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International Journal of Molecular... Jul 2021Mitochondria are considered to be important organelles in the cell and play a key role in the physiological function of the heart, as well as in the pathogenesis and... (Review)
Review
Mitochondria are considered to be important organelles in the cell and play a key role in the physiological function of the heart, as well as in the pathogenesis and development of various heart diseases. Under certain pathological conditions, such as cardiovascular diseases, stroke, traumatic brain injury, neurodegenerative diseases, muscular dystrophy, etc., mitochondrial permeability transition pore (mPTP) is formed and opened, which can lead to dysfunction of mitochondria and subsequently to cell death. This review summarizes the results of studies carried out by our group of the effect of astaxanthin (AST) on the functional state of rat heart mitochondria upon direct addition of AST to isolated mitochondria and upon chronic administration of AST under conditions of mPTP opening. It was shown that AST exerted a protective effect under all conditions. In addition, AST treatment was found to prevent isoproterenol-induced oxidative damage to mitochondria and increase mitochondrial efficiency. AST, a ketocarotenoid, may be a potential mitochondrial target in therapy for pathological conditions associated with oxidative damage and mitochondrial dysfunction, and may be a potential mitochondrial target in therapy for pathological conditions.
Topics: Drug Delivery Systems; Heart Failure; Humans; Isoproterenol; Mitochondria, Heart; Oxidation-Reduction; Xanthophylls
PubMed: 34360729
DOI: 10.3390/ijms22157964 -
Ecotoxicology and Environmental Safety Feb 2024Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the...
Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
Topics: Female; Animals; NF-E2-Related Factor 2; Zebrafish; Ferroptosis; Acetylcholinesterase; Flame Retardants; Kelch-Like ECH-Associated Protein 1; Reactive Oxygen Species; Organophosphorus Compounds; Oxidative Stress; Organophosphates; Xanthophylls
PubMed: 38219622
DOI: 10.1016/j.ecoenv.2024.115960 -
Microbial Cell Factories Jun 2022Astaxanthin is a ketocarotenoid with high antioxidant power used in different fields as healthcare, food/feed supplementation and as pigmenting agent in aquaculture....
BACKGROUND
Astaxanthin is a ketocarotenoid with high antioxidant power used in different fields as healthcare, food/feed supplementation and as pigmenting agent in aquaculture. Primary producers of astaxanthin are some species of microalgae, unicellular photosynthetic organisms, as Haematococcus lacustris. Astaxanthin production by cultivation of Haematococcus lacustris is costly due to low biomass productivity, high risk of contamination and the requirement of downstream extraction processes, causing an extremely high price on the market. Some microalgae species are also primary producers of omega-3 fatty acids, essential nutrients for humans, being related to cardiovascular wellness, and required for visual and cognitive development. One of the main well-known producers of omega-3 fatty eicosapentaenoic acid (EPA) is the marine microalga Nannochloropsis gaditana (named also Microchloropsis gaditana): this species has been already approved by the Food and Drug Administration (FDA) for human consumption and it is characterized by a fast grow phenotype.
RESULTS
Here we obtained by chemical mutagenesis a Nannochloropsis gaditana mutant strain, called S4, characterized by increased carotenoid to chlorophyll ratio. S4 strain showed improved photosynthetic activity, increased lipid productivity and increased ketocarotenoids accumulation, producing not only canthaxanthin but also astaxanthin, usually found only in traces in the WT strain. Ketocarotenoids produced in S4 strain were extractible in different organic solvents, with the highest efficiency observed upon microwaves pre-treatment followed by methanol extraction. By cultivation of S4 strain at different irradiances it was possible to produce up to 1.3 and 5.2 mgL day of ketocarotenoids and EPA respectively, in a single cultivation phase, even in absence of stressing conditions. Genome sequencing of S4 strain allowed to identify 199 single nucleotide polymorphisms (SNP): among the mutated genes, mutations in a carotenoid oxygenase gene and in a glutamate synthase gene could explain the different carotenoids content and the lower chlorophylls content, respectively.
CONCLUSIONS
By chemical mutagenesis and selection of strain with increased carotenoids to chlorophyll ratio it was possible to isolate a new Nannochloropsis gaditana strain, called S4 strain, characterized by increased lipids and ketocarotenoids accumulation. S4 strain can thus be considered as novel platform for ketocarotenoids and EPA production for different industrial applications.
Topics: Carotenoids; Chlorophyll; Eicosapentaenoic Acid; Microalgae; Stramenopiles; Xanthophylls
PubMed: 35710482
DOI: 10.1186/s12934-022-01847-9 -
International Journal of Environmental... Oct 2022Oxidative stress is associated with deterioration of endurance and muscle strength, which are mostly accompanied by aging. Astaxanthin supplement has excellent...
Oxidative stress is associated with deterioration of endurance and muscle strength, which are mostly accompanied by aging. Astaxanthin supplement has excellent antioxidant activity without any pro-oxidative properties. In this study, we investigated how astaxanthin supplementation affects walking endurance and muscle strength in nursing home residents. Healthy elderly individuals (age: 67 to 94) were divided into two groups: 13 subjects received a daily dose of 24 mg of astaxanthin for 16 weeks (astaxanthin group) and 11 subjects received a placebo (placebo group). These subjects were compared using body component measurements, serum d-ROM levels, the distance of 6-min walking, blood lactate levels after the 6-min walking test, and muscle strength. After supplementation, the levels of d-ROMs and blood lactate after the 6-min walking test in the astaxanthin group significantly decreased compared with the placebo group ( < 0.05). Additionally, the walking distance was significantly higher in the astaxanthin group than in the placebo group ( < 0.05), despite a significant reduction in lactate levels after 6-MWT ( < 0.05). However, no significant intergroup differences were observed in muscle mass and strength. Astaxanthin supplement for 16 weeks is effective to increase the endurance capacity of the elderly. Astaxanthin supplement suppresses d-ROMs at rest and lactic acid production after the 6-min walk test. In contrast, astaxanthin supplement did not show significant intergroup differences in the muscle mass and strength. Therefore, the effect was most likely accompanied by an increase in endurance instead of an increase in muscle strength.
Topics: Humans; Aged; Aged, 80 and over; Antioxidants; Walking; Oxidative Stress; Dietary Supplements; Lactic Acid; Nursing Homes
PubMed: 36294075
DOI: 10.3390/ijerph192013492 -
Biomolecules Mar 2023Astaxanthin is a carotenoid with excellent antioxidant activity. However, this small lipid-soluble molecule is insoluble in water and has low stability. Although this...
Astaxanthin is a carotenoid with excellent antioxidant activity. However, this small lipid-soluble molecule is insoluble in water and has low stability. Although this situation can be improved when astaxanthin is prepared as a nanosuspension, the aqueous form is still not as convenient and safe as the dry powder form for storage, transport, and use. The lyophilization process provides better protection for thermosensitive materials, but this leads to collapse and agglomeration between nanoparticles. To improve this situation, appropriate lyophilization protectants are needed to offer support between the nanoparticles, such as sugars, amino acids, and hydroxy alcohols. The purpose of this work is to screen lyophilization protectants by single-factor experiments and response surface optimization experiments and then explore the optimal ratio of compound lyophilization protectants, and finally, make excellent astaxanthin/BSA/chitosan nanosuspension (ABC-NPs) lyophilized powder. The work shows that the optimal ratio of the compounding lyophilization protectant is 0.46% oligomeric mannose, 0.44% maltose, and 0.05% sorbitol (/). The ABC-NPs lyophilized powder prepared under the above conditions had a re-soluble particle size of 472 nm, with a ratio of 1.32 to the particle size of the sample before lyophilization. The lyophilized powder was all in the form of a pink layer. The sample was fluffy and dissolved entirely within 10 s by shaking with water. Consequently, it is expected to solve the problem of inconvenient storage and transportation of aqueous drugs and to expand the application of nanomedicine powders and tablets.
Topics: Chitosan; Powders; Freeze Drying; Water; Nanoparticles
PubMed: 36979431
DOI: 10.3390/biom13030496 -
Nutrients Sep 2022Oxidative stress induces DNA damage which can be repaired by DNA repair proteins, such as Ku70/80. Excess reactive oxygen species (ROS) stimulate the activation of...
Oxidative stress induces DNA damage which can be repaired by DNA repair proteins, such as Ku70/80. Excess reactive oxygen species (ROS) stimulate the activation of caspase-3, which degrades Ku 70/80. Cells with decreased Ku protein levels undergo apoptosis. Astaxanthin exerts antioxidant activity by inducing the expression of catalase, an antioxidant enzyme, in gastric epithelial cells. Therefore, astaxanthin may inhibit oxidative stress-induced DNA damage by preventing Ku protein degradation and thereby suppressing apoptosis. Ku proteins can be degraded via ubiquitination and neddylation which adds ubiquitin-like protein to substrate proteins. We aimed to determine whether oxidative stress decreases Ku70/80 expression through the ubiquitin-proteasome pathway to induce apoptosis and whether astaxanthin inhibits oxidative stress-induced changes in gastric epithelial AGS cells. We induced oxidative stress caused by the treatment of β-D-glucose (G) and glucose oxidase (GO) in the cells. As a result, the G/GO treatment increased ROS levels, decreased nuclear Ku protein levels and Ku-DNA-binding activity, and induced the ubiquitination of Ku80. G/GO increased the DNA damage marker levels (γ-H2AX; DNA fragmentation) and apoptosis marker annexin V-positive cells and cell death. Astaxanthin inhibited G/GO-induced alterations, including Ku degradation in AGS cells. MLN4924, a neddylation inhibitor, and MG132, a proteasome inhibitor, suppressed G/GO-mediated DNA fragmentation and decreased cell viability. These results indicated that G/GO-induced oxidative stress causes Ku protein loss through the ubiquitin-proteasome pathway, resulting in DNA fragmentation and apoptotic cell death. Astaxanthin inhibited oxidative stress-mediated apoptosis via the reduction of ROS levels and inhibition of Ku protein degradation. In conclusion, dietary astaxanthin supplementation or astaxanthin-rich food consumption may be effective for preventing or delaying oxidative stress-mediated cell damage by suppressing Ku protein loss and apoptosis in gastric epithelial cells.
Topics: Annexin A5; Antioxidants; Apoptosis; Caspase 3; Catalase; DNA; DNA-Binding Proteins; Epithelial Cells; Glucose; Glucose Oxidase; Ku Autoantigen; Oxidative Stress; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Proteolysis; Reactive Oxygen Species; Ubiquitins; Xanthophylls
PubMed: 36235593
DOI: 10.3390/nu14193939 -
Marine Drugs Nov 2020Carotenoids, one of the most common types of natural pigments, can influence the colors of living organisms. More than 750 kinds of carotenoids have been identified.... (Review)
Review
Carotenoids, one of the most common types of natural pigments, can influence the colors of living organisms. More than 750 kinds of carotenoids have been identified. Generally, carotenoids occur in organisms at low levels. However, the total amount of carotenoids in nature has been estimated to be more than 100 million tons. There are two major types of carotenoids: carotene (solely hydrocarbons that contain no oxygen) and xanthophyll (contains oxygen). Carotenoids are lipid-soluble pigments with conjugated double bonds that exhibit robust antioxidant activity. Many carotenoids, particularly astaxanthin (ASX), are known to improve the antioxidative state and immune system, resulting in providing disease resistance, growth performance, survival, and improved egg quality in farmed fish without exhibiting any cytotoxicity or side effects. ASX cooperatively and synergistically interacts with other antioxidants such as α-tocopherol, ascorbic acid, and glutathione located in the lipophilic hydrophobic compartments of fish tissue. Moreover, ASX can modulate gene expression accompanying alterations in signal transduction by regulating reactive oxygen species (ROS) production. Hence, carotenoids could be used as chemotherapeutic supplements for farmed fish. Carotenoids are regarded as ecologically friendly functional feed additives in the aquaculture industry.
Topics: Animal Feed; Animals; Aquaculture; Carotenoids; Dietary Supplements; Fishes; Food Safety; Humans; Nutritive Value; Seafood; Xanthophylls
PubMed: 33227976
DOI: 10.3390/md18110568 -
Marine Drugs May 2020Astaxanthin is a naturally occurring red carotenoid pigment belonging to the family of xanthophylls, and is typically found in marine environments, especially in... (Review)
Review
Astaxanthin is a naturally occurring red carotenoid pigment belonging to the family of xanthophylls, and is typically found in marine environments, especially in microalgae and seafood such as salmonids, shrimps and lobsters. Due to its unique molecular structure, astaxanthin features some important biologic properties, mostly represented by strong antioxidant, anti-inflammatory and antiapoptotic activities. A growing body of evidence suggests that astaxanthin is efficacious in the prevention and treatment of several ocular diseases, ranging from the anterior to the posterior pole of the eye. Therefore, the present review aimed at providing a comprehensive evaluation of current clinical applications of astaxanthin in the management of ocular diseases. The efficacy of this carotenoid in the setting of retinal diseases, ocular surface disorders, uveitis, cataract and asthenopia is reported in numerous animal and human studies, which highlight its ability of modulating several metabolic pathways, subsequently restoring the cellular homeostatic balance. To maximize its multitarget therapeutic effects, further long-term clinical trials are warranted in order to define appropriate dosage, route of administration and exact composition of the final product.
Topics: Animals; Anti-Inflammatory Agents; Crustacea; Dietary Supplements; Eye Diseases; Humans; Marine Biology; Xanthophylls
PubMed: 32370045
DOI: 10.3390/md18050239 -
Marine Drugs Jul 2015Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed.... (Review)
Review
Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma (PPARγ). Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Proliferation; Gap Junctions; Humans; NF-kappa B; Signal Transduction; Xanthophylls
PubMed: 26184238
DOI: 10.3390/md13074310 -
Molecules (Basel, Switzerland) Feb 2019Astaxanthin, a natural pigment carotenoid, is well known for its potential benefits to human health. However, its applications in the food industry are limited, due to...
Astaxanthin, a natural pigment carotenoid, is well known for its potential benefits to human health. However, its applications in the food industry are limited, due to its poor water-solubility and chemical instability. Six different emulsifiers were used to prepare astaxanthin-loaded emulsions, including whey protein isolate (WPI), polymerized whey protein (PWP), WPI-lecithin, PWP-lecithin, lecithin, and Tween20. The droplet size, zeta potential, storage stability, cytotoxicity, and astaxanthin uptake by Caco-2 cells were all investigated. The results showed that the droplet size of the emulsions ranged from 194 to 287 nm, depending on the type of emulsifier used. The entrapment efficiency of astaxanthin was as high as 90%. The astaxanthin-loaded emulsions showed good physicochemical stability during storage at 4 °C. The emulsifier type had a significant impact on the degradation rate of astaxanthin ( < 0.05). Cellular uptake of astaxanthin encapsulated into the emulsions was significantly higher than free astaxanthin ( < 0.05). Emulsion stabilized with WPI had the highest cellular uptake of astaxanthin (10.0 ± 0.2%), followed, in order, by that with PWP (8.49 ± 0.1%), WPI-lecithin (5.97 ± 0.1%), PWP-lecithin (5.05 ± 0.1%), lecithin (3.37 ± 0.2%), and Tween 20 (2.1 ± 0.1%). Results indicate that the whey protein-based emulsion has a high potential for improving the cellular uptake of astaxanthin.
Topics: Biological Transport; Caco-2 Cells; Carotenoids; Drug Carriers; Drug Liberation; Emulsifying Agents; Emulsions; Humans; Lecithins; Molecular Structure; Particle Size; Polymerization; Polysorbates; Solubility; Structure-Activity Relationship; Surface Properties; Water; Whey Proteins; Xanthophylls
PubMed: 30781596
DOI: 10.3390/molecules24040727