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  • 1.
    Anvari, Ebrahim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wikström, Per
    Walum, Erik
    Welsh, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice2015In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 49, no 11, p. 1308-1318Article in journal (Refereed)
    Abstract [en]

    In type 2 diabetes, it has been proposed that pancreatic beta-cell dysfunction is promoted by oxidative stress caused by NADPH oxidase (NOX) overactivity. Five different NOX enzymes (NOX1-5) have been characterized, among which NOX1 and NOX2 have been proposed to negatively affect beta-cells, but the putative role of NOX4 in type 2 diabetes-associated beta-cell dysfunction and glucose intolerance is largely unknown. Therefore, we presently investigated the importance of NOX4 for high-fat diet or HFD-induced glucose intolerance using male C57BL/6 mice using the new NOX4 inhibitor GLX351322, which has relative NOX4 selectivity over NOX2. In HFD-treated male C57BL/6 mice a two-week treatment with GLX351322 counteracted non-fasting hyperglycemia and impaired glucose tolerance. This effect occurred without any change in peripheral insulin sensitivity. To ascertain that NOX4 also plays a role for the function of human beta-cells, we observed that glucose- and sodium palmitate-induced insulin release from human islets in vitro was increased in response to NOX4 inhibitors. In long-term experiments (1-3 days), high-glucose-induced human islet cell reactive oxygen species (ROS) production and death were prevented by GLX351322. We propose that while short-term NOX4-generated ROS production is a physiological requirement for beta-cell function, persistent NOX4 activity, for example, during conditions of high-fat feeding, promotes ROS-mediated beta-cell dysfunction. Thus, selective NOX inhibition may be a therapeutic strategy in type 2 diabetes.

  • 2.
    Artemenko, Konstantin A
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mass-spectrometry-based characterization of oxidations in proteins2015In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 49, no 5, p. 477-93Article, review/survey (Refereed)
    Abstract [en]

    Protein modifications such as oxidations have a strong impact on protein function and activity in various organisms. High-resolution mass spectrometric techniques in combination with various sample preparation methodologies allow for the in-detail characterization of protein structures and strongly contribute to a greater understanding of the impact of protein modifications in nature. This paper outlines the general workflows for the characterization of oxidation sites in proteins by mass spectrometry (MS). Different types of oxidations are taken into consideration; both qualitative and quantitative aspects of MS-based approaches are presented with respect to oxidized proteins. Both bottom-up and top-down MS approaches are described and evaluated; a wide range of the particular applications corresponding to these techniques is also presented. Furthermore, the common advantages and downsides of these techniques are assessed. The approaches for enrichment of low-abundance oxidized proteins are extensively presented for different cysteine oxidations and protein carbonylations. A short description about databases and bioinformatic software solutions for oxidative protein prediction, identification, and biological interpretation is also given in this review.

  • 3.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    F2-isoprostane induced prostaglandin formation in the rabbit2006In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 40, no 3, p. 273-277Article in journal (Refereed)
    Abstract [en]

    F2-isoprostanes, non-enzymatic free radical mediated products of arachidonic acid, have shown to form during various oxidant stress status and have potent biological effects. This study investigates to what extent 8-iso-PGF (a major F2-isoprostane), a bioactive product of lipid peroxidation can modify endogenous prostaglandin F (PGF) formation since prostaglandins are inflammatory as well as potent vasoregulatory substances that modulate diverse important physiological functions, and also form during acute and chronic inflammation. An immediate appearance and disappearance of 8-iso-PGF was seen in both plasma and urine within a short interval after i.v. administration of 43 μg/kg of 8-iso-PGF to the rabbits. A successive but differential formation of PGF resulted in a rapid and pulsatile increase of plasma 15-keto-dihydro-PGF, a major metabolite of primary PGF. Later, this compound was excreted efficiently as intact compound into the urine during the 3 h of experiment. A 8-fold increase of PGF metabolite in plasma at 10 min and 12-fold increase in the urine at 30–60 after the i.v. administration of 8-iso-PGF was observed which continued throughout the 3 h of experiment. This observation suggests that pharmacologically administered or endogenously produced 8-iso-PGF during oxidant stress induces prostaglandin formation presumbly through the classical cyclooxygenase-catalysed arachidonic acid oxidation which might be inflammatory itself to the cells and exerts further vasoconstrictive effects.

  • 4.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Jarosinska, Dorota
    Sällsten, Gerd
    Mazzolai, Barbarra
    Barregård, Lars
    Regulatory factors of basal F2-isoprostane formation: population, age, gender and smoking habits in humans2009In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 43, no 1, p. 85-91Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is assumed to be the key underlying factor in the pathogenesis of many common diseases. This study describes the basal levels of 8-iso-PGF(2alpha ), a major F(2)-isoprostane and an in vivo oxidative stress biomarker in healthy subjects from three countries, namely Italy, Poland and Sweden, in relation to their smoking habits, age and gender. It studied urinary 8-iso-PGF(2alpha ) in 588 subjects from Sweden (n=220), Italy (n=203) and Poland (n=165). Polish subjects had the highest levels of F(2)-isoprostanes followed by the Swedish and Italians when adjusted for smoking, age, sex and creatinine and the inter-country differences were statistically significant. Smokers had significantly higher levels of 8-iso-PGF(2alpha ) compared to non-smokers in all countries and there was a moderate decrease with age. Women had only slightly lower 8-iso-PGF(2alpha ) than men. There is a difference in F(2)-isoprostane levels in vivo between countries. Smoking, age and gender affect isoprostane formation and should be taken into consideration in clinical studies of oxidative stress.

  • 5.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Liu, Xiaoli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nozari, Ala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Miclescu, Adriana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation2003In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 37, no 3, p. 251-256Article in journal (Refereed)
    Abstract [en]

    Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.

  • 6.
    Helmersson, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Alfthan, Georg
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Serum selenium predicts levels of F2-isoprostanes and prostaglandin F2alpha in a 27 year follow-up study of Swedish men2005In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 39, no 7, p. 763-770Article in journal (Refereed)
    Abstract [en]

    Low concentrations of selenium (Se) predict mortality and cardiovascular diseases in some populations. The effect of Se on in vivo indicators of oxidative stress and inflammation, two important features of atherosclerosis, in human populations is largely unexplored. This study investigated the longitudinal association between serum selenium (s-Se) and a golden standard indicator of oxidative stress in vivo (8-iso-prostaglandin F2, a major F2-isoprostane), an indicator of cyclooxygenase (COX)-mediated inflammation (prostaglandin F2), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and serum amyloid A protein (SAA) in a follow-up study of 27 years. The s-Se was measured in 615 Swedish men at 50 years of age in a health investigation. The status of oxidative stress and inflammation was evaluated in a re-investigation 27 years later by quantification of urinary 8-iso-PGF2 and 15-keto-dihydro- PGF2 (a major metabolite of PGF2) and serum hsCRP, SAA and IL-6. Men in the highest quartile of s-Se at age 50 had decreased levels of 8-iso-PGF2 compared to all lower quartiles   and decreased levels of PGF2 compared to all lower quartiles   at follow-up. These associations were independent of BMI, diabetes, hyperlipidemia, hypertension, smoking, -tocopherol and β-carotene at baseline. The s-Se was not associated with hsCRP, SAA or IL-6 at follow-up. In conclusion, high concentrations of s-Se predict reduced levels of oxidative stress and subclinical COX-mediated (but not cytokine-mediated) inflammation in a male population. The associations between Se, oxidative stress and inflammation, respectively, might be related to the proposed cardiovascular protective property of Se.

  • 7.
    Lindström, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Raqib, Rubhana
    El Arifeen, Shams
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Associations between oxidative parameters in pregnancy and birth anthropometry in a cohort of women and children in rural Bangladesh: The MINIMat-cohort2012In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 46, no 3, p. 253-264Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is suggested as a potential mechanism in impaired foetal growth, smaller birth size and thus subsequently adult chronic diseases. We have investigated associations between oxidative stress in pregnancy and birth anthropometry (weight, height, head and chest circumferences). In the MINIMat-trial (Maternal and Infant Nutrition Interventions, Matlab) in rural Bangladesh, free 8-iso-prostaglandin P-2 alpha (lipid peroxidation) was analysed in pregnancy week 14 and 30 and 8-Hydroxy-2 '-Deoxyguanosine (DNA oxidation) in week 19. We found that higher levels of lipid peroxidation in early pregnancy were associated with larger infant size (birth length and chest circumference). In late pregnancy, no clear pattern of associations was found. Increasing level of DNA oxidation was associated with lower birth length in girls but no other associations were found. In conclusion, a higher level of lipid peroxidation in early (but not late) pregnancy was associated with a favourable larger birth size suggesting that timing of lipid peroxidation is of importance.

  • 8. Mukanganyama, Stanley
    et al.
    Naik, Yogesh S.
    Widersten, Mikael
    Mannervik, Bengt
    Hasler, Julia A.
    Proposed reductive metabolism of artemisinin by glutathione transferases in vitro2001In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 35, p. 427-434Article in journal (Refereed)
  • 9.
    Palm, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    F(2)-isoprostanes, tocopherols and normal pregnancy2009In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 43, no 6, p. 546-552Article in journal (Refereed)
    Abstract [en]

    This study investigates oxidative stress and antioxidants in normal human pregnancy and post-partum period. Thirty-seven healthy women with normal pregnancies were included. Both urinary and serum samples were collected throughout the pregnancy and post-partum period. Oxidative stress was estimated by measuring the reliable in vivo marker, namely 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha,) an F(2)-isoprostane) and antioxidant status was evaluated by measuring alpha- and gamma-tocopherol in serum samples. Pregnancy was associated with successively increased levels of 8-iso-PGF(2alpha) with advancing gestational age. The median post-partum value corresponded to the values observed in early gestation and a significant decrease was observed from late pregnancy to the post-partum period. Lipid-adjusted alpha- and gamma-tocopherol levels decreased with advancing gestational age. This longitudinal study suggests that mild oxidative stress is involved in normal human pregnancy.

  • 10.
    Rytter, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Johansson, Clara
    Department of Biosciences and Nutrition, Karolinska Institute.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjödin, Anders
    Department of Human Nutrition, Faculty of Life Science, University of Copenhagen.
    Möller, Lennart
    Department of Biosciences and Nutrition, Karolinska Institute.
    Åkesson, Björn
    Department of Pure and Applied Biochemistry, Biomedical Nutrition, Lunds University.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Biomarkers of oxidative stress in overweight men are not influenced by a combination of antioxidants2010In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 44, no 5, p. 522-528Article in journal (Refereed)
    Abstract [en]

    The effect of antioxidant supplementation on biomarkers of oxidative stress was investigated in a 6-week intervention study in 60 overweight men. The supplement contained a combination of antioxidants aiming to correspond to the antioxidant content found in a diet rich in fruit and vegetables. Placebo, single or double dose of antioxidants was provided to the subjects. Metabolic variables, plasma antioxidants and biomarkers of oxidative stress (lipid peroxidation and DNA damage) were measured. No effect of supplementation on biomarkers of oxidative stress was observed. Both intervention groups showed substantial increases of plasma antioxidants. This study demonstrated that supplementation with a combination of antioxidants did not affect lipid peroxidation and DNA damage in overweight men, despite increased concentrations of plasma antioxidants. The absence of antioxidant supplement effect might possibly be explained by the chosen study group having a normal level of oxidative stress, duration of the intervention and/or doses of antioxidants.

     

  • 11.
    Rytter, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University.
    Åsgård, Rikard
    Department of Biosciences and Nutrition, Karolinska Institute.
    Ersson, Clara
    Department of Biosciences and Nutrition, Karolinska Institute.
    Moussavian, Shahnaz
    Department of Biosciences and Nutrition, Karolinska Institute.
    Sjödin, Anders
    Department of Human Nutrition, Faculty of Life Science, University of Copenhagen.
    Abramsson-Zetterberg, Lilianne
    National Food Administration.
    Möller, Lennart
    Department of Biosciences and Nutrition, Karolinska Institute.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Supplementation with a combination of antioxidants does not affect glycaemic control, oxidative stress or inflammation in type 2 diabetes subjects2010In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 44, no 12, p. 1445-1453Article in journal (Refereed)
    Abstract [en]

    The present clinical trial examined the influence of a supplement, containing a combination of antioxidants extracted from fruit, berries and vegetables, on levels of plasma antioxidants (tocopherols, carotenoids and ascorbate), glycaemic control (blood glucose, HbA1c, insulin), oxidative stress biomarkers (F2-isoprostane, malondialdehyd, nitrotyrosine, 8-oxo-7, 8-dihydro-2'-deoxyguanosine, formamidopyrimidine glycosylase sites, frequency of micronucleated erythrocytes) and inflammatory markers (interleukin-6, C-reactive protein, prostaglandin F-metabolite) in type 2 diabetes. Forty subjects were randomly assigned to control, single or double dose group and completed the study. In summary, 12 weeks of antioxidant supplementation did neither affect glycaemic control nor the levels of biomarkers of oxidative stress or inflammation, despite substantially increased plasma concentrations of antioxidants. The absence of an effect may be explained by the selected study subjects with relatively well-controlled diabetes, a high intake of fruit and vegetable and levels of plasma antioxidants, biomarkers of oxidative stress and inflammatory markers comparable to those found in healthy subjects.

  • 12.
    Wagner, Sandra
    et al.
    Univ Paris 11, UVSQ, Univ Paris Saclay, Inserm U1018, Villejuif, France..
    Apetrii, Mugurel
    Hop Ambroise Pare, AP HP, Serv Nephrol, Boulogne, France.;Univ Med & Pharm Gr T Popa, Dept Nephrol, Iasi, Romania..
    Massy, Ziad A.
    Univ Paris 11, UVSQ, Univ Paris Saclay, Inserm U1018, Villejuif, France.;Hop Ambroise Pare, AP HP, Serv Nephrol, Boulogne, France..
    Kleber, Marcus E.
    Friedrich Schiller Univ, Inst Nutr, Jena, Germany.;Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Mannheim, Germany..
    Delgado, Graciela E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Mannheim, Germany..
    Scharnagel, Hubert
    Med Univ Graz, Inst Clin Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Mannheim, Germany.;Med Univ Graz, Inst Clin Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria.;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany. CHU Nancy, Ctr Invest Clin Plurithemat 14 33, INSERM, Nancy, France..
    Metzger, Marie
    Univ Paris 11, UVSQ, Univ Paris Saclay, Inserm U1018, Villejuif, France..
    Rossignol, Patrick
    ALTIR, Vandoeuvre Les Nancy, France..
    Jardine, Alan
    British Heart Fdn Glasgow, Cardiovasc Res Ctr, Glasgow, Lanark, Scotland..
    Holdaas, Hallvard
    Natl Hosp Norway, Oslo, Norway..
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Schmieder, Roland
    Univ Hosp Erlangen Numberg, Erlangen, Germany..
    Stengel, Benedicte
    Univ Paris 11, UVSQ, Univ Paris Saclay, Inserm U1018, Villejuif, France..
    Zannad, Faiez
    Oxidized LDL, statin use, morbidity, and mortality in patients receiving maintenance hemodialysis2017In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 51, no 1, p. 14-23Article in journal (Refereed)
    Abstract [en]

    Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2 +/- 13.8 U/L in AURORA and did not differ between treatment groups, and 74.6 +/- 28.1 U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population.

  • 13.
    Åsgård, Rikard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hellman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Effect of beta-carotene on catechol-induced genotoxicity in vitro: Evidence of both enhanced and reduced DNA damage2013In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 47, no 9, p. 692-698Article in journal (Refereed)
    Abstract [en]

    Intake of antioxidants from the diet has been recognized to have beneficial health effects, but the potential benefit of taking antioxidants such as beta-carotene as supplements is controversial. The aim of the present study was to evaluate the potential protective effects of a physiologically relevant concentration (2 mu M) of beta-carotene on the DNA damaging effects of catechol in mouse lymphoma L5178Y cells. Two different exposure protocols were used: simultaneous exposure to beta-carotene and catechol for 3 h; and exposure to catechol for 3 h after 18 h pre-treatment with the vitamin. DNA damage was evaluated using the comet assay (employing one procedure for general damage, and another procedure, which also included oxidative DNA damage). Independent of exposure protocol and procedure for comet assay, beta-carotene did not increase the basal level of DNA damage. However, at the highest concentration of catechol (1 mM), beta-carotene was found to clearly increase the level of catechol-induced DNA damage, especially in the pre-treated cells. Interestingly, an opposite effect was observed at lower concentrations of catechol, but the beta-carotene related reduction of catechol-induced genotoxicity was significant (P < 0.05) only for the procedure including oxidative damage induced by 0.5 mM catechol. Taken together our results indicate that beta-carotene can both reduce and enhance the DNA damaging effects of a genotoxic agent such as catechol. This indicates that it is the level of catechol-induced DNA damage that seems to determine whether beta-carotene should be regarded as a beneficial or detrimental agent when it comes to its use as a dietary supplement.

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