basal expression. The data suggest that Nrf2 generally modulates the basal expression of HO-1, while c-Jun mediates HO-1 induction in response to tBHQ. The results of co-immunoprecipitation assays demonstrated a physical interaction between Nrf2 and c-Jun in tBHQ-treated astrocytes. The results suggest that Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction in tBHQ-treated rat primary astrocytes.« less

Copper-induced peroxidation of phosphatidylserine-containing liposomes is inhibited by nanomolar concentrations of specific antioxidants.

PubMed

Gal, S; Lichtenberg, D; Bor, A; Pinchuk, I

2007-12-01

Copper-induced peroxidation of liposomal palmitoyllinoleoyl-phosphatidylcholine (PLPC) is inhibited by alpha-tocopherol at micromolar concentrations. In our previous study we found that when the liposomes contain phosphatidylserine (PS), nanomolar concentrations of Toc were sufficient to inhibit peroxidation. In an attempt to gain understanding of the origin of this extreme antioxidative potency, we tested the antioxidative potency of 36 additional antioxidants and the dependence of their potency on the presence of PS in the liposomes. The results of these studies reveal that only 11 of the tested antioxidants possess similar antioxidative potency to that of Toc. These include trolox, butylated hydroxytoluene (BHT), curcumin, nordihydroguaiaretic acid (NDGA), diethylstilbestrol (DES), 2 of the 13 tested flavonoids (luteolin and 7,3',4'-trihydroxyflavone; T-414), alpha-naphthol, 1,5-, 1,6- and 1,7-dihydroxynaphthalenes (DHNs). Propyl gallate (PG), methyl syringate, rosmarinic acid, resveratrol, other flavonoids, as well as beta-naphthol, 1,2-, 1,3-, 1,4-, 2,3-, 2,6-, and 2,7-DHNs were either moderately antioxidative or pro-oxidative. For liposomes made of PLPC (250 microM) and PS (25 microM) the "lag" preceding copper-induced peroxidation (5 microM copper) was doubled upon addition of 30-130nM of the "super-active" antioxidants. We propose that the mechanism responsible for the extreme antioxidative potency against copper-induced peroxidation in PS-containing liposomes involves replenishment of the antioxidant in a ternary PS-copper-antioxidant complex. Based on structure-activity relationship of the 37 tested antioxidants, the "super-antioxidative potency" is attributed to the recycling of relatively stable semiquinone or semiquinone-like radicals.

Portable ceria nanoparticle-based assay for rapid detection of food antioxidants (NanoCerac)

PubMed Central

Sharpe, Erica; Frasco, Thalia; Andreescu, Daniel; Andreescu, Silvana

2012-01-01

With increased awareness of nutrition and the advocacy for healthier food choices, there exists a great demand for a simple, easy-to-use test that can reliably measure the antioxidant capacity of dietary products. We report development and characterization of a portable nanoparticle based-assay, similar to a small sensor patch, for rapid and sensitive detection of food antioxidants. The assay is based on the use of immobilized ceria nanoparticles, which change color after interaction with antioxidants by means of redox and surface chemistry reactions. Monitoring corresponding optical changes enables sensitive detection of antioxidants in which the nanoceria provides an optical ‘signature’ of antioxidant power, while the antioxidants act as reducing agents. The sensor has been tested for the detection of common antioxidant compounds including ascorbic acid, gallic acid, vanilic acid, quercetin, caffeic acid, and epigallocatechin gallate and its function has been successfully applied for the assessment of antioxidant activity in real samples (teas and medicinal mushrooms). The colorimetric response was concentration dependent, with detection limits ranging from 20–400 μM depending on the antioxidant involved. Steady-state color intensity was achieved within seconds upon addition of antioxidants. The results are presented in terms of Gallic Acid Equivalents (GAE). The sensor performed favorably when compared with commonly used antioxidant detection methods. This assay is particularly appealing for remote sensing applications, where specialized equipment is not available, and also for high throughput analysis of a large number of samples. Potential applications for antioxidant detection in remote locations are envisioned. PMID:23139929

Transcriptional regulation of bone sialoprotein gene by Porphyromonas gingivalis lipopolysaccharide.

PubMed

Li, Xinyue; Kato, Naoko; Mezawa, Masaru; Li, Zhengyang; Wang, Zhitao; Yang, Li; Sasaki, Yoko; Kaneko, Takashi; Takai, Hideki; Yoshimura, Atsutoshi; Ogata, Yorimasa

2010-07-01

Lipopolysaccharide (LPS) is a major mediator of inflammatory response. Periodontopathic bacterium Porphyromonas gingivalis LPS has quite different character from Escherichia coli LPS. E. coli LPS is agonist for Toll-like receptor 4 (TLR4), whereas P. gingivalis LPS worked as antagonist for TLR4. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. To investigate the effects of P. gingivalis LPS on BSP transcription, we used rat osteoblast-like ROS17/2.8 cells. BSP mRNA levels were decreased by 0.1 microg/ml and increased by 0.01 microg/ml P. gingivalis LPS at 12 h. Results of luciferase assays showed that 0.1 microg/ml decreased and 0.01 microg/ml P. gingivalis LPS increased BSP transcription in -116 to +60 BSP construct. The effects of P. gingivalis LPS were abrogated by double mutations in cAMP response element (CRE) and FGF2 response element (FRE). Tyrosine kinase inhibitor herbimycin A, ERK1/2 inhibitor and antioxidant N-acetylcystein inhibited effects of P. gingivalis LPS. Protein kinase A inhibitor and PI3-kinase/Akt inhibitor only abolished the effect of 0.01 microg/ml P. gingivalis LPS. Furthermore, 0.1 microg/ml LPS decreased the CRE- and FRE-protein complexes formation, whereas 0.01 microg/ml P. gingivalis LPS increased the nuclear protein binding to CRE and FRE. ChIP assays revealed increased binding of CREB1, JunD, Fra2, Runx2, Dlx5, and Smad1 to a chromatin fragment containing the CRE and FRE by 0.01 microg/ml P. gingivalis LPS. These studies therefore indicated that 0.1 microg/ml suppressed, and 0.01 microg/ml P. gingivalis LPS increased BSP gene transcription mediated through CRE and FRE elements in the rat BSP gene promoter. J. Cell. Biochem. 110: 823-833, 2010. (c) 2010 Wiley-Liss, Inc.

UV-B radiation-induced oxidative stress and p38 signaling pathway involvement in the benthic copepod Tigriopus japonicus.

PubMed

Kim, Bo-Mi; Rhee, Jae-Sung; Lee, Kyun-Woo; Kim, Min-Jung; Shin, Kyung-Hoon; Lee, Su-Jae; Lee, Young-Mi; Lee, Jae-Seong

2015-01-01

Ultraviolet B (UV-B) radiation presents an environmental hazard to aquatic organisms. To understand the molecular responses of the intertidal copepod Tigriopus japonicus to UV-B radiation, we measured the acute toxicity response to 96 h of UV-B radiation, and we also assessed the intracellular reactive oxygen species (ROS) levels, glutathione (GSH) content, and antioxidant enzyme (GST, GR, GPx, and SOD) activities after 24 h of exposure to UV-B with LD50 and half LD50 values. Also, expression patterns of p53 and hsp gene families with phosphorylation of p38 MAPK were investigated in UV-B-exposed copepods. We found that the ROS level, GSH content, and antioxidant enzyme activity levels were increased with the transcriptional upregulation of antioxidant-related genes, indicating that UV-B induces oxidative stress by generating ROS and stimulating antioxidant enzymatic activity as a defense mechanism. Additionally, we found that p53 expression was significantly increased after UV-B irradiation due to increases in the phosphorylation of the stress-responsive p38 MAPK, indicating that UV-B may be responsible for inducing DNA damage in T. japonicus. Of the hsp family genes, transcriptional levels of hsp20, hsp20.7, hsp70, and hsp90 were elevated in response to a low dose of UV-B radiation (9 kJ m(-2)), suggesting that these hsp genes may be involved in cellular protection against UV-B radiation. In this paper, we performed a pathway-oriented mechanistic analysis in response to UV-B radiation, and this analysis provides a better understanding of the effects of UV-B in the intertidal benthic copepod T. japonicus. Copyright © 2014 Elsevier Inc. All rights reserved.

Glutathione S-transferase pi expression regulates the Nrf2-dependent response to hormetic diselenides.

PubMed

Bartolini, D; Commodi, J; Piroddi, M; Incipini, L; Sancineto, L; Santi, C; Galli, F

2015-11-01

Glutathione S-transferase pi (GSTP), a phase II gene downstream of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant-responsive element (ARE)/electrophile response element (EpRE) transcription pathway, plays a key role in both the signaling and detoxification response to Se-organic compounds with thiol peroxidase activity. We here investigated the role of GSTP on the Nrf2 activation response of cells challenged with a new class of diselenides derived from the basic structure of diphenyl diselenide [(PhSe)2]. These diselenides, and particularly 2,2'-diselenyl dibenzoic acid (DSBA), behave as mild thiol peroxidases leading to a moderate generation of H2O2 and NOx, and signaling of stress-activated and survival-promoting MAPKs, which ultimately control the mitochondrial pathway of apoptosis. Used in murine embryonic fibroblasts (MEFs) and HepG2 human hepatocarcinoma cells to produce submaximal conditions of stress, the diselenide compounds stimulated Nrf2 nuclear translocation and then the transcription of the same Nrf2 gene as well as of GSTP and other phase II genes. This resulted in a higher degree of protection against H2O2 cytotoxicity (hormetic effect). Diselenide toxicity increased in GSTP knockout MEFs by a higher generation of NOx and stress activated protein kinase (SAPK)/JNK activation. A lowered hormetic potential of these cells was observed in association with an abnormal expression and nuclear translocation of Nrf2 protein. Immunoprecipitation and affinity purification experiments revealed the existence of an Nrf2/GSTP complex in MEFs and HepG2 cells. Covalent oligomers of GSTP subunits were observed in DSBA-treated HepG2 cells. In conclusion, GSTP gene expression influences the Nrf2-dependent response to hormetic diselenides. Mechanistic interpretation for this GSTP-dependent effect may include a direct and redox-sensitive interaction of GSTP with Nrf2 protein. Copyright © 2015 Elsevier Inc. All rights reserved.

COMBINED EFFECTS OF CO2 AND O3 ON ANTIOXIDATIVE AND PHOTOPROTECTIVE DEFENSE SYSTEMS IN NEEDLES OF PONDEROSA PINE

EPA Science Inventory

To determine interactive effects of important environmental stresses on biochemical defense mechanisms of tree seedlings, we studied responses to elevated O3 and elevated atmospheric CO2 on antioxidative and photoprotective systems in needles of ponderosa pine (Pinus ponderosa Do...

Involvement of Superoxide Dismutases in the Response of Escherichia coli to Selenium Oxides

PubMed Central

Bébien, Magali; Lagniel, Gilles; Garin, Jérôme; Touati, Danièle; Verméglio, André; Labarre, Jean

2002-01-01

Selenium can provoke contrasting effects on living organisms. It is an essential trace element, and low concentrations have beneficial effects, such as the reduction of the incidence of cancer. However, higher concentrations of selenium salts can be toxic and mutagenic. The bases for both toxicity and protection are not clearly understood. To provide insights into these mechanisms, we analyzed the proteomic response of Escherichia coli cells to selenate and selenite treatment under aerobic conditions. We identified 23 proteins induced by both oxides and ca. 20 proteins specifically induced by each oxide. A striking result was the selenite induction of 8 enzymes with antioxidant properties, particularly the manganese and iron superoxide dismutases (SodA and SodB). The selenium inductions of sodA and sodB were controlled by the transcriptional regulators SoxRS and Fur, respectively. Strains with decreased superoxide dismutase activities were severely impaired in selenium oxide tolerance. Pretreatment with a sublethal selenite concentration triggered an adaptive response dependent upon SoxRS, conferring increased selenite tolerance. Altogether, our data indicate that superoxide dismutase activity is essential for the cellular defense against selenium salts, suggesting that superoxide production is a major mechanism of selenium toxicity under aerobic conditions. PMID:11872706

Optimization of hull-less pumpkin seed roasting conditions using response surface methodology.

PubMed

Vujasinović, Vesna; Radočaj, Olga; Dimić, Etelka

2012-05-01

Response surface methodology (RSM) was applied to optimize hull-less pumpkin seed roasting conditions before seed pressing to maximize the biochemical composition and antioxidant capacity of the virgin pumpkin oils obtained using a hydraulic press. Hull-less pumpkin seeds were roasted for various lengths of time (30 to 70 min) at various roasting temperatures (90 to 130 °C), resulting in 9 different oil samples, while the responses were phospholipids content, total phenols content, α- and γ-tocopherols, and antioxidative activity [by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical assay]. Mathematical models have shown that roasting conditions influenced all dependent variables at P < 0.05. The higher roasting temperatures had a significant effect (P < 0.05) on phospholipids, phenols, and α-tocopherols contents, while longer roasting time had a significant effect (P < 0.05) on γ-tocopherol content and antioxidant capacity, among the samples prepared under different roasting conditions. The optimum conditions for roasting the hull-less pumpkin seeds were 120 °C for duration of 49 min, which resulted in these oil concentrations: phospholipids 0.29%, total phenols 23.06 mg/kg, α-tocopherol 5.74 mg/100 g, γ-tocopherol 24.41 mg/100 g, and an antioxidative activity (EC(50)) of 27.18 mg oil/mg DPPH. © 2012 Institute of Food Technologists®

Cancer chemoprevention by traditional chinese herbal medicine and dietary phytochemicals: targeting nrf2-mediated oxidative stress/anti-inflammatory responses, epigenetics, and cancer stem cells.

PubMed

Hun Lee, Jong; Shu, Limin; Fuentes, Francisco; Su, Zheng-Yuan; Tony Kong, Ah-Ng

2013-01-01

Excessive oxidative stress induced by reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive metabolites of carcinogens alters cellular homeostasis, leading to genetic/epigenetic changes, genomic instability, neoplastic transformation, and cancer initiation/progression. As a protective mechanism against oxidative stress, antioxidant/detoxifying enzymes reduce these reactive species and protect normal cells from endo-/exogenous oxidative damage. The transcription factor nuclear factor-erythroid 2 p45 (NF-E2)-related factor 2 (Nrf2), a master regulator of the antioxidative stress response, plays a critical role in the expression of many cytoprotective enzymes, including quinine oxidoreductase (NQO1), heme oxygenase-1 (HO-1), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST). Recent studies demonstrated that many dietary phytochemicals derived from various vegetables, fruits, spices, and herbal medicines induce Nrf2-mediated antioxidant/detoxifying enzymes, restore aberrant epigenetic alterations, and eliminate cancer stem cells (CSCs). The Nrf2-mediated antioxidant response prevents many age-related diseases, including cancer. Owing to their fundamental contribution to carcinogenesis, epigenetic modifications and CSCs are novel targets of dietary phytochemicals and traditional Chinese herbal medicine (TCHM). In this review, we summarize cancer chemoprevention by dietary phytochemicals, including TCHM, which have great potential as a safer and more effective strategy for preventing cancer.

ROS and brain diseases: the good, the bad, and the ugly.

PubMed

Popa-Wagner, Aurel; Mitran, Smaranda; Sivanesan, Senthilkumar; Chang, Edwin; Buga, Ana-Maria

2013-01-01

The brain is a major metabolizer of oxygen and yet has relatively feeble protective antioxidant mechanisms. This paper reviews the Janus-faced properties of reactive oxygen species. It will describe the positive aspects of moderately induced ROS but it will also outline recent research findings concerning the impact of oxidative and nitrooxidative stress on neuronal structure and function in neuropsychiatric diseases, including major depression. A common denominator of all neuropsychiatric diseases including schizophrenia and ADHD is an increased inflammatory response of the brain caused either by an exposure to proinflammatory agents during development or an accumulation of degenerated neurons, oxidized proteins, glycated products, or lipid peroxidation in the adult brain. Therefore, modulation of the prooxidant-antioxidant balance provides a therapeutic option which can be used to improve neuroprotection in response to oxidative stress. We also discuss the neuroprotective role of the nuclear factor erythroid 2-related factor (Nrf2) in the aged brain in response to oxidative stressors and nanoparticle-mediated delivery of ROS-scavenging drugs. The antioxidant therapy is a novel therapeutic strategy. However, the available drugs have pleiotropic actions and are not fully characterized in the clinic. Additional clinical trials are needed to assess the risks and benefits of antioxidant therapies for neuropsychiatric disorders.

Sulfur Mediated Alleviation of Mn Toxicity in Polish Wheat Relates to Regulating Mn Allocation and Improving Antioxidant System

PubMed Central

Sheng, Huajin; Zeng, Jian; Liu, Yang; Wang, Xiaolu; Wang, Yi; Kang, Houyang; Fan, Xing; Sha, Lina; Zhang, Haiqin; Zhou, Yonghong

2016-01-01

Sulfur (S) is an essential macronutrient that has been proved to play an important role in regulating plant responses to various biotic and abiotic stresses. The present study was designed to investigate the effect of S status on polish wheat plant response to Mn toxicity. Results showed that Mn stress inhibited plant growth, disturbed photosynthesis and induced oxidative stress. In response to Mn stress, polish wheat plant activated several detoxification mechanisms to counteract Mn toxicity, including enhanced antioxidant defense system, increased Mn distribution in the cell wall and up-regulated genes involved in S assimilation. Moderate S application was found to alleviate Mn toxicity mainly by sequestering excess Mn into vacuoles, inhibiting Mn translocation from roots to shoots, stimulating activities of antioxidant enzymes and enhancing GSH production via up-regulating genes involved in S metabolism. However, application of high level S to Mn-stressed plants did not significantly alleviated Mn toxicity likely due to osmotic stress. In conclusion, moderate S application is beneficial to polish wheat plant against Mn toxicity, S exerts its effects via stimulating the antioxidant defense system and regulating the translocation and subcellular distribution of Mn, in which processes GSH plays an indispensable role. PMID:27695467

Antioxidants in Translational Medicine

PubMed Central

Schmidt, Harald H.H.W.; Stocker, Roland; Vollbracht, Claudia; Paulsen, Gøran; Riley, Dennis

2015-01-01

Abstract Significance: It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. Recent Advances: The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. Critical Issues: Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. Future Directions: Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities. Antioxid. Redox Signal. 23, 1130–1143. PMID:26154592

Antioxidant potential of polyphenols and tannins from burs of Castanea mollissima Blume.

PubMed

Zhao, Shan; Liu, Jie Yuan; Chen, Si Yu; Shi, Ling Ling; Liu, Yu Jun; Ma, Chao

2011-10-12

Spiny burs of Castanea mollissima Blume (Chinese chestnut) are usually discarded as industrial waste during post-harvesting processing. The objective of this study was to establish an extraction and isolation procedure for tannins from chestnut burs, and to assess their potential antioxidant activity. Aqueous ethanol solution was used as extraction solvent, and HPD 100 macroporous resin column was applied for isolation. The influence of solvent concentration in the extraction and elution process on extraction yield, tannins and polyphenols content, as well as antioxidant potential, including DPPH and ABTS radical scavenging ability, reducing power ability and cellular antioxidant ability were assessed. In both the extraction and isolation process, 50% aqueous ethanol led to superior total tannins and polyphenols content as well as significantly higher antioxidant activity. In addition, the antioxidant activity and the total tannins content in extracts and fractions had a positive linear correlation, and the predominant components responsible for antioxidant activities were characterized as hydrolysable tannins. To the best of our knowledge, this is the first report on the enrichment of tannins from burs of C. mollissim using macroporous resin chromatography, and to assess the cellular antioxidant activity of them.

An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity

PubMed Central

Noack, Volker; Pak, Kwang; Jalota, Rahul; Kurabi, Arwa; Ryan, Allen F.

2017-01-01

Reactive oxygen species are important elements in ototoxic damage to hair cells (HCs), appearing early in the damage process. Higher levels of natural antioxidants are positively correlated with resistance to ototoxins and many studies have shown that exogenous antioxidants can protect HCs from damage. While a very wide variety of antioxidants with different characteristics and intracellular targets exist, most ototoxicity studies have focused upon one or a few well-characterized compounds. Relatively little research has attempted to determine the comparative efficacy of large variety of different antioxidants. This has been in part due to the lack of translation between cell culture and in vivo measures of efficacy. To circumvent this limitation, we used an in vitro assay based on micro-explants from the basal and middle turns of the neonatal mouse organ of Corti to screen a commercial redox library of diverse antioxidant compounds for their ability to protect mammalian HCs from a high dose of the ototoxic antibiotic gentamicin. The library included several antioxidants that have previously been studied as potential treatments for HC damage, as well as many antioxidants that have never been applied to ototoxicity. The micro-explants were treated with 200 μM gentamicin alone, gentamicin plus one of three dosages of a redox compound, the highest dosage of compound alone, or were untreated. HC counts were determined before the gentamicin insult and at 1, 2, and 3 days afterward to evaluate the HC survival. From a total of 81 antioxidant compounds, 13 exhibited significant protection of HCs. These included members of a variety of antioxidant classes with several novel antioxidants, not previously tested on HCs, appearing to alleviate the damaging gentamicin effect. Some compounds previously shown to be protective of HCs were correspondingly protective in this in vitro screen, while others were not. Finally, one of the three pro-oxidant compounds included in the library as well as six antioxidants exhibited evidence of toxicity in the absence of gentamicin. The results demonstrate the wide variability in the ability of antioxidants to protect HCs from high-dose gentamicin damage, and identify promising candidate leads for further study as potential drug targets. Highlights • A medium-throughput assay based on micro-explants of the organ of Corti was developed to screen mammalian cochlear hair cells for protection from damage by ototoxins. • Eighty one antioxidants and 3 pro-oxidants were evaluated for hair cell protection from high-dose gentamicin. • Thirteen antioxidants were significantly protective, while 6 proved to be damaging. • The use of a common assay permitted an evaluation of the relative capacity of different antioxidants for the protection of hair cells. PMID:28867994

Effects of Melatonin on Anti-oxidative Systems and Photosystem II in Cold-Stressed Rice Seedlings

PubMed Central

Han, Qiao-Hong; Huang, Bo; Ding, Chun-Bang; Zhang, Zhong-Wei; Chen, Yang-Er; Hu, Chao; Zhou, Li-Jun; Huang, Yan; Liao, Jin-Qiu; Yuan, Shu; Yuan, Ming

2017-01-01

Melatonin (N-acetyl-5-methoxytryptamine) plays important role in multiple plant developmental processes and stress responses. We investigated the possible mediatory role of melatonin in growth, photosynthesis, and the response to cold stress in rice by using three different experiments: soaking seed; immersing roots, and spraying to leaves with 0, 20, or 100 μM melatonin. After 6 days of cold stress, the growth of rice seedlings was significantly inhibited, but this inhibition was alleviated by exogenous melatonin. Furthermore, exogenous melatonin pretreatment alleviated the accumulation of reactive oxygen species, malondialdehyde and cell death induced by cold stress. Melatonin pretreatment also relieved the stress-induced inhibitions to photosynthesis and photosystem II activities. Further investigations showed that, antioxidant enzyme activities and non-enzymatic antioxidant levels were increased by melatonin pretreatments. The treatment methods of seed soaking and root immersion were more effective in improving cold stress resistance than the spraying method. The results also indicated the dose-dependent response of melatonin on rice physiological, biochemical, and photosynthetic parameters. PMID:28553310

Physiological Responses in Chinese Rare Minnow Larvae Following Exposure to Low-Dose Tributyltin.

PubMed

Li, Ping; Li, Zhi-Hua

2015-11-01

In the present study, the antioxidant response and acetylcholinesterase (AChE) activity were measured in Chinese rare minnow larvae (Gobiocypris rarus) after exposure to tributyltin (TBT) (0, 100, 400 and 800 ngL(-1)) for 7 days, as well as the expression of a series of genes, including cr, aptase and prl genes involved in the ion-regulatory process and igfbp3 and gh related to growth rate. Results shows that oxidative stress was generated in fish exposed to TBT, as evidenced by elevated malondialdehyde levels and the inhibition of antioxidant parameters. The activity of acetylcholinesterase (AChE) was also inhibited in fish under higher TBT stress. Moreover, genes involved in ion regulation and growth were affected, based on the regulated transcription of the cr, atpase, gh, prl and igfbp3 genes in the treated groups. The observed effects of TBT upon antioxidant responses and altered expression of genes provides insight into the use of these molecular biomarkers in evaluating mechanisms of TBT toxicity in fish.

Hepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative stress: Role of Nrf2 activation through ERK phosphorylation and AMPK-dependent inhibition of GSK-3β

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Jae-Sook; Kim, Eun-Kyung; Choi, Yong-Won

Oxidative stress can contribute to the development and progression of liver diseases, such as drug-induced or alcoholic liver injury, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis. Nectandrin B is a bioactive lignan isolated from nutmeg extract. To date, little information is available about its pharmacological activities in the liver. This study investigated the hepatocyte-protective effect of nectandrin B against tert-butylhydroperoxide-induced oxidative injury and the underlying molecular mechanism. The cell viability assay revealed that nectandrin B prevents apoptosis stimulated by tert-butylhydroperoxide in both HepG2 cells and primary mouse hepatocytes. Nectandrin B also attenuated ROS production and restored the depleted glutathione level.more » Real-time PCR and immunoblot analyses showed that the expression of glutamate-cysteine ligase, an enzyme responsible for the glutathione biosynthesis, was induced by nectandrin B, indicating its indirect antioxidative effect. The NF-E2-related factor-2 (Nrf2) regulates gene expression of an array of antioxidant enzymes in hepatocytes. Nectandrin B stimulated Nrf2 activation as evidenced by its enhanced nuclear accumulation and increased antioxidant response element (ARE)-luciferase activity. Intriguingly, the hepatocyte-protective effect of nectandrin B against oxidative damage was completely abrogated by Nrf2 knockdown using Nrf2 specific siRNA. Nectandrin B promoted ERK activation, but inactivated GSK-3β through the AMPK-mediated inhibitory phosphorylation. The enforced overexpression of dominant-negative mutant of MEK1 or AMPKα, or wild-type GSK-3β inhibited the increase in the NQO1-ARE-luciferase activity stimulated by nectandrin B, suggesting that both ERK and AMPK-GSK-3β signalings are involved in the activation of Nrf2/ARE pathway by nectandrin B. Consistent with this, cytoprotection and restoration of glutathione level by nectandrin B was also blocked by the overexpression of dominant-negative MEK1 or wild-type GSK-3β. Finally, our data demonstrate that nectandrin B has the ability to protect hepatocytes against oxidative injury through the activation of Nrf2/ARE pathway mediated by ERK phosphorylation and AMPK-dependent inactivation of GSK-3β. - Highlight: • Nectandrin B, a nutmeg lignan protects hepatocytes against oxidative damage. • Nectandrin B exerts an indirect antioxidative effect via the activation of Nrf2. • Both ERK and GSK-3β pathways contribute to the activation of Nrf2 and hepatocyte-protection by nectandrin B. • Nectandrin B can inactivate GSK-3β through the activation of AMPK in HepG2 cells.« less

Regulation of trace elements and redox status in striatum of adult rats by long-term aerobic exercise depends on iron uptakes.

PubMed

Wu, Hua-Bo; Xiao, De-Sheng

2017-03-06

We investigated the effects of aerobic exercise (AE) on trace element contents and redox status in the striatum of rats with different diet iron. Weaned female rats were randomly fed with iron-adequate diet (IAD), iron-deficient diet (IDD), and iron-overloaded diet (IOD). After feeding their respective diet for 1 month, the rats fed with same diet were divided into swimming and maintaining sedentary (S) group. After 3 months, the non-heme iron (NHI), Mn, Cu, and Zn in the striatum were measured. Meanwhile, malonaldehyde acid (MDA), total superoxide dismutase activity, hydroxyl radical scavenging activity, and total antioxidant capacity were also analyzed. As compared with respective S rats, Mn, Cu, and Zn contents were significantly decreased in IDDE, but no significantly changes could be seen in IADE or IODE. A negative correlation of NHI with Cu contents in IDDE and positive correlations of NHI with Cu, or Zn contents in IADE, or with Mn or Cu contents in IODE were observed. In addition, striatum MDA was significantly decreased and anti-oxidative variables were increased in IODE compared to IODS. Our results suggest that the modification of trace elements and redox status in the striatum of rats caused by AE depends on dietary iron contents and that AE may also regulate the metabolic relationship of iron storage with other trace elements. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidants in Translational Medicine.

PubMed

Schmidt, Harald H H W; Stocker, Roland; Vollbracht, Claudia; Paulsen, Gøran; Riley, Dennis; Daiber, Andreas; Cuadrado, Antonio

2015-11-10

It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities.

The Neglected Significance of “Antioxidative Stress”

PubMed Central

Poljsak, B.; Milisav, I.

2012-01-01

Oxidative stress arises when there is a marked imbalance between the production and removal of reactive oxygen species (ROS) in favor of the prooxidant balance, leading to potential oxidative damage. ROSs were considered traditionally to be only a toxic byproduct of aerobic metabolism. However, recently, it has become apparent that ROS might control many different physiological processes such as induction of stress response, pathogen defense, and systemic signaling. Thus, the imbalance of the increased antioxidant potential, the so-called antioxidative stress, should be as dangerous as well. Here, we synthesize increasing evidence on “antioxidative stress-induced” beneficial versus harmful roles on health, disease, and aging processes. Oxidative stress is not necessarily an un-wanted situation, since its consequences may be beneficial for many physiological reactions in cells. On the other hand, there are potentially harmful effects of “antioxidative stress,” especially in the cases of overconsumption of synthetic antioxidants. Antioxidants can neutralize ROS and decrease oxidative stress; however, this is not always beneficial in regard to disease formation or progression (of, e.g., cancer) or for delaying aging. PMID:22655114

Antioxidant Activities of Chokeberry Extracts and the Cytotoxic Action of Their Anthocyanin Fraction on HeLa Human Cervical Tumor Cells

PubMed Central

Rugină, Dumitriţa; Sconţa, Zoriţa; Leopold, Loredana; Pintea, Adela; Bunea, Andrea

2012-01-01

Abstract The present study evaluates the antioxidant activity of two Aronia melanocarpa cultivars—Viking and Aron—and of Aronia prunifolia hybrid in relationship with their phytochemical composition regarding the contents of total phenolics, flavonoids, procyanidins, and monomeric anthocyanins. The antioxidant capacity of the mentioned extracts of chokeberries was evaluated through five complementary assays: 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), H2O2 scavenging potential, oxygen radical absorbance capacity, ferric reducing antioxidant power, and cupric ion reducing antioxidant capacity. A. prunifolia hybrid was found to have the highest antioxidant activity and to be the richest in polyphenols, procyanidins, and anthocyanins compared with the A. melanocarpa cultivars. A good correlation was observed between antioxidant activity and total procyanidin and anthocyanin content. Cyanidin glycosides inhibited HeLa human cervical tumor cell proliferation and increased generation of reactive oxygen species after 48 h of treatment, suggesting that they could be responsible for the antiproliferative activity. These results may be significant for industry concerning food quality and disease prevention. PMID:22846076

Antioxidant response of ridgetail white prawn Exopalaemon carinicauda to harmful dinoflagellate Prorocentrum minimum exposure and its histological change

NASA Astrophysics Data System (ADS)

Mu, Cuimin; Ren, Xianyun; Ge, Qianqian; Wang, Jiajia; Li, Jian

2017-04-01

The dinoflagellate Prorocentrum minimum, one of the most widespread red tide causing species, affects marine aquaculture and ecosystems worldwide. In this study, ridgetail white prawn Exopalaemon carinicauda were exposed to P. minimum cells (5 × 104 cells mL-1) to investigate its harmful effects on the shrimp. Antioxidant activities and histological changes were used as indicators of health status of the shrimp. In 72 hours, the mortality of E. carinicauda was not affected, but its antioxidant response and histology were statistically different from those of control. Elevated superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities and depressed catalase (CAT) activity were observed in gill; while increased SOD, glutathione S-transferase (GST), CAT activities and modulated GPX activity were observed in hepatopancreas. Thus, antioxidant activities in gill and hepatopancreas seem to respond differentially to harmful alga exposure. Increased malondialdehyde (MDA) content in early a few hours indicates the damage of the antioxidant defense system. Although MDA content recovered to a low level thereafter, a series of histological abnormalities including accumulation or infiltration of hemocytes, tissue lesions and necrosis were discovered in gill and hepatopancreas. Exposure to P. minimum induced sublethal effects on E. carinicauda, including temporary oxidative damage and histological injury.

Oregano Essential Oil as an Antimicrobial and Antioxidant Additive in Food Products.

PubMed

Rodriguez-Garcia, I; Silva-Espinoza, B A; Ortega-Ramirez, L A; Leyva, J M; Siddiqui, M W; Cruz-Valenzuela, M R; Gonzalez-Aguilar, G A; Ayala-Zavala, J F

2016-07-26

Food consumers and industries urged the need of natural alternatives to assure food safety and quality. As a response, the use of natural compounds from herbs and spices is an alternative to synthetic additives associated with toxic problems. This review discusses the antimicrobial and antioxidant activity of oregano essential oil (OEO) and its potential as a food additive. Oregano is a plant that has been used as a food seasoning since ancient times. The common name of oregano is given to several species: Origanum (family: Lamiaceae) and Lippia (family: Verbenaceae), amongst others. The main compounds identified in the different OEOs are carvacrol and thymol, which are responsible for the characteristic odor, antimicrobial, and antioxidant activity; however, their content may vary according to the species, harvesting season, and geographical sources. These substances as antibacterial agents make the cell membrane permeable due to its impregnation in the hydrophobic domains, this effect is higher against gram positive bacteria. In addition, the OEO has antioxidant properties effective in retarding the process of lipid peroxidation in fatty foods, and scavenging free radicals. In this perspective, the present review analyzes and discusses the state of the art about the actual and potential uses of OEO as an antimicrobial and antioxidant food additives.

Influence of roasting on the antioxidant activity and HMF formation of a cocoa bean model systems.

PubMed

Oliviero, Teresa; Capuano, Edoardo; Cämmerer, Bettina; Fogliano, Vincenzo

2009-01-14

During the roasting of cocoa beans chemical reactions lead to the formation of Maillard reaction (MR) products and to the degradation of catechin-containing compounds, which are very abundant in these seeds. To study the modifications occurring during thermal treatment of fat and antioxidant rich foods, such as cocoa, a dry model system was set up and roasted at 180 degrees C for different times. The role played in the formation of MR products and in the antioxidant activity of the system by proteins, catechin, and cocoa butter was investigated by varying the model system formulation. Results showed that the antioxidant activity decreased during roasting, paralleling catechin concentration, thus suggesting that this compound is mainly responsible for the antioxidant activity of roasted cocoa beans. Model system browning was significantly higher in the presence of catechin, which contributed to the formation of water-insoluble melanoidins, which are mainly responsible for browning. HMF concentration was higher in casein-containing systems, and its formation was strongly inhibited in the presence of catechin. No effects related to the degree of lipid oxidation could be observed. Data from model systems obtained by replacing fat with water showed a much lower rate of MR development and catechin degradation but the same inhibitory effect of catechin on HMF formation.

Effect of Chitosan Coating on the Postharvest Quality and Antioxidant Enzyme System Response of Strawberry Fruit during Cold Storage

PubMed Central

Petriccione, Milena; Mastrobuoni, Francesco; Pasquariello, Maria Silvia; Zampella, Luigi; Nobis, Elvira; Capriolo, Giuseppe; Scortichini, Marco

2015-01-01

The effectiveness of chitosan fruit coating to delay the qualitative and nutraceutical traits of three strawberry cultivars, namely “Candonga”, “Jonica” and “Sabrina”, as well as the effects of chitosan on antioxidant enzymes were evaluated. The fruits were coated with 1% and 2% chitosan solution and stored at 2 °C for nine days. Samples were taken every three days. Physico-chemical (weight loss, soluble solid content and titratable acidity) and nutraceutical (total polyphenol, anthocyanin, flavonoid, ascorbic acid content and antioxidant capacity) properties along with the enzymatic activity (catalase (CAT), ascorbate peroxidase (APX), polyphenol oxidase (PPO), guaiacol peroxidase (GPX) and lipoxygenase (LOX)) were evaluated. Chitosan treatment significantly reduced water loss and delayed the qualitative changes in color, titratable acidity and ascorbic acid content in dose- and cultivar-dependent manners. Additionally, changes in the total polyphenol, anthocyanin and flavonoid contents and the antioxidant capacity of chitosan-coated strawberry fruits were delayed. Chitosan coating enhanced the activity of some antioxidant enzymes, preventing flesh browning and reducing membrane damage. A global view of the responses of the three strawberry cultivars to chitosan coating and storage temperature was obtained using principal component analysis. Chitosan-coated fruit exhibited a slower rate of deterioration, compared to uncoated fruit in all tested cultivars. PMID:28231220

Antioxidant supplement inhibits skeletal muscle constitutive autophagy rather than fasting-induced autophagy in mice.

PubMed

Qi, Zhengtang; He, Qiang; Ji, Liu; Ding, Shuzhe

2014-01-01

In this study, we tested the hypothesis that NAC administration leads to reduced oxidative stress and thus to decreased expression of autophagy markers in young mice. Our results reveal that NAC administration results in reduced muscle mRNA levels of several autophagy markers, including Beclin-1, Atg7, LC3, Atg9, and LAMP2. However, NAC supplement fails to block the activation of skeletal muscle autophagy in response to fasting, because fasting significantly increases the mRNA level of several autophagy markers and LC3 lipidation. We further examined the effects of NAC administration on mitochondrial antioxidant capacity in fed and 24-hour fasted mice. Our results clearly show that NAC administration depresses the expression of manganese superoxide dismutase (MnSOD) and TP53-induced glycolysis and apoptosis regulator (TIGAR), both of which play a predominant antioxidant role in mitochondria by reducing ROS level. In addition, we found no beneficial effect of NAC supplement on muscle mass but it can protect from muscle loss in response to fasting. Collectively, our findings indicate that ROS is required for skeletal muscle constitutive autophagy, rather than starvation-induced autophagy, and that antioxidant NAC inhibits constitutive autophagy by the regulation of mitochondrial ROS production and antioxidant capacity.

Antioxidant Supplement Inhibits Skeletal Muscle Constitutive Autophagy rather than Fasting-Induced Autophagy in Mice

PubMed Central

Qi, Zhengtang; He, Qiang; Ji, Liu; Ding, Shuzhe

2014-01-01

In this study, we tested the hypothesis that NAC administration leads to reduced oxidative stress and thus to decreased expression of autophagy markers in young mice. Our results reveal that NAC administration results in reduced muscle mRNA levels of several autophagy markers, including Beclin-1, Atg7, LC3, Atg9, and LAMP2. However, NAC supplement fails to block the activation of skeletal muscle autophagy in response to fasting, because fasting significantly increases the mRNA level of several autophagy markers and LC3 lipidation. We further examined the effects of NAC administration on mitochondrial antioxidant capacity in fed and 24-hour fasted mice. Our results clearly show that NAC administration depresses the expression of manganese superoxide dismutase (MnSOD) and TP53-induced glycolysis and apoptosis regulator (TIGAR), both of which play a predominant antioxidant role in mitochondria by reducing ROS level. In addition, we found no beneficial effect of NAC supplement on muscle mass but it can protect from muscle loss in response to fasting. Collectively, our findings indicate that ROS is required for skeletal muscle constitutive autophagy, rather than starvation-induced autophagy, and that antioxidant NAC inhibits constitutive autophagy by the regulation of mitochondrial ROS production and antioxidant capacity. PMID:25028602

Turmeric and black pepper spices decrease lipid peroxidation in meat patties during cooking.

PubMed

Zhang, Yanjun; Henning, Susanne M; Lee, Ru-Po; Huang, Jianjun; Zerlin, Alona; Li, Zhaoping; Heber, David

2015-05-01

Spices are rich in natural antioxidants and have been shown to be potent inhibitors of lipid peroxidation during cooking of meat. Turmeric contains unique conjugated curcuminoids with strong antioxidant activity. Piperine, one of the main constituents of black pepper, is known to increase the bioavailability of curcuminoids in mouse and human studies when consumed with turmeric. We investigated whether adding black pepper to turmeric powder may further inhibit lipid peroxidation when added to meat patties prior to cooking. The addition of black pepper to turmeric significantly decreased the lipid peroxidation in hamburger meat. When investigating the antioxidant activity of the main chemical markers, we determined that piperine did not exhibit any antioxidant activity. Therefore, we conclude that other black pepper ingredients are responsible for the increased antioxidant activity of combining black pepper with turmeric powder.

Turmeric and black pepper spices decrease lipid peroxidation in meat patties during cooking

PubMed Central

Zhang, Yanjun; Henning, Susanne M.; Lee, Ru-Po; Huang, Jianjun; Zerlin, Alona; Li, Zhaoping; Heber, David

2015-01-01

Abstract Spices are rich in natural antioxidants and have been shown to be potent inhibitors of lipid peroxidation during cooking of meat. Turmeric contains unique conjugated curcuminoids with strong antioxidant activity. Piperine, one of the main constituents of black pepper, is known to increase the bioavailability of curcuminoids in mouse and human studies when consumed with turmeric. We investigated whether adding black pepper to turmeric powder may further inhibit lipid peroxidation when added to meat patties prior to cooking. The addition of black pepper to turmeric significantly decreased the lipid peroxidation in hamburger meat. When investigating the antioxidant activity of the main chemical markers, we determined that piperine did not exhibit any antioxidant activity. Therefore, we conclude that other black pepper ingredients are responsible for the increased antioxidant activity of combining black pepper with turmeric powder. PMID:25582173

Bioavailability study of a polyphenol-enriched extract from Hibiscus sabdariffa in rats and associated antioxidant status.

PubMed

Fernández-Arroyo, Salvador; Herranz-López, María; Beltrán-Debón, Raúl; Borrás-Linares, Isabel; Barrajón-Catalán, Enrique; Joven, Jorge; Fernández-Gutiérrez, Alberto; Segura-Carretero, Antonio; Micol, Vicente

2012-10-01

The aqueous extracts of Hibiscus sabdariffa have been commonly used in folk medicine. Nevertheless, the compounds or metabolites responsible for its healthy effects have not yet been identified. The major metabolites present in rat plasma after acute ingestion of a polyphenol-enriched Hibiscus sabdariffa extract were characterized and quantified in order to study their bioavailability. The antioxidant status of the plasma samples was also measured through several complementary antioxidant techniques. High-performance liquid chromatography coupled to time-of-flight mass spectrometry (HPLC-ESI-TOF-MS) was used for the bioavailability study. The antioxidant status was measured by ferric reducing ability of plasma method, thiobarbituric acid reactive substances assay, and superoxide dismutase activity assay. Seventeen polyphenols and metabolites have been detected and quantified. Eleven of these compounds were metabolites. Although phenolic acids were found in plasma without any modification in their structures, most flavonols were found as quercetin or kaempferol glucuronide conjugates. Flavonol glucuronide conjugates, which show longer half-life elimination values, are proposed to contribute to the observed lipid peroxidation inhibitory activity in the cellular membranes. By contrast, phenolic acids appear to exert their antioxidant activity through ferric ion reduction and superoxide scavenging at shorter times. We propose that flavonol-conjugated forms (quercetin and kaempferol) may be the compounds responsible for the observed antioxidant effects and contribute to the healthy effects of H. sabdariffa polyphenolic extract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bauhinia variegata Leaf Extracts Exhibit Considerable Antibacterial, Antioxidant, and Anticancer Activities

PubMed Central

Mishra, Amita; Sharma, Amit Kumar; Kumar, Shashank; Saxena, Ajit K.; Pandey, Abhay K.

2013-01-01

The present study reports the phytochemical profiling, antimicrobial, antioxidant, and anticancer activities of Bauhinia variegata leaf extracts. The reducing sugar, anthraquinone, and saponins were observed in polar extracts, while terpenoids and alkaloids were present in nonpolar and ethanol extracts. Total flavonoid contents in various extracts were found in the range of 11–222.67 mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions exhibited considerable inhibition against Klebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains of E. coli, Proteus spp. and Pseudomonas spp. Minimum bactericidal concentration (MBC) values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest MBC (3.5 mg/mL) was recorded for ethanol extract against Pseudomonas spp. The antioxidant activity of the extracts was compared with standard antioxidants. Dose dependent response was observed in reducing power of extracts. Polar extracts demonstrated appreciable metal ion chelating activity at lower concentrations (10–40 μg/mL). Many extracts showed significant antioxidant response in beta carotene bleaching assay. AQ fraction of B. variegata showed pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1 human cancer cell lines with 90–99% cell growth inhibitory activity. Ethyl acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1 cell lines. The study demonstrates notable antibacterial, antioxidant, and anticancer activities in B. variegata leaf extracts. PMID:24093108

Disposable microfluidic sensor arrays for discrimination of antioxidants.

PubMed

Park, Seong H; Maruniak, Autumn; Kim, Jisun; Yi, Gi-Ra; Lim, Sung H

2016-06-01

A microfluidic colorimetric sensor array was developed for detection and identification of various antioxidants. The sensor was fabricated by a photolithographic method, and consists of an array of printed cross-responsive indicators. The microfluidic design also incorporates pre-activation spots to allow printing of chemically incompatible components separately. Separately printed oxidizer allowed an oxidation of adjacent redox indicators only when aqueous sample was added to the sensor cartridge. Antioxidants were primarily detected by measuring the extent of inhibition of this oxidation reaction. Using this flow-based technique, a clear differentiation of 8 different antioxidants and 4 different teas has been demonstrated with 98.5% sensitivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Long-term organic selenium supplementation overcomes the trade-off between immune and antioxidant systems in pacu (Piaractus mesopotamicus).

PubMed

Takahashi, Leonardo Susumu; Biller-Takahashi, Jaqueline Dalbello; Mansano, Cleber Fernando Menegasso; Urbinati, Elisabeth Criscuolo; Gimbo, Rodrigo Yukihiro; Saita, Marcos Vinícius

2017-01-01

Selenium (Se) is an essential nutrient for antioxidant defenses in fish because of its role in preventing immunosuppression caused by oxidative stress. In this study it was demonstrated the relation between the oxidative stress and immune status after a long Se supplementation period, as a result of the evaluation of immunological, hematological and antioxidant responses, as well as growth performance of pacu fed diets supplemented with different concentrations of organic selenium (0, 0.3, 0.6, 0.9, and 1.8 mg Se-yeast/kg, but the final analyzed selenium concentrations were 0.72, 0.94, 1.15, 1.57 and 2.51 mg/kg, respectively) for 65 days. Dietary Se supplementation at 1.15 mg Se-yeast/kg (analyzed value) restored the production of antioxidant enzymes (glutathione peroxidase (GPx) and glutathione S-transferase (GST)), and consequently allowed the increased of some immunological parameters (leukocyte respiratory burst activity and lysozyme activity), hematological parameters (red blood cell count (RBC), hematocrit (HTC), mean corpuscular volume (MCV), and white blood cell count (WBC)). Se supplementation in pacu diets at 1.15 mg Se-yeast/kg for 65 days improved immune response and antioxidant defenses, suggesting that oxidative stress impairs immune system response to prevent excessive reactive oxygen species in cells and indicating the occurrence of a physiological trade-off between immune and antioxidant systems. Higher Se levels, such as 1.57 mg Se-yeast/kg increased the leukocyte respiratory burst activity, the WBC and thrombocyte counts, the RBC and HTC, and the GST and GPx enzymes. However, 2.51 mg Se-yeast/kg decreased the lysozyme levels, the WBC and thrombocyte counts, the RBC, HTC and MCV, and the GST and GPx enzymes. Those findings are important to future studies because showed the negative effect of oxidative stress on immunity, and may help to prevent any inhibition of the expected immune response after immunomodulators administration and vaccination. Also it was possible to meet the dietary selenium requirement of pacu, that was estimated to be 1.56 mg/kg. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mitochondrial reactive oxygen species generation triggers inflammatory response and tissue injury associated with hepatic ischemia-reperfusion: therapeutic potential of mitochondrially-targeted antioxidants

PubMed Central

Mukhopadhyay, Partha; Horváth, Bėla; Zsengellėr, Zsuzsanna; Bátkai, Sándor; Cao, Zongxian; Kechrid, Malek; Holovac, Eileen; Erdėlyi, Katalin; Tanchian, Galin; Liaudet, Lucas; Stillman, Isaac E.; Joseph, Joy; Kalyanaraman, Balaraman; Pacher, Pál

2012-01-01

Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury, however its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explored the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2 hours of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute pro-inflammatory response (TNF-α, MIP-1αCCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6 hours of reperfusion and peaking at 24 hours). Mitochondrially-targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage. PMID:22683818

Effects of triclosan (TCS) on fecundity, the antioxidant system, and oxidative stress-mediated gene expression in the copepod Tigriopus japonicus.

PubMed

Park, Jun Chul; Han, Jeonghoon; Lee, Min-Chul; Seo, Jung Soo; Lee, Jae-Seong

2017-08-01

Triclosan (TCS) is an antimicrobial agent that has been widely dispersed and detected in the marine environment. However, the effects of TCS in marine invertebrates are poorly understood. In this study, the effects of TCS on life cycle history (e.g. mortality and fecundity) along with cellular reactive oxygen species (ROS) levels, GSH content, antioxidant enzymatic activities, and mRNA expression levels of oxidative stress-mediated genes were measured in the copepod Tigriopus japonicus. The no observed effect concentration (NOEC) and median lethal concentration (LC50) of TCS in the adult stage were determined to be 300μg/L and 437.476μg/L, respectively, while in the nauplius stages the corresponding values were 20μg/L, and 51.76μg/L, respectively. Fecundity was significantly reduced (P<0.05) in response to TCS at 100μg/L. Concentration- and time-dependent analysis of ROS, GSH content (%), and antioxidant enzymatic activities (e.g. GST, GPx, and SOD) were significantly increased (P<0.05) in response to TCS exposure. Additionally, mRNA expression of detoxification (e.g., CYPs) and antioxidant (e.g., glutathione S-transferase-sigma isoforms, Cu/Zn superoxide dismutase, catalase) genes was modulated in response to TCS exposure at different concentrations over a 24h period. Our results revealed that TCS can induce reduced fecundity and oxidative stress with transcriptional regulation of oxidative stress-mediated genes with activation of the antioxidant system in the copepod T. japonicus. Copyright © 2017 Elsevier B.V. All rights reserved.

Oxidative stress response in canine in vitro liver, kidney and intestinal models with seven potential dietary ingredients.

PubMed

Choi, Kyoungju; Ortega, Maria T; Jeffery, Brett; Riviere, Jim E; Monteiro-Riviere, Nancy A

2016-01-22

In vitro cell culture systems are a useful tool to rapidly assess the potential safety or toxicity of chemical constituents of food. Here, we investigated oxidative stress and organ-specific antioxidant responses by 7 potential dietary ingredients using canine in vitro culture of hepatocytes, proximal tubule cells (CPTC), bone marrow-derived mesenchymal stem cells (BMSC) and enterocyte-like cells (ELC). Cellular production of free radical species by denatonium benzoate (DB), epigallocatechin gallate (EPI), eucalyptol (EUC), green tea catechin extract (GTE) and sodium copper chlorophyllin (SCC), tetrahydroisohumulone (TRA) as well as xylitol (XYL) were continuously measured for reactive oxygen/nitrogen species (ROS/RNS) and superoxide (SO) for up to 24h. DB and TRA showed strong prooxidant activities in hepatocytes and to a lesser degree in ELC. DB was a weak prooxidant in BMSC. In contrast DB and TRA were antioxidants in CPTC. EPI was prooxidant in hepatocytes and BMSC but showed prooxidant and antioxidant activity in CPTC. SCC in hepatocytes (12.5mg/mL) and CPTC (0.78mg/mL) showed strong prooxidant and antioxidant activity in a concentration-dependent manner. GTE was effective antioxidant only in ELC. EUC and XYL did not induce ROS/RNS in all 4 cell types. SO production by EPI and TRA increased in hepatocytes but decreased by SCC in hepatocytes and ELC. These results suggest that organ-specific responses to oxidative stress by these potential prooxidant compounds may implicate a mechanism of their toxicities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ocimum basilicum affects tracheal responsiveness, lung inflammatory cells and oxidant-antioxidant biomarkers in sensitized rats.

PubMed

Eftekhar, Naeima; Moghimi, Ali; Hossein Boskabady, Mohammad; Kaveh, Mahsa; Shakeri, Farzaneh

2018-04-23

The anti-inflammatory and antioxidant effects of Ocimum basilicum (O. basilicum) was shown previously. In the present study, the effect of O. basilicum on tracheal responsiveness (TR) to methacholine and ovalbumin (OVA), bronchoalveolar lavage fluid (BALF) levels of oxidant-antioxidant biomarkers as well as total and differential white blood cell (WBC) in sensitized rats was examined. Six groups of rats including control (group C), sensitized rats to OVA (group S), S groups treated with three concentrations of O. basilicum (0.75, 1.50, and 3.00 mg/ml) and one concentration of dexamethasone (1.25 μg/ml) (n = 8 for all groups) were studied. TR to methacholine and OVA, total WBC count, percentages of eosinophils, monocytes, neutrophils, and levels of oxidant biomarkers were significantly increased but other measured parameters were significantly decreased in group S compared to group C. TR to methacholine and OVA, percentages of eosinophils, monocytes, neutrophils, and levels of oxidant biomarkers were significantly decreased but lymphocytes and antioxidant biomarkers were significantly increased in S groups treated with dexamethasone and at least two higher concentrations of the extract compared to group S. Total WBC count was also decreased in treated S groups with dexamethasone and high extract concentration. The effect of extract on most measured parameters was significantly lower than dexamethasone treatment. The effects of two higher concentrations of the extract on most variables were significantly higher than the effect of low extract concentration. These results showed the concentration-dependent effect of O. basilicum on tracheal responses, lung inflammatory cells, and oxidant-antioxidant parameters in sensitized rats.

Aeroallergens Induce Reactive Oxygen Species Production and DNA Damage and Dampen Antioxidant Responses in Bronchial Epithelial Cells.

PubMed

Chan, Tze Khee; Tan, W S Daniel; Peh, Hong Yong; Wong, W S Fred

2017-07-01

Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX. HDM stimulated cellular reactive oxygen species production, increased mitochondrial oxidative stress, and promoted nitrosative stress. Notably, expression of nuclear factor erythroid 2-related factor 2-dependent antioxidant genes was reduced immediately after HDM exposure, suggesting that HDM altered antioxidant responses. HDM exposure also reduced cell proliferation and induced cell death. Importantly, HDM-induced DNA damage can be prevented by the antioxidants glutathione and catalase, suggesting that HDM-induced reactive oxygen and nitrogen species can be neutralized by antioxidants. Mechanistic studies revealed that HDM-induced cellular injury is NADPH oxidase (NOX)-dependent, and apocynin, a NOX inhibitor, protected cells from double-strand breaks induced by HDM. Our results show that direct exposure of bronchial epithelial cells to HDM leads to the production of reactive oxygen and nitrogen species that damage DNA and induce cytotoxicity. Antioxidants and NOX inhibitors can prevent HDM-induced DNA damage, revealing a novel role for antioxidants and NOX inhibitors in mitigating allergic airway disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Antioxidant mediated response of Scoparia dulcis in noise-induced redox imbalance and immunohistochemical changes in rat brain.

PubMed

Wankhar, Wankupar; Srinivasan, Sakthivel; Rajan, Ravindran; Sheeladevi, Rathinasamy

2017-01-19

Noise has been regarded as an environmental/occupational stressor that causes damages to both auditory and non-auditory organs. Prolonged exposure to these mediators of stress has often resulted in detrimental effect, where oxidative/nitrosative stress plays a major role. Hence, it would be appropriate to examine the possible role of free radicals in brain discrete regions and the "antioxidants" mediated response of S. dulcis. Animals were subjected to noise stress for 15 days (100 dB/4 hours/day) and estimation of endogenous free radical and antioxidant activity were carried out on brain discrete regions (the cerebral cortex, cerebellum, brainstem, striatum, hippocampus and hypothalamus). The result showed that exposure to noise could alleviate endogenous free radical generation and altered antioxidant status in brain discrete regions when compared to that of the control groups. This alleviated free radical generation (H 2 O 2 and NO) is well supported by an upregulated protein expression on immunohistochemistry of both iNOS and nNOS in the cerebral cortex on exposure to noise stress. These findings suggest that increased free radical generation and altered anti-oxidative status can cause redox imbalance in the brain discrete regions. However, free radical scavenging activity of the plant was evident as the noise exposed group treated with S. dulcis[200 mg/(kg·b·w)] displayed a therapeutic effect by decreasing the free radical level and regulate the anti-oxidative status to that of control animals. Hence, it can be concluded that the efficacy of S. dulcis could be attributed to its free radical scavenging activity and anti-oxidative property.

Antioxidant mediated response of Scoparia dulcis in noise-induced redox imbalance and immunohistochemical changes in rat brain

PubMed Central

Wankhar, Wankupar; Srinivasan, Sakthivel; Rajan, Ravindran; Sheeladevi, Rathinasamy

2017-01-01

Noise has been regarded as an environmental/occupational stressor that causes damages to both auditory and non-auditory organs. Prolonged exposure to these mediators of stress has often resulted in detrimental effect, where oxidative/nitrosative stress plays a major role. Hence, it would be appropriate to examine the possible role of free radicals in brain discrete regions and the "antioxidants" mediated response of S. dulcis. Animals were subjected to noise stress for 15 days (100 dB/4 hours/day) and estimation of endogenous free radical and antioxidant activity were carried out on brain discrete regions (the cerebral cortex, cerebellum, brainstem, striatum, hippocampus and hypothalamus). The result showed that exposure to noise could alleviate endogenous free radical generation and altered antioxidant status in brain discrete regions when compared to that of the control groups. This alleviated free radical generation (H2O2 and NO) is well supported by an upregulated protein expression on immunohistochemistry of both iNOS and nNOS in the cerebral cortex on exposure to noise stress. These findings suggest that increased free radical generation and altered anti-oxidative status can cause redox imbalance in the brain discrete regions. However, free radical scavenging activity of the plant was evident as the noise exposed group treated with S. dulcis[200 mg/(kg·b·w)] displayed a therapeutic effect by decreasing the free radical level and regulate the anti-oxidative status to that of control animals. Hence, it can be concluded that the efficacy of S. dulcis could be attributed to its free radical scavenging activity and anti-oxidative property. PMID:28808196

Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages

PubMed Central

Chai, Jianshen; Luo, Li; Hou, Fengyan; Fan, Xia; Yu, Jing; Ma, Wei; Tang, Wangqi; Yang, Xue; Zhu, Junyu; Kang, Wenyuan; Yan, Jun; Liang, Huaping

2016-01-01

Macrophages are key responders of inflammation and are closely related with oxidative stress. Activated macrophages can enhance oxygen depletion, which causes an overproduction of reactive oxygen species (ROS) and leads to further excessive inflammatory response and tissue damage. Agmatine, an endogenous metabolite of L-arginine, has recently been shown to have neuroprotective effects based on its antioxidant properties. However, the antioxidant effects of agmatine in peripheral tissues and cells, especially macrophages, remain unclear. In this study we explored the role of agmatine in mediating antioxidant effects in RAW 264.7 cells and studied its antioxidant mechanism. Our data demonstrate that agmatine is an activator of Nrf2 signaling that markedly enhances Nrf2 nuclear translocation, increases nuclear Nrf2 protein level, up-regulates the expression of the Nrf2 downstream effector HO-1, and attenuates ROS generation induced by Lipopolysaccharide (LPS). We further demonstrated that the agmatine-induced activation of Nrf2 is likely through the PI3K/Akt pathway. LY294002, a specific PI3K/Akt inhibitor, abolished agmatine-induced HO-1 up-regulation and ROS suppression significantly. Inhibiting HO-1 pathway significantly attenuated the antioxidant effect of agmatine which the products of HO-1 enzymatic activity contributed to. Furthermore, the common membrane receptors of agmatine were evaluated, revealing that α2-adrenoceptor, I1-imidazoline receptor or I2-imidazoline receptor are not required by the antioxidant properties of agmatine. Taken together, our findings revealed that agmatine has antioxidant activity against LPS-induced ROS accumulation in RAW 264.7 cells involving HO-1 expression induced by Nrf2 via PI3K/Akt pathway activation. PMID:27685463

Antioxidant capacity of different fractions of vegetables and correlation with the contents of ascorbic acid, phenolics, and flavonoids.

PubMed

Ji, Linlin; Wu, Jianquan; Gao, Weina; Wei, Jingyu; Yang, Jijun; Guo, Changjiang

2011-01-01

The antioxidant capacity of different fractions of 17 vegetables were analyzed using ferric reducing antioxidant power assay (FRAP assay) after water and acetone extractions. The contents of ascorbic acid, phenolics, and flavonoids were determined and their correlations with FRAP value were investigated. The results showed that the peel or leaf fractions of vegetables were stronger than the pulp or stem fractions in antioxidant capacity based on total FRAP value. Lotus root peel was the highest and cucumber pulp the lowest in total FRAP value among the vegetable fractions analyzed. All water extracts were higher in FRAP value than the acetone extracts. The FRAP value was significantly correlated with the contents of ascorbic acid, phenolics, or flavonoids in water extracts, in which the phenolics contributed most based on multivariate regression analysis. We conclude that different vegetable fractions were remarkably different in antioxidant capacity. The phenolics are responsible mostly for the antioxidant capacity of vegetables in vitro. © 2011 Institute of Food Technologists®

Wheat bread enriched with green coffee - In vitro bioaccessibility and bioavailability of phenolics and antioxidant activity.

PubMed

Świeca, Michał; Gawlik-Dziki, Urszula; Dziki, Dariusz; Baraniak, Barbara

2017-04-15

The potential bioaccessibility and bioavailability of phenolics, caffeine and antioxidant activity of wheat bread enriched with green coffee were studied. Supplementation enhanced nutraceutical potential by improving phenolic content and lipid protecting capacity. The simulated-digestion-released phenolics (mainly caffeic acid, syringic acid and vanillic acid) from bread, also caused significant qualitative changes (chlorogenic acids were cleaved and significant amounts of caffeic acid and ferulic acid were determined). Compared to the control, for the bread with 1% and 5% of the functional component the contents of phenolics were 1.6 and 3.33 times higher. Also, an approximately 2.3-fold increase in antioxidant activity was found in bread containing 5% of the supplement. The compounds responsible for antioxidant potential have high bioaccessibility but poor bioavailability. The qualitative composition of the phenolic fraction has a key role in developing the antioxidant potential of bread; however, caffeine and synergism between antioxidants are also important considerations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Coffee component 3-caffeoylquinic acid increases antioxidant capacity but not polyphenol content in experimental cerebral infarction.

PubMed

Ruiz-Crespo, Silvia; Trejo-Gabriel-Galan, Jose M; Cavia-Saiz, Monica; Muñiz, Pilar

2012-05-01

Although coffee has antioxidant capacity, it is not known which of its bioactive compounds is responsible for it, nor has it been analyzed in experimental cerebral infarction. We studied the effect one of its compounds, 3-caffeoylquinic acid (3-CQA), at doses of 4, 25 and 100 μg on plasma antioxidant capacity and plasma polyphenol content, measuring the differences before and after inducing a cerebral infarction in an experimental rat model. We compared them with 3-caffeoylquinic-free controls. The increase in total antioxidant capacity was only higher than in controls in 3-CQA treated animals with the highest dose. This increase in antioxidant capacity was not due to an increase in polyphenols. No differences between the experimental and control group were found regarding polyphenol content and cerebral infarction volume. In conclusion, this increase in antioxidant capacity in the group that received the highest dose of 3-CQA was not able to reduce experimental cerebral infarction.

Pulmonary function response and effects of antioxidant genetic polymorphisms in healthy young adults exposed to low concentration ozone.

EPA Science Inventory

Rational: Ozone is known to induce a variety of pulmonary effects including decrement of spirometric lung function and inflammatory reaction, and antioxidant genes are known to play an important role in modulating the effects. It is unclear, however, if such effects may occur at...

The optimization of phenolic compounds extraction from cactus pear (Opuntia ficus-indica) skin in a reflux system using response surface methodology.

PubMed

Jorge, Aguirre Joya; Heliodoro, De La Garza Toledo; Alejandro, Zugasti Cruz; Ruth, Belmares Cerda; Noé, Aguilar Cristóbal

2013-06-01

To extract, quantify, and evaluate the phenolic content in Opuntia ficus-indica skin for their antioxidant capacity with three different methods (ABTS, DPPH, and lipid oxidation) and to optimize the extraction conditions (time, temperature and ethanol concentration) in a reflux system. The extraction process was done using a reflux system. A San Cristobal II experimental design with three variables and three levels was used. The variables evaluated were time of extraction (h), concentration of ethanol (%, v/v) and temperature (°C). The extraction process was optimized using a response surface methodology. It was observed that at higher temperature more phenolic compounds were extracted, but the antioxidant capacity was decreased. The optimum conditions for phenolic compounds extraction and antioxidant capacity mixing the three methods were as follows: 45% of ethanol, 80 °C and 2 hours of extraction. Values obtained in our results are little higher that other previously reported. It can be concluded the by-products of Opuntia ficus-indica represent a good source of natural antioxidants with possible applications in food, cosmetics or drugs industries.

Melatonin–sulforaphane hybrid ITH12674 induces neuroprotection in oxidative stress conditions by a ‘drug–prodrug’ mechanism of action

PubMed Central

Egea, Javier; Buendia, Izaskun; Parada, Esther; Navarro, Elisa; Rada, Patricia; Cuadrado, Antonio; López, Manuela G; García, Antonio G; León, Rafael

2015-01-01

Background and Purpose Neurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties. Experimental Approach Compound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug–prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia. Key Results ITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration-dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2–antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re-oxygenation from stress by increasing the expression of haem oxygenase-1 and reducing free radical production. Conclusion and Implications ITH12674 combines the signalling pathways of the parent compounds to improve its neuroprotective properties. This opens a new line of research for such hybrid compounds to treat neurodegenerative diseases. PMID:25425158