Chronic Ingestion of (3R,3′R,6′R)-Lutein and (3R,3′R)-Zeaxanthin in the Female Rhesus Macaque

Khachik, Frederick; London, Edra; Moura, Fabiana F. De; Johnson, Mary Ann; Steidl, Scott M.; DeTolla, Louis J.; Shipley, Steven T.; Sanchez, Rigoberto; Chen, Xue Qing; Flaws, Jodi A.; Lutty, Gerard A.; McLeod, Scott; Fowler, Bruce A.

doi:10.1167/iovs.06-0194

Cited by 25 publications

(25 citation statements)

References 34 publications

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“…To date, more than 700 carotenoids have been identified in nature of which mainly 6 carotenoids are detected at a high level in human plasma, including ␤-carotene, ␣-carotene, lutein, lycopene, ␤-cryptoxanthin and zeaxanthin (Al-Delaimy et al, 2005). The plasma carotenoid level is associated with less likely risks of cardiovascular diseases, cancers and age related diseases (Khachik et al, 2006;Pouchieu et al, 2014). Recently, some epidemiological studies have shown that the ␤-cryptoxanthin is one of the most important carotenoids in human plasma; dietary intake of ␤-cryptoxanthin from citrus fruits can reduce the risks of certain diseases, especially cancers, diabetes and rheumatism because of its antioxidative activity (Cerhan et al, 2003;Yamaguchi et al, 2006;Sugiura et al, 2011;Takayanagi et al, 2011;Yamaguchi, 2012;Iskandar et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Effect of blue LED light intensity on carotenoid accumulation in citrus juice sacs

Zhang

Yamawaki

et al. 2015

Journal of Plant Physiology

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In the present study, the effects of blue LED light intensity on carotenoid accumulation and expression of genes related to carotenoid biosynthesis were investigated in the juice sacs of Satsuma mandarin (Citrus unshiu Marc.) and Valencia orange (Citrus sinensis Osbeck) in vitro. The results showed that 100 μmol m(-2)s(-1) blue LED light (100B) was effective for increasing carotenoid content, especially β-cryptoxanthin, in Satsuma mandarin after cultured in vitro for four weeks. In Valencia orange, in contrast, 50 μmol m(-2)s(-1) blue LED light (50B) treatment was effective for inducing carotenoid accumulation through increasing the contents of two major carotenoids, all-trans-violaxanthin and 9-cis-violaxanthin. In addition, gene expression results showed that the simultaneous increases in the expression of genes (CitPSY, CitPDS, CitZDS, CitLCYb2, and CitHYb) involved in producing β,β-xanthophylls were well consistent with the accumulation of β-cryptoxanthin in Satsuma mandarin under 100B, and violaxanthin in Valencia orange under 50B. The results presented herein contribute to further elucidating the regulatory mechanism of carotenoid accumulation by blue LED light.

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Section: Introductionmentioning

confidence: 99%

Effect of blue LED light intensity on carotenoid accumulation in citrus juice sacs

Zhang

Yamawaki

et al. 2015

Journal of Plant Physiology

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“…Previously, we and others have reported the presence of several non-dietary metabolites such as (3R,3′S-meso)-zeaxanthin, (3R,3′S,6′R)-lutein (3′-epilutein), 3-hydroxy-β,ε-carotene-3′-one (3′-oxolutein), and 3-methoxyzeaxanthin (3-MZ) in the human cadaver retina using HPLC and spectroscopic detection methods (10)(11)(12)(13)(14)(15), but understanding the biochemical mechanisms of these biotransformations generally requires living animal models. Several living monkey studies have been reported recently, but primate studies are expensive and cumbersome to carry out, so an appropriate non-primate small animal model could also have great utility (16)(17)(18).…”

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confidence: 99%

Identification and Metabolic Transformations of Carotenoids in Ocular Tissues of the Japanese Quail Coturnix japonica

et al. 2007

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As in humans and monkeys, lutein [(3R,3′R,6′R)-βε, -carotene-3,3′-diol] and zeaxanthin [a mixture of (3R,3′R)-β,β-carotene-3,3′diol and (3R,3′S-meso)-β,β-carotene-3,3′-diol] are found in substantial amounts in the retina of the Japanese quail Coturnix japonica. This makes the quail retina an excellent non-primate small animal model for studying the metabolic transformations of these important macular carotenoids that are thought to play an integral role in protection against light-induced oxidative damage such as that found in age-related macular degeneration (AMD). In this study, we first identified the array of carotenoids present in the quail retina using C30-HPLC coupled with inline mass-spectral and photodiode-array detectors. In addition to dietary lutein (2.1%) and zeaxanthin (11.8%), we identified adonirubin (5.4%), 3′-oxolutein (3.8%), meso-zeaxanthin (3.0%), astaxanthin (28.2%), galloxanthin (12.2%), ε,ε-carotene (18.5%), and β-apo-2′-carotenol (9.5%) as major ocular carotenoids. We next used deuterium-labeled lutein and zeaxanthin as dietary supplements to study the pharmacokinetics and metabolic transformations of these two ocular pigments in serum and ocular tissues. We then detected and quantitated labeled carotenoids in ocular tissue using both HPLC-coupled mass spectrometry and non-invasive resonance Raman spectroscopy. Results indicated that dietary zeaxanthin is the precursor of 3′-oxolutein, β-apo-2′-carotenol, adonirubin, astaxanthin, galloxanthin, and ε, ε-carotene, whereas dietary lutein is the precursor for mesozeaxanthin. Studies also revealed that the pharmacokinetic patterns of uptake, carotenoid absorption, and transport from serum into ocular tissues were similar to results observed in most human clinical studies. KeywordsCarotenoid; Retina; Japanese quail; Lutein; Zeaxanthin; HPLC; APCI-MS Epidemiological and clinical studies in humans have generally demonstrated that there is an inverse relationship between nutritional consumption of antioxidants and prevalence of old age ocular disorders such as age-related macular degeneration (AMD) and cataract (1,2). The carotenoids lutein and zeaxanthin are notable examples because they are specifically concentrated in ocular tissues at high concentrations, and they are excellent absorbers of phototoxic blue light and reactive oxygen species (3,4). Studies using data from the Eye Disease Case Control (EDCC) Study Group have demonstrated that individuals with high blood levels of lutein and zeaxanthin and high consumption of foods rich in these same carotenoids had significantly lower risk of exudative AMD, and several follow up studies including the Age- † This work was supported by National Institute of Health Grant EY-11600 and by Research to Prevent Blindness, Inc. (New York, NY). In the human retina, dietary lutein [(3R,3′R,6′R)-β,ε-carotene-3,3′-diol] and zeaxanthin [(3R, 3′R)-β,β-carotene-3,3′-diol] are unevenly distributed in the retina, with millimolar concentrations found at the fovea with a lutein:zeaxanthin ratio of 1:2 and a...

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“…A recent study revealed that upon giving bcarotene to a healthy person, b-apo-8¢-carotenal increases in plasma (Ho et al, 2007). In addition, carotenoid supplementation gives rise to increased carotenoid metabolites in serum, plasma of human and monkey (Khachik et al, 2006a(Khachik et al, , 2006b, although a correlation of the increase in CDA levels and carotenoid supplementation is not fully revealed. There were abundant…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that carotenoids might undergo oxidation and form carotenoid-derived aldehydes (CDA), which would be toxic to tissues (Hurst et al, 2005;Molnar et al, 2005;Tanito et al, 2005;Kalariya et al, 2008). It was also reported that carotenoid supplementation in humans and monkeys significantly increases levels of their metabolites in serum and eye tissues (Khachik et al, 2006a(Khachik et al, , 2006b). Since carotenoids form highly reactive aldehydes, it is likely that the excessive use of carotenoids could result in increased carotenoid aldehyde generation in the human body (Kalariya et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Complement activation by carotenoid derived aldehydes in cultured human vein epithelial cells

Lin

Kang

et al. 2009

Phytotherapy Research

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This study was designed to determine the complement activation effects of carotenoid-derived aldehydes (CDA) on cultured human umbilical vein endothelial cells (HUVEC). A dose-dependent complement activation upon incubation of HUVEC with CDA was observed. Interestingly, the data showed that the alternative pathway was not activated. In addition, upon CDA treatment a significant number of apoptotic cells was also observed. The results revealed that CDA could activate the complement by way of the classical pathway. The study suggests that high carotenoid supplementation for the treatment of coronary heart disease should be used cautiously.

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Chronic Ingestion of (3R,3′R,6′R)-Lutein and (3R,3′R)-Zeaxanthin in the Female Rhesus Macaque

Abstract: The mean levels of L and Z in plasma and ocular tissues of the rhesus monkeys increase with supplementation and in most cases correlate with the levels of their metabolites. Supplementation of monkeys with L or Z at high doses, or their combination does not cause ocular toxicity.

Cited by 25 publications

References 34 publications

Effect of blue LED light intensity on carotenoid accumulation in citrus juice sacs

Effect of blue LED light intensity on carotenoid accumulation in citrus juice sacs

Identification and Metabolic Transformations of Carotenoids in Ocular Tissues of the Japanese Quail Coturnix japonica

Complement activation by carotenoid derived aldehydes in cultured human vein epithelial cells

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