Publications by authors named "Max Hansen"

22 Publications

  • Page 1 of 1

Reduction of Graft-versus-Host-Disease in NOD.Cg-Prkdc Il2rg/SzJ (NSG) Mice by Cotransplantation of Syngeneic Human Umbilical Cord-Derived Mesenchymal Stromal Cells.

Transplant Cell Ther 2021 May 5. Epub 2021 May 5.

Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.

Graft-versus-host disease (GVHD) is one of the major complications following hematopoietic stem cell transplantation, which remains the sole curative therapy for many malignant diseases of the hematopoietic system. The immunomodulatory potential of mesenchymal stromal cells (MSCs) to treat GVHD is currently being tested in various preclinical and clinical trials. Because the results of the preclinical and clinical trials on the use of MSCs to treat GVHD have not been consistent, we analyzed the potential beneficial effects of syngeneic versus allogenic treatment, culture expansion of MSCs, and various MSC cell doses and time points of MSC transplantation in a murine GVHD model. We established the murine GVHD model based on the transplantation of umbilical cord blood-derived hematopoietic stem cells (UC-HSCs) and used this model to assess the therapeutic potential of umbilical cord blood-derived MSCs (UC-MSCs). The use of HSC and MSC populations derived from the same donor allowed us to exclude third-party cells and test the UC-HSCs and UC-MSCs in a matched setting. Moreover, we were able to compare various doses, transplantation time points, and the influence of culture expansion of MSCs on the impact of treatment. This resulted in 16 different treatment groups. The most efficient setting for treatment of UC-HSC-induced GVHD reactions was based on the simultaneous administration of 1 × 10 culture-expanded, syngeneically matched UC-MSCs. This therapy effectively reduced the number of CD8 T cells in the blood, protected the mice from weight loss, and prolonged their survival until the end of observation period. Taken together, our data show beneficial effects of (1) syngeneic over allogeneic UC-HSCs and UC-MSCs, (2) culture-expanded cells over freshly isolated primary cells, (3) simultaneous over sequential administration, and (4) high doses of UC-MSCs. The animal model of GVHD established here is now available for more detailed studies, including a comparative analysis of the efficacy of MSCs derived from alternative sources, such as adipose tissue and bone marrow.
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http://dx.doi.org/10.1016/j.jtct.2021.04.018DOI Listing
May 2021

Dietary exposure to selected chemical contaminants in fish for the Danish population.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2020 Jun 28;37(6):1027-1039. Epub 2020 Apr 28.

National Food Institute, Technical University of Denmark , Kongens Lyngby, Denmark.

The exposure to selected chemical contaminants from fish has been calculated for the Danish population, both for adults (15-75 years of age) and children (4-14 years of age). The Danish mean consumption of fish is 21 g person day for adults and 12 g person day for children. Fish consumption is the main food group contributor for exposure to mercury and dioxins and dioxin-like polychlorinated biphenyls (PCDD/F and DL-PCB) for the Danish population. Comparison of the mean exposure with the TDI or TWI values shows for these substances as well as for perfluorooctane sulphuric acid (PFOS) that the exposure is below the TDI/TWI values. However, even without taking other food groups into account, PCDD/Fs and DL-PCB exposure is close to the actual TWI-value. Calculation of the Margin of Exposure (MOE) for the sum of hexabromocyclododecanes (HBCDD) and polycyclic aromatic hydrocarbons (PAHs) revealed fish consumption to be of low concern for the consumer health regarding these contaminants.
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http://dx.doi.org/10.1080/19440049.2020.1743374DOI Listing
June 2020

Suggestion for a subdivision of processed meat products on the Danish market based on their content of carcinogenic compounds.

Meat Sci 2019 Jan 30;147:91-99. Epub 2018 Aug 30.

National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.

Carcinogenic effects in humans are ascribed to processed meat by organisations such as International Agency for Research on Cancer, World Cancer Research Fund and American Institute for Cancer Research. However, the term 'processed meat' covers a heterogenic group of products whose content of potential hazards differ considerably. To improve estimates of associations between processed meat intake and cancer risk we investigated ways to divide processed meat into subgroups that more precisely reflects its carcinogenic characteristics. We collected ingredient lists and declarations of salt content for >1000 processed meat products on the Danish market and combined the information with knowledge related to processing parameters. Some compounds that could affect the products' carcinogenic characteristics, alone or in combination, were evaluated and compared for 12 types of processed meat products, and we suggest subgrouping of processed meat with similar level of carcinogenic potential, which could improve the understanding of the cancer risk associated with processed meat intake in scientific human studies.
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http://dx.doi.org/10.1016/j.meatsci.2018.08.025DOI Listing
January 2019

Human bocavirus is detected in human placenta and aborted tissues.

Influenza Other Respir Viruses 2019 01 30;13(1):106-109. Epub 2018 Sep 30.

Institut für Pathologie, Kliniken der Stadt Köln gGmbH, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne, Germany.

Background: To date, four human bocaviruses (HBoV) have been described. The most closely related viruses (bovine and canine parvoviruses) are associated with miscarriage in their hosts. The objective of this retrospective study was to determine the frequency of HBoV DNA in miscarriage.

Study Design: Tissue samples from 172 patients, in which miscarriage occurred, were included and tested with a published qPCR protocol. Positive PCRs were mutually confirmed by sequencing.

Results: 43 patients (25%) were positive for HBoV DNA. Of those, the majority of HBoV-positive samples were tissues from miscarriage (placenta: 6; aborted tissue products of conception: 37 specimens). The samples were not paired; either placental or aborted tissue was available.

Conclusions: The results show that, as long as no animal model is available, the role of HBoV in the occurrence of miscarriage requires additional prospective studies in order to investigate its significance and causal involvements of this pathogen.
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http://dx.doi.org/10.1111/irv.12609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304315PMC
January 2019

Apple pomace improves gut health in Fisher rats independent of seed content.

Food Funct 2018 May;9(5):2931-2941

Division for Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.

The mechanism behind the cholesterol lowering effects of apple pomace, a polyphenol- and fibre rich by-product in apple juice production, was investigated. Groups of male F344 rats were fed a control feed or the same feed with 2.1% or 6.5% dry apple pomace with or without seeds for 4 weeks. Effects on plasma cholesterol concentrations, excretion of bile acids, expression of genes involved in cholesterol- and bile acid synthesis, and other markers related to gut health were investigated. We found that pomace feeding decreased total-, LDL- and IDL-cholesterol concentrations compared to control. Higher production of SCFA, indicating elevated caecal fermentation, and increased excretion of total- and primary bile acids could explain the observed hypocholesterolemic effects of apple pomace, however, expression of selected genes involved in cholesterol and bile acid biosynthesis (Hmgcr and Cyp7a1) were not affected. We found no hepatotoxic or other effects of apple seeds. Altogether, our results indicate that apple pomace has beneficial effects on gut health, and that the cholesterol-lowering effect is linked to increased production of SCFA and excretion of bile acids. These effects are most likely linked to the fibre and other fruit constituents present in the pomace. Presence of apple seeds seems to impart no toxicity even at 6.5% pomace in the feed and seeds also had no influence on the biological effect of the pomace. In the future, apple pomace could potentially be used as a bioactive and possibly health promoting food ingredient.
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http://dx.doi.org/10.1039/c7fo01932gDOI Listing
May 2018

Effects of oily fish intake on cardiovascular risk markers, cognitive function, and behavior in school-aged children: study protocol for a randomized controlled trial.

Trials 2016 10 21;17(1):510. Epub 2016 Oct 21.

Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg C, Denmark.

Background: Most children in Western populations do not meet recommendations for fish consumption. Oily fish is an important source of n-3 long-chain polyunsaturated fatty acids (LCPUFA), which reduce blood pressure and plasma triacylglycerol in adults and may affect cognitive development and behavior. However, to our knowledge, the potential effects of oily fish on cardiometabolic health, cognitive function, and behavior in children have not been investigated. The aim of the FiSK Junior study is to investigate the effects of oily fish consumption on cardiovascular risk markers, cognitive function, and behavior in healthy children.

Methods/design: We are conducting a randomized controlled trial with 8- to 9-year-old Danish children, comparing the effect of consuming 300 g/week of oily fish with poultry (control) for 12 weeks between August 2016 and June 2017. The primary outcomes are blood pressure and fasting plasma triacylglycerol, which will be measured at baseline and endpoint. In addition, we will assess erythrocyte fatty acid composition (compliance), heart rate, plasma cholesterol, markers of glucose homeostasis, growth and body composition, dietary intake, and physical activity and sleep. We will also examine effects on cognitive function (attention, memory, and executive functions) by using standardized tests, behavior and emotions by administering parent-rated questionnaires and child interviews, and we will measure physiological stress response and cortisol levels. We need 150 children to complete the trial to detect a between-groups difference of 2.7 mmHg in diastolic blood pressure and 0.13 mmol/L in plasma triacylglycerol; thus, we aim to recruit 200 children. All outcomes will be analyzed in completer analysis supplemented with sensitivity analyses for the primary outcomes, and attention will be given to potential sex and genotype specificity.

Discussion: The results of the FiSK Junior study are expected to fill important gaps in the current knowledge about the importance of dietary fish and n-3 LCPUFA for children's health and development, and may be used when setting dietary recommendations.

Trial Registration: ClinicalTrials.gov identifier: NCT02809508 . Registered on 22 June 2016.
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http://dx.doi.org/10.1186/s13063-016-1647-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073969PMC
October 2016

Primary-like human hepatocytes genetically engineered to obtain proliferation competence display hepatic differentiation characteristics in monolayer and organotypical spheroid cultures.

Cell Biol Int 2016 Mar 18;40(3):341-53. Epub 2016 Jan 18.

Faculty of Science, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.

Primary human hepatocytes are in great demand during drug development and in hepatology. However, both scarcity of tissue supply and donor variability of primary cells create a need for the development of alternative hepatocyte systems. By using a lentivirus vector system to transfer coding sequences of Upcyte® proliferation genes, we generated non-transformed stable hepatocyte cultures from human liver tissue samples. Here, we show data on newly generated proliferation-competent HepaFH3 cells investigated as conventional two-dimensional monolayer and as organotypical three-dimensional (3D) spheroid culture. In monolayer culture, HepaFH3 cells show typical cobblestone-like hepatocyte morphology and anchorage-dependent growth for at least 20 passages. Immunofluorescence staining revealed that characteristic hepatocyte marker proteins cytokeratin 8, human serum albumin, and cytochrome P450 (CYP) 3A4 were expressed. Quantitative real-time PCR analyses showed that expression levels of analyzed phase I CYP enzymes were at similar levels compared to those of cultured primary human hepatocytes and considerably higher than in the liver carcinoma cell line HepG2. Additionally, transcripts for phase II liver enzymes and transporter proteins OATP-C, MRP2, Oct1, and BSEP were present in HepaFH3. The cells produced urea and converted model compounds such as testosterone, diclofenac, and 7-OH-coumarin into phases I and II metabolites. Interestingly, phases I and II enzymes were expressed at about the same levels in convenient monolayer cultures and complex 3D spheroids. In conclusion, HepaFH3 cells and related primary-like hepatocyte lines seem to be promising tools for in vitro research of liver functions and as test system in drug development and toxicology analysis.
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http://dx.doi.org/10.1002/cbin.10574DOI Listing
March 2016

Effect of increased intake of fish and mussels on exposure to toxic trace elements in a healthy, middle-aged population.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2015 11;32(11):1858-66. Epub 2015 Sep 11.

a Diet, Genes, and Environment , Danish Cancer Society Research Center , Copenhagen , Denmark.

Fish and shellfish are rich in essential nutrients, but are also a source of exposure to environmental contaminants. We aimed to investigate the effect of increased fish and mussel intake on mercury, arsenic, lead and cadmium blood concentrations. We randomly assigned 102 healthy men and women (all non-smokers) aged 48-76 years to an intervention group (n = 51) or a control group (n = 51). Intervention participants received a high amount of fish and mussels for 26 weeks (1 kg week(-1)). Controls received no intervention and were expected to eat less than 300 g of fish and mussels per week. Whole-blood concentrations of mercury, arsenic, lead and cadmium were determined using inductively coupled plasma-mass spectrometry. All available observations were included in linear multiple regression analysis to evaluate the effect of the intervention. The difference in mean change for intervention compared with control persons was 5.1 ng ml(-1) (95% confidence interval (CI) = 4.4, 5.8) for mercury, 7.1 ng ml(-1) (95% CI = 5.0, 9.2) for arsenic, and 2.6 ng ml(-1) (95% CI = 0.0, 5.2) for lead. For cadmium, the majority (65%) of the measured concentrations were below the limit of detection of 0.4 ng ml(-1), and the results are therefore not presented. In conclusion, whole-blood concentrations of mercury, arsenic and lead were significantly increased after 26 weeks intervention in this healthy, middle-aged population. The concentrations were not of health concern in this population, except for lead. For lead both the baseline and the post-intervention concentrations were high and exceeded the tolerable concentration levels.
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http://dx.doi.org/10.1080/19440049.2015.1072878DOI Listing
October 2016

Experimental productivity rate optimization of rare earth element separation through preparative solid phase extraction chromatography.

J Chromatogr A 2014 Jun 4;1348:47-51. Epub 2014 May 4.

Department of Chemical Engineering, Centre for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden. Electronic address:

Separating individual rare earth elements from a complex mixture with several elements is difficult and this is emphasized for the middle elements: Samarium, Europium and Gadolinium. In this study we have accomplished an overloaded one-step separation of these rare earth elements through preparative ion-exchange high-performance liquid chromatography with an bis (2-ethylhexyl) phosphoric acid impregnated column and nitric acid as eluent. An inductively coupled plasma mass spectrometry unit was used for post column element detection. The main focus was to optimize the productivity rate, subject to a yield requirement of 80% and a purity requirement of 99% for each element, by varying the flow rate and batch load size. The optimal productivity rate in this study was 1.32kgSamarium/(hmcolumn(3)), 0.38kgEuropium/(hmcolumn(3)) and 0.81kgGadolinium/(hmcolumn(3)).
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http://dx.doi.org/10.1016/j.chroma.2014.04.085DOI Listing
June 2014

Modelling and optimisation of preparative chromatographic purification of europium.

J Chromatogr A 2012 Jan 23;1220:21-5. Epub 2011 Nov 23.

Department of Chemical Engineering, Centre for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.

A model commonly used to describe the separation of biomolecules was used to simulate the harsh environment when eluting neodymium, samarium, europium and gadolinium with a hot acid. After calibration, the model was used to optimise the preparative separation of europium, as this is the most valuable of the four elements. A kinetic dispersive model with a Langmuir mobile phase modulator isotherm was used to describe the process. The equilibration constant, the stoichiometric coefficient and the column capacity for the components were calibrated. The model fitted the experimental observations well. Optimisation was achieved using a differential evolution method. As the two objective functions used in optimising the process, productivity and yield, are competing objectives, the result was not a single set point but a Pareto front.
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http://dx.doi.org/10.1016/j.chroma.2011.11.028DOI Listing
January 2012

Optimization of preparative chromatographic separation of multiple rare earth elements.

J Chromatogr A 2011 Dec 28;1218(51):9155-61. Epub 2011 Oct 28.

Lund University, Department of Chemical Engineering, Lund, Sweden.

This work presents a method to optimize multi-product chromatographic systems with multiple objective functions. The system studied is a neodymium, samarium, europium, gadolinium mixture separated in an ion exchange chromatography step. A homogeneous Langmuir Mobile Phase Modified model is calibrated to fit the experiments, and then used to perform the optimization task. For the optimization a multi-objective Differential Evolution algorithm was used, with weighting based on relative value of the components to find optimal operation points along the Pareto front. The objectives of the Pareto front are weighted productivity and weighted yield with purity as an equality constraint. A prioritizing scheme based on relative values is applied for determining the pooling order. A simple rule of thumb for pooling strategy selection is presented. The multi-objective optimization gives a Pareto front which shows the rule of thumb, as a gap in one of the objective functions.
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http://dx.doi.org/10.1016/j.chroma.2011.10.062DOI Listing
December 2011

Effects of apples and specific apple components on the cecal environment of conventional rats: role of apple pectin.

BMC Microbiol 2010 Jan 20;10:13. Epub 2010 Jan 20.

Department of Microbiology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.

Background: Our study was part of the large European project ISAFRUIT aiming to reveal the biological explanations for the epidemiologically well-established health effects of fruits. The objective was to identify effects of apple and apple product consumption on the composition of the cecal microbial community in rats, as well as on a number of cecal parameters, which may be influenced by a changed microbiota.

Results: Principal Component Analysis (PCA) of cecal microbiota profiles obtained by PCR-DGGE targeting bacterial 16S rRNA genes showed an effect of whole apples in a long-term feeding study (14 weeks), while no effects of apple juice, purée or pomace on microbial composition in cecum were observed. Administration of either 0.33 or 3.3% apple pectin in the diet resulted in considerable changes in the DGGE profiles.A 2-fold increase in the activity of beta-glucuronidase was observed in animals fed with pectin (7% in the diet) for four weeks, as compared to control animals (P < 0.01). Additionally, the level of butyrate measured in these pectin-fed animal was more than double of the corresponding level in control animals (P < 0.01). Sequencing revealed that DGGE bands, which were suppressed in pectin-fed rats, represented Gram-negative anaerobic rods belonging to the phylum Bacteroidetes, whereas bands that became more prominent represented mainly Gram-positive anaerobic rods belonging to the phylum Firmicutes, and specific species belonging to the Clostridium Cluster XIVa.Quantitative real-time PCR confirmed a lower amount of given Bacteroidetes species in the pectin-fed rats as well as in the apple-fed rats in the four-week study (P < 0.05). Additionally, a more than four-fold increase in the amount of Clostridium coccoides (belonging to Cluster XIVa), as well as of genes encoding butyryl-coenzyme A CoA transferase, which is involved in butyrate production, was detected by quantitative PCR in fecal samples from the pectin-fed animals.

Conclusions: Our findings show that consumption of apple pectin (7% in the diet) increases the population of butyrate- and beta-glucuronidase producing Clostridiales, and decreases the population of specific species within the Bacteroidetes group in the rat gut. Similar changes were not caused by consumption of whole apples, apple juice, purée or pomace.
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http://dx.doi.org/10.1186/1471-2180-10-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822772PMC
January 2010

Effects of an onion by-product on bioactivity and safety markers in healthy rats.

Br J Nutr 2009 Dec 17;102(11):1574-82. Epub 2009 Aug 17.

Department of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, Søborg, Denmark.

Onions are excellent sources of bioactive compounds including fructo-oligosaccharides (FOS) and polyphenols. An onion by-product was characterised in order to be developed as a potentially bioactive food ingredient. Our main aim was to investigate whether the potential health and safety effects of this onion by-product were shared by either of two derived fractions, an extract containing the onion FOS and polyphenols and a residue fraction containing mainly cell wall materials. We report here on the effects of feeding these products on markers of potential toxicity, protective enzymes and gut environment in healthy rats. Rats were fed during 4 weeks with a diet containing the products or a control feed balanced in carbohydrate. The onion by-product and the extract caused anaemia as expected in rodents for Allium products. No other toxicity was observed, including genotoxicity. Glutathione reductase (GR) and glutathione peroxidase (GPx1) activities in erythrocytes increased when rats were fed with the onion extract. Hepatic gene expression of Gr, Gpx1, catalase, 5-aminolevulinate synthase and NAD(P)H:quinone oxidoreductase was not altered in any group of the onion fed rats. By contrast, gamma-glutamate cysteine ligase catalytic subunit gene expression was upregulated but only in rats given the onion residue. The onion by-products as well as the soluble and insoluble fractions had prebiotic effects as evidenced by decreased pH, increased butyrate production and altered gut microbiota enzyme activities. In conclusion, the onion by-products have no in vivo genotoxicity, may support in vivo antioxidative defence and alter the functionality of the rat gut microbiota.
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http://dx.doi.org/10.1017/S0007114509990870DOI Listing
December 2009

Dietary carbohydrate source influences molecular fingerprints of the rat faecal microbiota.

BMC Microbiol 2006 Nov 30;6:98. Epub 2006 Nov 30.

Department of Microbiological Food Safety, Danish Institute for Food and Veterinary Research, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.

Background: A study was designed to elucidate effects of selected carbohydrates on composition and activity of the intestinal microbiota. Five groups of eight rats were fed a western type diet containing cornstarch (reference group), sucrose, potato starch, inulin (a long- chained fructan) or oligofructose (a short-chained fructan). Fructans are, opposite sucrose and starches, not digestible by mammalian gut enzymes, but are known to be fermentable by specific bacteria in the large intestine.

Results: Animals fed with diets containing potato starch, or either of the fructans had a significantly (p < 0.05) higher caecal weight and lower caecal pH when compared to the reference group, indicating increased fermentation. Selective cultivation from faeces revealed a higher amount of lactic acid bacteria cultivable on Rogosa agar in these animals. Additionally, the fructan groups had a lower amount of coliform bacteria in faeces. In the inulin and oligofructose groups, higher levels of butyrate and propionate, respectively, were measured.Principal Component Analysis of profiles of the faecal microbiota obtained by Denaturing Gradient Gel Electrophoresis (DGGE) of PCR amplified bacterial 16S rRNA genes as well as of Reverse Transcriptase-PCR amplified bacterial 16S rRNA resulted in different phylogenetic profiles for each of the five animal groups as revealed by Principal Component Analysis (PCA) of band patterns.

Conclusion: Even though sucrose and cornstarch are both easily digestible and are not expected to reach the large intestine, the DGGE band patterns obtained indicated that these carbohydrates indeed affected the composition of bacteria in the large gut. Also the two fructans resulted in completely different molecular fingerprints of the faecal microbiota, indicating that even though they are chemically similar, different intestinal bacteria ferment them. Comparison of DNA-based and RNA-based profiles suggested that two species within the phylum Bacteroidetes were not abundant in numbers but had a particularly high ribosome content in the animals fed with inulin.
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http://dx.doi.org/10.1186/1471-2180-6-98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693562PMC
November 2006

The effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status: a randomized trial among chronic hepatitis C virus-infected patients.

Eur J Gastroenterol Hepatol 2006 Sep;18(9):985-9

Department of Hepatology, Rigshospitalet, Copenhagen University Hospital, Denmark.

Objective: To assess the effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status.

Methods: We performed a randomized, placebo-controlled, double-blind trial to assess the effect of antioxidant supplementation on serum alanine aminotransferase, plasma hepatitis C viral load as well as oxidative and antioxidant markers in patients with hepatitis C virus infection. The participants received a daily dose of ascorbic acid (500 mg), D-alpha-tocopherol (945 IU) and selenium (200 microg) or placebo tablets for 6 months.

Results: Twenty-three patients were included. During supplementation, the antioxidant group had significantly higher levels of plasma ascorbic acid and alpha-tocopherol than the placebo group and the activity of erythrocyte glutathione peroxidase had significantly increased from baseline to month 6. No differences were observed in serum alanine aminotransferase and log10-transformed plasma hepatitis C virus-RNA between the groups or changes from the baseline at any time. No consistent differences between groups or changes from the baseline with respect to erythrocyte activities of antioxidative enzymes (glutathione reductase, superoxide dismutase and catalase) or plasma levels of oxidative markers (malondialdehyde and 2-amino-adipic semialdehyde) were found.

Conclusion: Supplementation with vitamin C, E and selenium increased the antioxidant status, but had no effects on alanine aminotransferase, viral load or oxidative markers.
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http://dx.doi.org/10.1097/01.meg.0000231746.76136.4aDOI Listing
September 2006

Sucrose and IQ induced mutations in rat colon by independent mechanism.

Mutat Res 2004 Oct;554(1-2):279-86

Danish Institute for Food and Veterinary Research, 19 Mørkhøj Bygade, DK-2860 Søborg.

Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions in colon and liver of rats and to increase the number of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To investigate a possible interaction between sucrose and IQ on the genotoxicity in rat liver and colon, we gave Big Blue rats a diet containing sucrose (0%, 3.45% or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ increased the mutation frequency in the colon. The effect of combined treatments with IQ and sucrose on the mutation frequencies was additive indicating that sucrose and IQ act independently. This was supported by the mutation spectra where sucrose expands the background mutations in the colon, whereas IQ, in other studies, more specifically has induced G:C --> T:A transversions. In the liver IQ increased the mutation frequency, whereas addition of sucrose reduced the effect of IQ in a dose-dependent manner. The level of bulky DNA adducts in liver and colon was increased in animals exposed to either sucrose or IQ. In animals exposed to IQ, addition of sucrose had marginal effects on the level of bulky DNA adducts. Markers of oxidative damage and DNA repair were generally unaffected by the treatments. In conclusion, sucrose and IQ in the diet induced mutations in the colon by independent mechanisms, whereas an interaction was observed in liver leading to a decrease in mutations by the combined treatment.
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http://dx.doi.org/10.1016/j.mrfmmm.2004.05.002DOI Listing
October 2004

The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy nonsmokers.

Am J Clin Nutr 2004 Jun;79(6):1060-72

Danish Institute for Food and Veterinary Research, Søborg, Denmark.

Background: Fruit and vegetables contain both nutritive and nonnutritive factors that might contribute to redox (antioxidant and prooxidant) actions.

Objective: We investigated the relative influence of nutritive and nonnutritive factors in fruit and vegetables on oxidative damage and enzymatic defense.

Design: A 25-d intervention study with complete control of dietary intake was performed in 43 healthy male and female nonsmokers who were randomly assigned to 1 of 3 groups. In addition to a basic diet devoid of fruit and vegetables, the fruit and vegetables (Fruveg) group received 600 g fruit and vegetables/d; the placebo group received a placebo pill, and the supplement group received a vitamin pill designed to contain vitamins and minerals corresponding to those in 600 g fruit and vegetables. Biomarkers of oxidative damage to protein and lipids and of antioxidant nutrients and defense enzymes were determined before and during intervention.

Results: Plasma lipid oxidation lag times increased during intervention in the Fruveg and supplement groups, and the increase was significantly higher in the former. Plasma protein carbonyl formation at lysine residues also increased in both of these groups. Glutathione peroxidase activity increased in the Fruveg group only. Other markers of oxidative damage, oxidative capacity, or antioxidant defense were largely unaffected by the intervention.

Conclusions: Fruit and vegetables increase erythrocyte glutathione peroxidase activity and resistance of plasma lipoproteins to oxidation more efficiently than do the vitamins and minerals that fruit and vegetables are known to contain. Plasma protein carbonyl formation at lysine residues increases because of the vitamins and minerals in fruit and vegetables.
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http://dx.doi.org/10.1093/ajcn/79.6.1060DOI Listing
June 2004

Dietary elevated sucrose modulation of diesel-induced genotoxicity in the colon and liver of Big Blue rats.

Arch Toxicol 2003 Nov 23;77(11):651-6. Epub 2003 Aug 23.

Institute of Public Health (c/o Department of Pharmacology), University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.

Earlier studies have indicated that sucrose possesses either co-carcinogenic or tumor-promoter effects in colon carcinogenesis induced by genotoxic carcinogens. In this study we investigated the role of sucrose on diesel exhaust particle (DEP)-induced genotoxicity in the colonic mucosa and liver. Big Blue rats were fed with DEP (0.8 ppm in feed) and/or sucrose (3.45% or 6.85% w/w in feed) for 3 weeks. DEP increased both DNA strand breaks and DNA adducts in colon. Interestingly, sucrose also increased the level of bulky DNA adducts in colon. DEP and sucrose had no effect on DNA strand-breaks and DNA adducts in liver. DEP and sucrose treatment did not have any effect on mutation frequency in colon and liver. Oxidative DNA damage detected as 8-oxodG (8-oxo-7,8-dihydro-2'-deoxyguanosine) and endonuclease III or formamidopyrimidine DNA glycosylase sensitive sites was unaltered in colon and liver. The mRNA expression levels of the DNA repair enzymes N-methylpurine DNA glycosylase ( MPG), 8-oxoguanine DNA glycosylase ( OGG1) and ERCC1 (part of the nucleotide excision repair complex) measured by reverse transcription-polymerase chain reaction were increased in liver by DEP feeding. In colon, expression was unaffected by DEP or sucrose feeding. Among biomarkers of oxidative stress, including vitamin C, malondialdehyde and protein oxidations (gamma-glutamyl semialdehyde and 2-amino adipic semialdehyde) in plasma and liver, only malondialdehyde was increased in plasma by sucrose/DEP feeding. In conclusion, sucrose feeding did not increase DEP-induced DNA damage in colon or liver.
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http://dx.doi.org/10.1007/s00204-003-0502-7DOI Listing
November 2003

Dietary low-dose sucrose modulation of IQ-induced genotoxicity in the colon and liver of Big Blue rats.

Mutat Res 2003 Jun;527(1-2):91-7

Institute of Public Health, Department of Pharmacology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.

Earlier studies have indicated that sucrose increases 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced aberrant crypt foci in the colon. In this study, we investigated the role of sucrose in IQ-induced genotoxicity of the colon mucosa and liver. Big Blue rats were fed with IQ (20 ppm in feed) and/or sucrose (3.45 or 6.85 wt.% in feed) for 3 weeks. IQ increased DNA strand breaks in the colon, whereas the mutation frequency was increased in the liver. The level of IQ-induced DNA adducts was elevated in both colon mucosa cells and liver. In the liver, high sucrose intake increased the level of DNA adducts above that of IQ and low sucrose intake. Oxidative DNA damage detected in terms of 7-hydro-8-oxo-2'-deoxyguanosine by HPLC-EC, or endonuclease III or formamidopyrimidine DNA glycosylase sensitive sites were unaltered in the colon and liver. Expression of ERCC1 and OGG1 mRNA levels were unaffected by IQ or sucrose feeding. Biomarkers of oxidative stress, including Vitamin C, malondialdehyde and protein oxidations (gamma-glutamyl semialdehyde and 2-amino adipic semialdehyde) were unaltered in plasma and in liver. In conclusion, sucrose feeding increases IQ-induced genotoxicity in liver but not in colon, suggesting different mechanisms for sucrose and IQ in colon mutagenesis.
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http://dx.doi.org/10.1016/s0027-5107(03)00058-7DOI Listing
June 2003

Personal PM2.5 exposure and markers of oxidative stress in blood.

Environ Health Perspect 2003 Feb;111(2):161-6

Institute of Public Health, University of Copenhagen, Denmark.

Ambient particulate air pollution assessed as outdoor concentrations of particulate matter less than or equal to 2.5 micro m in diameter (PM(2.5)) in urban background has been associated with cardiovascular diseases at the population level. However, the significance of individual exposure and the involved mechanisms remain uncertain. We measured personal PM(2.5) and carbon black exposure in 50 students four times in 1 year and analyzed blood samples for markers of protein and lipid oxidation, for red blood cell (RBC) and platelet counts, and for concentrations of hemoglobin and fibrinogen. We analyzed protein oxidation in terms of gamma-glutamyl semialdehyde in hemoglobin (HBGGS) and 2-aminoadipic semialdehyde in hemoglobin (HBAAS) and plasma proteins (PLAAS), and lipid peroxidation was measured as malondialdehyde (MDA) in plasma. Median exposures were 16.1 micro g/m(3) for personal PM(2.5) exposure, 9.2 micro g/m(3) for background PM(2.5) concentration, and 8.1 X 10(-6)/m for personal carbon black exposure. Personal carbon black exposure and PLAAS concentration were positively associated (p < 0.01), whereas an association between personal PM(2.5) exposure and PLAAS was only of borderline significance (p = 0.061). A 3.7% increase in MDA concentrations per 10 micro g/m(3) increase in personal PM(2.5) exposure was found for women (p < 0.05), whereas there was no significant relationship for the men. Similarly, positive associations between personal PM(2.5)exposure and both RBC and hemoglobin concentrations were found only in women (p < 0.01). There were no significant relationships between background PM(2.5) concentration and any of the biomarkers. This suggests that exposure to particles in moderate concentrations can induce oxidative stress and increase RBCs in peripheral blood. Personal exposure appears more closely related to these biomarkers potentially related to cardiovascular disease than is ambient PM(2.5) background concentrations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241344PMC
http://dx.doi.org/10.1289/ehp.111-1241344DOI Listing
February 2003

Inhalation of ozone induces DNA strand breaks and inflammation in mice.

Mutat Res 2002 Sep;520(1-2):63-71

National Institute of Occupational Health, Lersø Park Allé 105, DK-2100, Copenhagen, Denmark.

Ozone (O3) is a well-known oxidant pollutant present in photochemical smog. Although ozone is suspected to be a respiratory carcinogen it is not regulated as a carcinogen in most countries. The genotoxic and inflammatory effects of ozone were investigated in female mice exposed to ozone for 90 min. The tail moment in bronchoalveolar lavage (BAL) cells from BALB/c mice was determined by the comet assay as a measure of DNA strand breaks. Within the first 200 min after exposure, the BAL cells from the mice exposed to 1 or 2 ppm ozone had 1.6- and 2.6-fold greater tail moments than unexposed mice. After 200 min there was no effect. It could be ruled out that the effect during the first 200 min was due to major infiltration of lymphocytes or neutrophils. Unexpectedly, ozone had no effect on the content of 8-oxo-deoxyguanosine (8-oxo-dG) in nuclear DNA or on oxidised amino acids in the lung tissue. The mRNA level of the repair enzyme ERCC1 was not increased in the lung tissue. Inflammation was measured by the cytokine mRNA level in lung homogenates. An up to 150-fold induction of interleukin-6 (IL-6) mRNA was detected in the animals exposed to 2 ppm ozone compared to the air-exposed control mice. Also at 1 ppm ozone, the IL-6 mRNA was induced. The large induction of IL-6 mRNA in the lung took place after DNA strand breaks were induced in BAL. This does not support the notion that inflammatory reactions are the cause of DNA damage. To determine whether these exposures were mutagenic, Muta Mice were exposed to 2 ppm ozone, 90 min per day for 5 days. No treatment-related mutations could be detected in the cII transgene. These results indicate that a short episode of ozone exposure at five times the threshold limit value (TLV) in US induces lung inflammatory mediators and DNA damage in the cells in the lumen of the lung. This was not reflected by an induction of mutations in the lung of Muta Mice.
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http://dx.doi.org/10.1016/s1383-5718(02)00176-6DOI Listing
September 2002

A sucrose-rich diet induces mutations in the rat colon.

Cancer Res 2002 Aug;62(15):4339-45

Institute of Food Safety and Nutrition, Division of Biochemical and Molecular Toxicology, The Danish Veterinary and Food Administration, DK-2860 Søborg, Denmark.

A sucrose-rich diet has repeatedly been observed to have cocarcinogenic actions in the colon and liver of rats and to increase the number of aberrant crypt foci in rat colon. To investigate whether sucrose-rich diets might directly increase the genotoxic response in the rat colon or liver, we have added sucrose to the diet of Big Blue rats, a strain of Fischer rats carrying 40 copies of the lambda-phage on chromosome 4. Dietary sucrose was provided to the rats for 3 weeks at four dose levels including the background level in the purified diet [3.4% (control), 6.9%, 13.8%, or 34.5%] without affecting the overall energy and carbohydrate intake. We observed a dose-dependent increase in the mutation frequency at the cII site in the colonic mucosa with increased sucrose levels, reaching a 129% increase at the highest dose level. This would indicate a direct or indirect genotoxic effect of a sucrose-rich diet. No significant increase in mutations was observed in the liver. To seek an explanation for this finding, a variety of parameters were examined representing different mechanisms, including increased oxidative stress, changes in oxidative defense, effects on DNA repair, or changes in the background levels of DNA adducts. Sucrose did not increase the number of DNA strand breaks or oxidized bases assessed as endonuclease III-sensitive sites or 8-oxodeoxyguanosine in colon or liver. DNA repair capacity as determined by expression of the rERCC1 or rOGG1 genes was not increased in colon or liver, but the background level of DNA adducts (I-compounds) as determined by (32)P postlabeling was significantly decreased in colon. This decrease in colon I-compounds correlated inversely with both mutation frequency and ERCC1 DNA repair gene expression. Dietary sucrose did not change liver apoptosis or cell turnover as determined by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling assay and proliferating cell nuclear antigen. An increase in liver ascorbate was also observed, whereas oxidative damage was not observed in proteins or lipids in liver cytosol or in blood plasma. We conclude that a sucrose-rich diet directly or indirectly increases the mutation frequency in rat colon in a dose-dependent manner and concomitantly decreases the level of background DNA adducts, without a direct effect on the expression of major DNA repair enzyme systems. We also conclude that an oxidative mechanism for this effect of sucrose is unlikely. This is the first demonstration of a genotoxic action of increased dietary sucrose in vivo. Both sucrose intake and colon cancer rates are high in the Western world, and our present results call for an examination of a possible direct relationship between the two.
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August 2002