zeaxanthin and Disease-Models--Animal

Diabetic retinopathy (DR) is one of the most important microvascular complications of diabetes and remains the leading cause of blindness in the working-age individuals. The exact aetiopathogenesis of DR remains elusive despite major advances in basic science and clinical research. Oxidative damage as one of the underlying causes for DR is increasingly being recognised. In humans, three hydroxycarotenoids, lutein (L), zeaxanthin (Z) and

Topics: Animals; Antioxidants; Diabetic Retinopathy; Dietary Supplements; Disease Models, Animal; Humans; Lutein; Macular Degeneration; Neuroprotective Agents; Reactive Oxygen Species; Zeaxanthins

Saffron (Crocus savitus) is a Middle-Eastern herb with strong antioxidant properties. Its major constituents, safranal, crocin, and crocetin, are also antioxidants and bear structural similarities to other well-known natural antixodant substances, such as zeaxanthin. Given the role of oxidative stress in many diseases, considerable interest has been shown into the potential role of saffron supplementation as a treatment for a range of diseases. In vitro and animal studies have provided evidence that saffron and its constituents may be potent therapies for a range of pathologies, including Alzheimer's disease, age-related macular degeneration (AMD) and cardiac ischemia. Whether these findings translate into clinical efficacy, however, has as of yet been incompletely assessed. This makes assessing the role of saffron supplementation in these diseases difficult. Here, we review the current human clinical evidence supporting saffron supplementation as a treatment for a range of pathologies and the underlying science supporting its use.

Topics: Affect; Animals; Antioxidants; Cardiovascular System; Carotenoids; Clinical Trials as Topic; Cognition; Crocus; Cyclohexenes; Disease Models, Animal; Humans; Oxidative Stress; Phytotherapy; Plant Preparations; Reproduction; Terpenes; Vision, Ocular; Vitamin A; Zeaxanthins

Premature infants at risk of retinopathy of prematurity (ROP) miss placental transfer of the carotenoids lutein (L) and zeaxanthin (Z) during the third trimester. We previously demonstrated that prenatal L and Z supplementation raised carotenoid levels in infants at birth in the Lutein and Zeaxanthin in Pregnancy (L-ZIP) study (NCT03750968). Based on their antioxidant effects and bioavailability, we hypothesized that prenatal maternal supplementation with macular carotenoids would reduce the risk of ROP. To test this hypothesis, we utilized "macular pigment mice" genetically engineered to take up L and Z into the retina in a model of oxygen-induced retinopathy (OIR).. Pregnant Bco2-/- mice were divided into nine experimental subgroups based on the type of supplementation (L, Z, or placebo) and on the maternal supplementation start date corresponding to the three trimesters of human fetal development (E0, E11, and P1). Pups and nursing mothers were exposed to 75% O2 for 5 days (P7-P12) and returned to room air for 5 days (P12-P17). Pups were killed at P12 and P17, and their retinas were analyzed for vaso-obliteration and intravitreal neovascularization.. Pups of pregnant mice supplemented with L or Z had significant reductions in areas of vaso-obliteration and intravitreal neovascularization compared to placebo. Prenatal carotenoid supplementation starting at E0 or E11 was significantly more protective against OIR than postnatal supplementation starting at P1.. Prenatal supplementation with L and Z was beneficial in a mouse OIR model. We recommend testing prenatal L and Z supplementation in future human clinical trials to prevent ROP.

Topics: Animals; Dietary Supplements; Dioxygenases; Disease Models, Animal; Female; Humans; Infant; Infant, Newborn; Lutein; Macular Pigment; Mice; Oxygen; Placenta; Pregnancy; Retinopathy of Prematurity; Zeaxanthins

Asthma is a heterogeneous and complex chronic airway disease with a high incidence rate, characterized by chronic airway inflammation. Although the anti-inflammatory effect of zeaxanthin has been demonstrated in various disease models, its explicit role in allergic asthma remains elusive.. An allergic asthma model was established by ovalbumin (OVA) stimulation in BALB/c nude mice. The pathological examination, collagen deposition and expression of α-smooth muscle actin (α-SMA) in lung tissues were determined by hematoxylin and eosin (H&E), MASSON and immunofluorescence staining, respectively. Besides, the effect of zeaxanthin on inflammation and oxidative stress was assessed by the enzyme-linked immunosorbent assay (ELISA) and spectrophotometry measure. Moreover, the underlying mechanism was analyzed by detecting the expression of phosphorylated p38 (p-p38), p38, β-catenin, p-c-Jun N-terminal kinase (p-JNK) and JNK with western blot assays.. The distinct infiltration of inflammatory cells was observed in the OVA-induced asthma mice model with significantly increased concentrations of immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13 and eotaxin (p˂0.001), which were prominently reversed by zeaxanthin treatment (p˂0.001). In addition, zeaxanthin treatment decreased the OVA-induced collagen deposition and α-SMA expression. A similar inhibitory effect of zeaxanthin on the oxidative stress was also observed in the OVA-induced asthma mice model, as evidenced by the prominent decrease of malondialdehyde (MDA) concentration and the remarkable increase of superoxide dismutase (SOD), glutathione S transferase (GST) and Glutathione (GSH) concentrations (p˂0.001). Moreover, zeaxanthin introduction markedly reduced the relative expressions of p-p38/p38, β-catenin and p-JNK/JNK in the OVA-induced asthma mice model (p˂0.001), indicating that zeaxanthin suppressed the p38 mitogen-activated protein kinase (p38 MAPK)/β-catenin signaling pathway in the OVA-induced asthma mice model.. Zeaxanthin attenuated OVA-induced allergic asthma in mice via modulating the p38 MAPK/β-catenin signaling pathway.

Topics: Animals; Asthma; beta Catenin; Disease Models, Animal; Inflammation; Mice; Mice, Inbred BALB C; Mice, Nude; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Zeaxanthins

The stimulation of fat thermogenesis and modulation of the gut microbiota are promising therapeutic strategies against obesity. Zeaxanthin (ZEA), a carotenoid plant pigment, has been shown to prevent various diseases; however, the therapeutic mechanism for obesity remains unclear. Herein, whether ZEA improves obesity by activating the β3-adrenergic receptor (β3-AR) to stimulate white adipose tissue (WAT) thermogenesis and modulating the gut microbiota was investigated. C57BL6/N mice were fed a high-fat diet (HFD) supplemented with ZEA for 22 weeks. ZEA treatment reduced body weight, fat weight, adipocyte hypertrophy, liver weight, and lipid deposition, and improved dyslipidaemia, serum GPT, GOT, leptin, and irisin levels, glucose intolerance, and insulin resistance in HFD-fed mice. Mechanistically, ZEA treatment induced the expression of β3-AR and thermogenic factors, such as PRDM16, PGC-1α, and UCP1, in inguinal WAT (iWAT) and brown adipose tissue. ZEA treatment stimulated iWAT thermogenesis through the synergistic cooperation of key organelles, which manifested as an increased expression of lipid droplet degradation factors (ATGL, CGI-58 and pHSL), mitochondrial biogenesis factors (

Topics: Adipose Tissue; Animals; Disease Models, Animal; Energy Metabolism; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Obesity; Receptors, Adrenergic; Signal Transduction; Thermogenesis; Zeaxanthins

Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are the major factors underlying photoreceptor degeneration. Lutein, RR-zeaxanthin (3R,3’R-zeaxanthin) and RS (meso)-zeaxanthin (3R,3’S-RS- zeaxanthin) (L/Zi) could protect against cell damage by ameliorating OS in retina. In this study, we examined the effect of L/Zi supplementation in a mouse model of photoreceptor degeneration and investigated whether the treatment of L/Zi ameliorated OS and ERS. BALB/cJ mice after light exposure were used as the animal model. The protective effects of L/Zi were observed by electroretinography (ERG) and terminal deoxyuridine triphosphate nick-end labeling (TUNEL) analysis. The underlying mechanisms related to OS and ERS were explored by Western blotting. After L/Zi treatment, the ERG amplitudes were significantly higher, and the number of TUNEL-positive cells was significantly reduced compared to that of the vehicle group. Western blotting results revealed that OS was ameliorated according to the significant downregulation of phosphorylated c-Jun N-terminal kinase (p-JNK), and significant upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, ERS was reduced according to the significant downregulation of 78 kDa glucose-regulated protein (GRP78), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF4) and activating transcription factor (ATF6). Our data shows that L/Zi provided functional and morphological preservation of photoreceptors against light damage, which is probably related to its mitigation of oxidative and endoplasmic reticulum stress.

Topics: Activating Transcription Factor 4; Activating Transcription Factor 6; Animals; Antioxidants; Apoptosis; Disease Models, Animal; eIF-2 Kinase; Electroretinography; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Heat-Shock Proteins; Isomerism; JNK Mitogen-Activated Protein Kinases; Light; Lutein; Male; Mice, Inbred BALB C; NF-E2-Related Factor 2; Oxidative Stress; Phosphorylation; Photoreceptor Cells, Vertebrate; Retinal Diseases; Signal Transduction; Zeaxanthins

Oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD). The dry form of AMD (geographic atrophy) is characterized by loss of RPE, photoreceptors, and macular pigments. The cumulative effects of oxidative stress impact mitochondrial function in RPE. In Sod2flox/floxVMD2-cre mice, the RPE specific deletion of Sod2, the gene for mitochondrial manganese superoxide dismutase (MnSOD), leads to elevated oxidative stress in retina and RPE, and causes changes in the RPE and underlying Bruch's membrane that share some features of AMD. This study tested the hypothesis that zeaxanthin supplementation would reduce oxidative stress and preserve RPE structure and function in these mice. Zeaxanthin in retina/RPE/choroid and liver was quantified by LC/MS, retinal function and structure were evaluated by electroretinogram (ERG) and spectral domain optical coherence tomography (SD-OCT), and antioxidant gene expression was measured by RT-PCR. After one month of supplementation, zeaxanthin levels were 5-fold higher in the retina/RPE/choroid and 12-fold higher in liver than in unsupplemented control mice. After four months of supplementation, amplitudes of the ERG a-wave (function of rod photoreceptors) and b-wave (function of the inner retina) were not different in supplemented and control mice. In contrast, the c-wave amplitude (a measure of RPE function) was 28% higher in supplemented mice than in control mice. Higher RPE/choroid expression of antioxidant genes (Cat, Gstm1, Hmox1, Nqo1) and scaffolding protein Sqstm1 were found in supplemented mice than in unsupplemented controls. Reduced nitrotyrosine content in the RPE/choroid was demonstrated by ELISA. Preliminary assessment of retinal ultrastructure indicated that supplementation supported better preservation of RPE structure with more compact basal infoldings and intact mitochondria. We conclude that daily zeaxanthin supplementation protected RPE cells from mitochondrial oxidative stress associated with deficiency in the MnSOD and thereby improved RPE function early in the disease course.

Topics: Animals; Antioxidants; Atrophy; Dietary Supplements; Disease Models, Animal; Macular Degeneration; Male; Mice; Mice, Transgenic; Mitochondria; Oxidative Stress; Retina; Retinal Pigment Epithelium; Superoxide Dismutase; Zeaxanthins

Lutein, RR-zeaxanthin, and RS-zeaxanthin (L-Z) are antioxidants which can reduce endoplasmic reticulum stress (ERS) and oxidative stress (OS), and ameliorate neurodegenerative diseases. However, their treatment effect in the. L-Z (Lutemax 2020, 10 mg/kg) diluted in sunflower oil (SFO, 1 mg/ml) or the same volume of SFO was administrated via gavage from postnatal day 6 (P6) to P20 daily in L-Z group (n=5) or SFO group (n=6) of. The ERG amplitudes were larger in the L-Z group than those of the SFO group in all flash luminances of dark-adapted and light-adapted ERG (all. L-Z provide protection to the photoreceptors of

Topics: Animals; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Eye Proteins; Female; Lutein; Male; Mice; Photoreceptor Cells, Vertebrate; Retinitis Pigmentosa; Stereoisomerism; Zeaxanthins

Several studies associated high-fat intakes with a high incidence of age-related macular degeneration (AMD). Lutein and Zeaxanthin isomers (L/Zi) may counteract reactive oxygen species produced by oxidative stress. The present study was conducted to determine the possible effects of L/Zi administration on lipid profile, protein genes associated with oxidative stress and inflammation pathways in the obesity induced by a high-fat diet (HFD) in rodents.. Twenty-eight male Wistar rats were allocated into four groups as follows: (i) Control, (ii) Control + L/Zi, (iii) High Fat Diet (HFD), and (iv) HFD+ L/Z. L/Zi was administrated for 8 weeks at a daily dose of 100 mg/kg BW.. L/Zi administration significantly reduced insulin and free fatty acid (FFA) levels (P < 0.001) and ameliorated the oxidative damage by reducing malondialdehyde (MDA) concentration and increasing antioxidant enzymes activities of retina induced by HFD. In addition, supplementation decreased the levels of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM) (P < 0.001, respectively) and improved nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) gene proteins in retinal tissues (P < 0.001).. Rats fed with HFD exhibited increased oxidative stress and upregulation of inflammatory indicators. However, L/Zi supplementation modulates genes involved oxidative stress and inflammation including NF-κB and Nrf2 signaling pathways in the retina which may contribute to ameliorating retinal damage induced by HFD.

Topics: Animals; Blotting, Western; Diet, High-Fat; Disease Models, Animal; Lipid Metabolism; Lutein; Male; Obesity; Oxidative Stress; Rats; Rats, Wistar; Retina; Zeaxanthins

We quantified fundus autofluorescence (FAF) in the nonhuman primate retina as a function of age and diets lacking lutein and zeaxanthin (L/Z) and omega-3 fatty acids.. Quantitative FAF was measured in a cross-sectional study of rhesus macaques fed a standard diet across the lifespan, and in aged rhesus macaques fed lifelong diets lacking L/Z and providing either adequate or deficient levels of omega-3 fatty acids. Macular FAF images were segmented into multiple regions of interest, and mean gray values for each region were calculated using ImageJ. The resulting FAF values were compared across ages within the standard diet animals, and among diet groups and regions.. Fundus autofluorescence increased with age in the standard diet animals, and was highest in the perifovea. Monkeys fed L/Z-free diets with either adequate or deficient omega-3 fatty acids had significantly higher FAF overall than age-matched standard diet monkeys. Examined by region, those with adequate omega-3 fatty acids had higher FAF in the fovea and superior regions, while monkeys fed the diet lacking L/Z and omega-3 fatty acids had higher FAF in all regions.. Diets devoid of L/Z resulted in increased retinal autofluorescence, with the highest values in animals also lacking omega-3 fatty acids. The increase was equivalent to a 12- to 20-year acceleration in lipofuscin accumulation compared to animals fed a standard diet. Together these data add support for the role of these nutrients as important factors in lipofuscin accumulation, retinal aging, and progression of macular disease.

Topics: Aging; Animals; Cross-Sectional Studies; Dietary Supplements; Disease Models, Animal; Fatty Acids, Omega-3; Fluorescein Angiography; Fovea Centralis; Fundus Oculi; Lutein; Macaca mulatta; Retinal Diseases; Zeaxanthins

Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals.

Topics: Animals; beta Carotene; Carotenoids; Cholesterol; Diet; Disease Models, Animal; Energy Metabolism; Humans; Lipid Metabolism; Lipids; Lipolysis; Liver; Lutein; Metabolism; Mice; Transcriptome; Triglycerides; Zeaxanthins

Blue-light photooxidative damage has been implicated in the etiology of age-related macular degeneration (AMD). The macular pigment xanthophylls lutein (L) and zeaxanthin (Z) and n-3 fatty acids may reduce this damage and lower the risk of AMD. This study investigated the effects of the lifelong absence of xanthophylls followed by L or Z supplementation, combined with the effects of n-3 fatty acid deficiency, on acute blue-light photochemical damage.. Subjects included eight rhesus monkeys with no lifelong intake of xanthophylls and no detectable macular pigment. Of these, four had low n-3 fatty acid intake and four had adequate intakes. Control subjects had typical L, Z, and n-3 fatty acid intake. Retinas received 150-μm-diameter exposures of low-power 476-nm laser light at 0.5 mm (∼2°) eccentricity, which is adjacent to the macular pigment peak, and parafoveally at 1.5 mm (∼6°). Exposures of xanthophyll-free animals were repeated after supplementation with pure L or Z for 22 to 28 weeks. Ophthalmoscopically visible lesion areas were plotted as a function of exposure energy, with greater slopes of the regression lines indicating greater sensitivity to damage.. In control animals, the fovea was less sensitive to blue-light-induced damage than the parafovea. Foveal protection was absent in xanthophyll-free animals but was evident after supplementation. In the parafovea, animals low in n-3 fatty acids showed greater sensitivity to damage than animals with adequate levels.. After long-term xanthophyll deficiency, L or Z supplementation protected the fovea from blue light-induced damage, whereas adequate n-3 fatty acid levels reduced the damage in the parafovea.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Dietary Supplements; Disease Models, Animal; Fatty Acids, Omega-3; Fovea Centralis; Light; Lutein; Macaca mulatta; Macular Degeneration; Oxidative Stress; Radiation-Protective Agents; Xanthophylls; Zeaxanthins

Fat infiltration and inflammation cause liver injury and fibrosis and may progress to nonalcoholic steatohepatitis (NASH) and end-stage liver disease. Currently, there are no effective treatments for NASH. Zeaxanthin is a carotenoid which has been shown to be preferentially accumulated in the adipose tissue and liver. We hypothesized that treatment with zeaxanthin may decrease oxidative stress in the liver and, possibly, halt the inflammation and fibrosis associated with NASH. Here we tested zeaxanthin effects in preventing progression of liver injury in a model of NASH. Mongolian gerbils, fed a methionine-choline-deficient diet, were treated with different doses of zeaxanthin. We assessed histopathological changes by hematoxylin-eosin and Masson trichrome staining and determined oxidative stress by measuring lipid peroxidation. The obtained results show that zeaxanthin significantly prevented NASH progression by decreasing oxidative stress and liver fibrosis, thus suggesting a potential therapeutic application for this carotenoid in the management of NASH.

Topics: Animals; Disease Models, Animal; Disease Progression; Gerbillinae; Hepatitis; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; Oxidative Stress; Xanthophylls; Zeaxanthins

Light-absorbing and antiradical properties of the new product on a basis of lutein and zeaxanthin for correction of eye diseases in model system of initiated oxidation of isopropylbenzene were investigated. It is shown, that the product is the effective light-absorbing agent and inhibitor of free-radical oxidation in vitro. In experiments on animals (rat) the pharmacokinetics of the product was investigated at single oral administration. A simple, specific and sensitive RP-HPLC method for the determination of lutein in rat plasma was developed, which was applied to pharmacokinetic investigation in rats after oral administration of lutein at dose 20 mg/kg. It was established, that the peak plasma levels was achieved to 2 hour and the mean elimination half life was 2,4 hours.

Topics: Administration, Oral; Animals; Antioxidants; Chromatography, High Pressure Liquid; Disease Models, Animal; Eye Diseases; Free Radicals; Lutein; Oxidation-Reduction; Rats; Rats, Wistar; Spectrophotometry; Xanthophylls; Zeaxanthins

Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with beta-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as alpha-carotene, showed higher potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, beta-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; beta Carotene; Carotenoids; Colonic Neoplasms; Cryptoxanthins; Disease Models, Animal; Fruit; Humans; Lutein; Lycopene; Methylnitrosourea; Mice; Rats; Rats, Inbred F344; Skin Neoplasms; Tetradecanoylphorbol Acetate; Vegetables; Xanthophylls; Zeaxanthins