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Astaxanthin stimulates cell-mediated and humoral immune responses in cats
Abstract
Astaxanthin is a potent antioxidant carotenoid and may play a role in modulating immune response in cats. Blood was taken from female domestic shorthair cats (8-9 mo old; 3.2 ± 0.04 kg body weight) fed 0, 1, 5 or 10mg astaxanthin daily for 12 wk to assess peripheral blood mononuclear cell (PBMC) proliferation response, leukocyte subpopulations, natural killer (NK) cell cytotoxic activity, and plasma IgG and IgM concentration. Cutaneous delayed-type hypersensitivity (DTH) response against concanavalin A and an attenuated polyvalent vaccine was assessed on wk 8 (prior to vaccination) and 12 (post-vaccination). There was a dose-related increase in plasma astaxanthin concentrations, with maximum concentrations observed on wk 12. Dietary astaxanthin enhanced DTH response to both the specific (vaccine) and nonspecific (concanavalin A) antigens. In addition, cats fed astaxanthin had heightened PBMC proliferation and NK cell cytotoxic activity. The population of CD3(+) total T and CD4(+) T helper cells were also higher in astaxanthin-fed cats; however, no treatment difference was found with the CD8(+) T cytotoxic and MHC II(+) activated lymphocyte cell populations. Dietary astaxanthin increased concentrations of plasma IgG and IgM. Therefore, dietary astaxanthin heightened cell-mediated and humoral immune responses in cats.
... This chapter does not claim to be exhaustive, but its objective is to present the best-studied activities and their probable mechanisms of action. Biological activities described in this chapter and demonstrated by in vitro and in vivo studies are summarized in Table 1 while some clinical studies are presented in Table 2. [49,50,57,58] anti-inflammatory activity mouse, human cells [59][60][61][62][63][64] mouse, rat [61,62,[65][66][67] preventive effects on cardiovascular disease mouse, human cells [60,68] mouse, rat, rabbit [50,[69][70][71][72][73][74] prevention effects on diabetes rat, pig cells [75,76] mouse, rat [77][78][79][80][81][82][83] protective effects on liver rat, human cells [53,[84][85][86] mouse, rat [71,[87][88][89] immuno-modulating effects mouse cells [90] mouse, dog, cat [90][91][92][93] Anti-cancer activity mouse, rat, human cells [94][95][96][97] ...
... The immune system is a vital defense against tumors, cancerous growth, and infectious diseases. Immune cells are particularly sensitive to oxidative stress due to a high percentage of PUFA in their plasma membranes and their ability to produce oxidative products [91]. Astaxanthin harbored a potential value as a therapeutic or preventing agent for the management of immune diseases because astaxanthin significantly influenced the immune function in several in vitro and in vivo assays. ...
... Dietary astaxanthin also heightened cell-mediated and humoral immune responses in dogs [93] and cats [91]. In dogs, it was shown that dietary astaxanthin enhanced cutaneous delayed-type hypersensitivity (DTH) response to intradermal challenge with a vaccine, as well as Con A-induced lymphocyte proliferation and natural killer (NK) cell cytotoxic activity in a dose-dependent manner. ...
Astaxanthin shows many biological activities. It has acquired a high economic potential and its current market is dominated by its synthetic form. However, due to the increase of the health and environmental concerns from consumers, natural forms are now preferred for human consumption. Haematococcus pluvialis is artificially cultured at an industrial scale to produce astaxanthin used as a dietary supplement. However, due to the high cost of its cultivation and its relatively low biomass and pigment productivities, the astaxanthin extracted from this microalga remains expensive and this has probably the consequence of slowing down its economic development in the lower added-value market such as food ingredient. In this review, we first aim to provide an overview of the chemical and biochemical properties of astaxanthin, as well as of its natural sources. We discuss its bioavailability, metabolism, and biological activities. We present a state-of-the-art of the biology and physiology of H. pluvialis, and highlight novel insights into the biotechnological processes which allow optimizing the biomass and astaxanthin productivities. We are trying to identify some lines of research that would improve the industrial sustainability and economic viability of this bio-production and to broaden the commercial potential of astaxanthin produced from H. pluvialis.
... This chapter does not claim to be exhaustive, but its objective is to present the best-studied activities and their probable mechanisms of action. Biological activities described in this chapter and demonstrated by in vitro and in vivo studies are summarized in Table 1 while some clinical studies are presented in Table 2. [49,50,57,58] anti-inflammatory activity mouse, human cells [59][60][61][62][63][64] mouse, rat [61,62,[65][66][67] preventive effects on cardiovascular disease mouse, human cells [60,68] mouse, rat, rabbit [50,[69][70][71][72][73][74] prevention effects on diabetes rat, pig cells [75,76] mouse, rat [77][78][79][80][81][82][83] protective effects on liver rat, human cells [53,[84][85][86] mouse, rat [71,[87][88][89] immuno-modulating effects mouse cells [90] mouse, dog, cat [90][91][92][93] Anti-cancer activity mouse, rat, human cells [94][95][96][97] ...
... The immune system is a vital defense against tumors, cancerous growth, and infectious diseases. Immune cells are particularly sensitive to oxidative stress due to a high percentage of PUFA in their plasma membranes and their ability to produce oxidative products [91]. Astaxanthin harbored a potential value as a therapeutic or preventing agent for the management of immune diseases because astaxanthin significantly influenced the immune function in several in vitro and in vivo assays. ...
... Dietary astaxanthin also heightened cell-mediated and humoral immune responses in dogs [93] and cats [91]. In dogs, it was shown that dietary astaxanthin enhanced cutaneous delayed-type hypersensitivity (DTH) response to intradermal challenge with a vaccine, as well as Con A-induced lymphocyte proliferation and natural killer (NK) cell cytotoxic activity in a dose-dependent manner. ...
Astaxanthin shows many biological activities. It has acquired a high economic potential and its current market is dominated by its synthetic form. However, due to the increase of the health and environmental concerns from consumers, natural forms are now preferred for human consumption. Haematococcus pluvialis is artificially cultured at an industrial scale to produce astaxanthin used as a dietary supplement. However, due to the high cost of its cultivation and its relatively low biomass and pigment productivities, the astaxanthin extracted from this microalga remains expensive and this has probably the consequence of slowing down its economic development in the lower added-value market such as food ingredient. In this review, we first aim to provide an overview of the chemical and biochemical properties of astaxanthin, as well as of its natural sources. We discuss its bioavailability, metabolism, and biological activities. We present a state-of-the-art of the biology and physiology of H. pluvialis, and highlight novel insights into the biotechnological processes which allow optimizing the biomass and astaxanthin productivities. We are trying to identify some lines of research that would improve the industrial sustainability and economic viability of this bio-production and to broaden the commercial potential of astaxanthin produced from H. pluvialis.
... Single, oral doses of pure ß-carotene, astaxanthin or lycopene dose-dependently raised the corresponding plasma carotenoid levels in dogs and cats, with peaking times of about 6 or more than 12 hours (16)(17)(18)(19)(20). After daily intake for more than a week, the carotenoids in plasma, including lutein, approached a dose-dependent, steady state concentration (16)(17)(18)(19)(21)(22)(23)(24)(25)(26)(27)(28). Simultaneously, increased carotenoid levels in blood cells and tissues were observed (16-19, 25, 26). ...
... In cats, the feeding of diets with increasing lutein concentrations stimulated lymphocyte proliferation, but the dose-effect relationship was erratic (21). In dogs and cats, ingestion of purified astaxanthin increased both plasma IgG and lymphocyte proliferation, but with atypical dose responses (23,24). ...
... Oral astaxanthin increased DTH in dogs after injection of the vaccine, but not after phytohemagglutinin (24). In cats given astaxanthin at levels of about 15, 80 and 165 mg/kg dry, only the highest dose increased vaccine-induced DTH (23). ...
Carotenoids in petfood Carotenoids pertain to pigments synthesized by plants. They participate in capturing sunlight energy and furnish the variety of yellow to red colors in fruits and vegetables. Highlighted carotenoids in petfood are mostly linked with immunity support and high antioxidant value. The four health carotenoids concern beta-carotene, lycopene, lutein and astaxanthin. Prototypical ingredients, rather than concentrated additives, serve as carotenoid carriers. Beta-carotene is named after carrots and provides their yellowish-orange color. The intestinal wall of dogs takes up beta-carotene and can convert it into vitamin A. In contrast, cats require preformed vitamin A as they cannot synthesize it. "Carrots as natural source of beta-carotene" is a phrase used in some petfood promotional texts. Immune-health claims for dietary beta-carotene are not substantiated by published research in dogs and cats. Lycopene is responsible for the red color in tomatoes, lutein is so for the yellow-colored marigold flowers and astaxanthin for the red of krill shells and specific microalgae. Those natural sources function as carotenoid delivery vehicles in petfood. After feeding purified forms of lutein and astaxanthin to dogs and cats, indicators of the animals' immune responses were measured. The results do not provide solid evidence that lutein and astaxanthin enhance immunity. Data on lycopene are lacking. Antioxidants may neutralize unstable, reactive molecules (free radicals) and prevent them from doing damage to various chemical, bodily structures. There is no proof that the four carotenoids have antioxidant activity within the canine and feline body. And furthermore, it has not been demonstrated that added carotenoids in complete petfood improve immune and visible health of dogs and cats. Carotenoid structures Plant carotenoids are located in chloro-and chromoplasts. They give colors to non-green (parts of) plants, while being masked by the presence of green chlorophyll. Lycopene and ß-carotene are ranked among the carotenes. Lutein and astaxanthin belong to the oxycarotenoids/xanthophylls. All-trans lycopene (C 40 H 56) is a linear tetraterpene assembled from 8 isoprene units. ß-Carotene is formed by enzymatic conversion of lycopene's ends into six-carbon rings. Lutein results from end cyclization of lycopene and hydroxylation of each ring. Astaxanthin's rings have both a keto and hydroxyl group. Carotenoid carriers Carotenoid contents in plant materials are highly variable as they depend on many factors, including cultivar, growing conditions, harvest time and ripening stage. For the carotenoid carriers in petfood, the average amounts per kg dry matter are as follows: 0.7 g ß-carotene in carrots (1-3, Note 1), 2.0 g
... Common carp, Cyprinus carpio, treated with 50 and 100 mg kg −1 of AX supplemental diet against pathogens showed a considerable increase in serum phagocytic, respiratory burst, lysozyme, and bactericidal activities that led to a decrease in the proportion of death during the first 30 days after Aeromonas hydrophila infection (Ju et al. 2011). Many previous reports reported that AX directly or indirectly confers antioxidant activity and enhances innate, cell-mediated, and humoral immune responses (Jyonouchi et al. 2000;Kurihara et al. 2002;Park et al. 2011). The impacts of AX on innate immunity may be correlated to its ability to trigger further antimicrobial effects processes, such as lysosomal enzyme release, complementary elements, cationic peptides, and the synthesis of oxygen reactive species (Chew et al. 2011;Smith et al. 2013). ...
... Many previous reports reported that AX directly or indirectly confers antioxidant activity and enhances innate, cell-mediated, and humoral immune responses (Jyonouchi et al. 2000;Kurihara et al. 2002;Park et al. 2011). The impacts of AX on innate immunity may be correlated to its ability to trigger further antimicrobial effects processes, such as lysosomal enzyme release, complementary elements, cationic peptides, and the synthesis of oxygen reactive species (Chew et al. 2011;Smith et al. 2013). ...
Astaxanthin is the main natural C40 carotenoid used worldwide in the aquaculture industry. It normally occurs in red yeast Phaffia rhodozyma and green alga Haematococcus pluvialis and a variety of aquatic sea creatures, such as trout, salmon, and shrimp. Numerous biological functions reported its antioxidant and anti-inflammatory activities since astaxanthin possesses the highest oxygen radical absorbance capacity (ORAC) and is considered to be over 500 more times effective than vitamin E and other carotenoids such as lutein and lycopene. Thus, synthetic and natural sources of astaxanthin have a commanding influence on industry trends, causing a wave in the world nutraceutical market of the encapsulated product. In vitro and in vivo studies have associated astaxanthin’s unique molecular features with various health benefits, including immunomodulatory, photoprotective, and antioxidant properties, providing its chemotherapeutic potential for improving stress tolerance, disease resistance, growth performance, survival, and improved egg quality in farmed fish and crustaceans without exhibiting any cytotoxic effects. Moreover, the most evident effect is the pigmentation merit, where astaxanthin is supplemented in formulated diets to ameliorate the variegation of aquatic species and eventually product quality. Hence, carotenoid astaxanthin could be used as a curative supplement for farmed fish, since it is regarded as an ecologically friendly functional feed additive in the aquaculture industry. In this review, the currently available scientific literature regarding the most significant benefits of astaxanthin is discussed, with a particular focus on potential mechanisms of action responsible for its biological activities.
... In a study by Park et al. (2011), 12-week treatment program is established using 1, 5 and 10 mg/kg astaxanthin daily, and peripheral blood mononuclear cell proliferation response was investigated after astaxanthin treatment. The study concluded that helper T cell proliferation increases significantly in all treatment groups [152]. ...
... In a study by Park et al. (2011), 12-week treatment program is established using 1, 5 and 10 mg/kg astaxanthin daily, and peripheral blood mononuclear cell proliferation response was investigated after astaxanthin treatment. The study concluded that helper T cell proliferation increases significantly in all treatment groups [152]. Also, ß-carotene treatment at 30 mg twice daily for 4 weeks caused to an increase in CD4+ cells and increased immune response in HIV infections [153]. ...
Vitamin A is the first defined vitamin and is also known as an anti-inflammatory micronutrient. Although the primary biological function is the preservation of epithelial tissue integrity, vision, and growth, vitamin A also plays a role in immune system regulation. It is known that susceptibility to infections increases in developing countries due to vitamin A deficiency. Therefore, the purpose of this review is to evaluate the role of vitamin A on the immune system in line with current studies. In this review, we focused on the immunobiological effects of vitamin A and its precursors. Vitamin A refers to retinoids and carotenoids, but both function in the body through the most active form, all trans retinoic acid. All trans retinoic acid has the highest affinity of nuclear retinoic acid receptor. Reports from in-vivo and in-vitro studies shown that the formation of retinoic acid/retinoic acid receptor complex is important in the generation of innate and adaptive immune cell response. In addition to immune cell response, vitamin A also plays an important role in mucus secretion, morphological formation and functional maturation of epithelial cells. In this way, vitamin A appears to contribute to immune development by regulating immune cell response and providing mechanistic defense. Vitamin A has received particular attention in recent years as the vitamin have been shown to have a crucial effect on the immune response. Although more randomized controlled studies are needed, data from observational human studies have shown that vitamin A is associated with infectious, inflammatory, allergic diseases, and cancers.
... Astaxanthin is often referred as a "super-antioxidant" molecule, because of its capacity to reduce free radicals and oxidative stress: 65 times greater than vitamin C, 54 times more than β-carotene, and 100 times more than α-tocopherol [22]. Additionally, the molecule also presents immunomodulating activity [23][24][25]. ...
... Molecules 2022, 27, x FOR PEER REVIEW 3 of 1 unicellular freshwater microalga found in temperate regions around the world and con sidered to be the main source of astaxanthin (3,3′-dihydroxy-β-carotene-4,4′-dione) [21 Astaxanthin is often referred as a "super-antioxidant" molecule, because of its capacity t reduce free radicals and oxidative stress: 65 times greater than vitamin C, 54 times mor than β-carotene, and 100 times more than α-tocopherol [22]. Additionally, the molecul also presents immunomodulating activity [23][24][25]. Miodesin TM has previously been shown to exert anti-inflammatory effects in reducin pelvic pain in patients with endometriosis and leiomyoma, supporting the role of natu rally occurring anti-inflammatory medications in the treatment of this disease [12,26,27 However, the underlying mechanisms involved in such beneficial effects remains unex plored. ...
Endometriosis presents high prevalence and its physiopathology involves hyperactivation of endometrial and vaginal cells, especially by bacteria. The disease has no cure and therapies aiming to inhibit its development are highly desirable. Therefore, this study investigated whether MiodesinTM (10 µg/mL = IC80; 200 µg/mL = IC50), a natural compound constituted by Uncaria tomentosa, Endopleura uchi, and astaxanthin, could exert anti-inflammatory and anti-proliferative effects against Lipopolysaccharides (LPS) stimulation in endometrial and Candida albicans vaginal cell lines. VK2 E6/E7 (vaginal) and KLE (epithelial) cell lines were stimulated with Candida albicans (1 × 107 to 5 × 107/mL) and LPS (1 μg/mL), respectively. MiodesinTM inhibited mRNA expression for Nuclear factor kappa B (NF-κB), ciclo-oxigenase 1 (COX-1), and phospholipase A2 (PLA2), beyond the C–C motif chemokine ligand 2 (CCL2), CCL3, and CCL5 in VK2 E6/E7 cells (p < 0.05). In addition, the inhibitory effects of both doses of MiodesinTM (10 µg/mL and 200 µg/mL) resulted in reduced secretion of interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor α (TNF-α) (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05) by VK2 E6/E7 cells. In the same way, COX-1 MiodesinTM inhibited LPS-induced hyperactivation of KLE cells, as demonstrated by reduced secretion of IL-1β, IL-6, IL-8, TNF-α (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05). Furthermore, MiodesinTM also inhibited mRNA expression and secretion of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor (VEGF), which are key regulators of invasion of endometrial cells. Thus, the study concludes that MiodesinTM presents beneficial effects in the context of endometriosis, positively affecting the inflammatory and proliferative response.
... Astaxanthin was shown to be effective not only in preventing oxidative stress in T lymphocytes (110)(111)(112)(113)(114)(115), but also in modulating their activity (115)(116)(117)(118)(119)(120)(121)(122)(123). In the aforementioned clinical study on healthy young women (17), astaxanthin supplementation stimulated mitogen-induced lymphoproliferation and increased the subpopulation of T lymphocytes, without changing the populations of T killer or T helper cells, as well as increased the response to tuberculin, an indicator of T lymphocyte function. ...
... The administration of astaxanthin in mice prevented renal fibrosis by mechanisms involving stimulation of T killer cell recruitment and increased production of IFN-γ (118). In cats, astaxanthin increased the immune response mediated by total T lymphocytes and T helper cells (119). ...
Cardiovascular diseases are the most common cause of mortality worldwide. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases; thus, anti‑inflammatory and antioxidant agents that modulate redox balance have become research targets so as to evaluate their molecular mechanisms of action and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant properties due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also has prominent anti‑inflammatory activity, possibly interrelated with its antioxidant effect, and is also involved in the modulation of lipid and glucose metabolism. Considering the potential beneficial effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, the aim of the present review was to describe the molecular and cellular mechanisms associated with the antioxidant and anti‑inflammatory properties of this carotenoid in cardiovascular diseases, particularly atherosclerosis. The beneficial properties and safety profile of astaxanthin indicate that this compound may be used for preventing progression or as an adjuvant in the treatment of cardiovascular diseases.
... If there is no evidence about the ability of ASX to prevent or counteract UV-mediated immunosuppression, ASX's general ability to boost the immune system has been highlighted in different studies. ASX boosted both humoral and cell-mediated immune response after polyvalent vaccination in beagle dogs and domestic shorthair cats [51,52]. Dogs were fed for 16 weeks with ASX 20 mg and at week 12, the polyvalent vaccine has been administered, while cats were fed for 12 weeks with ASX 10 mg and at week 8 the vaccine has been administered. ...
... A similar immunostimulant event occurs in murine spleen cells where ASX 20 nM increased IgG and IgM levels after 96 h treatment [53]. In dogs, but not in cats, ASX also mediated the cellular response increasing T-cell function, while in both cats and dogs it amplified natural killer (NK) cell cytotoxic activity both before and after vaccination [51,52]. ...
Every day, we come into contact with ultraviolet radiation (UVR). If under medical supervision, small amounts of UVR could be beneficial, the detrimental and hazardous effects of UVR exposure dictate an unbalance towards the risks on the risk-benefit ratio. Acute and chronic effects of ultraviolet-A and ultraviolet-B involve mainly the skin, the immune system, and the eyes. Photodamage is an umbrella term that includes general phototoxicity, photoaging, and cancer caused by UVR. All these phenomena are mediated by direct or indirect oxidative stress and inflammation and are strictly connected one to the other. Astaxanthin (ASX) and fucoxanthin (FX) are peculiar marine carotenoids characterized by outstanding antioxidant properties. In particular, ASX showed exceptional efficacy in counteracting all categories of photodamages, in vitro and in vivo, thanks to both antioxidant potential and activation of alternative pathways. Less evidence has been produced about FX, but it still represents an interesting promise to prevent the detrimental effect of UVR. Altogether, these results highlight the importance of digging into the marine ecosystem to look for new compounds that could be beneficial for human health and confirm that the marine environment is as much as full of active compounds as the terrestrial one, it just needs to be more explored.
... A significant amount of experimental evidences is available regarding to the potential benefits of astaxanthin in human health [60,[64][65][66][67]. The application of different test models has demonstrated that astaxanthin could be considered as a 'super-antioxidant' with the strongest antioxidant activity in comparison with other carotenoids [68], vitamin E and vitamin C [69]. ...
... Some studies claim the positive influence of astaxanthin in the gastrointestinal health [70,78] and as a therapeutic agent against cardiovascular disease [79][80][81][82]. The antioxidant activity of astaxanthin presents other collateral benefits in the enhancement of the immune system as it has been shown by in vitro and in vivo experimental animal models [65] and humans [83]. Diets rich in astaxanthin sources could be beneficial for population at higher risk of heart attacks, considering the evidences obtained on the inhibition of LDL oxidation by astaxanthin what may link the consumption of marine products with the prevention of atherosclerosis [84]. ...
The benefit of carotenoids to human health is undeniable and consequently, their use for this purpose is growing rapidly. Additionally, the nutraceutical properties of carotenoids have attracted attention of the food industry, especially in a new market area, the ‘cosmeceuticals.’ Marine organisms (microalgae, seaweeds, animals, etc.) are a rich source of carotenoids, with optimal properties for industrial production and biotechnological manipulation. Consequently, several papers have reviewed the analysis, characterization, extraction and determination methods, biological functions and industrial applications. But, now, the bioaccessibility and bioactivity of marine carotenoids has not been focused of any review, although important achievements have been published. The specific and diverse characteristic of the marine matrix determines the bioavailability of carotenoids, some of them unique in the nature. Considering the importance of the bioavailability not just from the health and nutritional point of view but also to the food and pharmaceutical industry, we consider that the present review responds to an actual demand.
... Humans exhibited elevated blood Astaxanthin levels and enhanced natural killer cell activity after eight weeks of Astaxanthin supplementation, which allowed them to more effectively target and kill virus-infected cells. The Astaxanthin supplemented group showed a considerable decrease in C-reactive protein (CRP), an increase in T and B cells, and a decrease in DNA damage [61]. ...
... Astaxanthin increases the numbers and activity of white blood cells called lymphocytes and natural killer cells that are responsible for creating the body's innate immune response to invaders [7][8][9]. ...
Gummy bears (German: Gummibär) are small, fruit-gum candies, similar to a jelly baby. The candy is roughly 2 cm (0.8 in) long and shaped in the form of a bear. Astaxanthin is a naturally occurring carotenoid that is derived from the microalgae Haematococcus pluvialis being the most powerful antioxidant known to science, it also has potent anti-inflammatory properties. Natural astaxanthin´s distinct advantage in comparison to other antioxidants is its ability to span the entire lipid bilayer of the cell membrane, thus providing superior protection from the inside out. Natural astaxanthin has a strong ability to both balance and strengthen the immune system
... This is why astaxanthin is considered as "super vitamin E" (Shimidzu et al. 1996). This particular antioxidant activity also contributes in other biological activities, such as anti-inflammatory, antitumor, preventive effects of diabetes, protection against heart liver and ocular diseases, protection against UV rays, lipid peroxidation, oxidative damage to LDL cholesterol (Guerin et al. 2003;Chang et al. 2010;Lu et al. 2010;Park et al. 2011;Ambati et al. 2014;Ranga et al. 2013a, b;Wibrand et al. 2013;Dong et al. 2013;Turkez et al. 2012;Chan et al. 2012;Iizuka et al. 2012;Yoshida et al. 2010;Bhuvaneswari et al. 2014). For this reason, astaxanthin produced by H. pluvialis covers more than 50% of the natural astaxanthin market in the global food industry (Shah et al. 2016;Khoo et al. 2019). ...
Haematococcus is a group of microalgae that is considered the richest source of natural astaxanthin. It gains attention of many researchers and companies because of its high price and the growing demand at international market. Astaxanthin is one of the most powerful antioxidants. This pigment has several applications in aquaculture, food, and cosmetic industries. However, it is economically disadvantageous for commercialization due to the low productivity of astaxanthin. For this reason, researchers have actively studied many strategies to improve the production of natural astaxanthin. Several studies have shown that astaxanthin yield increases rapidly when environmental conditions become unfavorable for normal cell growth. This chapter discusses the research work regarding the improvement of astaxanthin production from Haematococcus pluvialis under various stresses including nutrient deficiency, particularly nitrogen and carbon sources and other exogenous factors such as light intensity, pH, salinity, and temperature. This work also provides insight into the mechanisms of astaxanthin accumulation in Haematococcus.Keywords
Haematococcus pluvialis
Abiotic stressAstaxanthin accumulation
... Normal host defences are orchestrated by macrophages, which display a variety of cell surface receptors in order to direct migration (chemotaxis) to the infection sites, where they eliminate and clear pathogens by phagocytosis and subsequently present antigens to adaptive immune cells. Any inappropriate regulation of macrophages activity leads to human disease (Park et al., 2011). This process of migration and pathogen clearance occurs through the action of specific colony stimulating factore 1 (csf1) receptors tyrosine kinase by auto phosphorylation of csf1 during the infection (Pixley and Stanly, 2004). ...
... In contrast, lipid reserves may not be needed as a source of energy during migration, as brown skuas migrate over the sea where they can rest and feed regularly (Carneiro et al. 2016, Krietsch et al. 2017, Delord et al. 2018). In addition, krill has a high carotenoid content in different forms of astaxanthin (Yamaguchi et al. 1983), which is taken from the diet instead of from body reserves (Barbosa et al. 2013) and has an antioxidative and immune function (Miki 1991, Waldenstedt et al. 2003, Park et al. 2011. Therefore, krill could also be selected by skuas to compensate for a poor immunological condition, as indicated by the drop in the level of γ-globulins and IgY at the end of the breeding season . ...
Changes in seasonal resource availability and in energetic requirements as offspring grow may force parents to change their trophic ecology throughout the breeding season. Brown skuas Stercorarius antarcticus breed in a highly seasonal environment where the availability of their main food resource changes during the season. We studied the feeding plasticity of breeding brown skuas by assessing their isotopic diet and movement patterns at different stages of their breeding cycle. Blood δ ¹⁵ N values indicated that penguin chicks Pygoscelis spp. and Antarctic krill Euphausia superba constituted most of the diet of brown skuas (up to ~70%), and that there was an increase in the ingestion of lower trophic level prey (most likely Antarctic krill ) throughout the breeding period (from 30-46%). This contrasts with movement analysis indicating that 65% of the overall foraging locations were within penguin rookeries. The apparent contradiction between the results from both techniques may be explained by a combination of some skuas feeding mostly at sea or on shore together with secondary ingestion of marine resources from the penguins’ gut by feeding mostly within penguin rookeries. Krill obtained in that way may provide protein to replenish reserves before migration along with globulins through the intake of carotenoids. These results highlight the fact that the trophic ecology of species can be more complex than that suggested by one single method and emphasizes the importance of combining techniques to draw robust conclusions. In addition, our study indicates that skuas may select portions of prey to obtain specific resources to fulfill their nutritional requirements.
... Also the DNA damage biomarkers were observed to be decreased. The levels of T and B cells were got amplified and the concentration of C-reactive protein (CRP) was significantly lowered in the AST supplemented group [174][175][176][177]. ...
Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) is an orange-red, lipophilic keto-carotenoid pigment. It is majorly found in marine ecosystems particularly in aquatic animals such as salmon, shrimp, trout, krill, crayfish, and so on. It is also synthesized in microalgae Heamatococcus pluvialis , Chlorococcum , Chlorella zofingiensis , red yeast Phaffia rhodozyma and bacterium Paracoccus carotinifaciens . Some aquatic and terrestrial creatures regarded as a primary and secondary sources of the astaxanthin producing and accumulating it through their metabolic pathways. Astaxanthin is the powerful antioxidant, nutritional supplement as well as promising therapeutic compound, observed to have activities against different ravaging diseases and disorders. Researchers have reported remarkable bioactivities of astaxanthin against major non-communicable chronic diseases such as cardiovascular diseases, cancer, diabetes, neurodegenerative, and immune disorders. The current review discusses some structural aspects of astaxanthin. It further elaborates its multiple potencies such as antioxidant, anti-inflammatory, anti-proliferative, anti-cancer, anti-obese, anti-diabetic, anti-ageing, anti-TB, anti-viral, anti-COVID 19, neuro-protective, nephro-protective, and fertility-enhancing properties. These potencies make it a more precious entity in the preventions as well as treatments of prevalent systematic diseases and/or disorders. Also, the review is acknowledging and documenting its powerful bioactivities in relation with the pharmaceutical as well as nutraceutical applicability.
Graphical Abstract
... In addition to balancing the immune system, astaxanthin can inhibit unnecessary inflammation by suppressing overactive immune responses (40). Astaxanthin increases the body's immune response by increasing the number and activity of lymphocytes and natural killer cells (41). Natural astaxanthin has clinically shown excellent and unique benefits in immunity, inflammatory diseases, and neurological problems. ...
Inflammation acts like a double-edged sword and can be harmful if not appropriately controlled. COVID-19 is created through a novel species of coronavirus SARS-CoV-2 (2019-nCoV). Elevated levels of inflammatory factors such as inter-leukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), etc. lead to Acute Respiratory Distress Syndrome (ARDS) and severe complications of infection in the lungs of coronavirus-infected patients. Astaxanthin is a natural and potent carotenoid with powerful antioxidant activity as well as an anti-inflammatory agent that supports good health. The effects of astaxanthin on the regulation of cyclooxygenase-2 (COX-2) pathways and the reduction and suppression of cytokines and other inflam-matory agents such as IL-6 and TNF-α have already been identified. Therefore, these unique features can make this natural compound an excellent option to minimize inflammation and its consequences.
... It has curative and preventive effects against inflammation, infectious diseases, and oxidative stress [54]. However, although some research has shown the positive effect of astaxanthin on the immune and inflammatory systems [55,58,59], other research presented no such particular changes [60,61]. In our study, regardless of the supplementation dose, astaxanthin did not affect IgM and IgG activities in serum. ...
In this study, we evaluated the impact of moderate and high dose dietary supplementation of astaxanthin on production performance, quality of eggs, and health status of laying hens. The experiment involved 480 laying hens, divided into four groups of eight replicates. The different groups named A1, A2, A3, and A4 were allocated the same diet supplemented with Haematococcus pluvialis powder to provide 0, 21.3, 42.6, and 213.4 mg of astaxanthin per kilogram of feed, respectively. One-way ANOVA and linear and quadratic regression analysis were used to assess the differences between the groups. The results showed that the production performance of laying hens and the physical quality of eggs did not significantly differ between the groups (p > 0.05). Astaxanthin distribution in tissues was typical per bird, whereas the egg yolk coloration and astaxanthin concentration increased with the supplementation dose (p < 0.001). However, there was a decrease in concentration and coloration efficacy of astaxanthin at high dose supplementation (213.4 mg/kg) compared to moderate doses (21.3 and 42.6 mg/kg). Blood biochemical tests showed some discrepancies that were not ascribed to the effect of diets, and the increase in liver weight in the A4 group compared to others was equated with an adaptation of laying hens to the high dose supplementation. Astaxanthin improved superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and diminished malondialdehyde (MDA) content in both liver and serum; meanwhile, the activities of SOD and GSH-Px in serum were similar between the moderate doses and high dose supplementation. Additionally, astaxanthin alleviated interleukin 2, 4, and 6 (IL-2, IL-4, and IL-6, respectively) in serum, showing the best effect in A3 and A4 groups. Besides, immunoglobulin G and M (IgG and IgM), as well as tumor necrosis factor-alpha and beta (TNF-α and TNF-β), were not much affected. It was concluded that although astaxanthin has no obvious adverse effect on the performance and health status of laying hens, it may not be valuable for egg fortification and health status improvement of laying hens at high dose supplementation. The high dose astaxanthin supplementation up to 213.4 mg/kg in the diet might be avoided.
... Anticancer [92] Antiproliferative activity [93] Bone disease [94] Immunoregulatory activity [95] Antimicrobial activity [92,96,97] Cytotoxic activity [98] Antityrosinase activity [98] Neuroprotection [99][100][101] Immune response [82,102] Cardiovascular prevention [15,[103][104][105] Anti-diabetes [50,106,107] Anti-hepatoprotective [108] Anti-gastric activity [109,110] Anti-inflammatory [105,[111][112][113][114] Anti-skin cancer [115][116][117] Protection from UV rays [117] Antioxidant activity [11,13,18,69,95,97,98,[117][118][119][120][121][122][123] process [40]. It demonstrates the important role of a controlled ROS generation in the proper functioning of the sperm, thus providing ROS with the main role in the process of maturation, other than the detrimental factor previously evaluated by the sperm [10]. ...
Astaxanthin (ASX) is a xanthophyll carotenoid, naturally synthesized by Algae, Yeast, and bacteria. They are not just a powerhouse of antioxidant properties but also possess anti-inflammatory and other bioactive properties. Haematococcus pluvialis is the potential ASX source and shows powerful regulation on many health diseases. Over the decades, numerous studies have emphasized its importance in many human health diseases such as neurodegenerative disorders, cardiovascular diseases, Alzheimer, Parkinson, skin allergies, COVID-19, and many more. The present review discusses available evidence on the functional activities of ASX in various diseases and summarizes the potential factors involved in ASX response and highlights the potential implications.
... In human lymphocytes, oxidative stress caused by a fatty acid mixture and mitochondrial damage can be reduced by AST, which can maintain and improve DNA function (Wolf et al., 2010;Campoio et al., 2011;Park et al., 2011). ...
Entacapone, a catechol-O-methyltransferase inhibitor, can strengthen the therapeutic effects of levodopa on the treatment of Parkinson's disease. However, few studies are reported on whether entacapone can affect hippocampal neurogenesis in mice. To investigate the effects of entacapone, a modulator of dopamine, on proliferating cells and immature neurons in the mouse hippocampal dentate gyrus, 60 mice (7 weeks old) were randomly divided into a vehicle-treated group and the groups treated with 10, 50, or 200 mg/kg entacapone. The results showed that 50 and 200 mg/kg entacapone increased the exploration time for novel object recognition. Immunohistochemical staining results revealed that after entacapone treatment, the numbers of Ki67-positive proliferating cells, doublecortin-positive immature neurons, and phosphorylated cAMP response element-binding protein (pCREB)-positive cells were significantly increased. Western blot analysis results revealed that treatment with tyrosine kinase receptor B (TrkB) receptor antagonist significantly decreased the exploration time for novel object recognition and inhibited the expression of phosphorylated TrkB and brain-derived neurotrophic factor (BDNF). Entacapone treatment antagonized the effects of TrkB receptor antagonist. These results suggest that entacapone treatment promoted hippocampal neurogenesis and improved memory function through activating the BDNF-TrkB-pCREB pathway. This study was approved by the Institutional Animal Care and Use Committee of Seoul National University (approval No. SNU-130730-1) on February 24, 2014. © 2021 Wolters Kluwer Medknow Publications. All rights reserved.
... Furthermore, AST can reduce lipid peroxidation and protein damage in diabetic rats, decrease the oxidation of apolipoproteins, and be used as an inhibitor to prevent arteriosclerosis and ischemic brain injury (Marin et al., 2011;Song et al., 2014;Ma et al., 2015). In human lymphocytes, oxidative stress caused by a fatty acid mixture and mitochondrial damage can be reduced by AST, which can maintain and improve DNA function (Wolf et al., 2010;Campoio et al., 2011;Park et al., 2011). ...
Oxidative stress is currently considered to be the main cause of brain aging. Astaxanthin can improve oxidative stress under multiple pathological conditions. It is therefore hypothesized that astaxanthin might have therapeutic effects on brain aging. To validate this hypothesis and investigate the underlying mechanisms, a mouse model of brain aging was established by injecting amyloid beta (Aβ)25-35 (5 μM, 3 μL/injection, six injections given every other day) into the right lateral ventricle. After 3 days of Aβ25-35injections, the mouse models were intragastrically administered astaxanthin (0.1 mL/d, 10 mg/kg) for 30 successive days. Astaxanthin greatly reduced the latency to find the platform in the Morris water maze, increased the number of crossings of the target platform, and increased the expression of brain-derived neurotrophic factor, synaptophysin, sirtuin 1, and peroxisome proliferator-activated receptor-γ coactivator 1α. Intraperitoneal injection of the sirtuin 1 inhibitor nicotinamide (500 μM/d) for 7 successive days after astaxanthin intervention inhibited these phenomena. These findings suggest that astaxanthin can regulate the expression of synaptic proteins in mouse hippocampus through the sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α signaling pathway, which leads to improvements in the learning, cognitive, and memory abilities of mice. The study was approved by the Animal Ethics Committee, China Medical University, China (approval No. CMU2019294) on January 15, 2019. © 2021 Wolters Kluwer Medknow Publications. All rights reserved.
... Astaxanthin (AXN) from various microalgae and yeast has been approved by United States FDA as a neutraceutical and also as a nutraceutical supplement for about 15 years [5,6]. Studies using various in vitro and animal models documented significant health benefits including mediating immune response [7], inhibiting growth of colorectal cancer cells [8], improving rodent memory functions [9] and protection against UV rays mediated photooxidation, antioxidant and antiinflammatory functions [2]. In addition, reports suggest that the unique structural properties of AXN endure it to span cell membrane and quenches free radicals thereby serving as a better pharmaceutical agent [10,11]. ...
Astaxanthin (AXN) is known to have health benefits by epidemiological studies. Therefore, it is of interest to assess the effect of AXN (derived from indigenous unicellular green alga Haematococcus lacustris) to modulate cell cycle arrest, lysosomal acidification and eventually apoptosis using in vitro in A549 lung cancer cells. Natural extracts of astaxanthin were obtained by standardized methods as reported earlier and characterized by standard HPLC and MS. Treatment of A549 cells with AXN (purified fraction) showed significant reduction in cell viability (about 50%) as compared to crude extract at 50µM concentration. Thus, we show the anticancer effects and lysosomal acidification in A549 cells by Astaxanthin from Haematococcus lacustris for further consideration. Together, our results demonstrated the anticancer potential of AXN from Haematococcus lacustris, which is found to be mediated via its ability to induce cell cycle arrest, lysosomal acidification and apoptotic induction.
... [6] Astaxanthin increases the numbers and activity of white blood cells called lymphocytes and natural killer cells that are responsible for creating the body's innate immune response to invaders. [7][8][9] ISSN: 2582-5267 www.ajbsr.net 42 ...
... While also helping suppress the overactive immune responses that create needless inflammation [6]. Astaxanthin increases the numbers and activity of white blood cells called lymphocytes and natural killer cells that are responsible for creating the body's innate immune response to invaders [7][8][9]. ...
... Based on several studies on various cancers, astaxanthin supplementation inhibits carcinogenesis in the rat colon (Tanaka et al., 1995), mice urinary bladder (Tanaka et al., 1994) and oral cavity (Tanaka et al., 1995). In vivo studies of cats fed with dietary astaxanthin improved immune response with improving natural killer cell cytotoxic activity, T cell population, and peripheral blood mononuclear cell proliferation (Park et al., 2011). Astaxanthin exerts anti-inflammatory effect by enhancing the expression of cyclooxygenase (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), extracellular signal-regulated kinase-2 (ERK-2) and matrixmetallo proteinases (MMP) 2/9 in experimental rats (Nagendraprabhu & Sudhandiran, 2011). ...
... Although ATX does not have any direct link to managing or treating OA, it does have many health benefits that contribute to its use as a supplement. ATX in Flex Choice TM might have provided anti-OA effects in dogs by exerting anti-oxidative/antinitrosative, anti-inflammatory, immunomodulatory, analgesic, and cartilage repair effects [50,69,70,19,45,16]. In a number of studies, ATX has been reported to be safe from a dietary supplementation point of view [98,102,105,90,91]. ...
... There is no solid evidence that dietary astaxanthin enhances immunity in dogs and cats (35). Ingestion of purified astaxanthin increased both plasma IgG and lymphocyte proliferation, but with atypical dose responses (31,36). ...
Krill in petfood Krill meal and oil are present in some nutritional supplements, treats and complete foods for dogs and cats. The two ingredients concern Antarctic krill, swarming small, shrimp-like creatures fished commercially in the Southern Ocean. Krill feed on phytoplankton and are prey of many animals, including fish, seabirds and whales. Krill meal is whole, briefly cooked, dried and ground krill that is processed at sea, on board of factory trawlers. Extracting the oil from meal is done onshore. Crustaceous krill are positioned as superfood of the sea. Petfood products with krill meal/oil claim to promote a healthy coat, support skin, joints and cognitive function, and avert cellular damage by free radicals. The health claims for krill are compositional in nature, focusing on their omega-3 fatty acids, particularly EPA (eicosapentaenoic acid), and their reddish pigment, astaxanthin. Pets' intake of both constituents, while not unique to krill, is (normally) increased by supplemental krill. There are no published studies on dietary krill meal/oil in relation to health of skin, coat, joints and brain in dogs and cats. Complete, dry petfood with added krill meal ordinarily has an inclusion level lower than 5%. With negligible amounts of EPA in the base diet, the EPA associated with 5% krill meal (about 120 mg EPA per 100 g food) might improve inflammatory skin and joint diseases, but the proof is highly debatable while there is no evidence for prevention of the two conditions. Claimed krill effectiveness in fighting cognitive decline and free radicals remains unsubstantiated. The health claims for complete petfood with krill meal lack justification, which also applies to practical, maximum krill inclusion. Krill is promoted as a sustainable petfood ingredient due to restrained, eco-friendly harvesting, but resources for catching and processing should be considered also.
... The immunomodulatory action of astaxanthin has been also reported in dogs and cats, enhancing both cell-mediated and humoral immune responses. In these studies, astaxanthin increased Natural Killer (NK) cell cytotoxic activity, suggesting that astaxanthinmay regulate NK cells that serve as an immune surveillance system against tumors and virus-infected cells [206,207]. Astaxanthin is reported to improve the DNA repair capacity of cells exposed to UV radiation. In particular, astaxanthin was capable of minimizing DNA damage and influencing the kinetics of DNA repair [208]. ...
... The immunomodulatory action of astaxanthin has been also reported in dogs and cats, enhancing both cell-mediated and humoral immune responses. In these studies, astaxanthin increased natural killer (NK) cell cytotoxic activity, suggesting that astaxanthin may regulate NK cells that serve as an immunosurveillance system against tumors and virus-infected cells [194,195]. Astaxanthin is reported to improve the DNA repair capacity of cells exposed to UV radiation. In particular, astaxanthin was capable of minimizing DNA damage and in luencing the kinetics of DNA repair [196]. ...
... Astaxanthin is a xanthophyll carotenoid food supplement prevalent in marine organisms (Kidd, 2011). This potent antioxidant (Kidd, 2011) affects the Insulin\Insulin growth factor I (IGF1) and the nuclear kinase mitogen and stressactivated protein kinase-1 (MSK1) signaling pathways, which were found to be implicated in preconditioning, survival and longevity in vitro in human keratinocytes (Terazawa et al., 2012) and in vivo in Caenorhabditis elegans (Yazaki et al., 2011) Other in vivo experiments in animals have shown Astaxanthin is associated with reductions in C reactive protein and DNA damage and improvement of the cell-mediated and humoral immune responses (Park et al., 2011) and with improvement in cardiovascular parameters (Fassett and Coombes, 2012). In exercising mice Astaxanthin induced diminished fatigue, and reductions in blood lactate, oxidative damage to lipids and DNA, and muscle injury (Aoi et al., 2003;Ikeuchi et al., 2006). ...
Objectives: To examine the supplementation effects of the xanthophyll carotenoid Astaxanthin on physical performance and exertional heat strain in humans. Design: A randomized double blind placebo controlled trial. Methods: Twenty two male participants (Age: 23.14 ± 3.5 y, height: 175 ± 6 cm, body mass: 69.6 ± 8.7 kg, % body fat: 16.8 ± 3.8) received placebo (PLA, n = 10) or Astaxanthin (ATX, n = 12) 12 mg/day Per os (P.O), for 30 days, and were tested pre and post-supplementation with a maximal oxygen uptake (VO2 Max) test and the heat tolerance test (HTT) (2 h walk at 40°C, 40% relative humidity (RH), 5 kph, 2% incline). NIH database registration no. NCT02088242. Gas exchange, Heart rate (HR), Relative perceived exertion (RPE), and blood lactate were measured during the VO2 Max test. Heart rate (HR), rectal (Trec), and skin (Tskin) temperatures, RPE, and sweat rate (SR) were monitored in the HTT. Serum heat shock protein 72 (HSP72), Creatine phospho-kinase (CPK), C-reactive protein (CRP), and lipid profile were measured before and after the test. Results: The rise in blood lactate caused by the VO2 Max test was significantly diminished in the ATX group (9.4 ± 3.1 and 13.0 ± 3.1 mmole*l−1 in the ATX and PLA groups, respectively P < 0.02), as was the change in oxygen uptake during recovery (−2.02 ± 0.64 and 0.83 ± 0.79% of VO2 Max in the ATX and PLA group, respectively, p = 0.001). No significant differences were observed in the anaerobic threshold or VO2 Max. In the HTT, no significant physiological or biochemical differences were observed (HR <120 bpm, Trec rose by ~1°C to <38°C, no difference in SR). Conclusions: Astaxanthin supplementation improved exercise recovery. No benefit was observed for ATX over PLA in response to heat stress. Further examination of Astaxanthin in higher exertional heat strain is required.
... The immunomodulatory action of astaxanthin has been also reported in dogs and cats, enhancing both cell-mediated and humoral immune responses. In these studies, astaxanthin increased natural killer (NK cell cytotoxic activity, suggesting that astaxanthin may regulate NK cells that serve as an immunosurveillance system against tumors and virus-infected cells [199,200]. Astaxanthin is reported to improve the DNA repair capacity of cells exposed to UV radiation. In particular, astaxanthin was capable of minimizing DNA damage and influencing the kinetics of DNA repair [201]. ...
Skin aging is a complex biological process influenced by a combination of endogenous or intrinsic and exogenous or extrinsic factors. Because of the fact that skin health and beauty is considered one of the principal factors representing overall “well-being” and the perception of “health” in humans, several anti-aging strategies have been developed during the last years. In contrast to thin and atrophic, finely wrinkled and dry intrinsically aged skin, premature photoaged skin typically shows a thickened epidermis, mottled discoloration, deep wrinkles, laxity, dullness and roughness. Gradual loss of skin elasticity leads to the phenomenon of sagging. Slowing of the epidermal turnover rate and cell cycle lengthening coincides with a slower wound healing and less effective desquamation in older adults. This fact is important when esthetic procedures are scheduled. On the other side, many of these features are targets to product application or procedures to accelerate the cell cycle, in the belief that a faster turnover rate will yield improvement in skin appearance and will speed wound healing. A marked loss of fibrillin-positive structures as well as a reduced content of collagen type VII (Col-7, may contribute to wrinkles by weakening the bond between dermis and epidermis of extrinsically age skin. Sun-exposed aged skin is characterized by the solar elastosis. The sparse distribution and decrease in collagen content in photoaged skin can be due to increased collagen degradation by various matrix metalloproteinases, serine, and other proteases irrespective of the same collagen production. The overall collagen content per unit area of the skin surface is known to decline approximately 1%/year. Glycosaminoglycans (GAGs are among the primary dermal skin matrix constituents assisting in binding water. In photo-aged skin, GAGs may be associated with abnormal elastotic material and thus be unable to function effectively. The total hyaluronic acid (HA level in the dermis of skin that age intrinsically remains stable; however, epidermal HA diminishes markedly. Decreased estrogen levels may play a role in skin aging in women and compounds stimulating estrogen receptors could potentially counteract some of the visible signs of aging. As people live longer, women spend a larger portion of their lives in a post-menopausal state, with a deficiency of estrogen as compared to their younger selves. Changes in diet and increasing exercise, together with a regimen of antioxidants, nutritional supplements, and growth factors, can alter how the genes express themselves. Both factors can greatly enhance the healing capability of the skin and can improve the results of cosmetic surgeries.
... The immunomodulatory action of astaxanthin has been also reported in dogs and cats, enhancing both cell-mediated and humoral immune responses. In these studies, astaxanthin increased natural killer (NK) cell cytotoxic activity, suggesting that astaxanthinmay regulate NK cells that serve as an immunosurveillance system against tumors and virusinfected cells [206,207]. Astaxanthin is reported to improve the DNA repair capacity of cells exposed to UV radiation. In particular, astaxanthin was capable of minimizing DNA damage and influencing the kinetics of DNA repair [208]. ...
... In order to investigate the function of AST on immune system, Park et al. (2011) set female domestic cats as model animals. The results showed that the proliferation of peripheral blood mononuclear cells and the activity of natural killer cells increased in cats fed with AST. ...
Background
Astaxanthin (AST) is a kind of carotenoid natural pigment that has been widely found in plants, crustaceans' shell, flamingos' feathers and microorganisms. Due to its various biological activities, AST has suggested as an important compound in biochemical researches and has great application potentials in cosmetics, human nutritional health products, as well as medicines. Unfortunately, the poor water solubility, chemical instability and low oral bioavailability make AST difficult to be applied in food systems. Besides, the amount of natural AST is limited, and how to extract and utilize AST efficiently is in great demand.
Scope and approach
This review highlights the considerable potential of AST products in food processing by evaluating the advantages and disadvantages of different extraction strategies. Moreover, AST have some shortages on physicochemical properties, which limits its application in foods. Therefore, the review focuses on the comparison and discussion of different AST-loaded delivery systems, as well as its application status.
Key findings and conclusions
Natural AST are commonly extracted from Haematococcus pluvialis, crustaceans, and bird feathers by corresponding appropriate methods. Solvent extraction, oil stripping, enzymatic hydrolysis, supercritical fluid extraction and microwave-assisted extraction are mostly applied to accumulate AST with high yields. Delivery systems such as emulsions, nanoparticles and liposomes may improve the stability and bioavailability of AST.
... The immunomodulatory action of astaxanthin has been also reported in dogs and cats, enhancing both cell-mediated and humoral immune responses. In these studies, astaxanthin increased natural killer (NK) cell cytotoxic activity, suggesting that astaxanthinmay regulate NK cells that serve as an immunosurveillance system against tumors and virusinfected cells [206,207]. Astaxanthin is reported to improve the DNA repair capacity of cells exposed to UV radiation. In particular, astaxanthin was capable of minimizing DNA damage and influencing the kinetics of DNA repair [208]. ...
As the most voluminous organ of the body that is exposed to the outer environment, the skin suffers from both intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, laxity, and rough-textured appearance. This aging process is accompanied with phenotypic changes in cutaneous cells as well as structural and functional changes in extracellular matrix components such as collagens and elastin. With intrinsic aging, structural changes occur in the skin as a natural consequence of the biological changes over time and produce a certain number of histological, physiological, and biochemical modifications. Intrinsic aging is determined genetically (influence of gender and ethnic group), variable in function of skin site, and also influenced by hormonal changes. Visually it is characterized by fine wrinkles. By comparison, “photoaging” is the term used to describe the changes occurring in the skin, resulting from repetitive exposure to sunlight. The histological, physiological, and biochemical changes in the different layers of the skin are much more drastic. From a mechanical point of view, human skin appears as a layered composite containing the stiff thin cover layer presented by the stratum corneum, below which are the more compliant layers of viable epidermis and dermis and further below the much more compliant adjacent layer of subcutaneous white adipose tissue.
... Moreover, Schizochytrium sp. produces high amounts of xanthophylls (Aki et al., 2003) which possess immunomodulatory properties that promote cellular and humoral responses (Park et al., 2011;Ghodratizadeh et al., 2014). ...
Although oral subunit vaccines are highly relevant in the fight against widespread diseases, their high cost, safety and proper immunogenicity are attributes that have yet to be addressed in many cases and thus these limitations should be considered in the development of new oral vaccines. Prominent examples of new platforms proposed to address these limitations are plant cells and microalgae. Schizochytrium sp. constitutes an attractive expression host for vaccine production because of its high biosynthetic capacity, fast growth in low cost culture media, and the availability of processes for industrial scale production. In addition, whole Schizochytrium sp. cells may serve as delivery vectors; especially for oral vaccines since Schizochytrium sp. is safe for oral consumption, produces immunomodulatory compounds, and may provide bioencapsulation to the antigen, thus increasing its bioavailability. Remarkably, Schizochytrium sp. was recently used for the production of a highly immunoprotective influenza vaccine. Moreover, an efficient method for transient expression of antigens based on viral vectors and Schizochytrium sp. as host has been recently developed. In this review, the potential of Schizochytrium sp. in vaccinology is placed in perspective, with emphasis on its use as an attractive oral vaccination vehicle.
... It has been reported that AST has significant effects on immune function both in vitro and in vivo 18,19 . For example, AST can improve immune cell proliferation and reduce humoral immune response and increase immunoglobulin production 20,21 . ...
Background
Multiple Sclerosis (MS) has been explained as an autoimmune mediated disorder in central nerve system. Since conventional therapies for MS are not able to stop or reverse the destruction of nerve tissue, stem cell-based therapy has been proposed for the treatment of MS. Astaxanthin (AST) is a red fat-soluble xanthophyll with neuroprotection activity. The aim of this study was evaluation of pre-inducer function of AST on differentiation of human Adipose-Derived Stem Cells (hADSCs) into oligodendrocyte precursor cells.
Methods
After stem cell isolation, culture and characterization by flow cytometry, hanging drop technique was done for embryoid body formation. In the following, hADSCs were differentiated into oligodendrocyte cells in the presence of AST at various concentrations (1, 5, and 10 ng/ml). Finally, immunocytochemistry and real-time PCR techniques were used for assessment of oligodendrocyte differentiation.
Results
Flow cytometry results indicated that hADSCs were CD44, CD49-positive, but were negative for CD14, CD45 markers. In addition, immunocytochemistry results revealed that, in AST treated groups, the mean percentage of Olig 2 and A2B5 positive cells increased especially in 5 ng/ml AST treated group compared to control group (p<0.001). Moreover, real-time PCR analysis confirmed the results of immunocytochemistry.
Conclusion
Since hADSCs have the potential to differentiate into multi lineage cells and due to important functions of AST in regulating various cellular processes, it seems that AST can be used as a promoter for oligodendrocyte differentiation of hADSCs for being used in cell transplantation in multiple sclerosis.
Astaxanthin is a very strong antioxidant typically fed to rainbow trout mainly to alter the color of its’ meat to red. In our study, we incorporate a relatively low concentration of astaxanthin into the diet of common carp to enhance the chemical parameters and oxidation stability of carp meat without altering the typical coloration of meat. Also, we observed the fatty acid profile of reared fish. We observed an increase in protein content in animals with astaxanthin dietary addition. It was not statistically significant, but we observed a lowering of fat content in experimental groups. Regarding lipid oxidation, we did not observe any significant effect of astaxanthin on malondialdehyde production in samples. Fatty acid profiles were determined by gas chromatography and then compared. Only significant differences were observed in stearic and arachidonic acid and in the experimental group with lower astaxanthin addition. Our results conclude that dietary astaxanthin has no adverse effect on fatty acid profile or oxidation stability during storage (at -18 °C). On the other hand, astaxanthin has the potential to enhance the protein and lower the fat content, even in low concentrations.
Cancer is known as a very dangerous and incurable disease, with symptoms such as pain and disability. In recent years, changes in the way people live have increased the prevalence of breast cancer in different societies. This terrible disease has increased research in this field. Astaxanthin is one of the most famous natural carotenoids, which, due to its strong antioxidant activity, can prevent cardiovascular diseases, strengthen the body's immune system, and prevent cell ageing. In this study, the effect of astaxanthin on MCF-7 cancer cells was investigated. After culturing the cells in 96-well plates, they were treated with different concentrations of astaxanthin and then evaluated using the MTT method. The results showed that astaxanthin can inhibit cell growth and induce apoptosis, and this effect is enhanced by increasing the concentration of astaxanthin, so that at a concentration of 100 μM, the rate of apoptosis increased to 35%. Therefore, it can be concluded that astaxanthin may be used as a control treatment for cancer.
AST exerts anti-inflammatory effects and may target IL-6 to inhibit the positive feedback loop of inflammatory factors, thereby effectively reducing adverse inflammatory responses.
Supplementation of micronutrients is considered to be crucial in the reinforcement of the skin’s barrier. In this paper, 14 nutritional compounds commonly used in food or pharmaceutic industries were analyzed in terms of influencing skin conditions. The major objective of this paper was to provide a narrative review of the available literature regarding several chosen compounds that are currently widely recommended as supplements that aim to maintain proper and healthy skin conditions. We conducted a review of the literature from PubMed, Scopus, and Web of Science until September 2023 without any other restrictions regarding the year of the publication. Ultimately, we reviewed 238 articles, including them in this review. Each of the reviewed compounds, including vitamin A, vitamin C, vitamin D, vitamin E, curcumin, chlorella, Omega-3, biotin,Ppolypodium leucotomos, Simmondsia chinesis, gamma oryzanol, olive leaf extract, spirulina, and astaxanthin, was observed to present some possible effects with promising benefits for a skin condition, i.e., photoprotective radiation. Adding them to the diet or daily routine might have a positive influence on some skin inflammatory diseases such as atopic dermatitis or psoriasis. Further, UV radiation protection facilitated by some supplements and their impact on human cells might be helpful during chemotherapy or in preventing melanoma development. Further research is needed because of the lack of clear consensus regarding the doses of the described compounds that could provide desirable effects on the skin.
Objectives
Astaxanthin is a dark red keto-carotenoid found in aquatic animals such as salmon and shrimp, and algae (Haematococcus pluvialis). Astaxanthin has a unique molecular structure that may facilitate anti-oxidative, immunomodulatory, and anti-inflammatory effects during physiological stress. The primary objective of this study was to examine the efficacy of 4-week ingestion of astaxanthin in moderating exercise-induced inflammation and immune dysfunction using a multi-omics approach.
Methods
This study employed a randomized, double blind, placebo controlled, crossover design with two 4-week supplementation periods and a 2-week washout period. Study participants were randomized to astaxanthin and placebo trials, with supplements ingested daily for 4 weeks prior to running 2.25 h at close to 70%VO2max (including 30 min of 10% downhill running). After the washout period, participants repeated all procedures using the counterbalanced supplement. The astaxanthin capsule contained 8 mg of algae astaxanthin. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5, 3, and 24 h-post-exercise. Plasma aliquots were assayed using untargeted proteomics, and targeted oxylipin and cytokine panels.
Results
The 2.25 h running bout induced significant muscle soreness, muscle damage, and inflammation. Astaxanthin supplementation had no effect on exercise-induced muscle soreness, muscle damage, and increases in six plasma cytokines and 42 oxylipins. Notably, astaxanthin supplementation countered exercise-induced decreases in 82 plasma proteins (during 24 h recovery). Biological process analysis revealed that most of these proteins were involved in immune-related functions such as defense responses, complement activation, and humoral immune system responses. Twenty plasma immunoglobulins were identified that differed significantly between the astaxanthin and placebo trials. Plasma levels of IgM decreased significantly post-exercise but recovered after the 24 h post-exercise recovery period in the astaxanthin but not the placebo trial.
Discussion
These data support that 4-week astaxanthin versus placebo supplementation did not counter exercise-induced increases in plasma cytokines and oxylipins but was linked to normalization of post-exercise plasma levels of numerous immune-related proteins including immunoglobulins within 24 h. Short-term astaxanthin supplementation (8 mg/day during a 4-week period) provided immune support for runners engaging in a vigorous 2.25 h running bout and uniquely countered decreases in plasma immunoglobulin levels.
Bağışıklık sistemi, konağı tehdit edici patojen mikroorganizmalara karşı korumakla görevlidir. İyi bir bağışıklık sistemi, patojenik organizmalara karşı savunma sağlar ve gıda bileşenlerinin de katkısıyla direnç kazandırır. Yetersiz beslenme bağışıklık sistemini zayıflatır ve bireyi enfeksiyona karşı daha duyarlı hale getirir. Beslenmede su ürünleri, içerdiği besin bileşenlerinden dolayı insan beslenmesinde ve bağışıklık sistemi üzerindeki katkısı düşünüldüğünde önemli bir yere sahiptir. Su ürünleri - özellikle balık; çoklu doymamış yağ asitleri (omega-3 gibi), melatonin, triptofan, taurin ve poliaminler gibi immün düzenleyici aminoasitleri, yağda çözünen A, D ve E vitaminlerini, suda çözünen B6 ve B12 vitaminlerini ve selenyum, fosfor, kalsiyum ve çinko gibi bağışıklığı güçlendirmek için önemli olan mineralleri içerir. Kabuklu su canlılarında bol bulunan karotenoidler A vitamininin ön maddeleleri olmaları ve bu suretle de vücut savunma sistemine katılmaları bakımından önemli bileşiklerdir. Bu çalışmada, su ürünleri besin bileşenlerinin bağışıklık sistemi üzerine etkileri incelenmiştir.
Diabetes remains a major health emergency in our entire world, affecting hundreds of millions of people worldwide. In conjunction with its much-dreaded complications (e.g., nephropathy, neuropathy, retinopathy, cardiovascular diseases, etc.) it substantially reduces the quality of life, increases mortality as well as economic burden among patients. Over the years, oxidative stress and inflammation have been highlighted as key players in the development and progression of diabetes and its associated complications. Much research has been devoted, as such, to the role of antioxidants in diabetes. Astaxanthin is a powerful antioxidant found mostly in marine organisms. Over the past years, several studies have demonstrated that astaxanthin could be useful in the treatment and management of diabetes. It has been shown to protect β-cells, neurons as well as several organs including the eyes, kidney, liver, etc. against oxidative injuries experienced during diabetes. Furthermore, it improves glucose and lipid metabolism along with cardiovascular health. Its beneficial effects are exerted through multiple actions on cellular functions. Considering these and the fact that foods and natural products with biological and pharmacological activities are of much interest in the 21st-century food and drug industry, astaxanthin has a bright prospect in the management of diabetes and its complications.
Posljednjih godina u suvremenom svijetu dominira visokoprerađena i osiromašena
hrana čija prekomjerna konzumacija može utjecati na zdravlje potrošača.
Prehrambena industrija prilagođava se prehrambenim navikama i potrebama
potrošača proizvodnjom funkcionalnih proizvoda u cilju prihvatljivosti i očuvanja
senzorskih svojstava. Za potrebe ovog istraživanja kao dodatak za obogaćivanje
keksa u cilju dobivanja funkcionalnog proizvoda koristili su se različiti zaslađivači
(med, kokosov šećer i šećer) i bezglutenska brašna (heljda, rogač, suncokretovo i
kokosovo brašno) u cilju razvoja keksa nižeg glikemijskog indeksa prihvatljivih
senzorskih svojstava. U istraživanju je dobrovoljno sudjelovalo 6 zdravih ispitanika,
oba spola, starosti od 22 do 24 godine. Rezultati mjerenja šećera u krvi pokazali su
značajno smanjenje glikemijskog indeksa upotrebom meda i kokosovog šećera kao
zaslađivača. Pored zaslađivača utjecaj na glikemijski indeks imao je i keks s
dodatkom kokosovog i suncokretovog brašna. Svi uzorci s dodatkom šećera slabije
su senzorski ocijenjeni u odnosu na uzorke s dodatkom meda i kokosovog šećera
kao zasalađivača. Dobiveni funkcionalni proizvodi, uz pozitivni utjecaj na
smanjenje glikemijskog indeksa različitih vrsta keksa, imaju zbog jednostavne
proizvodnje potencijal za komercijalizaciju, kao i prihvatljivost širem krugu
potrošača.
Ključne riječi: keks, med, kokosov šećer, bezglutenska brašna
Posljednjih godina u suvremenom svijetu dominira visokoprerađena i osiromašena
hrana čija prekomjerna konzumacija može utjecati na zdravlje potrošača.
Prehrambena industrija prilagođava se prehrambenim navikama i potrebama
potrošača proizvodnjom funkcionalnih proizvoda u cilju prihvatljivosti i očuvanja
senzorskih svojstava. Za potrebe ovog istraživanja kao dodatak za obogaćivanje
keksa u cilju dobivanja funkcionalnog proizvoda koristili su se različiti zaslađivači
(med, kokosov šećer i šećer) i bezglutenska brašna (heljda, rogač, suncokretovo i
kokosovo brašno) u cilju razvoja keksa nižeg glikemijskog indeksa prihvatljivih
senzorskih svojstava. U istraživanju je dobrovoljno sudjelovalo 6 zdravih ispitanika,
oba spola, starosti od 22 do 24 godine. Rezultati mjerenja šećera u krvi pokazali su
značajno smanjenje glikemijskog indeksa upotrebom meda i kokosovog šećera kao
zaslađivača. Pored zaslađivača utjecaj na glikemijski indeks imao je i keks s
dodatkom kokosovog i suncokretovog brašna. Svi uzorci s dodatkom šećera slabije
su senzorski ocijenjeni u odnosu na uzorke s dodatkom meda i kokosovog šećera
kao zasalađivača. Dobiveni funkcionalni proizvodi, uz pozitivni utjecaj na
smanjenje glikemijskog indeksa različitih vrsta keksa, imaju zbog jednostavne
proizvodnje potencijal za komercijalizaciju, kao i prihvatljivost širem krugu
potrošača.
Ključne riječi: keks, med, kokosov šećer, bezglutenska brašna
The effects of astaxanthin supplementationon the growth, innate immunity and antioxidant defence system of loach (Paramisgurnus dabryanus) were investigated in this study. A total of 450 fish (initial average weights of 3.00 ± 0.10 g) were fed five diets with graded levels of astaxanthin (0.00, 50.00, 100.00, 150.00 and 200.00 mg/kg) for 56 days. The results showed that astaxanthin supplementation significantly stimulated the growth (FBW, WG, FER, HSI), innate immunity (AKP activity in the hepatopancreas, intestinal tract, muscle and skin and LZM activity in the hepatopancreas, intestinal tract and skin), antioxidant ability (T‐SOD, GSH‐PX and CAT activities and T‐AOC, GSH and MDA contents in the hepatopancreas, intestinal tract, muscle and skin) of loach. Moreover, dietary astaxanthin supplementation significantly up‐regulated the relative mRNA levels of Nrf2 and Maf, and down‐regulated the relative mRNA level of Keap1 in the hepatopancreas when the supplementation levels of astaxanthin were 50–200 mg/kg. In conclusion, the diets with 100–151.06 mg/kg astaxanthin supplementation were optimal for loach, which based on the growth, immunity and antioxidant‐related indicators, and the astaxanthin supplementation regulated the antioxidant ability partially referring to Keap1‐Nrf2 signallings.
Microalgae have been envisioned as the source of food, feed, health nutraceuticals, and cosmetics. Among various microalgae, Haematococcus pluvialis (H. pluvialis) is known to be the richest feedstock of natural astaxanthin. Astaxanthin is a highly effective antioxidation material and is being widely used in aquaculture, nutraceuticals, pharmacology, and feed industries. Here, we present a microfluidic chip consisting of micropillar array and six sets of culture chambers, which enables to sort motile flagellated vegetative stage of H. pluvialis (15-20 µm) from cyst stage H. pluvialis as well as to culture the selected cells under a mechanically stressed microenvironment. The micropillar array successfully sorted only the early motile vegetative stage cells (avg. size = 19.8 ± 1.6 µm), where these sorted cells were uniformly loaded inside each culture chamber (229 ± 39 cells/chamber). Mechanical stress levels applied to the cells was controlled by designing the culture chambers with different heights (5-70 µm). Raman analysis results revealed that the mechanical stress indeed induced the accumulation of astaxanthin in H. pluvialis. Also, the most effective chamber height enhancing the astaxanthin accumulation (i.e., 15 µm) was successfully screened using the developed chip. Approximately 9 times more astaxanthin accumulation was detected after 7 days of culture compared to the no mechanical stress condition. The results clearly demonstrate the capability of the developed chip to investigate bio metabolite accumulation of microalgae induced by mechanical stress, where the amount was quantitatively analyzed in a label-free manner. We believe the developed chip has a great potential for studying the effects of mechanical stress on not only H. pluvialis but also various microalgal species in general.
Green microalga Haematococcus pluvialis produces a keto-carotenoid astaxanthin with a high antioxidant activity during induction of vegetative cells to cyst cells. Astaxanthin plays an important role in the food, cosmetics, nutraceutical, and aquaculture industries. Wastewater provides water and necessary nutrients for algae cultivation. Microalgae can be used as an economical and feasible way of wastewater treatment coupling with the concurrent creation of high-value products. Microalgae show higher efficiency in nutrient removal than other microorganisms because the nutrients (ammonia, nitrate, phosphate, urea and trace elements) present in various wastewaters are essential for microalgal growth. Although there are a substantial number of researches available on the utilization of various microalgae species for wastewater treatment and nutrient removal, wastewater treatment and astaxanthin production by Haematococcus pluvialis are less investigated. This chapter describes the current knowledge about microalga H. pluvialis-derived astaxanthin, its application and market potential, and culture conditions and nutritional requirements of this microalgal cell growth and astaxanthin formation. The potentiality of microalgae cultivation using various wastewater and integration of H. pluvialis culture in different wastewater streams and nutrient removal and biomass production efficiency are also discussed. Furthermore, the challenges associated with growing H. pluvialis in wastewaters and possible ways to overcome such challenges have been highlighted.
Present study was conducted on 12 Karan Fries (Holstein Friesian X Tharparkar) heifers (10–12 months) to assess the effect of astaxanthin supplementation on heat stress amelioration and inhibition of NF-κB signaling pathway for prevention of heat stress–induced inflammatory changes and apoptosis in the cell during the summer season. The heifers were randomly and equally divided into two groups, i.e., control (fed as per ICAR 2013) and treatment groups (additionally supplemented astaxanthin at a dose rate of 0.25 mg/kg BW/day/animal). Temperature humidity index used to assess the levels of summer stress during the experimental period. Blood samples were collected at the fortnightly interval for quantification of plasma cortisol and IL-12 from both the groups of the heifers and from collected blood samples, RNA was isolated and transcribed into cDNA for real time PCR, for genes expression of NF-κB, IL-2, caspase-3, and Bcl-2. Plasma cortisol, IL-12 levels, and expression pattern of NF-κB, IL-2, and caspase-3 were significantly (P ≤ 0.05) lower in treatment group of Karan Fries heifers than control group, whereas, Bcl-2 was higher (P ≤ 0.05) in astaxanthin supplemented group. The temperature humidity index had a positive correlation (P ≤ 0.05) with plasma cortisol and IL-12 and expression pattern of NF-κB, IL-2, and caspase-3. However, it was negatively correlated with Bcl-2. The supplementation of astaxanthin can ameliorate the impact of summer stress through NF-κB downregulation, might be due to the quenching of free radicals, which regulates the expression of pro-inflammatory mediators and apoptotic genes.
Review of Astaxanthin's health benefits and important information for use as a human nutritional supplement.
Even though lutein can stimulate immunity and decrease cancer growth, no systematic studies are available on the uptake of lutein in mice. We studied the uptake of lutein in 8-wk-old female BALB/c mice fed a diet containing 0, 0.05, 0.1, 0.2 or 0.4% lutein. Mice were killed on d 0, 3, 7, 14, 21 and 28 (n = 6/period), and blood, spleen and liver were collected. Food intake and body, liver and spleen weights did not differ among treatment groups. Lutein + zeaxanthin were not detectable in the plasma, liver and spleen of unsupplemented mice. Mice fed lutein showed very rapid lutein + zeaxanthin absorption. On d 3, concentrations of plasma lutein + zeaxanthin had rapidly increased (P < 0.05) in lutein-fed mice and no further increases were observed. Plasma lutein + zeaxanthin concentrations did not differ among lutein-fed mice by d 7 (2.58 ± 0.2 μmol/L). Even though maximal uptake of plasma lutein + zeaxanthin was observed by d 3, uptake of lutein + zeaxanthin by the liver and especially by the spleen generally continued to increase (P < 0.05) through d 28 to reach concentrations of 0.11 ± 0.001 (spleen) and 0.71 ± 0.0002 (liver) nmol/g. Therefore, dietary lutein is readily absorbed into the plasma and taken up by liver and spleen of mice. Plasma lutein + zeaxanthin concentrations were higher than in human studies; however, mice were fed lutein at a level several hundredfold greater than in humans. The liver is a major storage organ for lutein + zeaxanthin in mice. Uptake of lutein + zeaxanthin by the spleen suggests a role for lutein in modulating immunity.
The biochemical characteristics of the Liver and blood in rainbow trout (Oncorhynchus mykiss) fed a diet supplemented by red yeast (Phaffia rhodozyma) containing astaxanthin (Ast) as its principal carotenoid pigment or synthetic Ast were studied. Surprisingly, the hepatosomatic indices and serum glutamic-oxaloacetic transaminase activities of fish fed a diet containing red yeast or synthetic Ast were significantly lower than those of fish fed a control diet. The mean amount of serum lipid peroxide of fish fed a diet containing red yeast or synthetic Ast was also lower than that of the control fish. It was suggested that the dietary red yeast and synthetic Ast have the potential for improving not only the pigmentation of fish muscle but also the health of fish in aquaculture (e.g. improvement of liver function and increase of defensive potential level against oxidative stress).
Research on the uptake and transport of astaxanthin is lacking in most species. We studied the uptake of astaxanthin by plasma, lipoproteins and leukocytes in domestic dogs and cats.
Mature female Beagle dogs (18 to 19 mo old; 11 to 14 kg BW) were dosed orally with 0, 0.1, 0.5, 2.5, 10 or 40 mg astaxanthin and blood taken at 0, 3, 6, 9, 12, 18 and 24 h post-administration (n = 8/treatment). Similarly, mature domestic short hair cats (12 mo old; 3 to 3.5 kg body weight) were fed a single dose of 0, 0.02, 0.08, 0.4, 2, 5, or 10 mg astaxanthin and blood taken (n = 8/treatment) at the same interval.
Both dogs and cats showed similar biokinetic profiles. Maximal astaxanthin concentration in plasma was approximately 0.14 mumol/L in both species, and was observed at 6 h post-dosing. The plasma astaxanthin elimination half-life was 9 to 18 h. Astaxanthin was still detectable by 24 h in both species. In a subsequent study, dogs and cats were fed similar doses of astaxanthin daily for 15 to 16 d and astaxanthin uptake by plasma, lipoproteins, and leukocytes studied. In both species, plasma astaxanthin concentrations generally continued to increase through d 15 or 16 of supplementation. The astaxanthin was mainly associated with high density lipoprotein (HDL). In blood leukocytes, approximately half of the total astaxanthin was found in the mitochondria, with significant amounts also associated with the microsomes and nuclei.
Dogs and cats absorb astaxanthin from the diet. In the blood, the astaxanthin is mainly associated with HDL, and is taken up by blood leukocytes, where it is distributed to all subcellular organelles. Certain aspects of the biokinetic uptake of astaxanthin in dogs and cats are similar to that in humans.
Astaxanthin modulates immune response, inhibits cancer cell growth, reduces bacterial load and gastric inflammation, and protects against UVA-induced oxidative stress in in vitro and rodent models. Similar clinical studies in humans are unavailable. Our objective is to study the action of dietary astaxanthin in modulating immune response, oxidative status and inflammation in young healthy adult female human subjects.
Participants (averaged 21.5 yr) received 0, 2, or 8 mg astaxanthin (n = 14/diet) daily for 8 wk in a randomized double-blind, placebo-controlled study. Immune response was assessed on wk 0, 4 and 8, and tuberculin test performed on wk 8.
Plasma astaxanthin increased (P < 0.01) dose-dependently after 4 or 8 wk of supplementation. Astaxanthin decreased a DNA damage biomarker after 4 wk but did not affect lipid peroxidation. Plasma C-reactive protein concentration was lower (P < 0.05) on wk 8 in subjects given 2 mg astaxanthin. Dietary astaxanthin stimulated mitogen-induced lymphoproliferation, increased natural killer cell cytotoxic activity, and increased total T and B cell subpopulations, but did not influence populations of Thelper, Tcytotoxic or natural killer cells. A higher percentage of leukocytes expressed the LFA-1 marker in subjects given 2 mg astaxanthin on wk 8. Subjects fed 2 mg astaxanthin had a higher tuberculin response than unsupplemented subjects. There was no difference in TNF and IL-2 concentrations, but plasma IFN-gamma and IL-6 increased on wk 8 in subjects given 8 mg astaxanthin.
Therefore, dietary astaxanthin decreases a DNA damage biomarker and acute phase protein, and enhances immune response in young healthy females.
Even though lutein can stimulate immunity and decrease cancer growth, no systematic studies are available on the uptake of lutein in mice. We studied the uptake of lutein in 8-wk-old female BALB/c mice fed a diet containing 0, 0.05, 0.1, 0.2 or 0.4% lutein. Mice were killed on d 0, 3, 7, 14, 21 and 28 (n = 6/period), and blood, spleen and liver were collected. Food intake and body, liver and spleen weights did not differ among treatment groups. Lutein + zeaxanthin were not detectable in the plasma, liver and spleen of unsupplemented mice. Mice fed lutein showed very rapid lutein + zeaxanthin absorption. On d 3, concentrations of plasma lutein + zeaxanthin had rapidly increased (P < 0.05) in lutein-fed mice and no further increases were observed. Plasma lutein + zeaxanthin concentrations did not differ among lutein-fed mice by d 7 (2.58 +/- 0.2 micromol/L). Even though maximal uptake of plasma lutein + zeaxanthin was observed by d 3, uptake of lutein + zeaxanthin by the liver and especially by the spleen generally continued to increase (P < 0.05) through d 28 to reach concentrations of 0.11 +/- 0.001 (spleen) and 0.71 +/- 0. 0002 (liver) nmol/g. Therefore, dietary lutein is readily absorbed into the plasma and taken up by liver and spleen of mice. Plasma lutein + zeaxanthin concentrations were higher than in human studies; however, mice were fed lutein at a level several hundredfold greater than in humans. The liver is a major storage organ for lutein + zeaxanthin in mice. Uptake of lutein + zeaxanthin by the spleen suggests a role for lutein in modulating immunity.
The role of beta-carotene on immune response in domestic dogs is not known. Female Beagle dogs were fed 0, 2, 20 or 50 mg beta-carotene/d; blood was sampled at wk 0, 1, 2, 4 and 8 for analysis of the following: lymphoproliferation, leukocyte subpopulations and concentrations of interleukin-2 (IL-2), immunoglobulin (Ig)G and IgM. Delayed-type hypersensitivity (DTH) response was assessed at wk 0, 3 and 7. beta-Carotene supplementation increased plasma beta-carotene concentrations in a dose-dependent manner. Compared with unsupplemented dogs, those fed 20 or 50 mg of beta-carotene had higher CD4+ cell numbers and CD4:CD8 ratio. However, there was no treatment difference in CD8+, CD21+ and major histocompatability complex (MHC) class II+ cells. Plasma IgG, but not IgM concentration was higher in dogs fed beta-carotene throughout the study period. The DTH response to phytohemagglutinin (PHA) and vaccine was heightened in beta-carotene-supplemented dogs. beta-Carotene feeding did not influence mitogen-induced lymphocyte proliferation or IL-2 production. Immune response was impaired in dogs classified as low beta-carotene absorbers compared with similar dogs fed the same amount of beta-carotene. Therefore, dietary beta-carotene heightened cell-mediated and humoral immune responses in dogs.
Dietary antioxidants may attenuate oxidative damage from strenuous exercise in various tissues. Beneficial effects of the antioxidant astaxanthin have been demonstrated in vitro, but not yet in vivo. We investigated the effect of dietary supplementation with astaxanthin on oxidative damage induced by strenuous exercise in mouse gastrocnemius and heart. C57BL/6 mice (7 weeks old) were divided into groups: rested control, intense exercise, and exercise with astaxanthin supplementation. After 3 weeks of exercise acclimation, both exercise groups ran on a treadmill at 28 m/min until exhaustion. Exercise-increased 4-hydroxy-2-nonenal-modified protein and 8-hydroxy-2'-deoxyguanosine in gastrocnemius and heart were blunted in the astaxanthin group. Increases in plasma creatine kinase activity, and in myeloperoxidase activity in gastrocnemius and heart, also were lessened by astaxanthin. Astaxanthin showed accumulation in gastrocnemius and heart from the 3 week supplementation. Astaxanthin can attenuate exercise-induced damage in mouse skeletal muscle and heart, including an associated neutrophil infiltration that induces further damage.
Strenuous exercise increases oxygen consumption and causes disturbance of intracellular pro-oxidant–antioxidant homeostasis. The mitochondrial electron transport chain, polymorphoneutrophil, and xanthine oxidase have been identified as major sources of intracellular free radical generation during exercise. Reactive oxygen species pose a serious threat to the cellular antioxidant defense system, such as diminished reserve of antioxidant vitamins and glutathione, and increased tissue susceptibility to oxidative damage. However, enzymatic and nonenzymatic antioxidants have demonstrated great adaptation to acute and chronic exercise. The delicate balance between pro-oxidants and antioxidants suggests that supplementation of antioxidants may be desirable for physically active individuals under certain physiological conditions by providing a larger protective margin.
Carotenoids can be effective singlet oxygen quenchers and inhibit free-radical induced lipid peroxidation. A remarkable property of β-carotene (1a) is the change from an antioxidant to a prooxidant depending on oxygen pressure and concentration. In the present study a considerable number of carotenoids (1a, 2c, 2d, 2e, 3a, 4a, 5a, 6a, 7a, 8a, 8h, 8i, 8j, 9f, 10a, 11a, 12g) was investigated using two independent approaches: 1. Comparison of their effects on inhibition of the free-radical oxidation of methyl linoleate, and 2. The direct study of the effect of oxygen partial pressure upon their rates of oxidation. It is shown that some carotenoids (7a, 8a) are even more effective than the well-known compounds β-carotene (1a) and astaxanthin (5a) and are powerful antioxidants without any prooxidative property. Different carotenoids display different behaviour depending on chain length and end groups. The influence of these functional groups on the antioxidative reactivity is discussed.
The immune system plays an essential role in maintaining the body’s overall health and resistance to diseases. It comprises
two branches, known as the innate or antigen-nonspecific branch, and the adaptive or antigen-specific branch. A truly effective
immune defence is based on a balance of the different arms of the whole immune system. The human immune response system is
very complex and carotenoids have been reported to have effects on many different aspects. To understand the significance
of this it is necessary to have a working knowledge of the immune system. An outline of the main features and principles is
given below, but the non-specialist reader is recommended to consult a modern biology or biochemistry textbook, or an introductory
book on immunology.
Flow cytometry is becoming a commonly used technique to characterize a variety of cells. It provides a powerful application to rapidly determine the relative percentages of T-lymphocyte subsets and B-lymphocytes. The effectiveness of its application, however, is dependent on standardization, especially in a clinical setting. Application of flow cytometry to veterinary diagnostics has been limited by the unavailability of reagents and by the unstandardized characterization of normal values using antibodies not commercially available, but typically provided through the generosity of other researchers. This paper presents a standardized gating protocol, and average values and ranges observed for normal canine and feline blood lymphocytes using commercially available antibodies to cell surface markers for CD5, CD3, CD4, CD8, MHC II, and B lymphocytes. The averages for these markers on gated lymphocytes were as follows: Canine CD5 83.3%, Canine CD4 45.0%, Canine CD8 28.8%, Canine MHC II 98.0%, Canine B Cell 12.9%, Canine CD4/CD8 ratio 1.87, Feline T lymphocytes 77.3%, Feline CD4 44.5%, Feline CD8 25.7%, Feline B Cell 24.1%, Feline CD4/CD8 Ratio 1.75. Normal values were also established for a mixed breed group of dogs, and old versus young dogs. This information will provide researchers and clinicians with a standardized protocol for gating, which establishes a basis for comparison between techniques, and a measure of phenotypic percentages for flow cytometry in normal dogs and cats based on this standardization and commercially available antibodies.
The molecular characteristics of the monolayers of astaxanthin with polar group on the β-ionone ring in the molecule and β-carotene without polar group and their interactions in mixed carotenoid–phospholipid monolayers and the effects of carotenoids on the phase behavior of the phospholipid bilayers were examined by the monolayer technique and differential scanning calorimetry (DSC). We found from the monolayer study that β-carotene had an amphiphilic nature. The molecular assembly of astaxanthin in the monolayer at the hydrophobic/hydrophilic interface was more stable than that of β-carotene. Dimyristoylphosphatidylcholine (DMPC) in the monolayer was miscible with astaxanthin in the range of 0–0.4 mol fractions of astaxanthin, but not fully miscible with β-carotene even at low concentrations below 0.1 mol fraction of β-carotene. Surface potential and compression/expansion cycles of β-carotene monolayer indicated the formation of molecular aggregates by itself. DSC study showed that when small amount of astaxanthin was added, the transition temperature of dipalmitoylphosphatidylcholine (DPPC) was markedly shifted to lower temperatures and that the transition peak was asymmetrically broadened, indicative of a significant depression in cooperativity of the gel to liquid–crystalline transition. The asymmetric DSC endothermic bands of DPPC incorporating small amounts of astaxanthin were well fit by deconvolution into two to three domains containing different concentrations of astaxanthin. On the contrary, the incorporation of β-carotene resulted in a small depression of the main transition temperature with a slight broadening of the transition peak, suggesting a small miscibility of β-carotene with the phospholipid bilayer or a formation of aggregates of β-carotene in the membranes. These results suggest that there would be a high localized concentration in the phase separated membrane for astaxanthin or β-carotene to function effectively as scavenger.
Helicobacter pylori is a Gram-negative bacterium affecting about half of the world population, causing chronic gastritis type B dominated by activated phagocytes. In some patients the disease evolves into gastric ulcer, duodenal ulcer, gastric cancer or MALT lymphoma. The pathogenesis is in part caused by the immunological response. In mouse models and in human disease, the mucosal immune response is characterized by activated phagocytes. Mucosal T-lymphocytes are producing IFN-γ thus increasing mucosal inflammation and mucosal damage. A low dietary intake of antioxidants such as carotenoids and vitamin C may be an important factor for acquisition of H. pylori by humans. Dietary antioxidants may also affect both acquisition of the infection and the bacterial load of H. pylori infected mice. Antioxidants, including carotenoids, have anti-inflammatory effects. The aim of the present study was to investigate whether dietary antoxidant induced modulation of H. pylori in mice affected the cytokines produced by H. pylori specific T-cells. We found that treatment of H. pylori infected mice with an algal cell extract containing the antioxidant astaxanthin reduces bacterial load and gastric inflammation. These changes are associated with a shift of the T-lymphocyte response from a predominant Th1-response dominated by IFN-γ to a Th1/Th2-response with IFN-γ and IL-4. To our knowledge, a switch from a Th1-response to a mixed Th1/Th2-response during an ongoing infection has not been reported previously.
The immuno-modulatory role of dietary lutein in domestic cats is unknown. Female Tabby cats (10-month old; n=56) were supplemented daily for 12 weeks with 0, 1, 5 or 10 mg lutein. Blood was collected on Weeks 0, 2, 4, 8 and 12 to assess the following: (1) mitogen-induced peripheral blood mononuclear cells (PBMCs) proliferation, (2) changes in PBMC subpopulations, (3) interleukin-2 (IL-2) production and (4) plasma immunoglobulin (Ig)G production. In addition, delayed-type hypersensitivity (DTH) response to concanavalin A (Con A) or a polyvalent vaccine was performed on Weeks 0, 6 and 12. Dietary lutein increased plasma lutein concentrations in a dose-dependent manner (p<0.001) and concentrations had not reached steady state after 12 weeks of feeding in cats given 5 or 10 mg lutein. Concentrations of plasma retinol and α-tocopherol were not influenced by diet. The DTH response to vaccine but not to Con A increased (p<0.05) in a dose-dependent manner on Week 6. Compared to control, cats fed lutein also showed enhanced Con A- and pokeweed mitogen-stimulated PBMCs proliferation. Dietary lutein also increased the percentages of CD4+ and CD21+ lymphocytes on Week 12 but had no significant effect on pan T, CD8 and MHC class II markers. Plasma IgG was higher (p<0.05) in cats fed 10 mg lutein on Weeks 8 and 12. These results support the immuno-modulatory action of lutein in domestic cats.
Astaxanthin and peridinin, two typical carotenoids of marine microalgae, and lycopene were incorporated in phosphatidylcholine multilamellar liposomes and tested as inhibitors of lipid oxidation. Contrarily to peridinin results, astaxanthin strongly reduced lipid damage when the lipoperoxidation promoters—H2O2, tert-butyl hydroperoxide (t-ButOOH) or ascorbate—and Fe2+:EDTA were added simultaneously to the liposomes. In order to check if the antioxidant activity of carotenoids was also related to their effect on membrane permeability, the peroxidation processes were initiated by adding the promoters to Fe2+-loaded liposomes (encapsulated in the inner aqueous solution). Despite that the rigidifying effect of carotenoids in membranes was not directly measured here, peridinin probably has decreased membrane permeability to initiators (t-ButOOH > ascorbate > H2O2) since its incorporation limited oxidative damage on iron-liposomes. On the other hand, the antioxidant activity of astaxanthin in iron-containing vesicles might be derived from its known rigidifying effect and the inherent scavenging ability.
The possible immuno-modulatory action of dietary lutein in dogs is not known. Female Beagle dogs (17–18-month old; 11.4±0.4 kg body weight) were supplemented daily with 0, 5, 10 or 20 mg lutein for 12 weeks. Delayed-type hypersensitivity (DTH) response to saline, phytohemagglutinin (PHA) and a polyvalent vaccine was assessed on Weeks 0, 6 and 12. Blood was sampled on Weeks 0, 2, 4, 8 and 12 to assess (1) lymphocyte proliferative response to PHA, concanavalin A (Con A), and pokeweed mitogen (PWM), (2) changes in peripheral blood mononuclear cell (PBMC) populations, (3) interleukin-2 (IL-2) production and (4) IgG and IgM production. After the completion of 12-week study, we continued to collect the blood weekly up to 17 weeks to evaluate the changes in immunoglobulin production upon first and second antigenic challenges on Weeks 13 and 15. Plasma lutein+zeaxanthin was undetectable in unsupplemented dogs but concentrations increased (P<0.05) rapidly on Week 2 in lutein-supplemented dogs. Thereafter, concentrations generally continued to increase in dose-dependent manner, albeit at a much slower rate. Dogs fed lutein had heightened DTH response to PHA and vaccine by Week 6. Dietary lutein increased (P<0.05) lymphocyte proliferative response to all three mitogens and increased the percentages of cells expressing CD5, CD4, CD8 and major histocompatibility complex class II (MHC II) molecules. The production of IgG increased (P<0.05) in lutein-fed dogs after the second antigenic challenge. Lutein did not influence the expression of CD21 lymphocyte marker, plasma IgM or IL-2 production. Therefore, dietary lutein stimulated both cell-mediated and humoral immune responses in the domestic canine.
The antioxidative biological effect of dietary red yeast, Phaffia rhodozyma, which is rich in astaxanthin, on rainbow trout, Oncorhynchus mykiss, was examined. The levels of serum transaminase (glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase) activities and of lipid peroxides (LPO) of fish fed oxidized oil were significantly higher than those of the control fish fed non-oxidized oil. However, the supply of red yeast considerably decreased both enzyme activities and LPO level. Furthermore, the serum lipid (triglycerides, total cholesterol and phospholipids) concentrations were also significantly decreased. Especially, the serum triglyceride level of fish fed the red yeast was as low as that of the control. It was also observed that there were no significant differences in muscle LPO levels between the fish fed red yeast and the control. The present results suggest for the first time that dietary red yeast may effectively suppress the LPO generation of tissue and normalize liver function as well as improving muscle pigmentation of trout. Thus, red yeast should have a reducing effect on oxidized oil-induced oxidative stress in fish.
No information is available on the possible role of astaxanthin on immune response in domestic canine. Female Beagle dogs (9-10 mo old; 8.2 ± 0.2 kg body weight) were fed 0, 10, 20 or 40 mg astaxanthin daily and blood sampled on wk 0, 6, 12, and 16 for assessing the following: lymphoproliferation, leukocyte subpopulations, natural killer (NK) cell cytotoxicity, and concentrations of blood astaxanthin, IgG, IgM and acute phase proteins. Delayed-type hypersensitivity (DTH) response was assessed on wk 0, 12 and 16. Plasma astaxanthin increased dose-dependently and reached maximum concentrations on wk 6. Dietary astaxanthin enhanced DTH response to vaccine, concanavalin A-induced lymphocyte proliferation (with the 20mg dose at wk 12) and NK cell cytotoxic activity. In addition, dietary astaxanthin increased concentrations of IgG and IgM, and B cell population. Plasma concentrations of C reactive protein were lower in astaxanthin-fed dogs. Therefore, dietary astaxanthin heightened cell-mediated and humoral immune response and reduced DNA damage and inflammation in dogs.
Mitochondrial damage and the proportion of effete mitochondria in cells increase with age. According to the mitochondrial theory of aging, this phenomenon is mostly due to oxidative damage and is a major (and, some argue, the main) determinant of aging. It will be argued briefly that this phenomenon plays a role that is not exclusively crucial in aging. It will also be contended, essentially on theoretical grounds (for lack of sufficient current information), that there is low probability that the accumulation of reduced degradation of affected mitochondria is due to diminished production of hydroxyl radicals, as suggested by Aubrey and de Grey (1997) and expanded by Kowald (in this issue). What seems more likely is that the phagolysosomal disposal system of effete mitochondria is considerably altered in cells of aging organisms. Also, in view of the significant role of damaged mitochondria in the initial steps in apoptosis and the lack of evidence of massive apoptosis of cells in senescent individuals, the damage that exists may be milder than anticipated by the mitochondrial theory of aging. A brief fundamental summary on the biology of mitochondria is included for the sake of better understanding the arguments presented in this article. Also, suggestions are made for experimental testing of the hypotheses presented by Aubrey and de Grey (1997) and Kowald (1999).
When the conjugated keto-carotenoids, either astaxanthin or canthaxanthin, are added to rat liver microsomes undergoing radical-initiated lipid peroxidation under air, they are as effective as alpha-tocopherol in inhibiting this process. This contrasts with the effect of beta-carotene, which is a much less potent antioxidant when added in this system, without the addition of other antioxidants.
The value of astaxanthin, a carotenoid pigment, in the treatment of oxidative injury is assessed. Astaxanthin protects the mitochondria of vitamin E-deficient rats from damage by Fe2(+)-catalyzed lipid peroxidation both in vivo and in vitro. The inhibitory effect of astaxanthin on mitochondrial lipid peroxidation is stronger than that of alpha-tocopherol. Thin layer chromatographic analysis shows that the change in phospholipid components of erythrocytes from vitamin E-deficient rats induced by Fe2+ and Fe3(+)-xanthine/xanthine oxidase system was significantly suppressed by astaxanthin. Carrageenan-induced inflammation of the paw is also significantly inhibited by administration of astaxanthin. These data indicate that astaxanthin functions as a potent antioxidant both in vivo and in vitro.
The effect of carotenoids on in vitro immunoglobulin (Ig) production by peripheral blood mononuclear cells (PBMNC) was examined by employing blood samples from adult volunteers and full-term newborn babies (umbilical cord blood). Under carotenoid-supplemented culture conditions, cells were stimulated by polyclonal stimulants, neoantigens, and a recall antigen (Ag), and IgM, IgA, and IgG levels in the culture supernatant were measured. Beta-carotene and astaxanthin were used as representatives of carotenoids with and without vitamin A activity, respectively. Astaxanthin enhanced IgM production in response to T-dependent Ag (TD-Ag) and a T-dependent polyclonal stimulant. Astaxanthin also augmented IgG production in response to a recall Ag. IgA production without supplemental carotenoids was negligible for all stimuli. However, in carotenoid-supplemented cultures, IgA production was significantly higher in response to a T-dependent polyclonal stimulant than in unsupplemented cultures. IgM and IgA production was augmented at 10(-8) mol/l astaxanthin, whereas astaxanthin enhanced IgG production in response to a recall Ag at 10(-10)-10(-9) mol/l. Similar enhancing actions of astaxanthin on IgM production were observed in cord blood mononuclear cells (CBMNC), although CBMNC produced less IgM than adult PBMNC. Beta-carotene did not have a significant effect on human Ig production. The carotenoid actions were not demonstrated under serum-free culture conditions; serum is essential for solubilization of carotenoids. In summary, this study has shown for the first time that astaxanthin, a carotenoid without vitamin A activity, enhances human Ig production in response to T-dependent stimuli.
Previously, we demonstrated an enhancement of in vitro antibody (Ab) production in response to T-dependent antigens (TD-Ag) by astaxanthin, a carotenoid without vitamin A activity. The effects of beta-carotene, a carotenoid with vitamin A activity, and lutein, another carotenoid without vitamin A activity, on in vitro Ab production were examined with spleen cells from young and old B6 mice. In addition, the in vivo effects of lutein, astaxanthin, and beta-carotene on Ab production were studied in young and old B6 mice. Lutein, but not beta-carotene, enhanced in vitro Ab production in response to TD-Ags. The depletion of T-helper cells prevented the enhancement of Ab production by lutein and astaxanthin. In vivo Ab production in response to TD-Ag was significantly enhanced by lutein, astaxanthin, and beta-carotene. The numbers of immunoglobulin M- and G-secreting cells also increased in vivo with the administration of these carotenoids when mice were primed with TD-Ags. Antibody production in response to TD-Ags in vivo and in vitro was significantly lower in old than in young B6 mice. Astaxanthin supplements partially restored decreased in vivo Ab production in response to TD-Ags in old B6 mice. Lutein and beta-carotene also enhanced in vivo Ab production in response to TD-Ags in old B6 mice, although to a lesser extent than did astaxanthin. However, none of the carotenoids had an effect on in vivo or in vitro Ab production in response to T-independent antigen. These results indicate significant immunomodulating actions of carotenoids for humoral immune responses to TD-Ags and suggest that carotenoid supplementation may be beneficial in restoring humoral immune responses in older animals.
Profiles of the local nitric oxide (.NO) diffusion-concentration product across the egg yolk phosphatidylcholine membrane in the absence and presence of 30 mol% cholesterol were obtained using line-broadening electron paramagnetic resonance (EPR) and lipid-soluble nitroxide spin labels. Membrane .NO permeability coefficients were calculated from these profiles. At 20 degrees C, values of 93 and 77 cm/s for membranes in the absence and presence of cholesterol were obtained, compared with 73 and 66 cm/s for water layers of the same thickness as the membranes. Fluid-phase membranes are not barriers to .NO transport. Cholesterol significantly increases .NO transport in the center of the lipid bilayer.
The ability of beta-carotene, lutein or astaxanthin to protect against UVA-induced oxidative stress in rat kidney fibroblasts (NRK) was assessed. Activities of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), and changes in thiobarbituric acid reactive substances (TBARS) were measured as indices of oxidative stress. Exposure to UVA light at a dose intensity of 5.6 mW/cm2 for 4 h resulted in a significant decrease in CAT and SOD activities and a significant increase in TBARS. No cytotoxicity, as indicated by lactate dehydrogenase (LDH) release, was observed. beta-Carotene (1 microM), lutein (1 microM) and astaxanthin (10 nM) protect against UVA light-induced oxidative stress in vitro with astaxanthin exhibiting superior protective properties.
Reactive oxygen species (ROS) are implicated in the mechanism of biological aging and exercise-induced oxidative damage. The present study examined the effect of an acute bout of exercise on intracellular ROS production, lipid and protein peroxidation, and GSH status in the skeletal muscle of young adult (8 mo, n = 24) and old (24 mo, n = 24) female Fischer 344 rats. Young rats ran on a treadmill at 25 m/min and 5% grade until exhaustion (55.4 +/- 2.7 min), whereas old rats ran at 15 m/min and 5% grade until exhaustion (58.0 +/- 2.7 min). Rate of dichlorofluorescin (DCFH) oxidation, an indication of ROS and other intracellular oxidants production in the homogenate of deep vastus lateralis, was 77% (P < 0.01) higher in rested old vs. young rats. Exercise increased DCFH oxidation by 38% (P < 0.09) and 50% (P < 0.01) in the young and old rats, respectively. DCFH oxidation in isolated deep vastus lateralis mitochondria with site 1 substrates was elevated by 57% (P < 0.01) in old vs. young rats but was unaltered with exercise. Significantly higher DCFH oxidation rate was also found in aged-muscle mitochondria (P < 0.01), but not in homogenates, when ADP, NADPH, and Fe(3+) were included in the assay medium without substrates. Lipid peroxidation in muscle measured by malondialdehyde content showed no age effect, but was increased by 20% (P < 0.05) with exercise in both young and old rats. Muscle protein carbonyl formation was unaffected by either age or exercise. Mitochondrial GSH/ GSSG ratio was significantly higher in aged vs. young rats (P < 0.05), whereas exercise increased GSSG content and decreased GSH/GSSG in both age groups (P < 0.05). These data provided direct evidence that oxidant production in skeletal muscle is increased in old age and during prolonged exercise, with both mitochondrial respiratory chain and NADPH oxidase as potential sources. The alterations of muscle lipid peroxidation and mitochondrial GSH status were consistent with these conclusions.
Mitochondrial damage and the proportion of effete mitochondria in cells increase with age. According to the mitochondrial theory of aging, this phenomenon is mostly due to oxidative damage and is a major (and, some argue, the main) determinant of aging. It will be argued briefly that this phenomenon plays a role that is not exclusively crucial in aging. It will also be contended, essentially on theoretical grounds (for lack of sufficient current information), that there is low probability that the accumulation of reduced degradation of affected mitochondria is due to diminished production of hydroxyl radicals, as suggested by Aubrey and de Grey (1997) and expanded by Kowald (in this issue). What seems more likely is that the phagolysosomal disposal system of effete mitochondria is considerably altered in cells of aging organisms. Also, in view of the significant role of damaged mitochondria in the initial steps in apoptosis and the lack of evidence of massive apoptosis of cells in senescent individuals, the damage that exists may be milder than anticipated by the mitochondrial theory of aging. A brief fundamental summary on the biology of mitochondria is included for the sake of better understanding the arguments presented in this article. Also, suggestions are made for experimental testing of the hypotheses presented by Aubrey and de Grey (1997) and Kowald (1999).
Strenuous exercise increases oxygen consumption and causes disturbance of intracellular pro-oxidant-antioxidant homeostasis. The mitochondrial electron transport chain, polymorphoneutrophil, and xanthine oxidase have been identified as major sources of intracellular free radical generation during exercise. Reactive oxygen species pose a serious threat to the cellular antioxidant defense system, such as diminished reserve of antioxidant vitamins and glutathione, and increased tissue susceptibility to oxidative damage. However, enzymatic and nonenzymatic antioxidants have demonstrated great adaptation to acute and chronic exercise. The delicate balance between pro-oxidants and antioxidants suggests that supplementation of antioxidants may be desirable for physically active individuals under certain physiological conditions by providing a larger protective margin.
The in vivo modulatory effect of beta-carotene, astaxanthin and canthaxanthin on lymphocyte function was investigated. Female BALB/c mice (8 wk old) were fed a basal diet containing 0, 0.1% or 0.4% beta-carotene, astaxanthin or canthaxanthin for 0, 2 or 4 wk (n = 8/diet/period). Splenic lymphocytes were isolated and mitogen-stimulated proliferation, IL-2 production and lymphocyte cytotoxicity were assessed. Body weight and feed intake were not different among dietary treatments. Plasma carotenoids were undetectable in unsupplemented mice but concentrations of the respective carotenoids were elevated in mice fed 0.1 or 0.4% beta-carotene (0.22 and 0.39 mumol/L), astaxanthin (16.4 and 50.2 mumol/L) and canthaxanthin (5.00 and 7.02 mumol/L) respectively. Mice fed both dietary levels of beta-carotene and astaxanthin had enhanced phytohemagglutinin-induced lymphoblastogenesis compared to unsupplemented mice (P < 0.03). No treatment difference was detected with concanavalin A- or lipopolysaccharide-induced lympho-proliferation nor with IL-2 production (P < 0.05). Astaxanthin (0.1%) also enhanced lymphocyte cytotoxic activity (P < 0.08). In contrast, canthaxanthin did not significantly influence any of the lymphocyte functions measured. Results indicate that beta-carotene and astaxanthin but not canthaxanthin exert enhanced splenic lymphocyte function in mice.
The antioxidant activities of astaxanthin and related carotenoids have been measured by employing a newly developed fluorometric assay. This assay is based on 4,4-difluoro-3,5-bis(4-phenyl-1, 3-butadienyl)-4-bora-3a,4a-diaza-s-indacene (BODIPY 665/676) as an indicator; 2,2'-azobis-2,4-dimethylvaleronitrile (AMVN) as a peroxyl radical generator; and 6-hydroxy-2,5,7, 8-tetramethylchroman-2-carboxylic acid (Trolox) as a calibrator in an organic and liposomal media. By employing this assay, three categories of carotenoids were examined: namely, the hydrocarbon carotenoids lycopene, alpha-carotene, and beta-carotene; the hydroxy carotenoid lutein; and the alpha-hydroxy-ketocarotenoid astaxanthin. The relative peroxyl radical scavenging activities of Trolox, astaxanthin, alpha-tocopherol, lycopene, beta-carotene, lutein, and alpha-carotene in octane/butyronitrile (9:1, v/v) were determined to be 1.0, 1.0, 1.3, 0.5, 0.4, 0.3, and 0.2, respectively. In dioleoylphosphatidyl choline (DOPC) liposomal suspension in Tri-HCl buffer (pH 7.4 at 40 degrees C), the relative reactivities of astaxanthin, beta-carotene, alpha-tocopherol, and lutein were found to be 1.00, 0.9, 0.6, and 0.6, respectively. When BODIPY 665/676 was replaced by 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a, 4a-diaza-s-indacene-3-undecanoic acid (BODIPY 581/591 C(11)) as an indicator, astaxanthin showed the highest antioxidant activity toward peroxyl radicals. The relative reactivities of Trolox, astaxanthin, alpha-tocopherol, alpha-carotene, lutein, beta-carotene, and lycopene were determined to be 1.0, 1.3, 0.9, 0.5, 0.4, 0.2, and 0.4, respectively.
Marine animals produce astaxanthin which is a carotenoid and antioxidant. In this study we determined the in vitro and ex vivo effects of astaxanthin on LDL oxidation. The oxidation of LDL was measured in a 1 ml reaction system consisting of increasing concentrations of astaxanthin (12.5, 25.0, 50.0 microg/ml), 400 microM V-70 (2, 2'-azobis(4-methoxy-2, 4-dimethylvaleronitrile)), and LDL (70 microg/ml protein). Astaxanthin dose, dependently significantly prolonged the oxidation lag time (31.5, 45.4, 65.0 min) compared with the control (19.9 min). For the ex vivo study 24 volunteers (mean age 28.2 [SD 7.8] years) consumed astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg per day for 14 days. No other changes were made in the diet. Fasting venous blood samples were taken at days 0, +14. LDL lag time was longer (5.0, 26.2, 42.3 and 30.7% respectively) compared with day 0 after consuming astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg for 14 days compared with day 0, but there was no difference in oxidation of LDL between day 0 (lag time 59.9+/-7.2 min) and day 14 (57.2+/-6.0 min) in the control group. Our results provide evidence that consumption of marine animals producing astaxanthin inhibits LDL oxidation and possibly therefore contributes to the prevention of atherosclerosis.
We investigated the effects of astaxanthin on the antitumor effector activity of natural killer (NK) cells suppressed by stress in mice in order to define the immunological significance of astaxanthin (ASX) when combined with restraint stress treatment. When the mice were treated with restraint stress alone, the total number of spleen cells, and the level NK cell activity per spleen were reduced to a nadir on day 3. The stress also caused a significant increase in the lipid peroxidation of liver tissue. ASX (100 mg/kg/day, p.o., 4 days) improved the immunological dysfunction induced by restraint stress. On the other hand, metastatic nodules were observed in the livers of syngenic DBA/2 mice on day 12 after inoculation of P815 mastocytoma cells. Hepatic metastasis was promoted further by restraint stress when applied on day 3 before the inoculation of P815. Daily oral administration of ASX (1 mg/kg/day, p.o., 14 days) markedly attenuated the promotion of hepatic metastasis induced by restraint stress. These results suggested that astaxanthin improves antitumor immune responses by inhibiting of lipid peroxidation induced by stress.
Carotenoids Against Disease. Part C. The Immune System and Disease Carotenoids
- B P Chew
- J S Park
Chew, B.P., Park, J.S., 2009. Carotenoids Against Disease. Part C. The
Immune System and Disease Carotenoids: Nutrition and Health, vol.