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Nordengen AL, Krutto A, Kværner AS, Alavi DT, Henriksen HB, Kolle Å, Henriksen C, Smeland S, Bøhn SK, Zheng C, Shaposhnikov S, Collins AR, Blomhoff R. Plant-based diet and oxidative stress-induced DNA damage in post-surgery colorectal cancer patients: Results from a randomized controlled trial. Free Radic Biol Med 2025; 233:240-249. [PMID: 40180023 DOI: 10.1016/j.freeradbiomed.2025.03.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/28/2025] [Accepted: 03/30/2025] [Indexed: 04/05/2025]
Abstract
Oxidative stress-induced DNA damage may impact long-term outcomes in colorectal cancer (CRC) patients. While bioactive compounds in plant foods have been linked to DNA protection, evidence among patients in remission remains limited. The present study aimed to investigate the effect of a one-year personalized intensive dietary intervention on DNA damage in post-surgery, non-metastatic CRC patients. Participants were enrolled 2-9 months after surgery in the ongoing randomized controlled trial, Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET). Eligible participants (aged 50-80 years, primary stage I-III CRC) were randomized to either a plant-based dietary intervention targeting oxidative stress and inflammation, or to a control group that received standard dietary advice as a part of routine cancer care. As a secondary analysis, this study included 156 participants (78 in the intervention group and 78 in the control group) from the total 503 patients enrolled in CRC-NORDIET study. DNA damage in peripheral mononuclear blood cells (PBMCs) was assessed using the enzyme-modified comet assay during a 12-month follow-up period. A significant intervention effect on DNA base oxidation from baseline to 12 months was observed (P = 0.04), representing a 32 % reduction in the intervention group compared to the control group. No significant effect on DNA strand breaks was found. In conclusion, adherence to a plant-based dietary pattern may reduce DNA base oxidation in post-surgery CRC patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01570010.
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Affiliation(s)
- Anne Lene Nordengen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway; Norgenotech AS, Oslo Cancer Cluster Incubator, Oslo, Norway; Department of Sport Science and Physical Education, Faculty of Health and Sport Sciences, University of Agder, Kristiansand, Norway.
| | - Annika Krutto
- Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Norway
| | - Ane S Kværner
- Section for Colorectal Cancer Screening, The Cancer Registry of Norway, Oslo, Norway
| | - Dena T Alavi
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway
| | - Hege B Henriksen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway
| | - Åshild Kolle
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway
| | - Christine Henriksen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway
| | - Sigbjørn Smeland
- Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Norway, Oslo, Norway
| | - Siv K Bøhn
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway
| | - Congying Zheng
- Norgenotech AS, Oslo Cancer Cluster Incubator, Oslo, Norway; Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translation Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | | | - Andrew R Collins
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway; Norgenotech AS, Oslo Cancer Cluster Incubator, Oslo, Norway
| | - Rune Blomhoff
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway; Department of Clinical Service, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway
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Marsal A, Sauvain JJ, Thomas A, Lyon-Caen S, Borlaza LJS, Philippat C, Jaffrezo JL, Boudier A, Darfeuil S, Elazzouzi R, Lepeule J, Chartier R, Bayat S, Slama R, Siroux V, Uzu G. Effects of personal exposure to the oxidative potential of PM 2.5 on oxidative stress biomarkers in pregnant women. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 911:168475. [PMID: 37951259 DOI: 10.1016/j.scitotenv.2023.168475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 10/30/2023] [Accepted: 11/08/2023] [Indexed: 11/13/2023]
Abstract
Oxidative stress is a prominent pathway for the health effects associated with fine particulate matter (PM2.5) exposure. Oxidative potential (OP) of PM has been associated to several health endpoints, but studies on its impact on biomarkers of oxidative stress remains insufficient. 300 pregnant women from the SEPAGES cohort (France) carried personal PM2.5 samplers for a week and OP was measured using ascorbic acid (AA) and dithiothreitol (DTT) assays, and normalized by 1) PM2.5 mass (OPm) and 2) sampled air volume (OPv). A pool of three urine spots collected on the 7th day of PM sampling was analyzed for biomarkers, namely 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA) and 8-isoprostaglandin-F2α (8-isoPGF2α). Associations were investigated using adjusted multiple linear regressions. OP effects were additionally investigated by stratifying by median PM2.5 concentration (14 μg m-3). In the main models, no association was observed with 8-isoPGF2α, nor MDA. An interquartile range (IQR) increase in OPmAA exposure was associated with increased 8-OHdG (percent change: 6.2 %; 95 % CI: 0.2 % to 12.6 %). In the stratified analysis, exposure to OPmAA was associated with 8-OHdG for participants exposed to low levels of PM2.5 (percent change: 11.4 %; 95 % CI: 3.3 % to 20.1 %), but not for those exposed to high levels (percent change: -1.0 %; 95 % CI: -10.6 % to 9.6 %). Associations for OPmDTT also followed a similar pattern (p-values for OPmAA-PM and OPmDTT-PM interaction terms were 0.12 and 0.11, respectively). Overall, our findings suggest that OPmAA may be associated with increased DNA oxidative damage. This association was not observed with PM2.5 mass concentration exposure. The effects of OPmAA in 8-OHdG tended to be stronger at lower (below median) vs. higher concentrations of PM2.5. Further epidemiological, toxicological and aerosol research are needed to further investigate the OPmAA effects on 8-OHdG and the potential modifying effect of PM mass concentration on this association.
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Affiliation(s)
- Anouk Marsal
- Univ. Grenoble Alpes, CNRS, INRAE, IRD, Grenoble INP, IGE, 38000 Grenoble, France; Agence de l'environnement et de la Maîtrise de l'Energie, 20, avenue du Grésillé, BP 90406 49004 Angers Cedex 01, France
| | - Jean-Jacques Sauvain
- Department of Occupational and Environmental Health, Center for Primary Care and Public Health (Unisanté), University Lausanne, Lausanne, Switzerland
| | - Aurélien Thomas
- Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland; Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland
| | - Sarah Lyon-Caen
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to the Development and Respiratory Health, Institute for Advanced Biosciences, 38000 Grenoble, France
| | | | - Claire Philippat
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to the Development and Respiratory Health, Institute for Advanced Biosciences, 38000 Grenoble, France
| | - Jean-Luc Jaffrezo
- Univ. Grenoble Alpes, CNRS, INRAE, IRD, Grenoble INP, IGE, 38000 Grenoble, France
| | - Anne Boudier
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to the Development and Respiratory Health, Institute for Advanced Biosciences, 38000 Grenoble, France; Pediatric Department, CHU Grenoble Alpes, Grenoble, France
| | - Sophie Darfeuil
- Univ. Grenoble Alpes, CNRS, INRAE, IRD, Grenoble INP, IGE, 38000 Grenoble, France
| | - Rhabira Elazzouzi
- Univ. Grenoble Alpes, CNRS, INRAE, IRD, Grenoble INP, IGE, 38000 Grenoble, France
| | - Johanna Lepeule
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to the Development and Respiratory Health, Institute for Advanced Biosciences, 38000 Grenoble, France
| | | | - Sam Bayat
- Department of Pulmonology and Physiology, CHU Grenoble Alpes, Grenoble, France; Univ. Grenoble Alpes, Inserm UA07 STROBE Laboratory, Grenoble, France
| | - Rémy Slama
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to the Development and Respiratory Health, Institute for Advanced Biosciences, 38000 Grenoble, France
| | - Valérie Siroux
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to the Development and Respiratory Health, Institute for Advanced Biosciences, 38000 Grenoble, France
| | - Gaëlle Uzu
- Univ. Grenoble Alpes, CNRS, INRAE, IRD, Grenoble INP, IGE, 38000 Grenoble, France.
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Fu Q, Zhang F, Vijayalakshmi A. The Protective Effect of Sanggenol L Against DMBA-induced Hamster Buccal Pouch Carcinogenesis Induces Apoptosis and Inhibits Cell Proliferative Signalling Pathway. Comb Chem High Throughput Screen 2024; 27:885-893. [PMID: 37496247 DOI: 10.2174/1386207326666230726140706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 05/21/2023] [Accepted: 06/09/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND Oral squamous cell carcinoma (OSCC) has a poor prognosis when treated with surgery and chemotherapy. Therefore, a new therapy and preventative strategy for OSCC and its underlying mechanisms are desperately needed. The purpose of this study was to examine the chemopreventive effects of sanggenol L on oral squamous cell carcinoma (OSCC). The research focused on molecular signalling pathways in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. AIM The purpose of this study was to look at the biochemical and chemopreventive effects of sanggenol L on 7,12-dimethylbenz(a)anthracene (DMBA)-induced HBP (hamster buccal pouch) carcinogenesis via cell proliferation and the apoptotic pathway. METHODS After developing squamous cell carcinoma, oral tumours continued to progress leftward into the pouch 3 times per week for 10 weeks while being exposed to 0.5 % reactive DMBA three times per week. Tumour growth was caused by biochemical abnormalities that induced inflammation, increased cell proliferation, and decreased apoptosis. RESULTS Oral sanggenol L (10 mg/kg bw) supplementation with cancer-induced model DMBApainted hamsters prevented tumour occurrences, improved biochemistry, inhibited inflammatory markers, decreased cell proliferation marker expression of tumour necrosis factor-alpha (TNF- α), nuclear factor (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and induced apoptosis. CONCLUSION Sanggenol L could be developed into a new medicine for the treatment of oral carcinogenesis.
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Affiliation(s)
- Qing Fu
- Department of Stomatology, People's Hospital of Qijiang District, Chongqing, 401420, China
| | - Fangming Zhang
- Department of Stomatology, The Fifth People's Hospital Of Wuxi, Wuxi, 214000, China
| | - Annamalai Vijayalakshmi
- Department of Biochemistry, Rabiammal Ahamed Maideen College for Women, Thiruvarur, Tamil Nadu, 610001, India
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Cassotta M, Cianciosi D, De Giuseppe R, Navarro-Hortal MD, Armas Diaz Y, Forbes-Hernández TY, Pifarre KT, Pascual Barrera AE, Grosso G, Xiao J, Battino M, Giampieri F. Possible role of nutrition in the prevention of inflammatory bowel disease-related colorectal cancer: A focus on human studies. Nutrition 2023; 110:111980. [PMID: 36965240 DOI: 10.1016/j.nut.2023.111980] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 01/10/2023] [Accepted: 01/22/2023] [Indexed: 02/05/2023]
Abstract
Patients with inflammatory bowel disease (IBD) are at substantially high risk for colorectal cancer (CRC). IBD-associated CRC accounts for roughly 10% to 15% of the annual mortality in patients with IBD. IBD-related CRC also affects younger patients compared with sporadic CRC, with a 5-y survival rate of 50%. Regardless of medical therapies, the persistent inflammatory state characterizing IBD raises the risk for precancerous changes and CRC, with additional input from several elements, including genetic and environmental risk factors, IBD-associated comorbidities, intestinal barrier dysfunction, and gut microbiota modifications. It is well known that nutritional habits and dietary bioactive compounds can influence IBD-associated inflammation, microbiome abundance and composition, oxidative stress balance, and gut permeability. Additionally, in recent years, results from broad epidemiologic and experimental studies have associated certain foods or nutritional patterns with the risk for colorectal neoplasia. The present study aimed to review the possible role of nutrition in preventing IBD-related CRC, focusing specifically on human studies. It emerges that nutritional interventions based on healthy, nutrient-dense dietary patterns characterized by a high intake of fiber, vegetables, fruit, ω-3 polyunsaturated fatty acids, and a low amount of animal proteins, processed foods, and alcohol, combined with probiotic supplementation have the potential of reducing IBD-activity and preventing the risk of IBD-related CRC through different mechanisms, suggesting that targeted nutritional interventions may represent a novel promising approach for the prevention and management of IBD-associated CRC.
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Affiliation(s)
- Manuela Cassotta
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
| | - Danila Cianciosi
- Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Rachele De Giuseppe
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy; NBFC, National Biodiversity Future Center, Palermo 90133, Italy
| | - Maria Dolores Navarro-Hortal
- Biomedical Research Centre, Institute of Nutrition and Food Technology "José Mataix Verdú," Department of Physiology, Faculty of Pharmacy, University of Granada, Armilla, Granada, Spain
| | - Yasmany Armas Diaz
- Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Tamara Yuliett Forbes-Hernández
- Biomedical Research Centre, Institute of Nutrition and Food Technology "José Mataix Verdú," Department of Physiology, Faculty of Pharmacy, University of Granada, Armilla, Granada, Spain
| | - Kilian Tutusaus Pifarre
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Project Department, Universidade Internacional do Cuanza, Cuito, Bié, Angola
| | - Alina Eugenia Pascual Barrera
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Department of Project Management, Universidad Internacional Iberoamericana, Campeche, Mexico
| | - Giuseppe Grosso
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, Universidade de Vigo - Ourense Campus, Ourense, Spain
| | - Maurizio Battino
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy; International Joint Research Laboratory of Intelligent Agriculture and Agri-products Processing, Jiangsu University, Zhenjiang, China
| | - Francesca Giampieri
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain.
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Nersesyan A, Kundi M, Fenech M, Stopper H, da Silva J, Bolognesi C, Mišík M, Knasmueller S. Recommendations and quality criteria for micronucleus studies with humans. MUTATION RESEARCH. REVIEWS IN MUTATION RESEARCH 2022; 789:108410. [PMID: 35690413 DOI: 10.1016/j.mrrev.2021.108410] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 12/15/2021] [Accepted: 12/17/2021] [Indexed: 06/15/2023]
Abstract
Micronucleus (MN) analyses in peripheral blood lymphocytes and exfoliated cells from different organs (mouth, nose, bladder and cervix) are at present the most widely used approaches to detect damage of genetic material in humans. MN are extranuclear DNA-containing bodies, which can be identified microscopically. They reflect structural and numerical chromosomal aberrations and are formed as a consequence of exposure to occupational, environmental and lifestyle genotoxins. They are also induced as a consequence of inadequate intake of certain trace elements and vitamins. High MN rates are associated with increased risk of cancer and a range of non-cancer diseases in humans. Furthermore, evidence is accumulating that measurements of MN could be a useful tool for the diagnosis and prognosis of different forms of cancer and other diseases (inflammation, infections, metabolic disorders) and for the assessment of the therapeutic success of medical treatments. Recent reviews of the current state of knowledge suggest that many clinical studies have methodological shortcomings. This could lead to controversial findings and limits their usefulness in defining the impact of exposure concentrations of hazardous chemicals, for the judgment of remediation strategies, for the diagnosis of diseases and for the identification of protective or harmful dietary constituents. This article describes important quality criteria for human MN studies and contains recommendations for acceptable study designs. Important parameters that need more attention include sufficiently large group sizes, adequate duration of intervention studies, the exclusion of confounding factors which may affect the results (sex, age, body mass index, nutrition, etc.), the evaluation of appropriate cell numbers per sample according to established scoring criteria as well as the use of proper stains and adequate statistical analyses.
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Affiliation(s)
- A Nersesyan
- Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - M Kundi
- Center for Public Health, Department of Environmental Health, Medical University of Vienna, Vienna, Austria
| | - M Fenech
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia; Universiti Kebangsaan Malaysia, Selangor, Malaysia; Genome Health Foundation, North Brighton, SA, Australia
| | - H Stopper
- Institute of Pharmacology and Toxicology, Wuerzburg University, Wuerzburg, Germany
| | - J da Silva
- Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA) & LaSalle University (UniLaSalle), Canoas, RS, Brazil
| | - C Bolognesi
- Environmental Carcinogenesis Unit, Ospedale Policlinico San Martino, Genoa, Italy
| | - M Mišík
- Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - S Knasmueller
- Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
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Short Overview of Some Assays for the Measurement of Antioxidant Activity of Natural Products and Their Relevance in Dermatology. Molecules 2021; 26:molecules26175301. [PMID: 34500732 PMCID: PMC8433703 DOI: 10.3390/molecules26175301] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/25/2021] [Accepted: 08/25/2021] [Indexed: 12/19/2022] Open
Abstract
Impaired systemic redox homeostasis is implicated in the onset and development of various diseases, including skin diseases. Therefore, continuous search for natural products with antioxidant bioactivities applicable in biomedicine is attractive topic of general interest. Research efforts aiming to validate antioxidant potentials of natural products has led to the development of several assays based on various test principles. Hence, understanding the advantages and limitations of various assays is important for selection of assays useful to study antioxidant and related bioactivities of natural products of biomedical interest. This review paper gives a short overview on some chemical and cellular bioassays used to estimate the antioxidant activity of chosen natural products together with a brief overview on the use of natural products with antioxidant activities as adjuvant medicinal remedies in dermatology.
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Søndergård SD, Cintin I, Kuhlman AB, Morville TH, Bergmann ML, Kjær LK, Poulsen HE, Giustarini D, Rossi R, Dela F, Helge JW, Larsen S. The effects of 3 weeks of oral glutathione supplementation on whole body insulin sensitivity in obese males with and without type 2 diabetes: a randomized trial. Appl Physiol Nutr Metab 2021; 46:1133-1142. [PMID: 33740389 DOI: 10.1139/apnm-2020-1099] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The effect of oral glutathione (GSH) supplementation was studied in obese subjects with and without type 2 diabetes (T2DM) on measures of glucose homeostasis and markers of oxidative stress. Twenty subjects (10 patients with T2DM and 10 obese subjects) were recruited for the study, and randomized in a double-blinded placebo-controlled manner to consume either 1000 mg GSH per day or placebo for 3 weeks. Before and after the 3 weeks insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp and a muscle biopsy was obtained to measure GSH and skeletal muscle mitochondrial hydrogen peroxide (H2O2) emission rate. Whole body insulin sensitivity increased significantly in the GSH group. Skeletal muscle GSH was numerically increased (∼19%) in the GSH group; no change was seen in GSH to glutathione disulfide ratio. Skeletal muscle mitochondrial H2O2 emission rate did not change in response to the intervention and neither did the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine or the DNA oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), although 8-oxodG decreased as a main effect of time. Oral GSH supplementation improves insulin sensitivity in obese subjects with and without T2DM, although it does not alter markers of oxidative stress. The study has been registered in clinicaltrials.gov (NCT02948673). Novelty: Reduced glutathione supplementation increases insulin sensitivity in obese subjects with and without T2DM. H2O2 emission rate from skeletal muscle mitochondria was not affected by GSH supplementation.
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Affiliation(s)
- Stine D Søndergård
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ida Cintin
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Anja B Kuhlman
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Thomas H Morville
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Marie Louise Bergmann
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Laura K Kjær
- Laboratory of Clinical Pharmacology, Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Henrik E Poulsen
- Laboratory of Clinical Pharmacology, Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Daniela Giustarini
- Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, Italy
| | - Ranieri Rossi
- Department of Biotechnology Chemistry and Pharmacy, University of Siena, Siena, Italy
| | - Flemming Dela
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Geriatrics, Bispebjerg University Hospital, Copenhagen, Denmark
| | - Jørn W Helge
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Steen Larsen
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
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TEKİN Z, KÜÇÜKBAY FZ, DİKME A. In Vitro Antioxidant Activities of Methanol Extracts of Three Achillea Species from Turkey. JOURNAL OF THE TURKISH CHEMICAL SOCIETY, SECTION A: CHEMISTRY 2021. [DOI: 10.18596/jotcsa.867455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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9
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Domínguez-Pérez LA, Beltrán-Barrientos LM, González-Córdova AF, Hernández-Mendoza A, Vallejo-Cordoba B. Artisanal cocoa bean fermentation: From cocoa bean proteins to bioactive peptides with potential health benefits. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104134] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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10
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Higher ultra-processed food intake is associated with higher DNA damage in healthy adolescents. Br J Nutr 2020; 125:568-576. [DOI: 10.1017/s0007114520001981] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AbstractUltra-processed food is one of the main contributors to energy supply and consumption in food systems worldwide, and evidence of their detrimental health outcomes in humans is emerging. This study aimed to assess ultra-processed food intake and its association with urinary levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in 139 healthy adolescents in Karaj City in Iran. Usual dietary intake was measured using a 168-item validated FFQ. The daily intake of ultra-processed food consumption was determined through the classification of NOVA, and general linear models were used to compare the urinary levels of 8-OHdG/creatinine (ng/mg creatinine) within tertiles of ultra-processed food intake. Adolescents in the higher tertile of ultra-processed food consumption had a significantly higher mean level of urinary 8-OHdG/creatinine in comparison with the lower tertiles in the crude model (Pfor trend: 0·003) and after adjustment for confounding variables, including total energy intake, sex, age, BMI for age Z-score, obesity and physical activity (Pfor trend: 0·004). This association was still significant after adjusting for dietary intake of whole grains, nuts, legumes, the ratio of MUFA:SFA (g/d) and Mediterranean dietary score (Pfor trend: 0·002). More studies are needed to explore the determinants of ultra-processed food supply, demand, consumption and health effects; such studies should be applied to develop evidence-informed policies and regulatory mechanisms to improve children’s and adolescents’ food environment policymaking and legislation with special attention to ultra-processed food.
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Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients. Int J Mol Sci 2020; 21:ijms21072473. [PMID: 32252452 PMCID: PMC7177219 DOI: 10.3390/ijms21072473] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/30/2020] [Accepted: 03/31/2020] [Indexed: 12/12/2022] Open
Abstract
Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.
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Panico A, Grassi T, Bagordo F, Idolo A, Serio F, Tumolo MR, De Giorgi M, Guido M, Tutino M, De Donno A. Micronucleus Frequency in Exfoliated Buccal Cells of Children Living in an Industrialized Area of Apulia (Italy). INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17041208. [PMID: 32069990 PMCID: PMC7068596 DOI: 10.3390/ijerph17041208] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 02/05/2020] [Accepted: 02/11/2020] [Indexed: 12/11/2022]
Abstract
Micronuclei (MN) are biomarkers of early biological effect often used for detecting DNA damage in human population exposed to genotoxic agents. The aim of this study was to evaluate the frequency of MN in exfoliated buccal cells of children living in an industrialized (impacted) area compared with that found in children living in a control area without significant anthropogenic impacts. A total of 462 6–8-year-old children (206 in the impacted area, 256 in the control area) attending primary school were enrolled. A questionnaire was administered to the parents of the recruited children to obtain information about personal data, lifestyles, and food habits of their children. Atmospheric particulate fractions were collected near the involved schools to assess the level of environmental exposure of the children. The presence of MN was highlighted in 68.4% of children living in the impacted area with a mean MN frequency of 0.66‰ ± 0.61‰. MN positivity and frequency were significantly lower in the control area (37.1% and 0.27‰ ± 0.43‰, respectively). The frequency of MN was positively associated with quasi-ultrafine particulate matter (PM0.5), traffic near the home, and consuming barbecued food; while adherence to the Mediterranean diet and practicing sport were negatively associated.
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Affiliation(s)
- Alessandra Panico
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; (A.P.); (T.G.); (A.I.); (F.S.); (M.D.G.); (M.G.); (A.D.D.)
| | - Tiziana Grassi
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; (A.P.); (T.G.); (A.I.); (F.S.); (M.D.G.); (M.G.); (A.D.D.)
| | - Francesco Bagordo
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; (A.P.); (T.G.); (A.I.); (F.S.); (M.D.G.); (M.G.); (A.D.D.)
- Correspondence: ; Tel.: +39-832-298-951
| | - Adele Idolo
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; (A.P.); (T.G.); (A.I.); (F.S.); (M.D.G.); (M.G.); (A.D.D.)
| | - Francesca Serio
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; (A.P.); (T.G.); (A.I.); (F.S.); (M.D.G.); (M.G.); (A.D.D.)
| | - Maria Rosaria Tumolo
- Institute for Research on Population and Social Policies, National Research Council (IRPPS-CNR), 72100 Brindisi, Italy;
- Institute of Clinical Physiology (CNR-IFC), 73100 Lecce, Italy
| | - Mattia De Giorgi
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; (A.P.); (T.G.); (A.I.); (F.S.); (M.D.G.); (M.G.); (A.D.D.)
| | - Marcello Guido
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; (A.P.); (T.G.); (A.I.); (F.S.); (M.D.G.); (M.G.); (A.D.D.)
| | - Maria Tutino
- Regional Agency for Environmental Protection (ARPA Puglia), 70126 Bari, Italy;
| | - Antonella De Donno
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; (A.P.); (T.G.); (A.I.); (F.S.); (M.D.G.); (M.G.); (A.D.D.)
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Lourenço SC, Moldão-Martins M, Alves VD. Antioxidants of Natural Plant Origins: From Sources to Food Industry Applications. Molecules 2019; 24:E4132. [PMID: 31731614 PMCID: PMC6891691 DOI: 10.3390/molecules24224132] [Citation(s) in RCA: 424] [Impact Index Per Article: 70.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 02/07/2023] Open
Abstract
In recent years, great interest has been focused on using natural antioxidants in food products, due to studies indicating possible adverse effects that may be related to the consumption of synthetic antioxidants. A variety of plant materials are known to be natural sources of antioxidants, such as herbs, spices, seeds, fruits and vegetables. The interest in these natural components is not only due to their biological value, but also to their economic impact, as most of them may be extracted from food by-products and under-exploited plant species. This article provides an overview of current knowledge on natural antioxidants: their sources, extraction methods and stabilization processes. In addition, recent studies on their applications in the food industry are also addressed; namely, as preservatives in different food products and in active films for packaging purposes and edible coatings.
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Affiliation(s)
| | | | - Vítor D. Alves
- LEAF, Linking, Landscape, Environment, Agriculture and Food, Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda, 1349-017 Lisboa, Portugal; (S.C.L.); (M.M.-M.)
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14
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Murphy N, Moreno V, Hughes DJ, Vodicka L, Vodicka P, Aglago EK, Gunter MJ, Jenab M. Lifestyle and dietary environmental factors in colorectal cancer susceptibility. Mol Aspects Med 2019; 69:2-9. [PMID: 31233770 DOI: 10.1016/j.mam.2019.06.005] [Citation(s) in RCA: 174] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 06/19/2019] [Accepted: 06/20/2019] [Indexed: 12/24/2022]
Abstract
Colorectal cancer (CRC) incidence changes with time and by variations in diet and lifestyle, as evidenced historically by migrant studies and recently by extensive epidemiologic evidence. The worldwide heterogeneity in CRC incidence is strongly suggestive of etiological involvement of environmental exposures, particularly lifestyle and diet. It is established that physical inactivity, obesity and some dietary factors (red/processed meats, alcohol) are positively associated with CRC, while healthy lifestyle habits show inverse associations. Mechanistic evidence shows that lifestyle and dietary components that contribute to energy excess are linked with increased CRC via metabolic dysfunction, inflammation, oxidative stress, bacterial dysbiosis and breakdown of gut barrier integrity while the reverse is apparent for components associated with decreased risk. This chapter will review the available evidence on lifestyle and dietary factors in CRC etiology and their underlying mechanisms in CRC development. This short review will also touch upon available information on potential gene-environment interactions, molecular sub-types of CRC and anatomical sub-sites within the colorectum.
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Affiliation(s)
- Neil Murphy
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Victor Moreno
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO). Hospitalet de Llobregat, Barcelona, Spain; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL). Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - David J Hughes
- Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Ludmila Vodicka
- Department of the Molecular Biology of Cancer, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Pavel Vodicka
- Department of the Molecular Biology of Cancer, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Elom K Aglago
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Marc J Gunter
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC-WHO), Lyon, France.
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15
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Møller P, Jensen A, Løhr M, Eriksen L, Grønbæk M, Loft S. Fish and salad consumption are inversely associated with levels of oxidatively damaged DNA in a Danish adult cohort. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2019; 843:66-72. [DOI: 10.1016/j.mrgentox.2018.11.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 10/26/2018] [Accepted: 11/17/2018] [Indexed: 01/06/2023]
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16
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Erikel E, Yuzbasioglu D, Unal F. In vitro genotoxic and antigenotoxic effects of cynarin. JOURNAL OF ETHNOPHARMACOLOGY 2019; 237:171-181. [PMID: 30890359 DOI: 10.1016/j.jep.2019.03.036] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 03/12/2019] [Accepted: 03/13/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cynarin is an artichoke phytochemical that possesses a variety of pharmacological features including free-radical scavenging and antioxidant activity. The origin of artichoke species appears to be Mediterranean region. Two of these species, globe artichoke (Cynara cardunculus var. scolymus L.) and cardoon (Cynara cardunculus var. altilis DC), are widely cultivated and consumed. This vegetable, as the basis of the mediterranean diet, has been used as herbal medicine for its therapeutic effects since ancient times. Therefore, this study was performed to determine genotoxic and antigenotoxic effects of cynarin against MMC (mitomycin C) and H2O2 (hydrogen peroxide) induced genomic instability using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN), and comet assays in human lymphocytes. MATERIALS AND METHODS Lymphocytes obtained from two healthy volunteers (1 male and 1 female) were exposed to different concentrations of cynarin (12-194 μM) alone and the combination of cynarin and MMC (0.60 μM) or cynarin and H2O2 (100 μM, only for comet assay). RESULTS Cynarin alone did not induce significant genotoxic effect in the CA, SCE (except 194 μM), MN, and comet assays. The combination of some concentrations of cynarin and MMC decreased the frequency of CAs, SCEs and MN induced by MMC. Furthermore, the combination of cynarin and H2O2 reduced all comet parameters at all the concentrations compared to H2O2 alone. While the highest concentrations of cynarin significantly decreased mitotic index (MI), the combination of cynarin and MMC increased the reduction of MI induced by MMC alone. CONCLUSION All the results obtained in this study demonstrated that cynarin exhibited antigenotoxic effects rather than genotoxic effects. It is believed that cynarin can act as a potential chemo-preventive against genotoxic agents.
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Affiliation(s)
- Esra Erikel
- Genetic Toxicology Laboratory, Department of Biology, Science Faculty, Gazi University, 06500, Teknikokullar, Ankara, Turkey.
| | - Deniz Yuzbasioglu
- Genetic Toxicology Laboratory, Department of Biology, Science Faculty, Gazi University, 06500, Teknikokullar, Ankara, Turkey.
| | - Fatma Unal
- Genetic Toxicology Laboratory, Department of Biology, Science Faculty, Gazi University, 06500, Teknikokullar, Ankara, Turkey.
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17
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De Almeida CV, de Camargo MR, Russo E, Amedei A. Role of diet and gut microbiota on colorectal cancer immunomodulation. World J Gastroenterol 2019; 25:151-162. [PMID: 30670906 PMCID: PMC6337022 DOI: 10.3748/wjg.v25.i2.151] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 12/20/2018] [Accepted: 12/27/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and it is characterized by genetic and epigenetic alterations, as well as by inflammatory cell infiltration among malignant and stromal cells. However, this dynamic infiltration can be influenced by the microenvironment to promote tumor proliferation, survival and metastasis or cancer inhibition. In particular, the cancer microenvironment metabolites can regulate the inflammatory cells to induce a chronic inflammatory response that can be a predisposing condition for CRC retention. In addition, some nutritional components might contribute to a chronic inflammatory condition by regulating various immune and inflammatory pathways. Besides that, diet strongly modulates the gut microbiota composition, which has a key role in maintaining gut homeostasis and is associated with the modulation of host inflammatory and immune responses. Therefore, diet has a fundamental role in CRC initiation, progression and prevention. In particular, functional foods such as probiotics, prebiotics and symbiotics can have a potentially positive effect on health beyond basic nutrition and have anti-inflammatory effects. In this review, we discuss the influence of diet on gut microbiota composition, focusing on its role on gut inflammation and immunity. Finally, we describe the potential benefits of using probiotics and prebiotics to modulate the host inflammatory response, as well as its application in CRC prevention and treatment.
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Affiliation(s)
| | - Marcela Rodrigues de Camargo
- Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry, São Paulo University, Bauru-Sao Paulo 17012901, Brazil
| | - Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50139, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), Florence 50139, Italy
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18
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Felix M, Cermeño M, Romero A, FitzGerald RJ. Characterisation of the bioactive properties and microstructure of chickpea protein-based oil in water emulsions. Food Res Int 2018; 121:577-585. [PMID: 31108784 DOI: 10.1016/j.foodres.2018.12.022] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 12/03/2018] [Accepted: 12/20/2018] [Indexed: 10/27/2022]
Abstract
Legumes, such as chickpea, represent a good source of high quality proteins for which there is an increasing global consumer demand. A chickpea protein concentrate (CP) was generated by isoelectric precipitation. Protein determination, electrophoretic and gel permeation chromatographic analysis revealed that the order of CP solubility was pH 7.5 > 2.5 > 5.0. Sunflower oil in water (O/W) emulsions were generated with the CP at pH 2.5, 5.0 and 7.5. Microstructural evaluation of the emulsions using laser light-scattering particle size analysis, optical microscopy and rheological analysis showed that smaller droplet size (3.1 ± 0.2 and 1.1 ± 0.1 μm) and the highest elastic moduli (876.0 ± 3.2 and 563.5 ± 6.5 Pa) were obtained in those emulsions generated with CP at pH 2.5 and 7.5. The ferric reducing (FRAP) and oxygen radical absorbance capacity (ORAC) values of the CP emulsions ranged from 194.5 ± 19.2 to 242.4 ± 8.4 μmol Trolox Eq·g-1 CP for FRAP at pH 2.5 and 5.0, respectively, and from 313.2 ± 2.6 to 369.0 ± 1.6 μmol Trolox eq·g-1 CP for ORAC at pH 5.0 and 2.5, respectively. The enzyme inhibitory activity of the emulsions was generally low irrespective of the pH value (c.a. 3 and 30% inhibition for dipeptidyl peptidase IV (DPP-IV) and angiotensin converting enzyme (ACE) activity, respectively). Simulated gastrointestinal digestion (SGID) of the emulsions significantly decreased their FRAP whereas it increased their ORAC values as well as their ACE and DPP-IV inhibitory activities irrespective of the pH value of the CP. These results demonstrate the potential application of reduced fat CP-stabilized emulsions for the provision of antioxidant and enzyme inhibitory activities.
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Affiliation(s)
- Manuel Felix
- Department of Biological Sciences, School of Natural Sciences, University of Limerick, Ireland; Departamento de Ingeniería Química, Escuela Politécnica Superior, Universidad de Sevilla, Sevilla 41011, Spain
| | - Maria Cermeño
- Department of Biological Sciences, School of Natural Sciences, University of Limerick, Ireland
| | - Alberto Romero
- Departamento de Ingeniería Química, Escuela Politécnica Superior, Universidad de Sevilla, Sevilla 41011, Spain
| | - Richard J FitzGerald
- Department of Biological Sciences, School of Natural Sciences, University of Limerick, Ireland.
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19
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Changes in Urinary Hydrogen Peroxide and 8-Hydroxy-2'-Deoxyguanosine Levels after a Forest Walk: A Pilot Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15091871. [PMID: 30158499 PMCID: PMC6163805 DOI: 10.3390/ijerph15091871] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 08/27/2018] [Accepted: 08/28/2018] [Indexed: 11/17/2022]
Abstract
Some studies have shown that exposure to forests has positive effects on human health, although the mechanisms underlying the health benefits of a forest environment have not been elucidated yet. The current study was aimed at examining how the levels of urinary hydrogen peroxide (H₂O₂) and 8-hydroxy-2'deoxyguanosine (8-OHdG) change after a forest or urban walk in healthy subjects. Twenty-eight volunteers (19 men and 9 women) participated in the study. The forest walks were carried out in a forest in Okayama Prefecture, Japan, and the urban walks (15 men and 7 women) were carried out in the downtown area of Okayama city, each for two hours. Spot urine samples were collected before the walk, the next day and one week after the forest or urban walk. Compared with pre-forest walk levels, urinary H₂O₂ (p < 0.1) and 8-OHdG (p < 0.1) concentrations significantly decreased in the participants the day after the forest walk; furthermore, urinary 8-OHdG remained at a low level even at one week after the forest walk (p < 0.05). However, there were no significant changes in the concentrations of these oxidative biomarkers after the urban walk. These findings suggest the possibility that exposure to forests may alleviate oxidative stress in the body.
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Association study of dietary non-enzymatic antioxidant capacity (NEAC) and colorectal cancer risk in the Spanish Multicase-Control Cancer (MCC-Spain) study. Eur J Nutr 2018; 58:2229-2242. [PMID: 29995245 DOI: 10.1007/s00394-018-1773-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 07/03/2018] [Indexed: 10/28/2022]
Abstract
PURPOSE Studies attempting to link dietary non-enzymatic antioxidant activity (NEAC) and colorectal cancer (CRC) risk have reported mixed results. We examined this association in the Spanish Multicase-Control Study considering the likely influence of coffee and other dietary factors. METHODS 1718 CRC cases and 3312 matched-controls provided information about diet through a validated 140-item food frequency questionnaire. Dietary NEAC was estimated for three methods [total radical-trapping antioxidant parameters (TRAP), ferric reducing/antioxidant power (FRAP) and TEAC-ABTS] using published values of NEAC content in food, with and without coffee's NEAC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated through unconditional logistic regression models adjusted for lifestyle and dietary factors. RESULTS Overall dietary intake of NEAC was significantly lower in cases compared to controls and associated with a significantly reduced CRC risk, in both men (ORQ5vsQ1 = 0.67, 95% CI 0.47-0.96 for FRAP) and women (ORQ5vsQ1 = 0.53, 95% CI 0.32-085 for FRAP), in multivariate models with and without the antioxidant contribution from coffee. The effect was similar for all the NEAC methods evaluated and for both colon and rectum. The association between dietary NEAC and CRC risk became non-significant when adjusting for fiber intake. However, intakes of NEAC and fiber were correlated. CONCLUSION This study indicates that intake of an antioxidant-rich plant-based diet, both with and without NEAC from coffee, is associated with decreased CRC risk.
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de Almeida CV, Taddei A, Amedei A. The controversial role of Enterococcus faecalis in colorectal cancer. Therap Adv Gastroenterol 2018; 11:1756284818783606. [PMID: 30013618 PMCID: PMC6044108 DOI: 10.1177/1756284818783606] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 05/17/2018] [Indexed: 02/04/2023] Open
Abstract
Colorectal cancer (CRC) is a complex and widespread disease, currently ranked as the third most frequent cancer worldwide. It is well known that the gut microbiota has an essential role in the initiation and promotion of different cancer types, particularly gastrointestinal tumors. In fact, bacteria can trigger chronic inflammation of the gastric mucosal, which can induce irreversible changes to intestinal epithelial cells, thus predisposing individuals to cancer. Some bacterial strains, such as Helicobacter pylori, Streptococcus bovis, Bacteroides fragilis, Clostridium septicum and Fusobacterium spp. have a well established role in CRC development. However, the role of Enterococcus faecalis still remains controversial. While part of the literature suggests a harmful role, other papers reported E. faecalis as an important probiotic microorganism, with great applicability in food products. In this review we have examined the vast majority of published data about E. faecalis either in CRC development or concerning its protective role. Our analysis should provide some answers regarding the controversial role of E. faecalis in CRC.
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Affiliation(s)
| | - Antonio Taddei
- Department of Surgery and Translational
Medicine, University of Florence, Florence, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical
Medicine, University of Florence, Viale Pieraccini, 6, 50139 Florence,
Italy
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22
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Møller P, Jantzen K, Løhr M, Andersen MH, Jensen DM, Roursgaard M, Danielsen PH, Jensen A, Loft S. Searching for assay controls for the Fpg- and hOGG1-modified comet assay. Mutagenesis 2017; 33:9-19. [DOI: 10.1093/mutage/gex015] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 09/05/2017] [Indexed: 11/14/2022] Open
Affiliation(s)
- Peter Møller
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
| | - Kim Jantzen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
| | - Mille Løhr
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
| | - Maria Helena Andersen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
| | - Ditte Marie Jensen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
| | - Martin Roursgaard
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
| | - Pernille Høgh Danielsen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
| | - Annie Jensen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
| | - Steffen Loft
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade, Copenhagen K, Denmark
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Pelletier G, Rigden M, Kauri LM, Shutt R, Mahmud M, Cakmak S, Kumarathasan P, Thomson EM, Vincent R, Broad G, Liu L, Dales R. Associations between urinary biomarkers of oxidative stress and air pollutants observed in a randomized crossover exposure to steel mill emissions. Int J Hyg Environ Health 2017; 220:387-394. [DOI: 10.1016/j.ijheh.2016.11.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 11/15/2016] [Accepted: 11/24/2016] [Indexed: 11/24/2022]
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24
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Coffee and oxidative stress: a human intervention study. Eur J Nutr 2016; 57:533-544. [DOI: 10.1007/s00394-016-1336-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 10/16/2016] [Indexed: 10/20/2022]
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25
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Nersesyan A, Hoelzl C, Ferk F, Mišík M, Al-Serori H, Setayesh T, Knasmueller S. Use of Single-cell Gel Electrophoresis Assays in Dietary Intervention Trials. THE COMET ASSAY IN TOXICOLOGY 2016. [DOI: 10.1039/9781782622895-00314] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The single-cell gel electrophoresis (SCGE) technique has been frequently used to investigate the impact of consumption of complex foods and individual constituents on DNA stability in humans. Since no division or cultivation of the indicator cells (in most studies lymphocytes) is required, this approach is less costly and time consuming than cytogenetic methods. Apart from single- and double-stand breaks and apurinic sites, which can be detected under standard conditions, it is also possible to assess the formation of oxidized DNA bases and alterations of DNA repair as well as protection of the DNA against chemical carcinogens. In total, 93 studies have been published since the first use of the Comet assay in this field in 1997. The results which emerged from these studies show that human foods contain specific highly protective components (e.g. gallic acid, xanthohumol, isoflavones); promising results were also obtained with beverages (coffee and other drinks), while mixed diets with vegetables and fruits conferred no or moderate protection; however, individual plant foods (e.g. kiwis and specific cruciferous vegetables) were highly protective. It is notable that prevention of DNA damage was rarely detected under standard conditions while evidence for reduced formation of oxidized DNA bases was found in approximately 30% of the trials. In some investigations it was possible to identify the modes of action by which specific compounds prevented damage of the genetic material in additional mechanistic experiments. The currently available data show that SCGE assays are a valuable tool for identifying dietary factors which improve the stability of the genetic material and prevent adverse health effects which are causally related to DNA damage.
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Affiliation(s)
- Armen Nersesyan
- Department of Internal Medicine I, Institute of Cancer Research, Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria
| | - Christine Hoelzl
- Department of Internal Medicine I, Institute of Cancer Research, Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria
| | - Franziska Ferk
- Department of Internal Medicine I, Institute of Cancer Research, Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria
| | - Miroslav Mišík
- Department of Internal Medicine I, Institute of Cancer Research, Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria
| | - Halh Al-Serori
- Department of Internal Medicine I, Institute of Cancer Research, Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria
| | - Tahereh Setayesh
- Department of Internal Medicine I, Institute of Cancer Research, Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria
| | - Siegfried Knasmueller
- Department of Internal Medicine I, Institute of Cancer Research, Medical University of Vienna Borschkegasse 8a 1090 Vienna Austria
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Margaritelis NV, Cobley JN, Paschalis V, Veskoukis AS, Theodorou AA, Kyparos A, Nikolaidis MG. Going retro: Oxidative stress biomarkers in modern redox biology. Free Radic Biol Med 2016; 98:2-12. [PMID: 26855421 DOI: 10.1016/j.freeradbiomed.2016.02.005] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 01/08/2016] [Accepted: 02/02/2016] [Indexed: 12/23/2022]
Abstract
The field of redox biology is inherently intertwined with oxidative stress biomarkers. Oxidative stress biomarkers have been utilized for many different objectives. Our analysis indicates that oxidative stress biomarkers have several salient applications: (1) diagnosing oxidative stress, (2) pinpointing likely redox components in a physiological or pathological process and (3) estimating the severity, progression and/or regression of a disease. On the contrary, oxidative stress biomarkers do not report on redox signaling. Alternative approaches to gain more mechanistic insights are: (1) measuring molecules that are integrated in pathways linking redox biochemistry with physiology, (2) using the exomarker approach and (3) exploiting -omics techniques. More sophisticated approaches and large trials are needed to establish oxidative stress biomarkers in the clinical setting.
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Affiliation(s)
- N V Margaritelis
- Department of Physical Education and Sports Science at Serres, Aristotle University of Thessaloniki, Agios Ioannis, 62110 Serres, Greece; Intensive Care Unit, 424 General Military Hospital of Thessaloniki, Thessaloniki, Greece
| | - J N Cobley
- Division of Sport and Exercise Sciences, Abertay University, Dundee, UK
| | - V Paschalis
- Department of Physical Education and Sport Science, University of Thessaly, Karies, Trikala, Greece; Department of Health Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus
| | - A S Veskoukis
- Department of Physical Education and Sports Science at Serres, Aristotle University of Thessaloniki, Agios Ioannis, 62110 Serres, Greece
| | - A A Theodorou
- Department of Health Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus
| | - A Kyparos
- Department of Physical Education and Sports Science at Serres, Aristotle University of Thessaloniki, Agios Ioannis, 62110 Serres, Greece
| | - M G Nikolaidis
- Department of Physical Education and Sports Science at Serres, Aristotle University of Thessaloniki, Agios Ioannis, 62110 Serres, Greece.
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Extracellular polysaccharide with novel structure and antioxidant property produced by the deep-sea fungus Aspergillus versicolor N 2 bc. Carbohydr Polym 2016; 147:272-281. [DOI: 10.1016/j.carbpol.2016.03.090] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Revised: 03/21/2016] [Accepted: 03/29/2016] [Indexed: 12/31/2022]
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Løhr M, Jensen A, Eriksen L, Grønbæk M, Loft S, Møller P. Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells. Oncotarget 2015; 6:2641-53. [PMID: 25650665 PMCID: PMC4413607 DOI: 10.18632/oncotarget.3202] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Accepted: 12/12/2014] [Indexed: 12/22/2022] Open
Abstract
Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged 18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency was observed for the level of hOGG1-sensitive sites, whereas there was no association with the level of strand breaks. The effect of age on oxidatively damaged DNA in women disappeared in multivariate models, which showed robust positive associations between DNA damage and plasma levels of triglycerides, cholesterol and glycosylated hemoglobin (HbA1c). In the group of men, there were significant positive associations between alcohol intake, HbA1c and FPG-sensitive sites in multivariate analysis. The levels of metabolic risk factors were positively associated with age, yet only few subjects fulfilled all metabolic syndrome criteria. In summary, positive associations between age and levels of oxidatively damaged DNA appeared mediated by age-related increases in metabolic risk factors.
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Affiliation(s)
- Mille Løhr
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark
| | - Annie Jensen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark
| | - Louise Eriksen
- National Institute of Public Health, University of Southern Denmark, Odense, Denmark
| | - Morten Grønbæk
- National Institute of Public Health, University of Southern Denmark, Odense, Denmark
| | - Steffen Loft
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark
| | - Peter Møller
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark
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Pérez-Jiménez J, Díaz-Rubio ME, Saura-Calixto F. Contribution of Macromolecular Antioxidants to Dietary Antioxidant Capacity: A Study in the Spanish Mediterranean Diet. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2015; 70:365-370. [PMID: 26482738 DOI: 10.1007/s11130-015-0513-6] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Epidemiological and clinical studies show that diets with a high antioxidant capacity, such us those rich in plant food and beverages, are associated with significant decreases in the overall risk of cardiovascular disease or colorectal cancer. Current studies on dietary antioxidants and dietary antioxidant capacity focus exclusively on low molecular weight or soluble antioxidants (vitamins C and E, phenolic compounds and carotenoids), ignoring macromolecular antioxidants. These are polymeric phenolic compounds or polyphenols and carotenoids linked to plant food macromolecules that yield bioavailable metabolites by the action of the microbiota with significant effects either local and/or systemic after absorption. This study determined the antioxidant capacity of the Spanish Mediterranean diet including for the first time both soluble and macromolecular antioxidants. Antioxidant capacity and consumption data of the 54 most consumed plant foods and beverages were used. Results showed that macromolecular antioxidants are the major dietary antioxidants, contributing a 61% to the diet antioxidant capacity (8000 μmol Trolox, determined by ABTS method). The antioxidant capacity data for foods and beverages provided here may be used to estimate the dietary antioxidant capacity in different populations, where similar contributions of macromolecular antioxidants may be expected, and also to design antioxidant-rich diets. Including macromolecular antioxidants in mechanistic, intervention and observational studies on dietary antioxidants may contribute to a better understanding of the role of antioxidants in nutrition and health.
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Affiliation(s)
- Jara Pérez-Jiménez
- Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Madrid, Spain
| | - M Elena Díaz-Rubio
- Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Madrid, Spain
| | - Fulgencio Saura-Calixto
- Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Madrid, Spain.
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von der Lippen C, Sahu S, Seifermann M, Tiwari VK, Epe B. The repair of oxidized purines in the DNA of human lymphocytes requires an activation involving NF-YA-mediated upregulation of OGG1. DNA Repair (Amst) 2015; 25:1-8. [DOI: 10.1016/j.dnarep.2014.10.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 10/17/2014] [Accepted: 10/22/2014] [Indexed: 10/24/2022]
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Ibero-Baraibar I, Azqueta A, Lopez de Cerain A, Martinez JA, Zulet MA. Assessment of DNA damage using comet assay in middle-aged overweight/obese subjects after following a hypocaloric diet supplemented with cocoa extract. Mutagenesis 2014; 30:139-46. [DOI: 10.1093/mutage/geu056] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Jensen A, Karottki DG, Christensen JM, Bønløkke JH, Sigsgaard T, Glasius M, Loft S, Møller P. Biomarkers of oxidative stress and inflammation after wood smoke exposure in a reconstructed Viking Age house. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2014; 55:652-661. [PMID: 24889798 DOI: 10.1002/em.21877] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Accepted: 05/06/2014] [Indexed: 06/03/2023]
Abstract
Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor combustion of wood for heating and cooking. The subjects were exposed to high indoor concentrations of PM2.5 (700-3,600 µg/m(3)), CO (10.7-15.3 ppm) and NO2 (140-154 µg/m(3)) during a 1-week stay. Nevertheless, there were unaltered levels of genotoxicity, determined as DNA strand breaks and formamidopyrimidine DNA glycosylase and oxoguanine DNA glycosylase 1 sensitive sites in peripheral blood mononuclear cells. There were also unaltered expression levels of OGG1, HMOX1, CCL2, IL8, and TNF levels in leukocytes. In serum, there were unaltered levels of C-reactive protein, IL6, IL8, TNF, lactate dehydrogenase, cholesterol, triglycerides, and high-density lipoproteins. The wood smoke exposure was associated with decreased serum levels of sICAM-1, and a tendency to decreased sVCAM-1 levels. There was a minor increase in the levels of circulating monocytes expressing CD31, whereas there were unaltered expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation.
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Affiliation(s)
- Annie Jensen
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Denmark
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Rajendran P, Nandakumar N, Rengarajan T, Palaniswami R, Gnanadhas EN, Lakshminarasaiah U, Gopas J, Nishigaki I. Antioxidants and human diseases. Clin Chim Acta 2014; 436:332-47. [PMID: 24933428 DOI: 10.1016/j.cca.2014.06.004] [Citation(s) in RCA: 297] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2014] [Revised: 06/04/2014] [Accepted: 06/05/2014] [Indexed: 12/26/2022]
Abstract
Oxidative stress plays a pivotal role in the development of human diseases. Reactive oxygen species (ROS) that includes hydrogen peroxide, hyphochlorus acid, superoxide anion, singlet oxygen, lipid peroxides, hypochlorite and hydroxyl radical are involved in growth, differentiation, progression and death of the cell. They can react with membrane lipids, nucleic acids, proteins, enzymes and other small molecules. Low concentrations of ROS has an indispensable role in intracellular signalling and defence against pathogens, while, higher amounts of ROS play a role in number of human diseases, including arthritis, cancer, diabetes, atherosclerosis, ischemia, failures in immunity and endocrine functions. Antioxidants presumably act as safeguard against the accumulation of ROS and their elimination from the system. The aim of this review is to highlight advances in understanding of the ROS and also to summarize the detailed impact and involvement of antioxidants in selected human diseases.
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Affiliation(s)
- Peramaiyan Rajendran
- NPO-International Laboratory of Biochemistry, 1-166, Uchide, Nakagawa-ku, Nagoya 454-0926, Japan
| | - Natarajan Nandakumar
- Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Israel
| | | | - Rajendran Palaniswami
- Department of Applied Zoology and Biotechnology, Vivekananda College (A Gurukula Institute of Life Training), Affiliated to Madurai Kamaraj University, Thiruvedakam West, Madurai 625234, India
| | - Edwinoliver Nesamony Gnanadhas
- Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
| | - Uppalapati Lakshminarasaiah
- Department of Clinical Biochemistry and Pharmacology, Soroka University Medical Center, Ben-Gurion University of the Negev, Be'er-Sheva 84105, Israel
| | - Jacob Gopas
- Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Israel; Oncology Department Soroka University Medical Center, Be'er-Sheva 84105, Israel
| | - Ikuo Nishigaki
- NPO-International Laboratory of Biochemistry, 1-166, Uchide, Nakagawa-ku, Nagoya 454-0926, Japan.
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Langie SA, Kowalczyk P, Tomaszewski B, Vasilaki A, Maas LM, Moonen EJ, Palagani A, Godschalk RW, Tudek B, van Schooten FJ, Berghe WV, Zabielski R, Mathers JC. Redox and epigenetic regulation of the APE1 gene in the hippocampus of piglets: The effect of early life exposures. DNA Repair (Amst) 2014; 18:52-62. [DOI: 10.1016/j.dnarep.2014.03.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Revised: 03/24/2014] [Accepted: 03/26/2014] [Indexed: 02/06/2023]
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Iwanaga S, Sakano N, Taketa K, Takahashi N, Wang DH, Takahashi H, Kubo M, Miyatake N, Ogino K. Comparison of serum ferritin and oxidative stress biomarkers between Japanese workers with and without metabolic syndrome. Obes Res Clin Pract 2014; 8:e201-98. [DOI: 10.1016/j.orcp.2013.01.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2012] [Revised: 12/10/2012] [Accepted: 01/09/2013] [Indexed: 10/27/2022]
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Bakuradze T, Lang R, Hofmann T, Eisenbrand G, Schipp D, Galan J, Richling E. Consumption of a dark roast coffee decreases the level of spontaneous DNA strand breaks: a randomized controlled trial. Eur J Nutr 2014; 54:149-56. [DOI: 10.1007/s00394-014-0696-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Accepted: 03/28/2014] [Indexed: 12/25/2022]
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37
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Measuring oxidative damage to DNA and its repair with the comet assay. Biochim Biophys Acta Gen Subj 2014; 1840:794-800. [DOI: 10.1016/j.bbagen.2013.04.022] [Citation(s) in RCA: 218] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Revised: 04/11/2013] [Accepted: 04/16/2013] [Indexed: 11/22/2022]
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The comet assay as a tool for human biomonitoring studies: The ComNet Project. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2014; 759:27-39. [DOI: 10.1016/j.mrrev.2013.10.001] [Citation(s) in RCA: 161] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 10/17/2013] [Accepted: 10/23/2013] [Indexed: 02/07/2023]
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Associations of job stress indicators with oxidative biomarkers in Japanese men and women. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2013; 10:6662-71. [PMID: 24317383 PMCID: PMC3881133 DOI: 10.3390/ijerph10126662] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Revised: 11/14/2013] [Accepted: 11/16/2013] [Indexed: 12/25/2022]
Abstract
Some researchers have suggested that oxidative damage may be one of the mechanisms linking job stress with coronary heart disease. The aim of this study was to investigate the association between job stress indicators and oxidative biomarkers. The study included 567 subjects (272 men, 295 women) who answered questionnaires related to their work and underwent a medical examination. Job stress evaluated using the demands-control-support model was measured using the Job Content Questionnaire. Effort-reward imbalance was measured using the Effort-Reward Imbalance Questionnaire. Urinary hydrogen peroxide (H2O2) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured by the modified ferrous ion oxidation xylenol orange version-1 method and enzyme-linked immunosorbent assay, respectively. In men, the changes in the odds ratios for high urinary H2O2 associated with a 1-standard-deviation (SD) increase in worksite social support were 0.69 (95% confidence interval (CI) 0.53, 0.91) univariately and 0.68 (95%CI 0.51, 0.90) after adjustment for covariates. The change in the odds ratio for high urinary H2O2 associated with a 1-SD increase in effort-reward ratio was 1.35 (95% CI 1.03, 1.78) after adjustment for covariates. In women, there were no significant associations of the two job stress indicators with urinary H2O2 and 8-OHdG levels after adjustment for covariates (p > 0.05).
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Ogino K, Wang DH, Kubo M, Obase Y, Setiawan H, Yan F, Takahashi H, Zhang R, Tsukiyama Y, Yoshida J, Zou Y. Association of serum arginase I with L-arginine, 3-nitrotyrosine, and exhaled nitric oxide in healthy Japanese workers. Free Radic Res 2013; 48:137-45. [PMID: 24060156 DOI: 10.3109/10715762.2013.842979] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The associations of serum arginase I with serum L-arginine, serum 3-nitrotyrosine, and fractional exhaled nitric oxide (FENO) were evaluated cross-sectionally in healthy Japanese workers. The serum median (minimum-maximum) levels of arginase I, 3-nitrotyrosine, and FENO in healthy people (n = 130) were 14.6 (0.94-108.1) ng/mL, 81.0 (0.27-298.6) pmol/mg protein, and 14.0 (5.0-110.0) parts per billion, respectively. Significant correlations of arginase I with FENO, L-arginine, 3-nitrotyrosine, and percent predicted forced expiratory volume in 1 s (FEV1 (% predicted)) were observed, and correlations of FENO with immunoglobulin E (IgE), NOx, arginase I, and sex and allergy were also observed. By multiple regression analysis, arginase I showed positive associations with FENO and 3-nitrotyrosine, and a negative association with L-arginine; and FENO showed positive associations with IgE and NO2(-) + NO3(-) (NOx), and a negative association with L-arginine, as well as an association with sex. Moreover, logistic regression analysis showed linear inverse associations of arginase I and 3-nitrotyrosine with L-arginine, and showed linear positive associations of FENO with IgE and NOx. It was concluded that serum arginase I might regulate serum L-arginine and 3-nitrotyrosine via L-arginine, and that IgE or NOx might regulate FENO in a healthy Japanese population.
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Affiliation(s)
- K Ogino
- Department of Public Health, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
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41
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The phenolic compounds and the antioxidant potential of infusion of herbs from the Brazilian Amazonian region. Food Res Int 2013. [DOI: 10.1016/j.foodres.2013.02.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Ogino K, Murakami I, Wang DH, Tsukiyama Y, Takahashi H, Kubo M, Sakano N, Setiawan H, Bando M, Ohmoto Y. Evaluation of serum arginase I as an oxidative stress biomarker in a healthy Japanese population using a newly established ELISA. Clin Biochem 2013; 46:1717-22. [PMID: 24005081 DOI: 10.1016/j.clinbiochem.2013.08.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2013] [Revised: 08/21/2013] [Accepted: 08/26/2013] [Indexed: 11/26/2022]
Abstract
OBJECTIVE We reported previously that serum arginase I increased in asthmatic patients and was associated with oxidative stress in a small healthy population. However, the exact association of arginase I with oxidative stress is not known. The present study aimed to analyze the association of arginase I with oxidative stress in a larger healthy population by a newly established ELISA. DESIGN AND METHODS The new ELISA for the measurement of human arginase I was established by generating recombinant arginase I protein in human arginase I gene-transfected Escherichia coli via an ARG1 cDNA fragment-inserted vector and -specific antibody in rabbits. Serum arginase I was evaluated in a cross-sectional study on a healthy population (n=721) by comparing a commercial ELISA kit with the new ELISA. RESULTS The mean levels of serum arginase I were 20.3 ± 0.7 ng/mL and 4.7 ± 0.2 ng/mL using the commercial ELISA kit and the new ELISA, respectively. Arginase I was correlated with WBC, RBC, hs-CRP, 8-OHdG, HDL-c, ALT, and BMI. Logistic regression analysis showed independent positive associations of arginase I with WBC, RBC, and urinary 8-OHdG and inverse independent associations with serum insulin and age. The association of arginase I with hs-CRP was not independent. CONCLUSION The independent associations of arginase I with urinary 8-OHdG and serum insulin may reflect its involvement in oxidative stress and diabetes mellitus.
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Affiliation(s)
- Keiki Ogino
- Department of Public Health, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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Wawrzyniak A, Górnicka M, Hamułka J, Gajewska M, Drywień M, Pierzynowska J, Gronowska-Senger A. α-Tocopherol, ascorbic acid, and β-carotene protect against oxidative stress but reveal no direct influence on p53 expression in rats subjected to stress. Nutr Res 2013; 33:868-75. [PMID: 24074745 DOI: 10.1016/j.nutres.2013.07.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Revised: 06/11/2013] [Accepted: 07/01/2013] [Indexed: 12/31/2022]
Abstract
We hypothesized that α-tocopherol, ascorbic acid, and β-carotene, either applied individually or in combination, would modulate redox homeostasis and affect the regulation of genes involved in DNA repair under stress conditions. To test this hypothesis, we analyzed the influence of these vitamins, either supplied individually or in combination, on the plasma lipid peroxide level and the hepatic level of 8-hydroxy-2'-deoxyguanosine in rats. We also evaluated the expression of p53 and Mdm2 protein in the intestinal epithelium, as these proteins are involved in the cellular regulation of DNA damage repair. Male Wistar rats (n = 112) were supplemented with α-tocopherol (2 mg), ascorbic acid (12 mg), and β-carotene (1 mg), both individually and in combination, for 14 days; 32 control rats were treated with placebo. Half of the animals in each group (n = 8) were subjected to 15-minute treadmill running at 20 m/min to cause exercise-induced oxidative stress. A statistically significant reduction in lipid peroxide levels was observed in the plasma of rats subjected to exercise and given 2 or 3 of the antioxidants (P < .0001). Exercise, as well as coadministration of the antioxidants, had no significant effect on the amount of DNA damage. Downward trends in the level of p53 protein expression were observed both in exercised and nonexercised animals, especially when the studied vitamins were administered in combination. Our findings suggest that α-tocopherol, ascorbic acid, and β-carotene, when given concurrently, have primarily antioxidant effects on lipids under stress but do not significantly affect the regulation of p53 gene expression.
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Affiliation(s)
- Agata Wawrzyniak
- Department of Human Nutrition, Faculty of Human Nutrition and Consumer Sciences, Warsaw University of Life Sciences (SGGW), Warsaw, Poland.
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Loft S, Olsen A, Møller P, Poulsen HE, Tjønneland A. Association between 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion and risk of postmenopausal breast cancer: nested case-control study. Cancer Epidemiol Biomarkers Prev 2013; 22:1289-96. [PMID: 23658396 DOI: 10.1158/1055-9965.epi-13-0229] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Oxidative stress may be important in carcinogenesis and a possible risk factor for breast cancer. The urinary excretion of oxidatively generated biomolecules, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), represents biomarkers of oxidative stress, reflecting the rate of global damage to DNA in steady state. METHODS In a nested case-control design, we examined associations between urinary excretion of 8-oxodG and risk of breast cancer in a population-based cohort of 24,697 postmenopausal women aged 50 to 64 years with 3 to 7 years follow-up. The accruing cases of breast cancer were matched to controls by age at diagnosis, baseline age, and hormone replacement therapy (HRT). Spot urine samples collected at entry was analyzed for 8-oxodG by high-performance liquid chromatography with electrochemical detection. Incidence rate ratio (IRR; 95% confidence intervals) based on 336 matched pairs with all information was estimated per unit increase in 8-oxodG divided by creatinine for all and estrogen receptor (ER) positive and negative breast cancers. RESULTS There was a borderline significant positive association between 8-oxodG and risk of all breast cancer (IRR: 1.08; 1.00-1.17 per unit increase in nmol/mmol creatinine). This association was significant with respect to the risk of ER-positive cancer (IRR: 1.11; 1.01-1.23) and among women not using HRT (IRR: 1.11; 0.97-1.26) or with low dietary iron intake (IRR: 1.10; 1.06-1.37 per unit increase) for all breast cancer. CONCLUSIONS We observed positive association between 8-oxodG excretion and risk of especially ER-positive breast cancer. IMPACT Our results suggest that oxidative stress with damage to DNA is important for the development of breast cancer.
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Affiliation(s)
- Steffen Loft
- Department of Public Health, Section of Enviromental Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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Inoue K, Sakano N, Ogino K, Sato Y, Wang DH, Kubo M, Takahashi H, Kanbara S, Miyatake N. Relationship between ceruloplasmin and oxidative biomarkers including ferritin among healthy Japanese. J Clin Biochem Nutr 2013; 52:160-6. [PMID: 23524455 PMCID: PMC3593134 DOI: 10.3164/jcbn.12-122] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2012] [Accepted: 12/10/2012] [Indexed: 12/11/2022] Open
Abstract
Serum ceruloplasmin (CP), a marker relevant to copper metabolism, is one of famous inflammation markers with a reduction in Wilson’s disease, whereas serum ferritin is a marker relevant to iron metabolism. Recently, ferritin is pointed out to be related with oxidative stress. However, there is still no population research which showed the relation of CP and ferritin. Therefore, we investigated the relationship between CP and ferritin including oxidative stress biomarkers among healthy Japanese (n = 389). We measured serum CP, ferritin, Fe, high-sensitivity C-reactive protein (hs-CRP), and urinary oxidative stress biomarkers [H2O2, 8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-isoprostane] and so on. Subjects showed that age; 41.7 ± 10.0 (year), CP; 31.9 ± 6.8 (mg/dl), ferritin; 123.5 ± 121.0 (ng/ml), hs-CRP; 0.89 ± 2.53 (mg/l), 8-OHdG; 10.2 ± 4.4 [ng/mg creatinine (Cre)] and H2O2; 6.5 ± 10.9 (µM/g Cre), (All data mentioned above were expressed as mean ± SD). CP was significantly and positively correlated with hs-CRP and inversely correlated with ferritin, Fe and 8-OHdG. By a multiple logistic regression analysis, odds ratio of CP according to quartiles of hs-CRP was 4.86, and according to quartiles of 8-OHdG was 0.39 after adjusting for age and other confounding factors. In conclusion, our findings suggest that CP was an antioxidative biomarker which controls oxidative stress, whereas ferritin was a marker which may participate in the generation of oxidative stress.
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Affiliation(s)
- Kiyomi Inoue
- Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558, Japan
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Sato Y, Ogino K, Sakano N, Wang DH, Yoshida J, Akazawa Y, Kanbara S, Inoue K, Kubo M, Takahashi H. Evaluation of urinary hydrogen peroxide as an oxidative stress biomarker in a healthy Japanese population. Free Radic Res 2013; 47:181-91. [DOI: 10.3109/10715762.2012.759218] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Collins AR. Kiwifruit as a modulator of DNA damage and DNA repair. ADVANCES IN FOOD AND NUTRITION RESEARCH 2013; 68:283-299. [PMID: 23394994 DOI: 10.1016/b978-0-12-394294-4.00016-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Kiwifruit are a rich source of vitamin C and other antioxidants. We have demonstrated the capacity of kiwifruit to protect cellular DNA against oxidative damage in single-dose human experiments and in longer term supplementation trials using the comet assay to measure both DNA-strand breaks and oxidized bases. Enhanced antioxidant status following a single large dose of kiwifruit is shown by an increased resistance of lymphocyte DNA to oxidation by H(2)O(2)in vitro. After 3 weeks (or more) of supplementation, endogenous base oxidation is significantly decreased. In addition to its antioxidant potential, kiwifruit stimulates base excision repair as measured in an in vitro assay with DNA containing 8-oxoguanine as substrate. The relevance of DNA damage protection and modulation of DNA repair to cancer risk is discussed.
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Heger A, Ferk F, Nersesyan A, Szekeres T, Kundi M, Wagner K, Haidinger G, Mišík M, Knasmüller S. Intake of a resveratrol-containing dietary supplement has no impact on DNA stability in healthy subjects. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2012; 749:82-6. [DOI: 10.1016/j.mrgentox.2012.07.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2012] [Revised: 06/20/2012] [Accepted: 07/25/2012] [Indexed: 11/27/2022]
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Bøhn SK, Ward NC, Hodgson JM, Croft KD. Effects of tea and coffee on cardiovascular disease risk. Food Funct 2012; 3:575-91. [PMID: 22456725 DOI: 10.1039/c2fo10288a] [Citation(s) in RCA: 97] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Tea and coffee have been associated with risk of cardiovascular disease (CVD), both positively and negatively. Epidemiological data suggest that black and green tea may reduce the risk of both coronary heart disease and stroke by between 10 and 20%. Experimental and clinical trial data generally indicate either neutral or beneficial effects on risk factors and pathways linked to the development of CVD. Controversy still exists regarding the effects of coffee, where there have been concerns regarding associations with hypercholesterolaemia, hypertension and myocardial infarction. However, long term moderate intake of coffee is not associated with detrimental effects in healthy individuals and may even protect against the risk of developing type 2 diabetes. The detrimental effects of coffee may be associated with the acute pressor effects, most likely due to caffeine at high daily intakes, and lipids from boiled coffee can contribute to raised serum cholesterol. Genetic polymorphisms in enzymes involved in uptake, metabolism and excretion of tea and coffee compounds are also associated with differential biological effects. Potential mechanisms by which tea and coffee phytochemicals can exert effects for CVD protection include the regulation of vascular tone through effects on endothelial function, improved glucose metabolism, increased reverse cholesterol transport and inhibition of foam cell formation, inhibition of oxidative stress, immunomodulation and effects on platelet function (adhesion and activation, aggregation and clotting). The phytochemical compounds in tea and coffee and their metabolites are suggested to influence protective endogenous pathways by modulation of gene-expression. It is not known exactly which compounds are responsible for the suggestive protective effects of tea and coffee. Although many biologically active compounds have been identified with known biological effects, tea and coffee contain many unidentified compounds with potential bioactivity.
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Affiliation(s)
- Siv K Bøhn
- School of Medicine and Pharmacology, The University of Western Australia-M570, 35 Stirling Highway, Crawley, WA 6009, Australia.
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Raaschou-Nielsen O, Andersen ZJ, Jensen SS, Ketzel M, Sørensen M, Hansen J, Loft S, Tjønneland A, Overvad K. Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study. Environ Health 2012; 11:60. [PMID: 22950554 PMCID: PMC3515423 DOI: 10.1186/1476-069x-11-60] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2012] [Accepted: 08/28/2012] [Indexed: 05/21/2023]
Abstract
BACKGROUND Traffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association. METHODS We followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993-1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO₂) since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs) with adjustment for potential confounders. RESULTS Mean levels of NO₂ at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06-1.51, per doubling of NO₂ concentration) and all causes (MRR, 1.13; 95% CI, 1.04-1.23, per doubling of NO₂ concentration) after adjustment for potential confounders. For participants who ate < 200 g of fruit and vegetables per day, the MRR was 1.45 (95% CI, 1.13-1.87) for mortality from cardiovascular disease and 1.25 (95% CI, 1.11-1.42) for mortality from all causes. CONCLUSIONS Traffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake.
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Affiliation(s)
| | - Zorana Jovanovic Andersen
- Danish Cancer Society Research Center, Copenhagen, Denmark
- Department of Public Health, Center for Epidemiology and Screening, University of Copenhagen, Copenhagen, Denmark
| | | | - Matthias Ketzel
- Department of Environmental Science, Aarhus University, Roskilde, Denmark
| | - Mette Sørensen
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Johnni Hansen
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Steffen Loft
- Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark
| | | | - Kim Overvad
- Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark
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