Publications by authors named "Nicole Seifert"

16 Publications

  • Page 1 of 1

Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.

Nutrients 2021 Mar 29;13(4). Epub 2021 Mar 29.

R&D Human Nutrition and Health, DSM Nutritional Products Ltd., 4002 Basel, Switzerland.

Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing and increasing butyrate-producing . Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.
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http://dx.doi.org/10.3390/nu13041125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066074PMC
March 2021

Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.

Gut Microbes 2021 Jan-Dec;13(1):1-20

R&D Human Nutrition and Health, DSM Nutritional Products Ltd ., Basel, Switzerland.

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity , but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.
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http://dx.doi.org/10.1080/19490976.2021.1875774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899684PMC
February 2021

A multi-omics analysis reveals the unfolded protein response regulon and stress-induced resistance to folate-based antimetabolites.

Nat Commun 2020 06 10;11(1):2936. Epub 2020 Jun 10.

Biochemistry I, University of Regensburg, Regensburg, Germany.

Stress response pathways are critical for cellular homeostasis, promoting survival through adaptive changes in gene expression and metabolism. They play key roles in numerous diseases and are implicated in cancer progression and chemoresistance. However, the underlying mechanisms are only poorly understood. We have employed a multi-omics approach to monitor changes to gene expression after induction of a stress response pathway, the unfolded protein response (UPR), probing in parallel the transcriptome, the proteome, and changes to translation. Stringent filtering reveals the induction of 267 genes, many of which have not previously been implicated in stress response pathways. We experimentally demonstrate that UPR-mediated translational control induces the expression of enzymes involved in a pathway that diverts intermediate metabolites from glycolysis to fuel mitochondrial one-carbon metabolism. Concomitantly, the cells become resistant to the folate-based antimetabolites Methotrexate and Pemetrexed, establishing a direct link between UPR-driven changes to gene expression and resistance to pharmacological treatment.
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http://dx.doi.org/10.1038/s41467-020-16747-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287054PMC
June 2020

Previous Interspecific Courtship Impairs Female Receptivity to Conspecifics in the Parasitoid Wasp But Not in .

Insects 2018 Sep 1;9(3). Epub 2018 Sep 1.

Institute of Zoology, University of Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.

Interspecific sexual interactions are not uncommon in animals. In sympatry, females often face the risk of accidentally mating with a heterospecific male. Based on the actual risks imposed by the environment at a given time and place, females should be able to adjust their mate acceptance in order to avoid interspecific copulations as well as accidentally refusing to mate with a conspecific. We investigate the ability of females of the two parasitoid wasp species () and () to adjust their mate acceptance in response to previous unsuccessful courtship by heterospecific males. We show that females are more reluctant to mate with a conspecific male when having been courted previously by a heterospecific male, but females are not. We argue that this strategy is reasonable for females but not for females, which follow a different strategy to avoid the fitness costs imposed by heterospecific copulations.
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http://dx.doi.org/10.3390/insects9030112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163980PMC
September 2018

Correction: The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro.

PeerJ 2018 17;6. Epub 2018 Aug 17.

R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland.

[This corrects the article DOI: 10.7717/peerj.5288.].
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http://dx.doi.org/10.7717/peerj.5288/correction-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097703PMC
August 2018

The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro.

PeerJ 2018 10;6:e5288. Epub 2018 Aug 10.

R&D Human Nutrition and Health, DSM Nutritional Products Ltd., Basel, Switzerland.

The beneficial effects of prebiotic fibres on human health have been related to their capacities to alter the gut microbiota and modify the growth of beneficial microorganisms. It is long appreciated that bacterial metabolites affect the host's physiology. The inner lining of the intestinal tract is the first level of interaction between the host and bacteria and their metabolites. Therefore, we set out to test the effects of five common dietary fibres (oat β-glucan 28%; oat β-glucan 94%; dried chicory root containing inulin 75%; xylo-oligosaccharide; inulin 90%) and maltodextrin, after fermentation by human gut microbiota in vitro, on measures of gut barrier integrity using a Caco-2/HT29-MTX co-culture as well as mucus production and immune parameters using HT29-MTX and HT29 cell models, respectively. Our data show that all fibres, fermentation products increased the tightness of the gut barrier with oat β-glucan 28% having the largest effect. Fermentation supernatants were tested also in models of the compromised gut barrier (leaky gut). After the addition of ethanol as basolateral stressor, only fermentation supernatant of oat β-glucan 28%, oat β-glucan 94% and maltodextrin improved the gut barrier integrity, while oat β-glucan 28% and dried chicory root containing inulin 75% significantly improved the gut barrier integrity after addition of rhamnolipids as apical stressor. Using the Luminex Technology, we demonstrated an important role of oat β-glucan fermentation products in modulating cytokine and chemokine productions. Furthermore, treating the goblet cells with effluent from xylo-oligosaccharide fermentation significantly increased mucus production. In summary, our data emphasize the potential positive effects of fermentation supernatant of dietary fibres on gut-related physiological outcomes and show that prebiotic fibres may have promising potential to induce specific gut health benefits.
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http://dx.doi.org/10.7717/peerj.5288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089210PMC
August 2018

Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes.

Molecules 2016 Apr 8;21(4):465. Epub 2016 Apr 8.

DSM Nutritional Products, Wurmisweg 576, P. O. Box 2676, Basel 4002, Switzerland.

Phenolic diterpenes present in Rosmarinus officinalis and Salvia officinalis have anti-inflammatory and chemoprotective effects. We investigated the in vitro effects of carnosol (CL), carnosic acid (CA), carnosic acid-12-methylether (CAME), 20-deoxocarnosol and abieta-8,11,13-triene-11,12,20-triol (ABTT) in murine macrophages (RAW264.7 cells) and human chondrocytes. The substances concentration-dependently reduced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in LPS-stimulated macrophages (i.e., acute inflammation). They significantly blunted gene expression levels of iNOS, cytokines/interleukins (IL-1α, IL-6) and chemokines including CCL5/RANTES, CXCL10/IP-10. The substances modulated the expression of catabolic and anabolic genes in chondrosarcoma cell line SW1353 and in primary human chondrocytes that were stimulated by IL-1β (i.e., chronic inflammation In SW1353, catabolic genes like MMP-13 and ADAMTS-4 that contribute to cartilage erosion were down-regulated, while expression of anabolic genes including Col2A1 and aggrecan were shifted towards pre-pathophysiological homeostasis. CL had the strongest overall effect on inflammatory mediators, as well as on macrophage and chondrocyte gene expression. Conversely, CAME mainly affected catabolic gene expression, whereas ABTT had a more selectively altered interleukin and chemokine gene exprssion. CL inhibited the IL-1β induced nuclear translocation of NF-κBp65, suggesting that it primarily regulated via the NF-κB signalling pathway. Collectively, CL had the strongest effects on inflammatory mediators and chondrocyte gene expression. The data show that the phenolic diterpenes altered activity pattern of genes that regulate acute and chronic inflammatory processes. Since the substances affected catabolic and anabolic gene expression in cartilage cells in vitro, they may beneficially act on the aetiology of osteoarthritis.
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http://dx.doi.org/10.3390/molecules21040465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274263PMC
April 2016

Vitamin E Supplementation Delays Cellular Senescence In Vitro.

Biomed Res Int 2015 3;2015:563247. Epub 2015 Nov 3.

DSM Nutritional Products Ltd., R & D Human Nutrition and Health, P.O. Box 2676, 4002 Basel, Switzerland.

Vitamin E is an important antioxidant that protects cells from oxidative stress-induced damage, which is an important contributor to the progression of ageing. Ageing can be studied in vitro using primary cells reaching a state of irreversible growth arrest called senescence after a limited number of cellular divisions. Generally, the most utilized biomarker of senescence is represented by the expression of the senescence associated β-galactosidase (SA-β-gal). We aimed here to study the possible effects of vitamin E supplementation in two different human primary cell types (HUVECs and fibroblasts) during the progression of cellular senescence. Utilizing an unbiased automated system, based on the detection of the SA-β-gal, we quantified cellular senescence in vitro and showed that vitamin E supplementation reduced the numbers of senescent cells during progression of ageing. Acute vitamin E supplementation did not affect cellular proliferation, whereas it was decreased after chronic treatment. Mechanistically, we show that vitamin E supplementation acts through downregulation of the expression of the cycline dependent kinase inhibitor P21. The data obtained from this study support the antiageing properties of vitamin E and identify possible mechanisms of action that warrant further investigation.
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http://dx.doi.org/10.1155/2015/563247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647025PMC
September 2016

Monoamine reuptake inhibition and mood-enhancing potential of a specified oregano extract.

Br J Nutr 2011 Apr 21;105(8):1150-63. Epub 2010 Dec 21.

DSM Nutritional Products Limited, Research and Development Human Nutrition and Health, PO Box 2676, CH-4002 Basel, Switzerland.

A healthy, balanced diet is essential for both physical and mental well-being. Such a diet must include an adequate intake of micronutrients, essential fatty acids, amino acids and antioxidants. The monoamine neurotransmitters, serotonin, dopamine and noradrenaline, are derived from dietary amino acids and are involved in the modulation of mood, anxiety, cognition, sleep regulation and appetite. The capacity of nutritional interventions to elevate brain monoamine concentrations and, as a consequence, with the potential for mood enhancement, has not been extensively evaluated. The present study investigated an extract from oregano leaves, with a specified range of active constituents, identified via an unbiased, high-throughput screening programme. The oregano extract was demonstrated to inhibit the reuptake and degradation of the monoamine neurotransmitters in a dose-dependent manner, and microdialysis experiments in rats revealed an elevation of extracellular serotonin levels in the brain. Furthermore, following administration of oregano extract, behavioural responses were observed in mice that parallel the beneficial effects exhibited by monoamine-enhancing compounds when used in human subjects. In conclusion, these data show that an extract prepared from leaves of oregano, a major constituent of the Mediterranean diet, is brain-active, with moderate triple reuptake inhibitory activity, and exhibits positive behavioural effects in animal models. We postulate that such an extract may be effective in enhancing mental well-being in humans.
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http://dx.doi.org/10.1017/S0007114510004940DOI Listing
April 2011

Transcriptomics does not show adverse effects of beta-carotene in A/J mice exposed to smoke for 2 weeks.

Arch Biochem Biophys 2007 Sep 18;465(2):336-46. Epub 2007 Jul 18.

DSM Nutritional Products, Human Nutrition and Health, PO Box 3255, Building 241/421, CH-4002 Basel, Switzerland.

Beta-carotene (betaC) supplementation in smokers was unexpectedly associated with increased incidence of lung cancer versus smoking alone. We performed a study in A/J mice to explore possible betaC/cigarette smoke (CS) interactions potentially influencing lung cancer risk in smokers. A/J mice received a diet containing 120 or 600 ppm betaC for six weeks, and exposed to mainstream CS (140 mg total suspended particulates/m(3)) during the last two weeks. Lung transcriptomics analysis revealed that CS induced drug metabolism, oxidative stress, extracellular matrix (ECM) degradation, inflammation markers, and apoptosis. betaC reduced CS-induced inflammation markers and ECM degradation. betaC modulated the CS effect on apoptosis without a clear pro- or anti-apoptotic trend. betaC alone induced only minor changes of gene expression. In conclusion, betaC/CS interactions caused gene regulations in lungs. CS was the main effector. The gene regulations overall did not indicate that betaC exacerbated CS effects. Dose-dependency of betaC effects was minor and not detectable by genome-wide data mining.
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http://dx.doi.org/10.1016/j.abb.2007.06.034DOI Listing
September 2007

A nonradioactive high-throughput/high-content assay for measurement of the human serotonin reuptake transporter function in vitro.

J Biomol Screen 2006 Dec 12;11(8):1027-34. Epub 2006 Nov 12.

Screening and Early Efficacy Group, Human Nutrition Research and Development, DSM Nutritional Products, Kaiseraugst, Switzerland.

Both the tricyclic and specific serotonin reuptake inhibitor classes of antidepressants act primarily by inhibiting the reuptake of released serotonin by the human serotonin reuptake transporter (hSERT). In this article, the authors describe the use of a fluorescent substrate of the transporter (4-(4-(dimethylamino)-styrl)-N-methylpyridinium, ASP) to develop a microplate-based high-throughput screen for hSERT function. The assay is sensitive to known inhibitors of serotonin uptake, including fluoxetine (Prozac), with the correct rank order of potency and IC(50) values close to those reported in the literature for tritiated serotonin uptake. The authors also describe the validation of the assay for natural product screening using a test set of 2400 pure phyto-chemicals and 80 plant extracts. The mean Z of the screened plates was 0.53. Hit rates, confirmation rates, and validation of the hits in a "classical" assay for serotonin uptake are all reported. The assay can also be read in "high-content" mode using a subcellular imaging device, which allows direct detection of possible assay interference by acutely cytotoxic compounds. Among the compounds identified were several previously reported inhibitors of the hSERT, as well as compounds having structural similarity to the tricyclic antidepressant drugs.
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http://dx.doi.org/10.1177/1087057106294698DOI Listing
December 2006

Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells.

Arch Biochem Biophys 2006 Nov 20;455(1):48-60. Epub 2006 Sep 20.

DSM Nutritional Products, R&D, Human Nutrition and Health, P. O. Box 3255, CH-4002 Basel, Switzerland.

High dose beta-carotene supplementation of smokers was associated with increased lung cancer risk in two intervention trials. It was proposed that generation of apocarotenals in smoke-exposed lungs impaired retinoic acid (RA) signaling, leading to squamous metaplasia and cell proliferation. To test this, we compared RA target gene regulation by retinoids, apocarotenals or beta-carotene by transcriptomics in BEAS-2B cells cultured to promote squamous differentiation. Retinoids, beta-carotene as well as apocarotenals induced known RA target genes. Retinoids upregulated involucrin, indicating that retinoids did not rescue BEAS-2B cells from squamous differentiation. Muc5AC, a marker for mucous differentiation, was transiently induced. beta-Carotene and apocarotenals less strongly induced involucrin and did not induce muc5AC. In summary, apocarotenals or beta-carotene upregulated RA target genes suggesting promotion, not inhibition, of RA signaling in BEAS-2B cells. Furthermore, apocarotenals and beta-carotene regulated gene expression independently of RA signaling. Squamous differentiation is not unequivocally linked to RA deficiency in BEAS-2B cells.
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http://dx.doi.org/10.1016/j.abb.2006.08.023DOI Listing
November 2006

beta-Carotene interferes with ultraviolet light A-induced gene expression by multiple pathways.

J Invest Dermatol 2005 Feb;124(2):428-34

DSM Nutritional Products, 205/217A, PO Box 3255, Department of Human Nutrition and Health, CH-4002 Basel, Switzerland.

Ultraviolet light A (UVA) exposure is thought to cause skin aging mainly by singlet oxygen ((1)O(2))-dependent pathways. Using microarrays, we assessed whether pre-treatment with the (1)O(2) quencher beta-carotene (betaC; 1.5 microM) prevents UVA-induced gene regulation in HaCaT human keratinocytes. Downregulation of growth factor signaling, moderate induction of proinflammatory genes, upregulation of immediate early genes including apoptotic regulators and suppression of cell cycle genes were hallmarks of the UVA effect. Of the 568 UVA-regulated genes, betaC reduced the UVA effect for 143, enhanced it for 180, and did not interact with UVA for 245 genes. The different interaction modes imply that betaC/UVA interaction involved multiple mechanisms. In unirradiated keratinocytes, gene regulations suggest that betaC reduced stress signals and extracellular matrix (ECM) degradation, and promoted keratinocyte differentiation. In irradiated cells, expression profiles indicate that betaC inhibited UVA-induced ECM degradation, and enhanced UVA induction of tanning-associated protease-activated receptor 2. Combination of betaC-promoted keratinocyte differentiation with the cellular "UV response" caused synergistic induction of cell cycle arrest and apoptosis. In conclusion, betaC at physiological concentrations interacted with UVA effects in keratinocytes by mechanisms that included, but were not restricted to (1)O(2) quenching. The retinoid effect of betaC was minor, indicating that the betaC effects reported here were predominantly mediated through vitamin A-independent pathways.
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http://dx.doi.org/10.1111/j.0022-202X.2004.23593.xDOI Listing
February 2005

Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate.

FASEB J 2005 Feb 15;19(2):272-4. Epub 2004 Nov 15.

DSM Nutritional Products, Human Nutrition and Health, Carotenoid Section, Basel, Switzerland.

Epidemiological evidence links consumption of lycopene, the red carotenoid of tomato, to reduced prostate cancer risk. We investigated the effect of lycopene in normal prostate tissue to gain insight into the mechanisms, by which lycopene can contribute to primary prostate cancer prevention. We supplemented young rats with 200 ppm lycopene for up to 8 wk, measured the uptake into individual prostate lobes, and analyzed lycopene-induced gene regulations in dorsal and lateral lobes after 8 wk of supplementation. Lycopene accumulated in all four prostate lobes over time, with all-trans lycopene being the predominant isoform. The lateral lobe showed a significantly higher total lycopene content than the other prostate lobes. Transcriptomics analysis revealed that lycopene treatment mildly but significantly reduced gene expression of androgen-metabolizing enzymes and androgen targets. Moreover, local expression of IGF-I was decreased in the lateral lobe. Lycopene also consistently reduced transcript levels of proinflammatory cytokines, immunoglobulins, and immunoglobulin receptors in the lateral lobe. This indicates that lycopene reduced inflammatory signals in the lateral prostate lobe. In summary, we show for the first time that lycopene reduced local prostatic androgen signaling, IGF-I expression, and basal inflammatory signals in normal prostate tissue. All of these mechanisms can contribute to the epidemiologically observed prostate cancer risk reduction by lycopene.
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http://dx.doi.org/10.1096/fj.04-1905fjeDOI Listing
February 2005

Beta-carotene inhibits UVA-induced matrix metalloprotease 1 and 10 expression in keratinocytes by a singlet oxygen-dependent mechanism.

Free Radic Biol Med 2004 Sep;37(5):654-70

Department Human Nutrition and Health, Carotenoid Group, DSM Nutritional Products, Basel, Switzerland.

UVA exposure causes skin photoaging by singlet oxygen (1)O(2)-mediated induction of, e.g., matrix metalloproteases (MMPs). We assessed whether pretreatment with beta-carotene, a (1)O(2) quencher and retinoic acid (RA) precursor, interferes with UVA-induced gene regulation. HaCaT keratinocytes were precultured with beta-carotene at physiological concentrations (0.5, 1.5, and 3.0 microM) prior to exposure to UVA from a Hönle solar simulator (270 kJ/m(2)). HaCaT cells accumulated beta-carotene in a time- and dose-dependent manner. UVA irradiation massively reduced the cellular beta-carotene content. Beta-carotene suppressed UVA-induction of MMP-1, MMP-3, and MMP-10, three major matrix metalloproteases involved in photoaging. We show that regulation by not only MMP-1, but also MMP-10, involves (1)O(2)-dependent mechanisms. Beta-carotene dose-dependently quenched (1)O(2)-mediated induction of MMP-1 and MMP-10. Thus, as in chemical solvent systems, beta-carotene quenches (1)O(2) also in living cells. Vitamin E did not cooperate with beta-carotene to further inhibit MMP induction. HaCaT cells produced weak retinoid activity from beta-carotene, as demonstrated by mild upregulation of RAR beta and activation of an RARE-dependent reporter gene. Beta-carotene did not regulate the genes encoding other RARs, RXRs, or the two beta-carotene cleavage enzymes. These results demonstrate that beta-carotene acts photoprotectively, and that this effect is mediated by (1)O(2) quenching.
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http://dx.doi.org/10.1016/j.freeradbiomed.2004.05.018DOI Listing
September 2004