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Antioxidants
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Carotenoids, Oxidative Stress and Disease
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Carotenoids, Oxidative Stress and Disease

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 100093

Special Issue Editor

Dr. Torsten Bohn

E-Mail Website
Guest Editor
Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg
Interests: human nutrition; chronic disease prevention; public health; epidemiology; bioavailability; digestion; biomarkers; oxidative stress markers; inflammation; micronutrients; metabolism; plant bioactives; transcription factors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxidative stress is involved in the aetiology of many diseases, including chronic diseases such as diabetes, atherosclerosis, and other cardiometabolic complications including the metabolic syndrome. Many of these health issues are related to dietary patterns and the intake of macro- and also micronutrients. However, in addition, plant bioactives have also been shown to play a role, and many of these phytochemicals or secondary plant compounds, including carotenoids, have been pointed out in epidemiological studies to be related to the prevalence of chronic diseases.

Among these plant bioactives, carotenoids—mostly of plant, but in part of fungal or bacterial origin—are a remarkable and promising group of terpenoids. Their dietary intake and plasma levels have been related to the incidence of diabetes and cardiovascular diseases, and even total mortality. While formerly mostly appraised for their antioxidant properties, quenching reactive oxygen species, it has become apparent that other qualities, such as their action on the cellular level—e.g., via nuclear receptors and transcription factors—do also appear to play a vital role. However, many studies have emphasized the relation of carotenoids and oxidative stress pathways and markers, and their relation to inflammation and disease. Nevertheless, many mechanistic aspects of carotenoids, such as their place and mode of action, metabolism and bioactive metabolites, and plasma and/or tissue concentrations required for positive health effects, among other things, remain poorly understood.

Thus, it is with great pleasure that I invite you to take part in this Special Issue and together try to describe our state-of-the-art knowledge of carotenoids, oxidative stress and related pathways, and their markers and diseases. Manuscripts dealing with mechanistic effects (based on cell models/in vitro) employing animal or human studies and observational studies related to oxidative stress and markers thereof are also welcome.

Dr. Torsten Bohn
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • animal and human studies
  • markers of oxidative stress and inflammation
  • chronic disease prevention
  • antioxidants
  • recommended intakes
  • dietary patterns
  • bioavailability
  • understudied and novel carotenoids
  • transcription and nuclear factors
  • public health.

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Published Papers (19 papers)

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16 pages, 2752 KiB  
Article
Astaxanthin Sensitizes Low SOD2-Expressing GBM Cell Lines to TRAIL Treatment via Pathway Involving Mitochondrial Membrane Depolarization
by Juhyun Shin, Arti Nile, Ramesh Kumar Saini and Jae-Wook Oh
Antioxidants 2022, 11(2), 375; https://doi.org/10.3390/antiox11020375 - 13 Feb 2022
Cited by 4 | Viewed by 2315
Abstract
Carotenoids have been suggested to have either anti- or pro-oxidative effects in several cancer cells, and those effects can trigger an unbalanced reactive oxygen species (ROS) production resulting in an apoptotic response. Our study aimed to evaluate the effect of the well-known carotenoid [...] Read more.
Carotenoids have been suggested to have either anti- or pro-oxidative effects in several cancer cells, and those effects can trigger an unbalanced reactive oxygen species (ROS) production resulting in an apoptotic response. Our study aimed to evaluate the effect of the well-known carotenoid 3, 3′-dihydroxy-β, β’-carotene-4, 4-dione (astaxanthin, AXT) on glioblastoma multiforme (GBM) cells, especially as a pretreatment of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), that was previously shown to increase ROS and to induce apoptosis in cancer cells. We found that AXT by itself did not trigger apoptosis in four investigated GBM cell lines upon a 24 h treatment at various concentrations from 2.5 to 50 µM. However, in U251-MG and T98-MG GBM cells, pretreatment of 2.5 to 10 µM AXT sensitized cells to TRAIL treatment in a statistically significant manner (p < 0.05) while it did not affect CRT-MG and U87-MG GBM cells. We further compared AXT-sensitive U251-MG and -insensitive CRT-MG response to AXT and showed that 5 µM AXT treatment had a beneficial effect on both cell lines, as it enhanced mitochondrial potential and TRAIL treatment had the opposite effect, as it decreased mitochondrial potential. Interestingly, in U251-MG, 5 µM AXT pretreatment to TRAIL-treated cells mitochondrial potential further decreased compared to TRAIL alone cells. In addition, while 25 and 50 ng/mL TRAIL treatment increased ROS for both cell lines, pretreatment of 5 µM AXT induced a significant ROS decrease in CRT-MG (p < 0.05) while less effective in U251-MG. We found that in U251-MG, superoxide dismutase (SOD) 2 expression and enzymatic activity were lower compared to CRT-MG and that overexpression of SOD2 in U251-MG abolished AXT sensitization to TRAIL treatment. Taken together, these results suggest that while AXT acts as an ROS scavenger in GBM cell lines, it also has some role in decreasing mitochondrial potential together with TRAIL in a pathway that can be inhibited by SOD2. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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23 pages, 3787 KiB  
Article
Effect of a Carotenoid Extract from Citrus reticulata By-Products on the Immune-Oxidative Status of Broilers
by Alexandros Mavrommatis, Maria-Eleftheria Zografaki, Sofia Marka, Eleni D. Myrtsi, Elisavet Giamouri, Christos Christodoulou, Epameinondas Evergetis, Vasilios Iliopoulos, Sofia D. Koulocheri, Georgia Moschopoulou, Panagiotis E. Simitzis, Athanasios C. Pappas, Emmanouil Flemetakis, Apostolis Koutinas, Serkos A. Haroutounian and Eleni Tsiplakou
Antioxidants 2022, 11(1), 144; https://doi.org/10.3390/antiox11010144 - 10 Jan 2022
Cited by 8 | Viewed by 2665
Abstract
Although carotenoids generally possess antimicrobial and antioxidant properties, the in vivo synergistic action of carotenoid blends derived from plant-based by-products has not been thoroughly studied. Therefore, the carotenoid characterization and antimicrobial potential of Citrus reticulata extract as well as the impact of this [...] Read more.
Although carotenoids generally possess antimicrobial and antioxidant properties, the in vivo synergistic action of carotenoid blends derived from plant-based by-products has not been thoroughly studied. Therefore, the carotenoid characterization and antimicrobial potential of Citrus reticulata extract as well as the impact of this carotenoid-rich extract (CCE) dietary supplementation on the performance, meat quality, and immune-oxidative status of broiler chickens were determined. One hundred and twenty one-day-old hatched chicks (Ross 308) were allocated to two dietary groups, with four replicate pens of 15 birds each. Birds were fed either a basal diet (CON) or the basal diet supplemented with 0.1% CCE (25 mg carotenoid extract included in 1 g of soluble starch) for 42 d. β-Cryptoxanthin, β-Carotene, Zeaxanthin, and Lutein were the prevailing carotenoid compounds in the Citrus reticulata extract. The CCE feed additive exerted inhibitory properties against both Gram-positive (Staphylococcus aureus) and negative (Klebsiella oxytoca, Escherichia coli, and Salmonella typhimurium) bacteria. Both the broiler performance and meat quality did not substantially differ, while the breast muscle malondialdehyde (MDA) concentration tended to decrease (p = 0.070) in the CCE-fed broilers. The inclusion of CCE decreased the alanine aminotransferase and MDA concentration, and the activity of glutathione peroxidase, while the activity of superoxide dismutase was increased in the blood. Catalase and NADPH oxidase 2 relative transcript levels were significantly downregulated in the livers of the CCE-fed broilers. Additionally, Interleukin 1β and tumor necrosis factor (TNF) relative transcript levels were downregulated in the livers of the CCE- fed broilers, while TNF and interferon γ (IFNG) tended to decrease in the spleens and bursa of Fabricius, respectively. The present study provided new insights regarding the beneficial properties of carotenoids contained in Citrus reticulata in broilers’ immune-oxidative status. These promising outcomes could be the basis for further research under field conditions. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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11 pages, 1135 KiB  
Communication
A Single Dose of Marine Chlorella vulgaris Increases Plasma Concentrations of Lutein, β-Carotene and Zeaxanthin in Healthy Male Volunteers
by Ana Teresa Serra, Sandra D. Silva, Luís Pleno de Gouveia, Agostinho M. R. C. Alexandre, Carolina V. Pereira, Ana Barbara Pereira, Ana Carvalho Partidário, Nuno Elvas Silva, Torsten Bohn, Vanessa S. S. Gonçalves, Gonçalo Real, Pedro Escudero, Naiara Fernández, Ana A. Matias and Maria Rosário Bronze
Antioxidants 2021, 10(8), 1164; https://doi.org/10.3390/antiox10081164 - 22 Jul 2021
Cited by 10 | Viewed by 4481
Abstract
The beneficial health effects of Chlorella vulgaris have been associated with the presence of several nutrients and antioxidants, including carotenoids. However, the in vivo bioavailability of Chlorella is still poorly evaluated. In this work, a human intervention study was conducted in 11 healthy [...] Read more.
The beneficial health effects of Chlorella vulgaris have been associated with the presence of several nutrients and antioxidants, including carotenoids. However, the in vivo bioavailability of Chlorella is still poorly evaluated. In this work, a human intervention study was conducted in 11 healthy men to evaluate the bioavailability of carotenoids within 3 days after the intake of a single dose (6 g) of dried marine Chlorella vulgaris containing lutein (7.08 mg), β-carotene (1.88 mg) and zeaxanthin (1.47 mg). Subjects were instructed to follow a low carotenoid diet during the experimental phase, starting 1 week earlier. On the day of the experiment, dried microalgae formulated in vegetarian hard capsules were ingested, and blood samples were collected up to 72 h for the analysis of plasma carotenoids concentration by high-performance liquid chromatography with diode-array detection. For all carotenoids, the estimated AUC and Cmax values were significantly different from zero (p < 0.05), indicating that a single dose of marine Chlorella vulgaris increased plasma concentrations of lutein (Cmin-corrected AUC = 1002 µg·h/L, Cmax = 20.4 µg/L), β-carotene (AUC = 1302 µg·h/L, Cmax = 34.9 µg/L) and zeaxanthin (AUC = 122.2 µg·h/L, Cmax = 3.4 µg/L). The bioavailability of other compounds, namely, polyunsaturated fatty acids and trace elements, was also assessed post-prandial for the first time, showing that linoleic acid, docosahexaenoic acid and iodine were absorbed after microalgae intake. These findings support the use of Chlorella vulgaris as a source of carotenoids, PUFA and essential trace elements with associated health benefits. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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12 pages, 1615 KiB  
Article
β-Carotene-Induced Alterations in Haemoglobin Affinity to O2
by Joanna Fiedor, Mateusz Przetocki, Aleksander Siniarski, Grzegorz Gajos, Nika Spiridis, Kinga Freindl and Kvetoslava Burda
Antioxidants 2021, 10(3), 451; https://doi.org/10.3390/antiox10030451 - 13 Mar 2021
Cited by 4 | Viewed by 2253
Abstract
β-Carotene (β-Crt) can be dispersed in hydrophobic regions of the membrane of red blood cells (RBC). Its location, orientation and distribution strongly depend on carotenoid concentration. In the present pilot trial (six human subjects involved), it is demonstrated that incubation of RBCs with [...] Read more.
β-Carotene (β-Crt) can be dispersed in hydrophobic regions of the membrane of red blood cells (RBC). Its location, orientation and distribution strongly depend on carotenoid concentration. In the present pilot trial (six human subjects involved), it is demonstrated that incubation of RBCs with β-Crt (1.8 × 107 β-Crt molecules per RBC, 50 μmol/L) results in expansion of the membrane of RBCs and slight elongation of the cell. The changes are of statistical significance, as verified by the Wilcoxon test at p < 0.05. They indicate (i) a highly random orientation and location of β-Crt inside the membrane and (ii) a tendency for its interaction with membrane skeleton proteins. The accompanying effect of decreased RBC resistance to lysis is possibly a result of the incorrect functioning of ion channels due to their modification/disruption. At higher β-Crt concentrations, its clustering inside membranes may occur, leading to further alterations in the shape and size of RBCs, with the most pronounced changes observed at 1.8 × 108 β-Crt molecules per RBC (500 μmol/L). Due to the reduced permeability of ions, such membranes exhibit increased resistance to haemolysis. Finally, we show that interactions of β-Crt with the membrane of RBCs lead to an alteration in haemoglobin-oxygen affinity, shifting the oxyhaemoglobin dissociation curve toward higher oxygen partial pressures. If the impact of β-Crt on a curve course is confirmed in vivo, one may consider its role in the fine tuning of O2 transportation to tissues. Hence, at low concentrations, providing unchanged elastic and functional properties of RBCs, it could serve as a beneficial agent in optimising heart performance and cardiovascular load. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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16 pages, 5879 KiB  
Article
Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2
by Sheetal Uppal, Sergey A. Dergunov, Weiyu Zhang, Susan Gentleman, T. Michael Redmond, Eugene Pinkhassik and Eugenia Poliakov
Antioxidants 2021, 10(3), 413; https://doi.org/10.3390/antiox10030413 - 09 Mar 2021
Cited by 4 | Viewed by 3071
Abstract
An extensive body of work has documented the antioxidant role of xanthophylls (lutein and zeaxanthin) in human health and specifically how they provide photoprotection in human vision. More recently, evidence is emerging for the transcriptional regulation of antioxidant response by lutein/lutein cleavage products, [...] Read more.
An extensive body of work has documented the antioxidant role of xanthophylls (lutein and zeaxanthin) in human health and specifically how they provide photoprotection in human vision. More recently, evidence is emerging for the transcriptional regulation of antioxidant response by lutein/lutein cleavage products, similar to the role of β-carotene cleavage products in the modulation of retinoic acid receptors. Supplementation with xanthophylls also provides additional benefits for the prevention of age-related macular degeneration (AMD) and attenuation of Alzheimer’s disease symptoms. Mammalian β-carotene oxygenase 2 (BCO2) asymmetrically cleaves xanthophylls as well as β-carotene in vitro. We recently demonstrated that mouse BCO2 (mBCO2) is a functionally palmitoylated enzyme and that it loses palmitoylation when cells are treated with β-carotene. The mouse enzyme is the easiest model to study mammalian BCO2 because it has only one isoform, unlike human BCO2 with several major isoforms with various properties. Here, we used the same acyl-RAC methodology and confocal microscopy to elucidate palmitoylation and localization status of mBCO2 in the presence of xanthophylls. We created large unilamellar vesicle-based nanocarriers for the successful delivery of xanthophylls into cells. We demonstrate here that, upon treatment with low micromolar concentration of lutein (0.15 µM), mBCO2 is depalmitoylated and shows partial nuclear localization (38.00 ± 0.04%), while treatment with zeaxanthin (0.45 µM) and violaxanthin (0.6 µM) induces depalmitoylation and protein translocation from mitochondria to a lesser degree (20.00 ± 0.01% and 35.00 ± 0.02%, respectively). Such a difference in the behavior of mBCO2 toward various xanthophylls and its translocation into the nucleus in the presence of various xanthophylls suggests a possible mechanism for transport of lutein/lutein cleavage products to the nucleus to affect transcriptional regulation. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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26 pages, 7452 KiB  
Article
Lutein Exerts Antioxidant and Anti-Inflammatory Effects and Influences Iron Utilization of BV-2 Microglia
by Ramóna Pap, Edina Pandur, Gergely Jánosa, Katalin Sipos, Attila Agócs and József Deli
Antioxidants 2021, 10(3), 363; https://doi.org/10.3390/antiox10030363 - 27 Feb 2021
Cited by 22 | Viewed by 3951
Abstract
Lutein is a tetraterpene carotenoid, which has been reported as an important antioxidant and it is widely used as a supplement. Oxidative stress participates in many human diseases, including different types of neurodegenerative disorders. Microglia, the primary immune effector cells in the central [...] Read more.
Lutein is a tetraterpene carotenoid, which has been reported as an important antioxidant and it is widely used as a supplement. Oxidative stress participates in many human diseases, including different types of neurodegenerative disorders. Microglia, the primary immune effector cells in the central nervous system, are implicated in these disorders by producing harmful substances such as reactive oxygen species (ROS). The protective mechanisms which scavenge ROS include enzymes and antioxidant substances. The protective effects of different carotenoids against oxidative stress have been described previously. Our study focuses on the effects of lutein on antioxidant enzymes, cytokines and iron metabolism under stress conditions in BV-2 microglia. We performed cell culture experiments: BV-2 cells were treated with lutein and/or with H2O2; the latter was used for inducing oxidative stress in microglial cells. Real-time PCR was performed for gene expression analyses of antioxidant enzymes, and ELISA was used for the detection of pro- and anti-inflammatory cytokines. Our results show that the application of lutein suppressed the H2O2-induced ROS (10′: 7.5 ng + 10 µM H2O2, p = 0.0002; 10 ng/µL + 10 µM H2O2, p = 0.0007), influenced iron utilization and changed the anti-inflammatory and pro-inflammatory cytokine secretions in BV-2 cells. Lutein increased the IL-10 secretions compared to control (24 h: 7.5 ng/µL p = 0.0274; 10 ng/µL p = 0.0008) and to 10 µM H2O2-treated cells (24 h: 7.5 ng/µL + H2O2, p = 0.0003; 10 ng/µL + H2O2, p = 0.0003), while it decreased the TNFα secretions compared to H2O2 treated cells (24 h: 7.5 ng/µL + H2O2, p < 0.0001; 10 ng/µL + H2O2, p < 0.0001). These results contribute to understanding the effects of lutein, which may help in preventing or suppressing ROS-mediated microglia activation, which is related to neuronal degeneration in oxidative stress scenario. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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19 pages, 2373 KiB  
Article
Microbial Production of Retinyl Palmitate and Its Application as a Cosmeceutical
by Bo Hyun Choi, Hee Jin Hwang, Ji Eun Lee, Soon Hwan Oh, Jae Sung Hwang, Bun Yeoul Lee and Pyung Cheon Lee
Antioxidants 2020, 9(11), 1130; https://doi.org/10.3390/antiox9111130 - 14 Nov 2020
Cited by 11 | Viewed by 4470
Abstract
Chemically synthesized retinyl palmitate has been widely used in the cosmetic and biotechnology industry. In this study, we aimed to demonstrate the microbial production of retinyl palmitate and the benefits of microbial retinyl palmitate in skin physiology. A heterologous retinyl palmitate biosynthesis pathway [...] Read more.
Chemically synthesized retinyl palmitate has been widely used in the cosmetic and biotechnology industry. In this study, we aimed to demonstrate the microbial production of retinyl palmitate and the benefits of microbial retinyl palmitate in skin physiology. A heterologous retinyl palmitate biosynthesis pathway was reconstructed in metabolically engineered Escherichia coli using synthetic expression modules from Pantoea agglomerans, Salinibacter ruber, and Homo sapiens. High production of retinyl palmitate (69.96 ± 2.64 mg/L) was obtained using a fed-batch fermentation process. Moreover, application of purified microbial retinyl palmitate to human foreskin HS68 fibroblasts led to increased cellular retinoic acid-binding protein 2 (CRABP2) mRNA level [1.7-fold (p = 0.001) at 100 μg/mL], acceleration of cell proliferation, and enhancement of procollagen synthesis [111% (p < 0.05) at 100 μg/mL], strongly indicating an anti-ageing-related effect of this substance. These results would pave the way for large-scale production of retinyl palmitate in microbial systems and represent the first evidence for the application of microbial retinyl palmitate as a cosmeceutical. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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21 pages, 1542 KiB  
Article
Consumption of Spinach and Tomato Modifies Lipid Metabolism, Reducing Hepatic Steatosis in Rats
by Laura Inés Elvira-Torales, Inmaculada Navarro-González, Joaquín Rodrigo-García, Juan Seva, Javier García-Alonso and María Jesús Periago-Castón
Antioxidants 2020, 9(11), 1041; https://doi.org/10.3390/antiox9111041 - 24 Oct 2020
Cited by 11 | Viewed by 3707
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently a serious and growing clinical problem in developed and developing countries and is considered one of the most frequent chronic liver diseases in the world. The aim of this study was to evaluate the functionality of [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is currently a serious and growing clinical problem in developed and developing countries and is considered one of the most frequent chronic liver diseases in the world. The aim of this study was to evaluate the functionality of dietary carotenoids provided by tomato and spinach in the dietary treatment of steatosis. Twenty-two Sprague-Dawley rats with induced steatosis were grouped into three groups and fed standard diet (CD group) and two experimental diets supplemented with 12.75% (LC12.75 group) and 25.5% (HC25.5 group) of a mixture of spinach and tomato powder. Rats fed carotenoid-rich feeds showed an improvement in the plasma biomarkers of steatosis, with lower levels of glucose, total cholesterol, VLDL, TG, proteins, ALT and AST. Likewise, a decrease in oxidative stress was observed, with a significant reduction of malondialdehyde (MDA) in plasma (up to 54%), liver (up to 51.42%) and urine (up to 78.89%) (p < 0.05) and an increase in plasma antioxidant capacity (ORAC) (up to 73.41%) (p < 0.05). Furthermore, carotenoid-rich diets led to an accumulation of carotenoids in the liver and were inversely correlated with the content of total cholesterol and hepatic triglycerides, increasing the concentrations of MUFA and PUFA (up to 32.6% and 48%, respectively) (p < 0.05). The accumulation of carotenoids in the liver caused the modulation of genes involved in lipid metabolism, and we particularly observed an overexpression of ACOX1, APOA1 and NRIH2 (LXR) and the synthesis of the proteins. This study suggests that dietary carotenoids from spinach and tomato aid in the dietary management of steatosis by reversing steatosis biomarkers. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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23 pages, 6439 KiB  
Article
Soluble Cyanobacterial Carotenoprotein as a Robust Antioxidant Nanocarrier and Delivery Module
by Eugene G. Maksimov, Alexey V. Zamaraev, Evgenia Yu. Parshina, Yury B. Slonimskiy, Tatiana A. Slastnikova, Alibek A. Abdrakhmanov, Pavel A. Babaev, Svetlana S. Efimova, Olga S. Ostroumova, Alexey V. Stepanov, Ekaterina A. Slutskaya, Anastasia V. Ryabova, Thomas Friedrich and Nikolai N. Sluchanko
Antioxidants 2020, 9(9), 869; https://doi.org/10.3390/antiox9090869 - 15 Sep 2020
Cited by 13 | Viewed by 2745
Abstract
To counteract oxidative stress, antioxidants including carotenoids are highly promising, yet their exploitation is drastically limited by the poor bioavailability and fast photodestruction, whereas current delivery systems are far from being efficient. Here we demonstrate that the recently discovered nanometer-sized water-soluble carotenoprotein from [...] Read more.
To counteract oxidative stress, antioxidants including carotenoids are highly promising, yet their exploitation is drastically limited by the poor bioavailability and fast photodestruction, whereas current delivery systems are far from being efficient. Here we demonstrate that the recently discovered nanometer-sized water-soluble carotenoprotein from Anabaena sp. PCC 7120 (termed AnaCTDH) transiently interacts with liposomes to efficiently extract carotenoids via carotenoid-mediated homodimerization, yielding violet–purple protein samples. We characterize the spectroscopic properties of the obtained pigment–protein complexes and the thermodynamics of liposome–protein carotenoid transfer and demonstrate the delivery of carotenoid echinenone from AnaCTDH into liposomes with an efficiency of up to 70 ± 3%. Most importantly, we show efficient carotenoid delivery to membranes of mammalian cells, which provides protection from reactive oxygen species (ROS). Incubation of neuroblastoma cell line Tet21N in the presence of 1 μM AnaCTDH binding echinenone decreased antimycin A ROS production by 25% (p < 0.05). The described carotenoprotein may be considered as part of modular systems for the targeted antioxidant delivery. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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16 pages, 3136 KiB  
Article
Lycopene Protects against Smoking-Induced Lung Cancer by Inducing Base Excision Repair
by Junrui Cheng, Baxter Miller, Emilio Balbuena and Abdulkerim Eroglu
Antioxidants 2020, 9(7), 643; https://doi.org/10.3390/antiox9070643 - 21 Jul 2020
Cited by 33 | Viewed by 4796
Abstract
Background: Oxidative stress plays a critical role in lung cancer progression. Carotenoids are efficient antioxidants. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial [...] Read more.
Background: Oxidative stress plays a critical role in lung cancer progression. Carotenoids are efficient antioxidants. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial cells. Methods: A549 cells were pretreated with 1-nM, 10-nM, 100-nM, 1-μM and 10-μM ATRA, β-carotene (BC) and lycopene for 24 h, followed by exposure to cigarette smoke using a smoking chamber. Results: The OxyBlot analysis showed that smoking significantly increased oxidative stress, which was inhibited by lycopene at 1 nM and 10 nM (p < 0.05). In the cells exposed to smoke, lycopene increased 8-oxoguanine DNA glycosylase (OGG1) expression at 1 nM, 10 nM, 100 nM, and 1 μM (p < 0.05), but not at 10 μM. Lycopene at lower doses also improved Nei like DNA glycosylases (NEIL1, NEIL2, NEIL3), and connexin-43 (Cx43) protein levels (p < 0.05). Interestingly, lycopene at lower concentrations promoted OGG1 expression within the cells exposed to smoke to an even greater extent than the cells not exposed to smoke (p < 0.01). This may be attributed to the increased SR-B1 mRNA levels with cigarette smoke exposure (p < 0.05). Conclusions: Lycopene treatment at a lower dosage could inhibit smoke-induced oxidative stress and promote genome stability. These novel findings will shed light on the molecular mechanism of lycopene action against lung cancer. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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18 pages, 2516 KiB  
Article
Neurosporaxanthin Overproduction by Fusarium fujikuroi and Evaluation of Its Antioxidant Properties
by Obdulia Parra-Rivero, Marcelo Paes de Barros, María del Mar Prado, José-Vicente Gil, Dámaso Hornero-Méndez, Lorenzo Zacarías, María J. Rodrigo, M. Carmen Limón and Javier Avalos
Antioxidants 2020, 9(6), 528; https://doi.org/10.3390/antiox9060528 - 16 Jun 2020
Cited by 14 | Viewed by 3143
Abstract
Neurosporaxanthin (NX) is a carboxylic carotenoid produced by some filamentous fungi, including species of the genera Neurospora and Fusarium. NX biosynthetic genes and their regulation have been thoroughly investigated in Fusarium fujikuroi, an industrial fungus used for gibberellin production. In this [...] Read more.
Neurosporaxanthin (NX) is a carboxylic carotenoid produced by some filamentous fungi, including species of the genera Neurospora and Fusarium. NX biosynthetic genes and their regulation have been thoroughly investigated in Fusarium fujikuroi, an industrial fungus used for gibberellin production. In this species, carotenoid-overproducing mutants, affected in the regulatory gene carS, exhibit an upregulated expression of the NX pathway. Based on former data on a stimulatory effect of nitrogen starvation on carotenoid biosynthesis, we developed culture conditions with carS mutants allowing the production of deep-pigmented mycelia. With this method, we obtained samples with ca. 8 mg NX/g dry mass, in turn the highest concentration for this carotenoid described so far. NX-rich extracts obtained from these samples were used in parallel with carS-complemented NX-poor extracts obtained under the same conditions, to check the antioxidant properties of this carotenoid in in vitro assays. NX-rich extracts exhibited higher antioxidant capacity than NX-poor extracts, either when considering their quenching activity against [O2(1Δg)] in organic solvent (singlet oxygen absorption capacity (SOAC) assays) or their scavenging activity against different free radicals in aqueous solution and in liposomes. These results make NX a promising carotenoid as a possible feed or food additive, and encourage further studies on its chemical properties. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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15 pages, 3856 KiB  
Article
Chemopreventive Effect of β-Cryptoxanthin on Human Cervical Carcinoma (HeLa) Cells Is Modulated through Oxidative Stress-Induced Apoptosis
by Enkhtaivan Gansukh, Arti Nile, Iyyakkannu Sivanesan, Kannan R. R. Rengasamy, Doo-Hwan Kim, Young-Soo Keum and Ramesh Kumar Saini
Antioxidants 2020, 9(1), 28; https://doi.org/10.3390/antiox9010028 - 27 Dec 2019
Cited by 15 | Viewed by 3769
Abstract
The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities of β-cryptoxanthin derived from mandarin oranges (Citrus unshiu Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established that β-cryptoxanthin significantly inhibited the proliferation of [...] Read more.
The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities of β-cryptoxanthin derived from mandarin oranges (Citrus unshiu Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established that β-cryptoxanthin significantly inhibited the proliferation of HeLa cells with the IC50 value of 4.5 and 3.7 µM after 24 and 48 h of treatments, respectively. β-cryptoxanthin-treated HeLa cells exhibited enhanced levels of oxidative stress correlated with significant downregulation of anti-apoptotic Bcl-2, and upregulation of pro-apoptotic Bax mRNA expression. Moreover, β-cryptoxanthin triggered nuclear condensation and disruption of the integrity of the mitochondrial membrane, upregulated caspase-3, -7, and -9 mRNA, and enhanced activation of caspase-3 proteins, resulting in nuclei DNA damage and apoptosis of HeLa cells. Remarkably, TUNEL assay carried out to detect nuclei DNA damage showed 52% TUNEL-positive cells after treatment with a physiological concentration of β-cryptoxanthin (1.0 μM), which validates its potential as an anticancer drug of natural origin. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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Review

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19 pages, 1775 KiB  
Review
Factors Differentiating the Antioxidant Activity of Macular Xanthophylls in the Human Eye Retina
by Justyna Widomska, Wieslaw I. Gruszecki and Witold K. Subczynski
Antioxidants 2021, 10(4), 601; https://doi.org/10.3390/antiox10040601 - 14 Apr 2021
Cited by 15 | Viewed by 3611
Abstract
Macular xanthophylls, which are absorbed from the human diet, accumulate in high concentrations in the human retina, where they efficiently protect against oxidative stress that may lead to retinal damage. In addition, macular xanthophylls are uniquely spatially distributed in the retina. The zeaxanthin [...] Read more.
Macular xanthophylls, which are absorbed from the human diet, accumulate in high concentrations in the human retina, where they efficiently protect against oxidative stress that may lead to retinal damage. In addition, macular xanthophylls are uniquely spatially distributed in the retina. The zeaxanthin concentration (including the lutein metabolite meso-zeaxanthin) is ~9-fold greater than lutein concentration in the central fovea. These numbers do not correlate at all with the dietary intake of xanthophylls, for which there is a dietary zeaxanthin-to-lutein molar ratio of 1:12 to 1:5. The unique spatial distributions of macular xanthophylls—lutein, zeaxanthin, and meso-zeaxanthin—in the retina, which developed during evolution, maximize the protection of the retina provided by these xanthophylls. We will correlate the differences in the spatial distributions of macular xanthophylls with their different antioxidant activities in the retina. Can the major protective function of macular xanthophylls in the retina, namely antioxidant actions, explain their evolutionarily determined, unique spatial distributions? In this review, we will address this question. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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42 pages, 3686 KiB  
Review
Recent Progress in Discovering the Role of Carotenoids and Their Metabolites in Prostatic Physiology and Pathology with a Focus on Prostate Cancer—A Review—Part I: Molecular Mechanisms of Carotenoid Action
by Joanna Dulińska-Litewka, Yoav Sharoni, Przemysław Hałubiec, Agnieszka Łazarczyk, Oskar Szafrański, James A. McCubrey, Bartosz Gąsiorkiewicz, Piotr Laidler and Torsten Bohn
Antioxidants 2021, 10(4), 585; https://doi.org/10.3390/antiox10040585 - 10 Apr 2021
Cited by 20 | Viewed by 3778
Abstract
Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention and medicine. One organ which has been especially targeted in many of these studies and [...] Read more.
Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention and medicine. One organ which has been especially targeted in many of these studies and clinical trials is the human prostate. Without doubt, carotenoids (and their endogenous derivatives—retinoids and other apo-carotenoids) are involved in intra- and intercellular signaling, cell growth and differentiation of prostate tissue. Due to the accumulation of new data on the role of different carotenoids such as lycopene (LC) and β-carotene (BC) in prostatic physiology and pathology, the present review aims to cover the past ten years of research in this area. Data from experimental studies are presented in the first part of the review, while epidemiological studies are disclosed and discussed in the second part. The objective of this compilation is to emphasize the present state of knowledge regarding the most potent molecular targets of carotenoids and their main metabolites, as well as to propose promising carotenoid agents for the prevention and treatment of prostatic diseases. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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51 pages, 40040 KiB  
Review
Fate of β-Carotene within Loaded Delivery Systems in Food: State of Knowledge
by Vaibhav Kumar Maurya, Amita Shakya, Manjeet Aggarwal, Kodiveri Muthukaliannan Gothandam, Torsten Bohn and Sunil Pareek
Antioxidants 2021, 10(3), 426; https://doi.org/10.3390/antiox10030426 - 10 Mar 2021
Cited by 20 | Viewed by 5232
Abstract
Nanotechnology has opened new opportunities for delivering bioactive agents. Their physiochemical characteristics, i.e., small size, high surface area, unique composition, biocompatibility and biodegradability, make these nanomaterials an attractive tool for β-carotene delivery. Delivering β-carotene through nanoparticles does not only improve its bioavailability/bioaccumulation in [...] Read more.
Nanotechnology has opened new opportunities for delivering bioactive agents. Their physiochemical characteristics, i.e., small size, high surface area, unique composition, biocompatibility and biodegradability, make these nanomaterials an attractive tool for β-carotene delivery. Delivering β-carotene through nanoparticles does not only improve its bioavailability/bioaccumulation in target tissues, but also lessens its sensitivity against environmental factors during processing. Regardless of these benefits, nanocarriers have some limitations, such as variations in sensory quality, modification of the food matrix, increasing costs, as well as limited consumer acceptance and regulatory challenges. This research area has rapidly evolved, with a plethora of innovative nanoengineered materials now being in use, including micelles, nano/microemulsions, liposomes, niosomes, solidlipid nanoparticles, nanostructured lipids and nanostructured carriers. These nanodelivery systems make conventional delivery systems appear archaic and promise better solubilization, protection during processing, improved shelf-life, higher bioavailability as well as controlled and targeted release. This review provides information on the state of knowledge on β-carotene nanodelivery systems adopted for developing functional foods, depicting their classifications, compositions, preparation methods, challenges, release and absorption of β-carotene in the gastrointestinal tract (GIT) and possible risks and future prospects. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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16 pages, 1376 KiB  
Review
Lycopene: A Critical Review of Digestion, Absorption, Metabolism, and Excretion
by Joseph Arballo, Jaume Amengual and John W. Erdman, Jr.
Antioxidants 2021, 10(3), 342; https://doi.org/10.3390/antiox10030342 - 25 Feb 2021
Cited by 62 | Viewed by 9304
Abstract
Lycopene is a non-provitamin A carotenoid that exhibits several health benefits. Epidemiological data support a correlation between lycopene intake and the attenuation of several chronic diseases, including certain types of cancers and cardiovascular diseases. It is currently unknown whether the beneficial effects are [...] Read more.
Lycopene is a non-provitamin A carotenoid that exhibits several health benefits. Epidemiological data support a correlation between lycopene intake and the attenuation of several chronic diseases, including certain types of cancers and cardiovascular diseases. It is currently unknown whether the beneficial effects are from the native structure of lycopene or its metabolic derivatives: lycopenals, lycopenols, and lycopenoic acids. This literature review focuses on the current research on lycopene digestion, absorption, metabolism, and excretion. This review primarily focuses on in vivo studies because of the labile nature and difficulty of studying carotenoids within in vitro experimental models. The studies presented address tissue accumulation of lycopene, the modification of bioavailability due to genetic and dietary factors, and lycopene cleavage by the enzymes ß-carotene oxygenase 1 (BCO1) and ß-carotene oxygenase 2 (BCO2). The current literature suggests that the majority of lycopene is cleaved eccentrically by BCO2, yet further research is needed to probe the enzymatic cleavage activity at the tissue level. Additionally, results indicate that single nucleotide polymorphisms and dietary fat influence lycopene absorption and thus modify its health effects. Further research exploring the metabolism of lycopene, the mechanisms related to its health benefits, and optimal diet composition to increase the bioavailability is required. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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26 pages, 394 KiB  
Review
Recent Progress in Discovering the Role of Carotenoids and Metabolites in Prostatic Physiology and Pathology—A Review—Part II: Carotenoids in the Human Studies
by Joanna Dulińska-Litewka, Przemysław Hałubiec, Agnieszka Łazarczyk, Oskar Szafrański, Yoav Sharoni, James A. McCubrey, Bartosz Gąsiorkiewicz and Torsten Bohn
Antioxidants 2021, 10(2), 319; https://doi.org/10.3390/antiox10020319 - 20 Feb 2021
Cited by 13 | Viewed by 3103
Abstract
Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention related to chronic diseases. One organ that has been especially targeted in many of these [...] Read more.
Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention related to chronic diseases. One organ that has been especially targeted in many of these studies and clinical trials is the human prostate. Without doubt, carotenoids (and their endogenous derivatives—retinoids and apo-carotenoids) are involved in a plethora of intra- and intercellular signaling, cell growth, and differentiation of prostate tissue. Due to the accumulation of new data on the role of different carotenoids, such as lycopene (LYC) and β-carotene (BC), in prostatic physiology and pathology, the present review aimed to cover the past ten years of research in this regard. Data from experimental studies are presented in the first part of the review, while epidemiological studies are disclosed in this second part. The objective of this compilation was to emphasize the present state of knowledge about the most potent molecular targets of carotenoids, as well as to propose promising carotenoid agents for the prevention and possible treatment of prostatic diseases. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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21 pages, 2996 KiB  
Review
A Mechanistic Review of β-Carotene, Lutein, and Zeaxanthin in Eye Health and Disease
by Fatima Tuj Johra, Asim Kumar Bepari, Anika Tabassum Bristy and Hasan Mahmud Reza
Antioxidants 2020, 9(11), 1046; https://doi.org/10.3390/antiox9111046 - 26 Oct 2020
Cited by 86 | Viewed by 20097
Abstract
Carotenoids are natural lipid-soluble antioxidants abundantly found as colorful pigments in fruits and vegetables. At least 600 carotenoids occur naturally, although about 20 of them, including β-carotene, α-carotene, lycopene, lutein, zeaxanthin, meso-zeaxanthin, and cryptoxanthin, are detectable in the human blood. They have distinct [...] Read more.
Carotenoids are natural lipid-soluble antioxidants abundantly found as colorful pigments in fruits and vegetables. At least 600 carotenoids occur naturally, although about 20 of them, including β-carotene, α-carotene, lycopene, lutein, zeaxanthin, meso-zeaxanthin, and cryptoxanthin, are detectable in the human blood. They have distinct physiological and pathophysiological functions ranging from fetal development to adult homeostasis. β-carotene is a precursor of vitamin A that essentially functions in many biological processes including vision. The human macula lutea and eye lens are rich in lutein, zeaxanthin, and meso-zeaxanthin, collectively known as macular xanthophylls, which help maintain eye health and prevent ophthalmic diseases. Ocular carotenoids absorb light from the visible region (400–500 nm wavelength), enabling them to protect the retina and lens from potential photochemical damage induced by light exposure. These natural antioxidants also aid in quenching free radicals produced by complex physiological reactions and, consequently, protect the eye from oxidative stress, apoptosis, mitochondrial dysfunction, and inflammation. This review discusses the protective mechanisms of macular xanthophylls in preventing eye diseases such as cataract, age-related macular degeneration, and diabetic retinopathy. Moreover, some preclinical animal studies and some clinical trials are discussed briefly to understand carotenoid safety and efficacy. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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17 pages, 1953 KiB  
Review
Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence
by Juhyun Shin, Min-Ho Song, Jae-Wook Oh, Young-Soo Keum and Ramesh Kumar Saini
Antioxidants 2020, 9(6), 532; https://doi.org/10.3390/antiox9060532 - 17 Jun 2020
Cited by 95 | Viewed by 11700
Abstract
Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the [...] Read more.
Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the pro-oxidant function of several common dietary carotenoids, including astaxanthin, β-carotene, fucoxanthin, and lycopene, has been investigated for their effective killing effects on various cancer cell lines. Besides, when carotenoids are delivered with ROS-inducing cytotoxic drugs (e.g., anthracyclines), they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants. These dynamic actions of carotenoids can optimize oxidative stress in normal cells while enhancing oxidative stress in cancer cells. This review discusses possible mechanisms of carotenoid-triggered ROS production in cancer cells, the activation of pro-apoptotic signaling by ROS, and apoptotic cell death. Moreover, synergistic actions of carotenoids with ROS-inducing anti-cancer drugs are discussed, and research gaps are suggested. Full article
(This article belongs to the Special Issue Carotenoids, Oxidative Stress and Disease)
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