astaxanthine and Body-Weight

This study was aimed to explore the effect of astaxanthin (ASTX) and copper (Cu) supplementation on the growth, immunity, antioxidant, and blood biochemical status of growing Murrah buffalo heifers. Twenty-eight Murrah buffalo heifers were selected and randomly divided into 4 groups (n = 7) after blocking by body weight (BW) (129.86 ± 5.37 kg) and age (9.05 ± 1.02 months). The heifers were fed basal total mixed ration diet without supplementation (CON) or with ASTX (0.20 mg/kg BW; AX), Cu (10 mg/kg DM; CU), or ASTX + Cu (0.20 mg/kg BW + 10 mg/kg DM; AX + CU) for 90 days of study period. The result showed that BW and dry matter intake (DMI) were significantly higher (P < 0.05) in AX + CU than that in other groups. The average daily gain (ADG) and feed conversion efficiency (FCE) were statistically higher (P < 0.05) in treatments than the values observed in CON. The feed conversion ratio (FCR) was reported significantly lower (P < 0.05) in the AX + CU group followed by AX, CU, and CON groups. The total leukocytes count (TLC), lymphocytes, and total immunoglobulin (TIG) were statistically higher (P < 0.05) in AX + CU groups than that found in other groups. However, neutrophil % decreased (P < 0.05) in the AX + CU group than its level in other groups. Superoxide dismutase (SOD), catalase (CAT), and total antioxidant (TAA) levels were observed higher (P < 0.05) in treatments supplemented with ASTX, Cu, or both than CON group. Thiobarbituric acid reactive substance (TBARS) concentration was lower (P < 0.05) in treatments than its level found in the CON group. Glucose level was higher (P < 0.05); however, non-esterifies fatty acid (NEFA) was lower (P < 0.05) in AX + CU than that in others groups. The level of cholesterol (CH), HDL cholesterol (HDL-CH), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were reported lower (P < 0.05) in the AX + CU group followed by CU, AX, and CON groups. The copper (Cu) level was higher (P < 0.05) in CU and AX + CU than AX and CON groups. The result of the present study indicated that the supplementation of ASTX, Cu alone, or their combination improved the growth, immunity, antioxidant status, and liver function of growing heifers.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animal Feed; Animals; Antioxidants; Aspartate Aminotransferases; Body Weight; Buffaloes; Catalase; Cattle; Cholesterol, HDL; Copper; Diet; Dietary Supplements; Fatty Acids, Nonesterified; Female; Glucose; Immunoglobulins; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Xanthophylls

The purpose of this study was to investigate the effect of astaxanthin on metabolic cataract in rats with type 1 diabetes and its antioxidant capacity to lens.. Rats were randomly divided into four groups (n = 8): control group, diabetes mellitus (DM) group, low-dose astaxanthin (DM + AL) and low-dose astaxanthin (DM + AH) group. A rat model of type I diabetes mellitus was established by intraperitoneal injection of 60 mg/kg streptozotocin (STZ). After successful modeling, rats in the administration group were given different doses of astaxanthin (AST) for 12 weeks. The lens opacity of rats was observed by slit-lamp camera system. The double antibody sandwich method was used to detect the levels of advanced glycation end product (AGE), lipid peroxide/malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) in the lens. Hematoxylin-eosin (HE) staining was used to examine the morphologic changes in the lens.. The severity of cataract in the lens was obviously increased after induced by STZ, whereas it was significantly decreased after treatment with AST (p < .05, respectively). In addition, in the AST groups, the levels of AGE and MDA in the lens tissue were notably decreased when compared with those in the DM group (p < .05, respectively). However, the levels of GSH, SOD, and CAT were increased in the AST group in comparison with those in the DM group (p < .05, respectively).. Astaxanthin may play an antioxidant role in the lens. Additionally, it exerts a protective function in the lens by delaying the development and progression of metabolic cataract and inhibiting the oxidative stress of lens in diabetic rats.

Topics: Animals; Anterior Eye Segment; Antioxidants; Blood Glucose; Body Weight; Cataract; Diabetes Mellitus, Type 1; Disease Progression; Lens, Crystalline; Male; Rats, Sprague-Dawley; Retina; Xanthophylls

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Body Weight; Cardiotonic Agents; Caspase 3; Caspase 9; Electrocardiography; Heart Rate; Kelch-Like ECH-Associated Protein 1; Male; Mice, Inbred C57BL; Mitochondria; Myocardium; Myocytes, Cardiac; NF-E2-Related Factor 2; Ochratoxins; Organ Size; Oxidative Stress; Protective Agents; Signal Transduction; Xanthophylls

Increasing pressure of life may bring some disease risks and stress injuries, which may destroy the immune system and result in intestinal mucosal immune disorders. In this study, the effects of different doses of ATX (30 mg per kg b.w., 60 mg per kg b.w. and 120 mg per kg b.w.) on intestinal mucosal functions were explored in cyclophosphamide (Cy)-induced immunodeficient mice. The results showed that continuous intraperitoneal injection of 100 mg per kg b.w. Cy for three days led to a persistent decrease of body weight and a range of abnormalities in the intestine of C57BL/6 mice. However, administration of ATX at 60 and 120 mg per kg b.w. could effectively prevent intestinal mucosa from this damage, including reduced levels of oxidative stress (MDA, GSH and GSH-PX), increased intestinal morphological structural integrity, stimulative growth of goblet cells and mucous secretion, decreased development of Paneth cells and expression levels of antimicrobial peptides (AMPs) (Reg-3γ and lysozyme), increased IgA secretion, ameliorative main gut flora (especially total bacteria, Lactobacillus and Enterobacteriaceae spp. ) and its metabolites (acetic acid, propionic acid and butyric acid). These protective effects of ATX were better than those of control-β-carotene in general. Our results may provide a new protective measure to keep intestinal mucosal barriers, which is of great significance for maintaining immune function in the body.

Topics: Animals; Body Weight; Butyric Acid; Cytokines; Fatty Acids, Volatile; Feces; Gastrointestinal Microbiome; Gene Expression Regulation; Goblet Cells; Intestinal Mucosa; Lactobacillus; Male; Mice; Mice, Inbred C57BL; Organ Size; Oxidative Stress; Paneth Cells; RNA, Messenger; Xanthophylls

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key cellular defense mechanism against oxidative stress. Recent studies have shown that astaxanthin protects against oxidative stress via Nrf2. In this study, we investigated the emphysema suppression effect of astaxanthin via Nrf2 in mice. Mice were divided into four groups: control, smoking, astaxanthin, and astaxanthin + smoking. The mice in the smoking and astaxanthin + smoking groups were exposed to cigarette smoke for 12 weeks, and the mice in the astaxanthin and astaxanthin + smoking groups were fed a diet containing astaxanthin. Significantly increased expression levels of Nrf2 and its target gene, heme oxygenase-1 (HO-1), were found in the lung homogenates of astaxanthin-fed mice. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was significantly decreased, and emphysema was significantly suppressed. In conclusion, astaxanthin protects against oxidative stress via Nrf2 and ameliorates cigarette smoke-induced emphysema. Therapy with astaxanthin directed toward activating the Nrf2 pathway has the potential to be a novel preventive and therapeutic strategy for COPD.

Topics: Animals; Body Weight; Emphysema; Female; Heme Oxygenase-1; Lung; Macrophages; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Neutrophils; NF-E2-Related Factor 2; Smoking; Xanthophylls

Osteoporosis is characterized by a reduction of the bone mineral density (BMD) and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST) has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we examined the antiosteoporotic effect of AST on bone mass in ovariectomized (OVX) mice and its possible mechanism of action. The administration of AST (5, 10 mg/kg) for 6 weeks suppressed the enhancement of serum calcium, inorganic phosphorus, alkaline phosphatase, total cholesterol, and tartrate-resistant acid phosphatase (TRAP) activity. The bone mineral density (BMD) and bone microarchitecture of the trabecular bone in the tibia and femur were recovered by AST exposure. Moreover, in the in vitro experiment, we demonstrated that AST inhibits osteoclast formation through the expression of the nuclear factor of activated T cells (NFAT) c1, dendritic cell-specific transmembrane protein (DC-STAMP), TRAP, and cathepsin K without any cytotoxic effects on bone marrow-derived macrophages (BMMs). Therefore, we suggest that AST may have therapeutic potential for the treatment of postmenopausal osteoporosis.

Topics: Animals; Biomarkers; Body Weight; Bone Density; Bone Marrow Cells; Bone Resorption; Cell Differentiation; Female; Femur; Gene Expression Regulation; Macrophages; Male; Mice, Inbred ICR; Organ Size; Osteoclasts; Osteogenesis; Osteoporosis; RANK Ligand; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Tibia; Uterus; Xanthophylls

Astaxanthin is a natural carotenoid with strong antioxidant activity that has been used for decades as a nutrient/color additive and it has recently been marketed as a health supplement. Astaxanthin can be synthesized in a wide range of microalgae, yeast, and bacteria. As genes directing astaxanthin biosynthesis in various organisms have been cloned, this study assessed the safety of astaxanthin crystal produced by Escherichia coli K-12 harboring plasmids carrying astaxanthin biosynthetic genes. The astaxanthin crystal contains a total carotenoid content of 950 mg/g and an astaxanthin content of 795 mg/g. Subchronic oral toxicity and prenatal developmental toxicity of the astaxanthin in rats were conducted in accordance with the Guidelines of Health Food Safety Assessment promulgated by Food and Drug Administration of Taiwan which is based on OECD guidelines 408 and 414. Both male and female Sprague-Dawley (SD) rats (12 for each gender) receiving the astaxanthin crystal at 1.2, 240.0, or 750.0 mg/kg/day in olive oil via oral gavage for 90 days showed no changes in body weight gains, hematology and serum chemistry values and hepatic enzyme stability, organ integrity and organ weight. Except the higher food consumption observed in rats receiving 750.0 mg/g astaxanthin crystal, administration of the astaxanthin crystal to 25-27 pregnant female rats in each group throughout the period of organogenesis (G6-G15) produced no adverse effects on fetal organogenesis. Based on the results, we propose that the no-observable-adverse-effect level (NOAEL) of the astaxanthin crystal extracted from genetically modified E. coli K-12 is 750.0 mg/kg bw/day.

Topics: Administration, Oral; Animals; Body Weight; Dose-Response Relationship, Drug; Escherichia coli K12; Female; Male; No-Observed-Adverse-Effect Level; Organ Size; Pregnancy; Rats; Rats, Sprague-Dawley; Taiwan; Time Factors; Xanthophylls

The hematopoietic system is especially sensitive to total body irradiation (TBI), and myelosuppression is one of the major effects of TBI. Astaxanthin (ATX) is a powerful natural anti-oxidant with low toxicity. In this study, the effect of ATX on hematopoietic system injury after TBI was investigated.. Flow cytometry was used to detect the proportion of hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs), the level of intracellular reactive oxygen species (ROS), expression of cytochrome C, cell apoptosis, and NRF2-related proteins. Immunofluorescence staining was used to detect Nrf2 translocation. Western blot analysis was used to evaluate the expression of apoptotic-related proteins. Enzymatic activities assay kits were used to analyze SOD2, CAT, and GPX1 activities.. Compared with the TBI group, ATX can improve radiation-induced skewed differentiation of peripheral blood cells and accelerate hematopoietic self-renewal and regeneration. The radio-protective effect of ATX is probably attributable to the scavenging of ROS and the reduction of cell apoptosis. These changes were associated with increased activation of Nrf2 and downstream anti-oxidative proteins, and regulation of apoptotic-related proteins.. This study suggests that ATX could be used as a potent therapeutic agent to protect the hematopoietic system against TBI-induced bone marrow suppression.

Topics: Animals; Apoptosis; Blood Cells; Body Weight; Bone Marrow Cells; Cell Differentiation; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Hematopoietic Stem Cells; Hematopoietic System; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; NF-E2-Related Factor 2; Oxidative Stress; Proto-Oncogene Proteins c-kit; Reactive Oxygen Species; Superoxide Dismutase; Whole-Body Irradiation; Xanthophylls

The objective of this study was to determine if astaxanthin (ASTX), a xanthophyll carotenoid, can prevent obesity-associated metabolic abnormalities, inflammation and fibrosis in diet-induced obesity (DIO) and nonalcoholic steatohepatitis (NASH) mouse models. Male C57BL/6J mice were fed a low-fat (6% fat, w/w), a high-fat/high-sucrose control (HF/HS; 35% fat, 35% sucrose, w/w), or a HF/HS containing ASTX (AHF/HS; 0.03% ASTX, w/w) for 30 weeks. To induce NASH, another set of mice was fed a HF/HS diet containing 2% cholesterol (HF/HS/HC) a HF/HS/HC with 0.015% ASTX (AHF/HS/HC) for 18 weeks. Compared to LF, HF/HS significantly increased plasma total cholesterol, triglyceride and glucose, which were lowered by ASTX. ASTX decreased hepatic mRNA levels of markers of macrophages and fibrosis in both models. The effect of ASTX was more prominent in NASH than DIO mice. In epididymal fat, ASTX also decreased macrophage infiltration and M1 macrophage marker expression, and inhibited hypoxia-inducible factor 1-α and its downstream fibrogenic genes in both mouse models. ASTX significantly decreased tumor necrosis factor α mRNA in the splenocytes from DIO mice upon lipopolysaccharides stimulation compared with those from control mice fed an HF/HS diet. Additionally, ASTX significantly elevated the levels of genes that regulate fatty acid β-oxidation and mitochondrial biogenesis in the skeletal muscle compared with control obese mice, whereas no differences were noted in adipose lipogenic genes. Our results indicate that ASTX inhibits inflammation and fibrosis in the liver and adipose tissue and enhances the skeletal muscle's capacity for mitochondrial fatty acid oxidation in obese mice.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Dietary Supplements; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Lipids; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Panniculitis; Xanthophylls

We evaluated whether orally administered astaxanthin (AST) protects against oxidative damage in the ocular tissues of streptozotocin (STZ)-induced diabetic rats.. Fifty 6-week-old female Wistar rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 40) or to remain uninduced (n = 10). The diabetic rats were randomly selected into four groups and they were separately administered normal saline, 0.6 mg/kg AST, 3 mg/kg AST, or 0.5 mg/kg lutein daily for eight weeks. Retinal functions of each group were evaluated by electroretinography. The expression of oxidative stress and inflammatory mediators in the ocular tissues was then assessed by immunohistochemistry, western blot analysis, ELISA, RT-PCR, and electrophoretic mobility shift assay (EMSA). Retinal functions were preserved by AST and lutein in different levels. Ocular tissues from AST- and lutein-treated rats had significantly reduced levels of oxidative stress mediators (8-hydroxy-2'-deoxyguanosine, nitrotyrosine, and acrolein) and inflammatory mediators (intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fractalkine), increased levels of antioxidant enzymes (heme oxygenase-1 and peroxiredoxin), and reduced activity of the transcription factor nuclear factor-kappaB (NF-κB).. The xanthophyll carotenoids AST and lutein have neuroprotective effects and reduce ocular oxidative stress, and inflammation in the STZ diabetic rat model, which may be mediated by downregulation of NF-κB activity.

Topics: Animals; Antioxidants; Aqueous Humor; Blood Glucose; Body Weight; Chemokine CCL2; Diabetes Mellitus, Experimental; Electroretinography; Female; Gene Expression; Gene Expression Regulation, Enzymologic; Inflammation Mediators; Intercellular Adhesion Molecule-1; Lutein; NF-kappa B; Oxidative Stress; Protective Agents; Rats; Retina; Retinal Ganglion Cells; RNA, Messenger; Xanthophylls

Lipopolysaccharide (LPS)-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST), a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA) apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group) were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10) for seven days and then were LPS-challenged (i.p., 5 mg/kg). The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), creatinine (CRE), hepatic malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS), suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day). Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity.

Topics: Animals; Antioxidants; Body Weight; Chemical and Drug Induced Liver Injury; Fibrinolytic Agents; Glutathione; Interleukin-6; Lipopolysaccharides; Liposomes; Male; Malondialdehyde; Nanocapsules; NF-kappa B; Nitric Oxide Synthase Type II; Organ Size; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Xanthophylls

A high-fat diet (HFD) promotes the oxidative stress formation, which in turn has hazardous effects on reproductive system and fertility. The present study examines the potential positive effects of a restricted high-fat diet (RHFD) and antioxidants consumption on sperm parameters and testis tissue in rats.. Male rats (n = 48) were divided into four groups (12 in each group): control group (Cont), HFD group, RHFD, and RHFD with astaxanthin and vitamins E and C group (RHFDA). After 12 weeks, serum analysis and sperm parameters study were performed. Sections of fixed testes were stained with Hematoxilin and Eosin to study the histological changes. A one-way ANOVA was used to compare the data.. HFD fed animals presented significant increase in weight load and serum low density lipoprotein (LDL-C) levels (P < 0.05). The sperm count in RHFD was lower than three other groups (P < 0.05) and sperm motility of RHFDA group was significantly higher than HFD and RHFD groups (P < 0.05). The histological study was showed a significant increase in spermatogonium number in RHFDA compared to three other groups (P < 0.05). The number of spermatocyte I and spermatid in RHFD was significantly (P < 0.05) lower than Cont and HFD groups.. HFD and obesity can affect sperm parameters and spermatogenesis and antioxidants consumption may improve their quality. Although the RHFD is a benefit way in weight loss and decrease of LDL-C of serum, but it is suggested that is not effective on sperm quality improvement.

Topics: Animals; Antioxidants; Ascorbic Acid; Body Weight; Caloric Restriction; Diet, High-Fat; Infertility, Male; Lipoproteins, LDL; Male; Obesity; Oxidative Stress; Rats; Rats, Wistar; Sperm Count; Sperm Motility; Spermatids; Spermatocytes; Vitamin E; Xanthophylls

Astaxanthin, a naturally occurring xanthophyll, is commercially used as a coloring agent in salmon feed, but also marketed as a dietary supplement. The objective of this study was to investigate the subchronic toxicity of synthetic [3S, 3'S]-Astaxanthin in rats. A powder formulation containing approximately 20% [3S, 3'S]-Astaxanthin was administered via the diet to groups of 10 male and 10 female Wistar rats at concentrations of 5000, 15,000 and 50,000 ppm for a period of 13 weeks. A formulation of comparable composition but without [3S, 3'S]-Astaxanthin served as a placebo control. There were no effects observed on survival, clinical examinations, clinical pathology, estrous cycle as well as on sperm parameters. At terminal necropsy, a macroscopically visible brown-blue discoloration of the gastrointestinal contents was noted which was considered to be secondary to the violet-brown color of the test material. No other significant or dose-related abnormalities were found in the tissues collected at termination. Our observations support that ingestion of [3S, 3'S]-Astaxanthin of up to 700-920 mg/kg bw/day in rats in a gelatin/carbohydrate formulation is without adverse effects.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Bilirubin; Blood Glucose; Body Weight; Cholesterol; Creatinine; Dietary Supplements; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Male; Organ Size; Rats; Rats, Wistar; Serum Albumin; Toxicity Tests, Subchronic; Triglycerides; Xanthophylls

Chronic inflammation appears to play a critical role in sickness behavior caused by diabetes mellitus. Astaxanthin has been used in treating diabetes mellitus and diabetic complications because of its neuroprotective and anti-inflammatory actions. However, whether astaxanthin can improve sickness behavior induced by diabetes and its potential mechanisms are still unknown. The aim of this study was to investigate the effects of astaxanthin on diabetes-elicited abnormal behavior in mice and its corresponding mechanisms. An experimental diabetic model was induced by streptozotocin (150 mg/kg) and astaxanthin (25 mg/kg/day) was provided orally for 10 weeks. Body weight and water consumption were measured, and the sickness behavior was evaluated by the open field test (OFT) and closed field test (CFT). The expression of glial fibrillary acidic protein (GFAP) was measured, and the frontal cortical cleaved caspase-3 positive cells, interleukin-6 (IL-6), and interleukin-1β (IL-1β) expression levels were also investigated. Furthermore, cystathionine β-synthase (CBS) in the frontal cortex was detected to determine whether the protective effect of astaxanthin on sickness behavior in diabetic mice is closely related to CBS. As expected, we observed that astaxanthin improved general symptoms and significantly increase horizontal distance and the number of crossings in the OFT and CFT. Furthermore, data showed that astaxanthin could decrease GFAP-positive cells in the brain and down-regulate the cleaved caspase-3, IL-6, and IL-1β, and up-regulate CBS in the frontal cortex. These results suggest that astaxanthin provides neuroprotection against diabetes-induced sickness behavior through inhibiting inflammation, and the protective effects may involve CBS expression in the brain.

Topics: Animals; Anti-Inflammatory Agents; Body Weight; Brain; Diabetes Mellitus, Experimental; Drinking; Illness Behavior; Male; Mice; Mice, Inbred ICR; Treatment Outcome; Xanthophylls

Diabetes-induced cognitive deficit (DICD) is a prevalent disease with substantial morbidity and mortality and as a global health problem with serious economic burdens. Astaxanthin (AST) has a good prospect in production of nutritional, medical, and particularly functional health drug. The present study was aimed to study the effect of AST on DICD in diabetes mellitus (DM) rat through suppression of oxidative stress, nitric oxide synthase (NOS) pathway, inflammatory reaction and upregulation of PI3K/Akt. In the study, Morris water maze teat was used to detect the cognitive function of DM rat. Afterwards, we measured the body weight and blood glucose levels of DM rats. Then, oxidative stress, the activities of eNOS and iNOS, and inflammatory factors were analyzed using a commercial kit in cerebral cortex and hippocampus. Finally, the caspase-3/9 and phosphoinositide 3-kinase (PI3K)/Akt expressions were also checkout with Real Time PCR and immunoblotting, respectively. In this experiment, AST could availably enhance the body weight and reduce blood glucose levels of DM rats. Moreover, AST could observably perfect cognitive function of DM rat. Next, the activities of oxidative stress, nitric oxide synthase and inflammation were distinctly diminution in DM rat, after the treatment of AST. Furthermore, our present results demonstrated that AST had the protective effect on the brain cell of DM rat, decreased the caspase-3/9 expression and promoted the expression of PI3K/Akt in cerebral cortex and hippocampus.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Blood Glucose; Body Weight; Brain; Caspase 3; Caspase 9; Cognition; Cognition Disorders; Diabetes Mellitus, Experimental; Inflammation; Inflammation Mediators; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Rats, Wistar; Signal Transduction; Time Factors; Xanthophylls

The present investigation in Sprague-Dawley rats (SD) was designed to examine effects of astaxanthin (Asta) at different doses on elevated blood pressure (BP) and glucose-insulin perturbations produced by heavy sucrose ingestion. We also examined effects of Asta on BP during restraint stress. SD were divided into six groups each containing eight rats. All SD ate a basic diet of ground regular rat chow with sucrose added at 30% w/w. The Control group received only the basic diet containing added sucrose, while the other five groups each received the same diet with added test material: captopril, (30 mg/Kg), pioglitazone (15.0 mg/Kg), low Asta (25 mg/Kg), medium Asta (50 mg/kg) or high Asta (100 mg/Kg). Many tests were carried out to examine the mechanisms behind the effects of Asta on BP (serum ACE activity, losartan challenge, and LNAME challenge) and the glucose-insulin system (glucose tolerance, HOMA measurement, and insulin challenge). In SD, a relatively low dose of Asta decreased SBP, but produced no major changes in the glucose-insulin system simulating results from a previous study using Zucker Fatty Rats. Increasing the dose of Asta resulted in both a lowering of elevated systolic BP and enhanced insulin sensitivity determined by many different estimations. BP lowering was consistent with changes in the renin-angiotensin (RAS) and nitric oxide (NO) systems. At the examined doses of each, captopril lowered BP in SD without influencing glucose-insulin metabolism, whereas pioglitazone favorably affected glucose-insulin metabolism while showing essentially no effects on BP. Accordingly, Asta beneficially affects both sucrose-induced elevations of BP and insulin resistance at relatively high doses in SD. Also, Asta at higher doses lessens restraint stress, whereas, captopril and pioglitazone did not at the doses examined, even though they influenced the BP and glucose-insulin systems respectively.

Topics: Animals; Blood Pressure; Body Weight; Dose-Response Relationship, Drug; Drinking Behavior; Feeding Behavior; Glucose Tolerance Test; Insulin Resistance; Male; Rats; Rats, Sprague-Dawley; Xanthophylls

The present study was designed to examine whether astaxanthin (ASX, 3,3-dihydroxybeta, beta-carotene-4,4-dione, CAS 472-61-7), a dietary antioxidant carotenoid that is naturally present in algae, crustaceans, and fish, has a protective effect on endothelial dysfunction of aortas in diabetic rats and the possible molecular mechanism involved. Male Wistar rats were randomly divided into four groups: control rats, diabetic rats, diabetic rats treated with ASX (10 mg/kg/d), and control rats treated with ASX. Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/ kg). STZ-induced diabetes in rats was complicated with excessive oxidative stress and endothelial dysfunction, increased serum oxidized low-density lipoprotein (ox-LDL) and aortic malondialdehyde (MDA) levels, inhibited endothelium-dependent vasorelaxation to acetylcholine (ACh) and unaffected endothelium-dependent vasorelaxation to sodium nitroprusside (SNP). Simultaneously, lectin-like oxLDL receptor-i (LOX-1) expression was enhanced and endothelial nitric oxide (NO) synthase (eNOS) expression was reduced in the aortas of diabetic rats. ASX treatment could significantly decrease serum oxLDL and aortic MDA levels, attenuate blunted endothelium-dependent vasodilator responses to ACh, upregulate eNOS expression, and decrease LOX-1 expression. These results indicated that ASX could ameliorate diabetic endothelial dysfunction by inhibiting the ox-LDLLOX-1-eNOS pathway. Treatment with ASX might be clinically useful for diabetic complications associated with endothelial dysfunction.

Topics: Animals; Biomarkers; Blotting, Western; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium; Fibrinolytic Agents; Fluorescent Antibody Technique; Isometric Contraction; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Muscle, Smooth, Vascular; Oxidative Stress; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Vasodilation; Xanthophylls

Astaxanthin, a natural nutritional component, is marketed as a dietary supplement around the world. The primary commercial source for astaxanthin is Haematococcus pluvialis (microalgae). The objective of the present study was to investigate the acute and subchronic toxicity of an astaxanthin-rich biomass of H. pluvialis (AstaCarox). The oral LD(50) of the biomass in rats was greater than 12g/kg body weight. In the subchronic study, Wistar rats (10/sex/group) were fed diets containing 0%, 1%, 5% and 20% of the biomass (weight/weight) for 90 days. trans-Astaxanthin was quantifiable in the plasma of the high-dose treated group only. Compared to the control group, no treatment-related biologically significant effects of astaxanthin were noted on body weight or body weight gain. Biomass feeding did not affect hematological parameters. In the high-dose group, slightly elevated alkaline phosphatase and changes in some urine parameters and an increase in kidney weight in both sexes were noted. Histopathology examinations did not reveal adverse effects except for a marginal increase in pigment in the straight proximal tubule of the kidney in 5/10 female rats treated with the high-dose. These changes were not considered as toxicologically significant. Although the rats in high-dose group received about 9% more fat, it is unlikely that this confounding factor significantly altered the outcome. The no-observed adverse-effect-levels (NOAEL) of the astaxanthin-rich biomass for male and female rats were determined as 14,161 and 17,076mg/kg body weight/day, or 465 and 557mg astaxanthin/kg/day, respectively, the highest dose tested.

Topics: Animals; Biomass; Blood Cell Count; Blood Chemical Analysis; Body Weight; Chlorophyta; Dose-Response Relationship, Drug; Eating; Female; Lethal Dose 50; Male; Organ Size; Rats; Rats, Sprague-Dawley; Survival Analysis; Urinalysis; Xanthophylls

Intracellular redox balance may affect nutrient metabolism in skeletal muscle. Astaxanthin, a carotenoid contained in various natural foods, exerts high antioxidative capacity in the skeletal muscles. The present study investigated the effect of astaxanthin on muscle lipid metabolism in exercise. ICR mice (8 weeks old) were divided into four different groups: sedentary, sedentary treated with astaxanthin, running exercise, and exercise treated with astaxanthin. After 4 weeks of treatment, exercise groups performed treadmill running. Astaxanthin increased fat utilization during exercise compared with mice on a normal diet with prolongation of the running time to exhaustion. Colocalization of fatty acid translocase with carnitine palmitoyltransferase I (CPT I) in skeletal muscle was increased by astaxanthin. We also found that hexanoyl-lysine modification of CPT I was increased by exercise, while astaxanthin prevented this increase. In additional experiment, we found that astaxanthin treatment accelerated the decrease of body fat accumulation with exercise training. Our results suggested that astaxanthin promoted lipid metabolism rather than glucose utilization during exercise via CPT I activation, which led to improvement of endurance and efficient reduction of adipose tissue with training.

Topics: Animals; Body Composition; Body Weight; Carnitine O-Palmitoyltransferase; CD36 Antigens; Energy Metabolism; Fatty Acids, Nonesterified; Glycogen; Lactic Acid; Lipid Metabolism; Mice; Mice, Inbred ICR; Muscle, Skeletal; Organ Size; Oxidation-Reduction; Physical Conditioning, Animal; Physical Endurance; Substrate Specificity; Xanthophylls

Cyclophosphamide (CP), an alkylating agent used in the treatment of several cancers as well as an immunosuppressant in rheumatoid arthritis. It is used against several cancers due to its broad spectrum efficacy, but at the same time possesses unwanted risks for occupational exposure as well as therapy related toxicities to patients. The present study was aimed to investigate the protective effect of astaxanthin (AST) a red carotenoid pigment on CP induced germ cell toxicity in male mice. CP was administered intraperitoneally (i.p.) at the dose of 50, 100 and 200mg/kg body weight to mice (20-25 g) once in a week for a period of five weeks. AST was given at the dose of 25mg/kg per oral (p.o.) for five consecutive days in a week for five weeks. The animals were sacrificed one week after the last injection of CP. The protective effect of AST against CP induced male germ cell toxicity was evaluated using body weight, testes and epididymis weight, sperm count, sperm head morphology, sperm comet assay, histology of testes and TUNEL assay. AST treatment significantly improved the testes weight, sperm count and sperm head morphology as compared to only CP treated animals. The result of comet assay showed that AST treatment significantly restored the sperm DNA damage induced by CP. Further, AST treatment showed protection against CP induced testicular toxicity as evident from testes histology and TUNEL assay. The present results indicate the chemoprotective potential of AST against CP induced germ cell toxicity in mice.

Topics: Animals; Antimutagenic Agents; Antineoplastic Agents, Alkylating; Apoptosis; Body Weight; Comet Assay; Cyclophosphamide; DNA Damage; Dose-Response Relationship, Drug; Drug Antagonism; Epididymis; In Situ Nick-End Labeling; Injections, Intraperitoneal; Male; Mice; Organ Size; Sperm Count; Sperm Head; Testis; Xanthophylls

Glucose and lipid metabolic parameters play crucial roles in metabolic syndrome and its major feature of insulin resistance. This study was designed to investigate whether dietary astaxanthin oil (ASX-O) has potential effects on metabolic syndrome features in an SHR/NDmcr-cp (cp/cp) rat model. Oral administration of ASX (50 mg/kg/day) for 22 weeks induced a significant reduction in arterial blood pressure in SHRcp. It also significantly reduced the fasting blood glucose level, homeostasis index of insulin resistance (HOMA-IR), and improved insulin sensitivity. The results also showed an improved adiponectin level, a significant increase in high-density lipoprotein cholesterol, a significant decrease in plasma levels of triglycerides, and non-esterified fatty acids. Additionally, ASX showed significant effects on the white adipose tissue by decreasing the size of the fat cells. These results suggest that ASX ameliorates insulin resistance by mechanisms involving the increase of glucose uptake, and by modulating the level of circulating lipid metabolites and adiponectin.

Topics: Adiponectin; Adipose Tissue; Administration, Oral; Animals; Blood Cell Count; Blood Glucose; Blood Pressure; Body Weight; Cell Size; Heart Rate; Hypertension; Insulin; Insulin Resistance; Lipid Metabolism; Male; Metabolic Syndrome; Rats; Rats, Inbred SHR; Rats, Wistar; Xanthophylls

Astaxanthin is a natural antioxidant carotenoid that occurs in a wide variety of living organisms. We investigated the effects of astaxanthin supplementation in obese mice fed a high-fat diet. Astaxanthin inhibited the increases in body weight and weight of adipose tissue that result from feeding a high-fat diet. In addition, astaxanthin reduced liver weight, liver triglyceride, plasma triglyceride, and total cholesterol. These results suggest that astaxanthin might be of value in reducing the likelihood of obesity and metabolic syndrome in affluent societies.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Weight; Cholesterol, Dietary; Diet; Dietary Fats; Eating; Female; Lipid Metabolism; Lipids; Liver; Mice; Obesity; Organ Size; Oxygen Consumption; Triglycerides; Xanthophylls

The effects of policosanol (P), of extract of red yeast rice (rice fermented with Monascus purpureus) (RYE) and of astaxanthin (A) (constituents of Armolipid) were investigated in a model of experimental atherosclerosis provoked in the rabbit by atherogenic cholesterol-enriched feed (ACEF). P and RYE and their combination were able to lower the increase of serum total cholesterol and of LDL cholesterol elicited by 3-month feeding with ACEF. They also were able to reduce the increase of blood malondialdehyde (MDA), a tracer of lipid peroxidation by the free radicals released by ACEF. When combined, the substances developed either additive or potentiated effects, supporting the rationale of their combination. Remarkable was the protective effect on lipid infiltration in the aortic wall provoked by ACEF, which was reduced by P and by RYE and almost completely prevented by the addition of A to the P-RYE combination. The results support the rationale of a combination of P, RYE and A as a useful food supplement in hyperlipemic patients.

Topics: Animals; Anticholesteremic Agents; Aorta; Arteriosclerosis; beta Carotene; Body Weight; Cholesterol; Diet, Atherogenic; Drugs, Chinese Herbal; Fatty Alcohols; Female; Free Radicals; Malondialdehyde; Monascus; Rabbits; Triglycerides; Xanthophylls

Astaxanthin is one of many carotenoids present in marine animals, vegetables and fruits. Since carotenoids are known to have antioxidant properties, we tested to determine if astaxanthin could have protective effects in the CCl4-treated rat liver by activating the antioxidant system. Astaxanthin blocked the increase of glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate transaminase (GTP) activity and thiobarbituric acid reactive substances (TBARS) in response to carbon tetrachloride (CCl4), while causing an increase in glutathione (GSH) levels and superoxide dismutase (SOD) activities in the CCl4-treated rat liver. These results suggest that astaxanthin protects liver damage induced by CCl4 by inhibiting lipid peroxidation and stimulating the cellular antioxidant system.

Topics: Adjuvants, Immunologic; Animals; beta Carotene; Body Weight; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Glutathione Reductase; Lipid Peroxidation; Liver; Male; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Xanthophylls

A 13-week oral repeated dose toxicity study of haematococcus color, a food additive mainly composed of astaxanthin, was conducted in male and female F344 rats. Rats were randomly divided into 4 groups each consisting of 10 males and 10 females and given CRF-1 powder diet containing 0%, 0.025%, 0.075%, and 0.25% haematococcus color, correspond to 0%, 0.5%, 1.5%, and 5% as the product. None of the animals died during the administration period. There were no exposure-related changes in body weight gain or food consumptions. Serum biochemical examinations showed dose-related increase in cholesterol, but the differences were slight and not defined as an adverse effect. No effects related to treatment were noted in hematological examinations and organ weights, and no abnormalities that could be ascribed to exposure to heamatococcus color were observed in histopathological examinations. In conclusion, ingestion of haematococcus color in the diet for 13 weeks does not cause any toxicological changes in F344 rats.

Topics: Animals; beta Carotene; Blood; Body Weight; Eating; Female; Food Coloring Agents; Male; Organ Size; Rats; Rats, Inbred F344; Time Factors; Xanthophylls

The chemopreventive effects of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX), on urinary bladder carcinogenesis induced by N-butyl-N(4-hydroxybutyl)nitrosamine (OH-BBN) was investigated in male ICR mice. Mice were given 250 p.p.m. OH-BBN in drinking water for 20 weeks and after a 1 week interval with tap water, water containing AX or CX at a concentration of 50 p.p.m. was administered during subsequent 20 weeks. Other groups of mice were treated with AX or CX alone or untreated. At the end of the study (week 41), the incidences of preneoplastic lesions and neoplasms in the bladder of mice treated with OH-BBN and AX or CX were smaller than those of mice given OH-BBN. In particular, AX administration after OH-BBN exposure significantly reduced the incidence of bladder cancer (transitional cell carcinoma) (P < 0.003). However, the inhibition of the frequencies of such lesions in mice treated with OH-BBN and CX was not significant. Treatment with AX or CX also decreased the number/nucleus of silver-stained nucleolar organizer region proteins (AgNORs), a new index of cell proliferation, in the transitional epithelium exposed to OH-BBN. Preneoplasms and neoplasms induced by OH-BBN, and the antiproliferative potential, was greater for AX than CX. These results indicate that AX is a possible chemopreventive agent for bladder carcinogenesis and such an effect of AX may be partly due to suppression of cell proliferation.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Body Weight; Butylhydroxybutylnitrosamine; Canthaxanthin; Carotenoids; Liver; Male; Mice; Mice, Inbred ICR; Nucleolus Organizer Region; Organ Size; Precancerous Conditions; Silver Staining; Urinary Bladder Neoplasms; Xanthophylls

The chemopreventive action of carotenoids on proteinuria and lymphadenopathy were examined in autoimmune-prone MRL-lpr/lpr (MRL/l) mice. They were fed a synthetic full-fed diet (16-18 kcal/mouse/day) with supplementation of beta-carotene or astaxanthin (0.19 mumoles/mouse, 3 times a week), and the development of lymphadenopathy and proteinuria were examined. MRL/l mice fed a full-fed diet without the supplementation of carotenoids or those fed a calorie-restricted (CR) diet (10-11 kcal/mouse/day, 60% calorie intake of full-fed mice) were employed as controls. CR dramatically delayed the development of proteinuria and lymphadenopathy, as reported previously. Carotenoids also significantly delayed the onset of these symptoms in MRL/l mice fed a full-fed diet. Carotenoids were half as effective as CR and astaxanthin, a carotenoid without provitamin A activity, which appeared to exert more significant preventive actions than beta-carotene in delaying the development of these symptoms. Similar chemopreventive actions of carotenoids were also demonstrated in MRL/l mice fed a regular diet (Lab Chow). CR has been shown to augment IL-2 production and to decrease serum prolactin levels in this strain, which may be related to its dramatic preventive action of autoimmunity. However, carotenoids did not affect IL-2 production nor prolactin levels in full-fed MRL/l mice. The chemopreventive actions of carotenoids observed in autoimmune-prone MRL/l mice may be attributed to yet unknown mechanisms, apart from their provitamin A activity or oxygen-quenching activity.

Topics: Animals; Autoimmune Diseases; beta Carotene; Body Weight; Carotenoids; Diet, Reducing; Energy Intake; Female; Food, Fortified; Interleukin-2; Lymph Nodes; Lymphocyte Activation; Lymphoproliferative Disorders; Mice; Mice, Mutant Strains; Organ Size; Prolactin; Proteinuria; T-Lymphocytes; Xanthophylls