Guido R M M Haenen

Maastricht University, Maestricht, Limburg, Netherlands

Are you Guido R M M Haenen?

Claim your profile

Publications (220)620.85 Total impact

  • Source
    Aalt Bast, Guido R M M Haenen
  • Jules Coenegracht, Guido R M M Haenen
    [show abstract] [hide abstract]
    ABSTRACT: Aan antioxidanten wordt veel toegeschreven. Dat ze ziektes kunnen genezen. Dat ze veroudering tegengaan. Dat je er niet genoeg van binnen kunt krijgen. Of juist dat ze helemaal niet goed voor je zijn, zelfs gevaarlijk en giftig. Tovermiddel of hype: wat is waar en wat is niet waar? 9 vragen en antwoorden over antioxidanten.
    Gezond idee. 02/2014;
  • Wybo Algra, Aalt Bast, Guido R M M Haenen
    [show abstract] [hide abstract]
    ABSTRACT: Pokon voor tumorcellen Wybo Algra − 08/02/14, 22:03 Weer een illusie armer: de wonderbaarlijke antioxidanten blijken bij nader inzien helemaal niet zo gezond. Zeker niet voor kankerpatiënten. 'Vrije radicalen of antioxidanten, wat zijn nu eigenlijk de 'bad guys'?' Zie het als een klassieke strijd tussen goed en kwaad, maar dan op het niveau van moleculen, atomen en elektronen. In de microkosmos van de menselijke cel heb je vrije radicalen. Die zijn fout. De afgelopen dertig jaar werden ze in verband gebracht met suikerziekte, kanker, hart-en vaatziekten en allerlei andere aandoeningen. En je hebt antioxidanten. Die maken korte metten met de gehate vrije radicalen en zijn dus goed. Antioxidanten staan synoniem voor anti-veroudering, anti-kanker, anti-verzin het maar, en dienen dus overvloedig geconsumeerd en gesmeerd te worden. Met die kraakheldere boodschap wisten voedingsfabrikanten en reclamemakers wel raad. Maar onder wetenschappers slaat meer en meer de twijfel toe over die wonderbaarlijke antioxidanten. Zelfs wordt inmiddels de vraag gesteld: vrije radicalen of antioxidanten, wat zijn nu eigenlijk de 'bad guys'? Antioxidanten: blijf er vanaf als je wordt behandeld voor kanker Onlangs sprak het orakel, in de persoon van James Watson. Hij won in 1962 de Nobelprijs, samen met Francis Crick, voor zijn baanbrekende onderzoek naar de dubbele helixstructuur van DNA. Als zo'n man van zich doet horen, dan wordt er geluisterd. Ditmaal trakteerde de 85-jarige Watson de wetenschap op een waar manifest van ettelijke kantjes over de stand van zaken in het kankeronderzoek. Taaie kost, klonk het. Maar niet mis te verstaan was Watsons boodschap over antioxidanten: blijf er vanaf als je wordt behandeld voor kanker. Geen antioxidantenrijke voeding, en zeker geen potjes en strips met supplementen. En of ongeneeslijke kankervormen over tien jaar met succes te behandelen zijn, hangt er van af of wetenschappers manieren vinden om het gehalte aan antioxidanten in de tumor niet omhoog, maar juist omlaag te krijgen. Zijn redenering klinkt heel logisch. Normale lichaamscellen, betoogt Watson, beschikken over de ingebouwde mogelijkheid om zichzelf op enig moment, onder specifieke omstandigheden, te vernietigen. Dat is een nuttig mechanisme, bijvoorbeeld om oude en beschadigde cellen op te ruimen. Voor zo'n geplande celdood zijn vrije radicalen nodig. http://www.trouw.nl/tr/nl/6700/Wetenschap/article/detail/3593122/2014/02/08/Pokon-voor-tumorcellen.dhtml
    Trouw. 02/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: The flavonoid 7-mono-O-(β-hydroxyethyl)-rutoside (monoHER) is an effective protector against doxorubicin induced toxicity which has been related to the antioxidant activity of monoHER. The present study examines the potential relevance of the direct scavenging activity of the flavonoid. The potency of the direct antioxidant effect was confirmed by its instantaneous protection against intracellular oxidative stress in human umbilical vein endothelial cells at therapeutically achievable concentrations (EC50 = 60 nM) underpinning the involvement of a direct scavenging activity. This direct effect of monoHER is substantiated by (i) its site specific scavenging effect, i.e. on a molecular level monoHER is positioned at the location of radical formation, (ii) its position in the antioxidant network, i.e. on a biochemical level oxidized monoHER quickly reacts with ascorbate or glutathione, (iii) its location in the vascular system, i.e. on a cellular level monoHER is localized in the endothelial and smooth muscle cells in the vascular wall. It is concluded that the flavonoid monoHER can display a physiologically important direct antioxidant effect.
    Toxicology in Vitro 01/2014; · 2.65 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Acrolein is a thiol reactive compound present in cigarette smoke and plays a pivotal role in the deleterious effects of smoking. Acrolein causes toxicity in human bronchial epithelial cells in a dose dependent manner. GSH forms the first line of defense against acrolein-induced toxicity. At high doses of acrolein (⩾ 10 μM) the capacity of the cellular protection by GSH is overwhelmed and GSH is not able to quench all the acrolein, resulting in cytotoxicity. At a relatively low dose of acrolein (3 μM), no cytotoxicity is observed due to protection by GSH. Moreover we found that exposure to a low dose of acrolein protects cells against the toxic effect of a second higher dose of acrolein. The adaptation to acrolein is induced via Nrf2 mediated gene expression of γ-glutamylcysteine synthetase leading to elevated GSH levels. This upregulation of the protection by GSH demonstrates a hormetic response to acrolein. Hormesis is an adaptive or compensatory response induced by a relatively subtle challenge of homeostasis by a toxic compound. Insight into the mechanism of hormesis is mandatory for a more accurate societal regulation of toxic compounds.
    Biochemical and Biophysical Research Communications 01/2014; · 2.41 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Antioxidants act in conjunction. It has been tried to capture this phenomenon with so-called overall antioxidant status measurements like ORAC and TEAC. The apparent simplicity of measuring parameters like ORAC and TEAC has led to many flawed interpretations. There is however value in these parameters when applied in a thoughtful manner. It is illustrated that in vitro and in vivo comparison of fruits and products is possible with these parameters. They can also be used to discover new bioactive ingredients in tissue or in plants. Oxidative stress is associated with many diseases, which are characterized by a chronic, often mild inflammatory response. Oxidative stress is connected to inflammation. Antioxidants frequently modulate this inflammatory process. Also in this respect, it has to be underlined that plant bioactive components all act differently in this oxidative/inflammatory stress. This obviously offers possibilities to adjust our diet further for optimal health. http://www.actahort.org/members/showpdf?booknrarnr=1017_35
    Acta horticulturae 01/2014; 1017.
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Various health benefits of the cocoa flavanol (-)-epicatechin (EC) have been attributed to its antioxidant and anti-inflammatory potency. In the present study we investigated whether EC is able to prevent deterioration of the anti-inflammatory effect of the glucocorticoid (GC) cortisol in the presence of oxidative stress. It was found that cortisol reduces inflammation in differentiated monocytes. Oxidative stress extinguishes the anti-inflammatory effect of cortisol, leading to cortisol resistance. EC reduces intracellular oxidative stress as well as the development of cortisol resistance. This further deciphers the enigmatic mechanism of EC by which it exerts its anti-inflammatory and antioxidant action. The observed effect of the cocoa flavanol EC will especially be of relevance in pathophysiological conditions with increased oxidative stress and consequential GC resistance and provides a fundament for the rational use of dietary antioxidants.
    Pharmacological Research 11/2013; · 4.35 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Background: Drug-induced pulmonary toxicity is a serious and expanding problem with often unknown aetiology. Many drugs are metabolized by cytochrome P450 (CYP) enzymes. Objective: To establish whether allelic variation in CYP polymorphic genes contributes to variability in drug response and unexpected toxicity. Methods: A case-control study was conducted. The cases consisted of patients with drug-induced interstitial lung disease (DI-ILD; n = 59). Two control groups were used: one group of healthy volunteers (n = 173) and one group of patients with idiopathic pulmonary fibrosis (IPF; n = 110). Results: Of the patients with DI-ILD 91.5% (54/59) had at least one of the studied variant genes compared with 70.5% (122/173, p < 0.001) of the healthy volunteers and 69.1% (76/110, p < 0.001) of the IPF patients. The percentage of individuals with one or more variant CYP genes was higher in the DI-ILD group. Odds ratios were significantly increased and ranged from 3.25 to 40.8, indicating a significant association between the development of DI-ILD and the presence of one or more variant CYP genes. Conclusion: DI-ILD appeared to be associated with the presence of at least one variant CYP allele. This study supports the potential usefulness of personalized medicine by genotyping aiming to improve efficacy, tolerability and drug safety.
    Drug Safety 08/2013; 31(12). · 3.41 Impact Factor
  • Aalt Bast, Guido R M M Haenen
  • Aalt Bast, Guido R M M Haenen
  • Aalt Bast, Guido R M M Haenen
  • Aalt Bast, Guido R M M Haenen
    [show abstract] [hide abstract]
    ABSTRACT: http://www.cell.com/trends/pharmacological-sciences/abstract/S0165-6147(13)00098-9 http://download.cell.com/trends/pharmacological-sciences/pdf/PIIS0165614713000989.pdf?intermediate=true Oxidative damage is a common cellular event involved in numerous diseases and drug toxicities. Antioxidants prevent or delay oxidative damage, and therefore there has been extensive research into the discovery of natural and newly designed antioxidants. Initial excitement regarding the potential health benefits of antioxidants has diminished. Currently, it is even claimed that antioxidants increase mortality. The antioxidant pendulum appears to swing from healthy to toxic and from general panacea to insignificant ingredient. Owing to the polarity of views towards antioxidants, nutritional recommendation ranges from advice to increase antioxidant status in plasma to the notion that it is a useless measurement. Such views, lacking sufficient scientific support, lead to misconceptions, which in our opinion hinder the rational use of food supplements and impedes the design and development of new antioxidant drugs. As a result, good opportunities might easily be missed. The major misconceptions are: • Misconception 1: antioxidants cure any disease • Misconception 2: antioxidants increase mortality • Misconception 3: the more the better • Misconception 4: at high doses, antioxidants become pro-oxidant • Misconception 5: any antioxidant will do • Misconception 6: theoretically, antioxidants cannot behave as such • Misconception 7: antioxidant status measures health • Misconception 8: once used, antioxidants are inactive • Misconception 9: natural antioxidants are superior • Misconception 10: antioxidant drugs do not work
    Trends in Pharmacological Sciences 06/2013; 34(8):430. · 9.25 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Plasma citrate levels were found to be elevated in nonalcoholic fatty liver disease (NAFLD) patients. Cellular experiments indicated that increased citrate levels might originate from an excess of fatty acids. The impact of elevated citrate levels on oxidative stress was examined. It was found that citrate stimulated hydrogen peroxide induced intracellular oxidative stress in HepG2 cells. This was related to the promotion of iron mediated hydroxyl radical formation from hydrogen peroxide by citrate. The stimulating effect of citrate on the reactivity of iron promotes oxidative stress, a crucial process in the progression of NAFLD.
    FEBS letters 06/2013; · 3.54 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Accumulating evidence suggests that foods rich in flavanols decrease the risk of developing cardiovascular diseases. Attenuation of oxidative stress was suggested to contribute to the cardiovascular benefit of flavanols. Up to now it was unclear whether flavanol metabolites can also protect cells from oxidative stress. The aim of the present study was to determine the potential contribution of several glucuronidated, methylated and sulfated metabolites of (-)-epicatechin (EC) and (+)-catechin (Cat) to the protection of human vascular endothelial cells (HUVECs) against oxidative stress. The relative potency of the tested compounds to scavenge superoxide anion radicals showed that a free catechol moiety in the molecule is important for the direct antioxidant activity. EC and Cat (0.5, 1, 10µM) were potent radical scavengers and provided protection against intracellular oxidative stress induced by hydrogen peroxide. Although the metabolites provided less intracellular protection compared to EC and Cat, the tested methylated and glucuronidated metabolites reduced oxidative stress significantly in HUVECs. Our results indicate that the metabolites have a relevant contribution in the intracellular protection of EC and Cat against oxidative stress. Also, the direct antioxidant activity plays an important role in this protection.
    European journal of pharmacology 06/2013; · 2.59 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: INTRODUCTION: Consumption of n-3 polyunsaturated fatty acids (PUFA) and antioxidant polyphenols is considered to decline the risk of cardiovascular disease. MATERIALS AND METHODS: To provide an explanation for this cardioprotective effect, we performed an intervention study with proatherogenic Apoe(-/-) mice which were fed during eight weeks with a high fat diet supplemented with either walnuts (rich in n-3 PUFA and antioxidant compounds), walnut oil (with n-3 PUFA only) or sunflower oil as a control (12 mice per group). RESULTS: Feeding walnuts, but not walnut oil, caused a 55% reduction in atherosclerotic plaque development in the aortic arch in comparison to the control diet. This was associated with reduced staining of plaques for CD36, a scavenger receptor expressed by macrophages. Feeding mice with walnuts also lowered plasma levels of triglycerides, cholesterol and prothrombin with 36%, 23% and 21 %, respectively, compared to control diet. In addition, accumulation of lipids in the liver was decreased, while plasma antioxidant capacity was increased. On the other hand, feeding mice with walnut oil did not provoke significant changes in these parameters in comparison to the control diet. Platelet activation and thrombus formation under flow remained unchanged with either diet. CONCLUSIONS: In Apoe(-/-) mice on high fat diet, intake of dietary walnut (but not walnut oil) beneficially influences lipid metabolism and atherosclerotic plaque development, with no more than limited effects on platelet and coagulation function.
    Thrombosis Research 01/2013; · 3.13 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Maternal intake of flavonoids, known for their antioxidant properties, may affect her offspring's susceptibility to develop chronic diseases at adult age, especially those related to oxidative stress, via developmental programming. Therefore, we supplemented female mice to the flavonoids genistein and quercetin during gestation, to study its effect on antioxidant capacities in lung and liver of adult offspring. Maternal intake of quercetin increased the expression of Nrf2 and Sod2 in fetal liver at gestational day 14.5. At adult age, in utero exposure to both flavonoids resulted in the increased expression of several enzymatic antioxidant genes, which was more pronounced in the liver than in the adult lung. Moreover, prenatal genistein exposure induced the non-enzymatic antioxidant capacity in the adult lung, partly via increasing glutathione levels. Prenatal exposure to both flavonoids resulted in significantly lower levels of oxidative stress induced DNA damage in liver only. Our observations lead to the hypothesis that a pre-emptive trigger of the antioxidant defense system in utero had a persistent effect on antioxidant capacity and as a result decreased oxidative stress induced DNA damage in the liver.
    Free radical biology & medicine 01/2013; · 5.42 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Cardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant) on antioxidant capacity and exercise-induced cardiac troponin release in cyclists. Thirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O2 uptake 60±5 mL·kg(-1)·min(-1), Wmax 5.4±0.5 W·kg(-1); mean ± SD) were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day), or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (≈ 120 min). The pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0-4.2) to 4.7 ng/L (IQR 3.7-6.7), immediately post-exercise (p<0.001). Four weeks of astaxanthin supplementation significantly increased mean basal plasma astaxanthin concentrations from non-detectable values to 175±86 µg·kg(-1). However, daily astaxanthin supplementation had no effect on exercise-induced cardiac troponin T release (p = 0.24), as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde). Markers of inflammation (high-sensitivity C-reactive protein) and exercise-induced skeletal muscle damage (creatine kinase) were equally unaffected by astaxanthin supplementation. Despite substantial increases in plasma astaxanthin concentrations, astaxanthin supplementation did not improve antioxidant capacity in well-trained cyclists. Accordingly, exercise-induced cardiac troponin T concentrations were not affected by astaxanthin supplementation. ClinicalTrials.gov NCT01241877.
    PLoS ONE 01/2013; 8(11):e79280. · 3.73 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: INTRODUCTION: Astaxanthin is a lipid-soluble carotenoid found in a variety of aquatic organisms. Prolonged astaxanthin supplementation has been reported to increase fat oxidative capacity and improve running time to exhaustion in mice. These data suggest that astaxanthin may be applied as a potent ergogenic aid in humans. PURPOSE: To assess the impact of 4 wks astaxanthin supplementation on substrate use and subsequent time trial performance in well-trained cyclists. METHODS: Using a double-blind parallel design, 32 young, well-trained male cyclists or triathletes (age: 25±1 y, weight: 73±1 kg, VO2peak: 60±1 mL·kg·min, Wmax: 395±7 W) were supplemented for 4 wks with 20 mg astaxanthin per day (ASTA) or a placebo (PLA). Before and after the supplementation period, subjects performed 60 min of exercise (50% Wmax), followed by a ~1 h time trial. RESULTS: Daily astaxanthin supplementation significantly increased basal plasma astaxanthin concentrations from non-detectable values to 187±19 μg·kg (P<0.05). This elevation was not reflected in greater total plasma anti-oxidant capacity (P=0.90) or attenuated malondialdehyde levels (P=0.63). Whole-body fat oxidation rates during submaximal exercise did not differ between groups and did not change over time (from 0.71±0.04 to 0.68±0.03 g·min and 0.66±0.04 to 0.61±0.05 g·min in the PLA and ASTA group, respectively; P=0.73). No improvements in time trial performance were observed in either group (from 236±9 to 239±7 and from 238±6 to 244±6 W in the PLA and ASTA group, respectively; P=0.63). CONCLUSIONS: Prolonged astaxanthin supplementation does not augment anti-oxidant capacity, increase fat oxidative capacity, or improve time trial performance in trained cyclists.
    Medicine and science in sports and exercise 12/2012; · 3.71 Impact Factor

Publication Stats

5k Citations
620.85 Total Impact Points

Institutions

  • 1999–2014
    • Maastricht University
      • • Department of Toxicology
      • • Department of Pharmacology
      Maestricht, Limburg, Netherlands
  • 2010
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 2001–2008
    • TNO
      Delft, South Holland, Netherlands
    • University of Oslo
      • Department of Chemistry
      Oslo, Oslo, Norway
  • 2007
    • Louisiana State University Health Sciences Center New Orleans
      • Department of Pharmacology and Experimental Therapeutics
      Baton Rouge, LA, United States
  • 2006–2007
    • Aston University
      • School of Life and Health Sciences
      Birmingham, ENG, United Kingdom
  • 2004
    • Heinrich-Heine-Universität Düsseldorf
      • Institut für Toxikologie
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1988–2001
    • VU University Amsterdam
      • • Department of Medical Oncology
      • • Amsterdam Center for Drug Research
      Amsterdam, North Holland, Netherlands
  • 2000
    • Stanford University
      • Department of Pediatrics
      Stanford, CA, United States
  • 1989–2000
    • University of Amsterdam
      • Department of Medical Oncology
      Amsterdam, North Holland, Netherlands
  • 1996–1998
    • Leiden University
      • Leiden Amsterdam Center for Drug Research
      Leiden, South Holland, Netherlands
  • 1983–1984
    • Universiteit Utrecht
      • Division of Pharmacoepidemiology and Pharmacotherapy
      Utrecht, Provincie Utrecht, Netherlands