astaxanthine and Disease-Models--Animal

Fetal alcohol spectrum disorder is caused by maternal ethanol exposure; it causes physical, behavioral, cognitive, and neural impairments (Murawski et al., 2015). Mechanisms of FASD causing damage are not yet fully elucidated. Oxidative stress might be one of its mechanisms (Henderson et al., 1995). Yet no effective treatment against FASD has been found other than ethanol abstention (Long et al., 2010).. This review summarizes relevant literatures regarding interventions targeting oxidative stress that may relieve fetal alcohol spectrum disorder.. Astaxanthin was found to mitigate embryonic growth retardation induced by prenatal ethanol treatment through ameliorating the down regulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA) caused by alcohol in a mice model (Zheng et al., 2014; Vabulas et al., 2002). Vitamin E protected against fatal alchol spectrum disorders by ameliorating oxidative stress in rat models (Mitchell et al., 1999a), and yielded a better outcome when it was combined with Vitamin C (Packer et al., 1979; Peng et al., 2005). Vitamin C mitigated embryonic retardation caused by alcohol and reversed ethanol induced NF-κB activation and ROS (reactive oxygen species) formation in a Xenopus laevis model (Peng et al., 2005). Beta carotene supplement was proved to protect against neurotoxicity in hippocampal cultures of embryos induced by alcohol in a rats model (Mitchell et al., 1999a). Prenatal folic acid supplement reversed the decrease of body weight caused by maternal ethanol treatment and ameliorated the increment of glutathione reductase specific activities as well as the increase of thiobarbituric acid reactive substances (TBARS) induced by alcohol in a rats model (Cano et al., 2001). Omega-3 fatty acids reversed the decrease of reduced glutathione (GSH) levels in brain caused by prenatal ethanol treatment in a rats model (Patten et al., 2013). EUK-134 treatment reduced the incidence of forelimb defects caused by ethanol treatment in a mice model (Chen et al., 2004). Pretreatment of activity-dependent neurotrophic factor-9 (ADNF-9) and NAPVSIPQ (NAP) protected against prenatal ethanol induced fetal death as well as fetal growth abnormalities in a mice model, and such treatment reversed the decrease of the rate of reduced glutathione (GSH)/ oxidative glutathione (GSSG) caused by alcohol (Spong et al., 2001).. By now interventions against fetal alcohol spectrum disorder targeting oxidative stress includes astaxanthin, Ascorbic acid (Vitamin C), Vitamin E, beta-carotene, (-)-Epigallocatechin-3-gallate (EGCG), Omega-3 fatty acids, etc (see Fig. 1). However, most interventions are only assayed in animal models, more clinical trials are needed to show whether antioxidants make an effort against FASD damage.

Topics: Animals; Disease Models, Animal; Fetal Alcohol Spectrum Disorders; Humans; Oxidative Stress; Xanthophylls

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Beta-Cryptoxanthin; Carotenoids; Cell Polarity; Disease Models, Animal; Disease Progression; Homeostasis; Humans; Kupffer Cells; Liver; Macrophage Activation; Metabolic Syndrome; Micronutrients; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Xanthophylls

The consumption of marine fishes and general seafood has long been recommended by several medical authorities as a long-term nutritional intervention to preserve mental health, hinder neurodegenerative processes, and sustain cognitive capacities in humans. Most of the neurological benefits provided by frequent seafood consumption comes from adequate uptake of omega-3 and omega-6 polyunsaturated fatty acids, n-3/n-6 PUFAs, and antioxidants. Optimal n-3/n-6 PUFAs ratios allow efficient inflammatory responses that prevent the initiation and progression of many neurological disorders. Moreover, interesting in vivo and clinical studies with the marine antioxidant carotenoid astaxanthin (present in salmon, shrimp, and lobster) have shown promising results against free radical-promoted neurodegenerative processes and cognition loss. This review presents the state-of-the-art applications of n-3/n-6 PUFAs and astaxanthin as nutraceuticals against neurodegenerative diseases associated with exacerbated oxidative stress in CNS. The fundamental "neurohormesis" principle is discussed throughout this paper. Finally, new perspectives for the application of a natural combination of the aforementioned anti-inflammatory and antioxidant agents (found in krill oil) are also presented herewith.

Topics: Animals; Brain; Dietary Supplements; Disease Models, Animal; Euphausiacea; Fatty Acids, Omega-3; Fish Oils; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Observational Studies as Topic; Oxidation-Reduction; Oxidative Stress; Shellfish; Xanthophylls

Astaxanthin is a xanthophyll carotenoid present in microalgae, fungi, complex plants, seafood, flamingos and quail. It is an antioxidant with anti-inflammatory properties and as such has potential as a therapeutic agent in atherosclerotic cardiovascular disease. Synthetic forms of astaxanthin have been manufactured. The safety, bioavailability and effects of astaxanthin on oxidative stress and inflammation that have relevance to the pathophysiology of atherosclerotic cardiovascular disease, have been assessed in a small number of clinical studies. No adverse events have been reported and there is evidence of a reduction in biomarkers of oxidative stress and inflammation with astaxanthin administration. Experimental studies in several species using an ischaemia-reperfusion myocardial model demonstrated that astaxanthin protects the myocardium when administered both orally or intravenously prior to the induction of the ischaemic event. At this stage we do not know whether astaxanthin is of benefit when administered after a cardiovascular event and no clinical cardiovascular studies in humans have been completed and/or reported. Cardiovascular clinical trials are warranted based on the physicochemical and antioxidant properties, the safety profile and preliminary experimental cardiovascular studies of astaxanthin.

Topics: Animals; Antioxidants; Atherosclerosis; Cardiovascular Diseases; Disease Models, Animal; Humans; Inflammation; Oxidative Stress; Xanthophylls

Astaxanthin (1), a red-orange carotenoid pigment, is a powerful biological antioxidant that occurs naturally in a wide variety of living organisms. The potent antioxidant property of 1 has been implicated in its various biological activities demonstrated in both experimental animals and clinical studies. Compound 1 has considerable potential and promising applications in human health and nutrition. In this review, the recent scientific literature (from 2002 to 2005) is covered on the most significant activities of 1, including its antioxidative and anti-inflammatory properties, its effects on cancer, diabetes, the immune system, and ocular health, and other related aspects. We also discuss the green microalga Haematococcus pluvialis, the richest source of natural 1, and its utilization in the promotion of human health, including the antihypertensive and neuroprotective potentials of 1, emphasizing our experimental data on the effects of dietary astaxanthin on blood pressure, stroke, and vascular dementia in animal models, is described.

Topics: Animals; Antihypertensive Agents; Antioxidants; Disease Models, Animal; Health; Humans; Molecular Structure; Nutritional Physiological Phenomena; Xanthophylls

The chronic active inflammation caused by Helicobacter pylori is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins are involved in the inflammatory process. The aim of this study was to investigate the effect of astaxanthin on gastric inflammation in patients with functional dyspepsia. Forty-four consecutive patients were included, and biopsies were examined for IL-4, IL-6, IL-8, IL-10, interferon-gamma, CD4, CD8, CD14, CD19, CD25 and CD30. Patients were randomized: 21 patients were treated with 40 mg of astaxanthin daily, and 23 patients were treated with a placebo. There was a significant decrease in gastric inflammation in H. pylori-positive patients from both groups. There were no significant changes in the density of H. pylori or in any of the interleukins during or after treatment. There was a significant up-regulation of CD4 and down-regulation of CD8 in patients with H. pylori treated with astaxanthin. Astaxanthin had an effect on the inflammation and on the density of H. pylori in mice in a study where the diet could be standardized without antioxidants (Bennedsen et al., 1999). These dietary conditions are impossible in studies involving humans, and may be due to the minor effect when the host have access to antioxidants in their diet.

Topics: Adult; Aged; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, CD; Biomarkers; Biopsy; Colony Count, Microbial; Cytokines; Disease Models, Animal; Dyspepsia; Female; Helicobacter Infections; Humans; Inflammation; Male; Mice; Middle Aged; Stomach; Xanthophylls

Topics: Animals; Animals, Newborn; Disease Models, Animal; Enterocolitis, Necrotizing; Intestinal Mucosa; Intestines; Rats

Orally targeted strategy of anti-inflammatory agents has attracted tremendous attention for reducing highly health-care costs and enhancing the intervention efficiency of ulcerative colitis (UC). Herein, we developed a new kind of sequence-targeted astaxanthin nanoparticles for UC treatment. Astaxanthin nanoparticles were firstly designed by self-assembly method using (3-carboxypentyl) (triphenyl) phosphonium bromide (TPP)-modified whey protein isolate (WPI)-dextran (DX) conjugates. Subsequently, lipoic acid (LA) modified hyaluronic acid (HA) was coated on the surface of the nanoparticles by double emulsion evaporation method. Exhilaratingly, the constructed sequence-targeted astaxanthin nanoparticle exhibited excellent macrophages and mitochondria targeting ability, with a Pearson's correlation coefficient of 0.84 adstnd 0.92, respectively. In vivo imaging elucidated an obvious accumulation of the sequence-targeted nanoparticles in colon tissues in UC mice. Meanwhile, the reduction stimulus release features of astaxanthin were observed in the presence of 10 mM of glutathione (GSH) at pH 7.4. Most importantly, in vivo experiments indicated that sequence-targeted astaxanthin nanoparticles could markedly alleviate inflammation by moderating the TLR4/MyD88/NF-κB signaling pathway. What's more, the composition of gut microbiota and the production of short chain fatty acid were also improved upon the uptake of sequence-targeted astaxanthin nanoparticles. Our results suggested this novel astaxanthin nanoparticles, which showed sequence-targeted ability and reduction response feature, could be exploited as a promising strategy for effective UC treatment.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Colon; Disease Models, Animal; Mice; Nanoparticles; NF-kappa B

Oxidative stress and chronic inflammation play key roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and anti-inflammatory effects This study aimed to explore the protective role and underlying mechanism of AXT in the pathogenesis of COPD. In this study, we found AXT alleviated pulmonary emphysema in a CS-exposed mouse model and regulated the expression of MMP-9/TIMP-1. And, AXT attenuates CSE-induced small airway fibrosis. Meanwhile, AXT inhibited Nrf2-modulated oxidative stress and the p65 NF-κB-regulated inflammatory pathway in both the mouse model and CSE-treated HBE cells. Mechanistically, AXT could directly bind to SIRT1 (the binding energy of the complex was -8.8 kcal/mol) and regulate the deacetylation activity of SIRT1. Finally, by activating SIRT1 deacetylation, AXT deacetylated Nrf2 and contributed to its action of reducing oxidative stress by generating antioxidant enzymes, and inhibiting p65 NF-κB transcriptional activity to suppress the inflammatory response. Our results show that treatment with AXT significantly reverses the oxidative stress and inflammation induced by cigarette smoke both in vivo and in vitro in a sirtuin 1-dependent manner.

Topics: Animals; Antioxidants; Cigarette Smoking; Disease Models, Animal; Inflammation; Mice; NF-E2-Related Factor 2; NF-kappa B; Nicotiana; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Sirtuin 1

Spinal cord edema is a quick-onset phenomenon with long-term effects. This complication is associated with inflammatory responses, as well as poor motor function. No effective treatment has been developed against spinal edema, which urges the need to provide novel therapies. Astaxanthin (AST) is a fat-soluble carotenoid with anti-inflammatory effects and a promising candidate for treating neurological disorders. This study aimed to investigate the underlying mechanism of AST on the inhibition of spinal cord edema, astrocyte activation, and reduction of inflammatory responsesin a rat compression spinal cord injury (SCI) model. Male rats underwent laminectomy at thoracic 8-9, and the SCI model was induced using an aneurysm clip. After SCI, rats received dimethyl sulfoxide or AST via intrathecal injection. The effects of AST were examined on the motor function, spinal cord edema, integrity of blood-spinal cord barrier (BSCB), and expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4), and matrix metallopeptidase- 9 (MMP-9) post-SCI. We showed that AST potentially improved the recovery of motor function and inhibited the spinal cord edema via maintaining the integrity of BSCB, reducing the expression of HMGB1, TLR4, and NF-κB, MMP-9 as well as downregulation of astrocyte activation (GFAP) and AQP4 expression. AST improves motor function and reduces edema and inflammatory responses in the spinal tissue. These effects are mediated by suppression of the HMGB1/TLR4/NF-κB signaling pathway, suppressing post-SCI astrocyte activation, and decreasing AQP4 and MMP-9 expression.

Topics: Animals; Antioxidants; Astrocytes; Disease Models, Animal; Edema; HMGB1 Protein; Injections, Spinal; Male; Matrix Metalloproteinase 9; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Spinal Cord; Spinal Cord Injuries; Toll-Like Receptor 4

Treatment of neuropathic pain remains a challenge for modern medicine due to the insufficiently understood molecular mechanisms of its development and maintenance. One of the most important cascades that modulate the nociceptive response is the family of mitogen-activated protein (MAP) kinases and phosphatidylinositol-3-kinase (PI3K), as well as nuclear factor erythroid 2-related factor 2 (Nrf2). The aim of this study was to determine the effect of nonselective modulators of MAP kinases-fisetin (ERK1/2 and NFκB inhibitor, PI3K activator), peimine (MAPK inhibitor), astaxanthin (MAPK inhibitor, Nrf2 activator) and artemisinin (MAPK inhibitor, NFκB activator), as well as bardoxolone methyl (selective activator of Nrf2) and 740 Y-P (selective activator of PI3K)-in mice with peripheral neuropathy and to compare their antinociceptive potency and examine their effect on analgesia induced by opioids. The study was performed using albino Swiss male mice that were exposed to chronic constriction injury of the sciatic nerve (CCI model). Tactile and thermal hypersensitivity was measured using von Frey and cold plate tests, respectively. Single doses of substances were administered intrathecally on day 7 after CCI. Among the tested substances, fisetin, peimine, and astaxanthin effectively diminished tactile and thermal hypersensitivity in mice after CCI, while artemisinin did not exhibit analgesic potency in this model of neuropathic pain. Additionally, both of the activators tested, bardoxolone methyl and 740 Y-P, also showed analgesic effects after intrathecal administration in mice exposed to CCI. In the case of astaxanthin and bardoxolone methyl, an increase in analgesia after combined administration with morphine, buprenorphine, and/or oxycodone was observed. Fisetin and peimine induced a similar effect on tactile hypersensitivity, where analgesia was enhanced after administration of morphine or oxycodone. In the case of 740 Y-P, the effects of combined administration with each opioid were observed only in the case of thermal hypersensitivity. The results of our research clearly indicate that substances that inhibit all three MAPKs provide pain relief and improve opioid effectiveness, especially if they additionally block NF-κB, such as peimine, inhibit NF-κB and activate PI3K, such as fisetin, or activate Nrf2, such as astaxanthin. In light of our research, Nrf2 activation appears to be particularly beneficial. The abovementioned substances bring promising resul

Topics: Analgesia; Analgesics; Analgesics, Opioid; Animals; Artemisinins; Disease Models, Animal; Hyperalgesia; Male; Mice; Morphine; Neuralgia; NF-E2-Related Factor 2; NF-kappa B; Oxycodone; Phosphatidylinositol 3-Kinases

Defective degradation and clearance of amyloid-β as well as inflammation per se are crucial players in the pathology of Alzheimer's disease (AD). A defective transport across the blood-brain barrier is causative for amyloid-β (Aβ) accumulation in the brain, provoking amyloid plaque formation. Using primary porcine brain capillary endothelial cells and murine organotypic hippocampal slice cultures as in vitro models of AD, we investigated the effects of the antioxidant astaxanthin (ASX) on Aβ clearance and neuroinflammation. We report that ASX enhanced the clearance of misfolded proteins in primary porcine brain capillary endothelial cells by inducing autophagy and altered the Aβ processing pathway. We observed a reduction in the expression levels of intracellular and secreted amyloid precursor protein/Aβ accompanied by an increase in ABC transporters ABCA1, ABCG1 as well as low density lipoprotein receptor-related protein 1 mRNA levels. Furthermore, ASX treatment increased autophagic flux as evidenced by increased lipidation of LC3B-II as well as reduced protein expression of phosphorylated S6 ribosomal protein and mTOR. In LPS-stimulated brain slices, ASX exerted anti-inflammatory effects by reducing the secretion of inflammatory cytokines while shifting microglia polarization from M1 to M2 phenotype. Our data suggest ASX as potential therapeutic compound ameliorating AD-related blood brain barrier impairment and inflammation.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Anti-Inflammatory Agents; Autophagy; Blood-Brain Barrier; Disease Models, Animal; Endothelial Cells; Inflammation; Mice; Mice, Transgenic; Swine

Parkinson's disease (PD) is the second largest neurodegenerative disorder caused by the decreased number of dopaminergic (DAc) neurons in the substantia nigra pars compacta (SNpc). There is evidence that oxidative stress can contribute degeneration of DAc neurons in SNpc which is mainly caused by apoptotic cell death. Thus, suppressing oxidative stress and apoptosis of DAc neurons is an effective strategy to mitigate the progress of PD. Astaxanthin (AST) is a carotenoid, which mainly exists in marine organisms and is a powerful biological antioxidant. In this study, we aimed to determine the neuroprotective effect of AST on paraquat (PQ) -induced models of PD in vitro and in vivo. Here, we showed that AST significantly enhanced cell survival of SH-SY5Y cells against PQ toxicity by suppressing apoptotic cell death and oxidative stress. Moreover, we found that AST significantly ameliorated PQ-induced behavioral disorders associated with PD in C57BL/6 J mice and the damage to DAc neurons in the SNpc of mice. Lastly, we found that the neuroprotective effects of AST were conducted through inhibiting PQ-induced activation of MAPK signaling. In conclusion, our study indicates that AST had a strong protective effect on PQ-induced oxidative stress and antagonized apoptotic cell death in SH-SY5Y cells and PQ-induced mice PD model, which might provide new insights of AST for PD treatment.

Topics: Animals; Disease Models, Animal; Dopaminergic Neurons; Humans; Mice; Mice, Inbred C57BL; Neuroblastoma; Paraquat; Parkinson Disease

This study aimed to develop a novel astaxanthin nanoparticle using gum arabic (GA) and whey protein powder enriched with milk fat globule membranes (MFGM-WPI) as carriers and to investigate its effect and alleviation mechanism on colitis in mice. We demonstrated that MFGM-GA-astaxanthin could improve the bioaccessibility of astaxanthin and cope with oxidative stress more effectively in a Caco-2 cell model.

Topics: Animals; Caco-2 Cells; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Nanoparticles; Oxidative Stress

Intestinal microbiota and metabonomics were integrated to investigate the efficiency of non-saponification or saponification astaxanthin (N-Asta or S-Asta) derived from

Topics: Acetaminophen; Animals; Antioxidants; Disease Models, Animal; Gastrointestinal Microbiome; Male; Metabolome; Metabolomics; Oxidative Stress; Rats; Rats, Sprague-Dawley; Xanthophylls

Astaxanthin (Ax) with a strong antioxidant activity is beneficial to human health, but its application is limited by its highly unsaturated structure and poor water-solubility. Ax-enriched colon targeted alginate particles (Ax-Alg) was prepared by high-pressure spraying and ionic gelation, and most of particles was in the range of 0.5-3.2 μm in a diameter. The in vitro models showed that Ax-Alg can maintain the structural integrity in the different conditions (pH, heat and ion). In addition, Ax-Alg can well tolerate the conditions in the mouth, stomach and small intestine and reach the colon where Ax was released due to fermentation of gut microbiota. Mice experiment showed that Ax-Alg reduced dextran sulfate sodium-induced colitis, involving weight loss, disease activity index, colonic mucosal integrity and inflammation, and oxidative damage. On the other hand, Ax-Alg regulated the gut microbiota composition and reduced the abundances of Bacteroidetes members that had positive correlation with ulcerative colitis. Ax-Alg had better effect on the treatment of ulcerative colitis than oil-in-water emulsion, which can be attributed to the synergistic effect of Ax and alginate. This study can be helpful for the application of colon-targeted delivery system in the foods and treatment of colon diseases.

Topics: Alginates; Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Mice; Microspheres; Xanthophylls

Excitotoxicity and oxidative stress are central to the pathology of the nervous system, and inhibition of excitotoxicity induced by glutamate is one of the therapeutic goals determined for stroke. The present study aimed to investigate the effects of Astaxanthin, a potent natural antioxidant, on complications caused by acute cerebral stroke. In this research, 60 male Wistar rats were used which were divided into 5 groups as follow: (1) the sham group (vehicle), (2) the ischemic control group (vehicle), and the ischemic groups treated by Astaxanthin with doses of 25, 45, and 65 mg/kg. In the ischemic groups, ischemic model was performed by middle cerebral artery occlusion (MCAO) method, and the Astaxanthin administration was carried out after the artery occlusion and before opening the artery. The obtained results indicated that Astaxanthin could significantly reduce stroke volume, neurological deficits, and lipid peroxidation. Moreover, it was able to restore total oxidant status (TOS) and caspase 3 level to the normal level. The activity of antioxidant enzyme glutathione peroxidase (GPX), and the expression of catalase, GPx and nuclear factor kappa B (NFκb) genes, which were reduced after ischemia, were increased. This phenomenon was particularly pronounced for glutamate transporter 1 (GLT-1). Furthermore, Astaxanthin decreased the augmented pro-apoptotic gene Bax and restored the reduced Bcl2 expression to the normal level. Significant effects on the P53 and PUMA expression were not observed. Overall, the medium dosage of Astaxanthin appears to be more effective in reducing the complications of ischemia, particularly on our major study endpoints (stroke volume and neurological defects). Longer studies with a more frequent administration of Astaxanthin are required to better understand the precise mechanism of Astaxanthin.

Topics: Animals; Antioxidants; Brain Injuries; Brain Ischemia; Disease Models, Animal; Infarction, Middle Cerebral Artery; Male; Neuroprotective Agents; Rats; Rats, Wistar; Reperfusion; Reperfusion Injury; Stroke; Xanthophylls

Sarcopenia is a complication of Chronic Obstructive Pulmonary Disease (COPD) that negatively affects physical activity and quality of life. However, the underlying mechanism by which COPD affects skeletal muscles remains to be elucidated. Therefore, we investigated the association between oxidative stress and structural alterations in muscles in elastase-induced emphysema mouse models.. Twelve-week-old male C57BL/6J mice were treated with either intratracheal porcine pancreatic elastase (PPE) dissolved in saline, or saline alone. The mice were euthanized 12 weeks after treatment, and the lungs and limb muscles were used for protein analysis of oxidative stress, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and muscle atrophy signaling pathway related with oxidative stress. Furthermore, C57BL/6J mice treated with PPE or saline were analyzed for the effects of oral administration of astaxanthin or p38 inhibitor.. The weight of the soleus muscle, proportion of type I muscle fibers, and cross-sectional areas of muscle fibers in the PPE group were lower than those in the control group. Oxidative stress marker levels in the PPE group were elevated in skeletal muscles. The p38 MAPK signaling pathway was activated in the soleus muscles, leading to the activation of the ubiquitin-proteasome system and autophagy. Astaxanthin and p38 inhibitors attenuated alterations in muscle structure through the deactivation of the p38 MAPK signaling pathway.. This study provides first evidence in COPD mouse model that oxidative stress trigger a series of muscle structural changes. Our findings suggest a novel target for sarcopenia in COPD.

Topics: Animals; Disease Models, Animal; Lung; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Pancreatic Elastase; Pulmonary Disease, Chronic Obstructive; Quality of Life; Sarcopenia; Swine

Astaxanthin (AST) has a variety of biochemical effects, including anti-inflammatory, antioxidative, and antihypertensive functions. The aim of the present study was to determine whether AST ameliorates blood pressure in salt-induced prehypertensive rats by ROS/MAPK/NF-κB pathways in hypothalamic paraventricular nucleus.To explore the central effects of AST on the development of blood pressure, prehypertensive rats were induced by a high-salt diet (HS, 8% NaCl) and its control groups were treated with normal-salt diet (NS, 0.3% NaCl). The Dahl salt-sensitive (S) rats with HS diet for 6 weeks received AST or vehicle by gastric perfusion for 6 weeks. Compared to those with NS diet, rats with HS diet exhibited increased mean arterial pressure (MAP) and heart rate (HR). These increases were associated with higher plasma level of norepinephrine (NE), interleukin 1β (IL-1β), and interleukin 6 (IL-6); elevated PVN level of reactive oxygen species (ROS), NOX2, and NOX4, that of IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), phosphorylation extracellular-signal-regulated kinase (p-ERK1/2), phosphorylation Jun N-terminal kinases (p-JNK), nuclear factor-kappa B (NF-κB) activity; and lower levels of IL-10, superoxide dismutase (SOD), and catalase (CAT) in the PVN. In addition, our data demonstrated that chronic AST treatment ameliorated these changes in the HS but not NS diet rats. These data suggested that AST could alleviate prehypertensive response in HS-induced prehypertension through ROS/MAPK/NF-κB pathways in the PVN.

Topics: Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Antioxidants; Arterial Pressure; Disease Models, Animal; Male; Mitogen-Activated Protein Kinases; NF-kappa B; Oxidative Stress; Paraventricular Hypothalamic Nucleus; Phosphorylation; Prehypertension; Rats, Inbred Dahl; Reactive Oxygen Species; Signal Transduction; Sodium Chloride, Dietary; Xanthophylls

One of the main functions of the sensory system in our body is to maintain somatosensory homeostasis. Recent reports have led to a significant advance in our understanding of pain signaling mechanisms; however, the exact mechanisms of pain transmission have remained unclear. There is an urgent need to reveal the precise signaling mediators of pain to provide alternative therapeutic agents with more efficacy and fewer side effects. Accordingly, although the anti-inflammatory, antioxidative and anti-neuropathic effects of astaxanthin (AST) have been previously highlighted, its peripheral antinociceptive mechanisms are not fully understood. In this line, considering the engagement of l-arginine/nitric oxide (NO)/cyclic GMP (cGMP)/potassium channel (KATP) signaling pathway in the antinociceptive responses, the present study evaluated its associated role in the antinociceptive activity of AST. Male mice were intraperitoneally (i.p.) injected with l-arginine (100 mg/kg), SNAP (1 mg/kg), L-NAME (30 mg/kg), sildenafil (5 mg/kg), and glibenclamide (10 mg/kg) alone and prior to the most effective dose of AST. Following AST administration, intraplantarly (i.pl) injection of formalin was done, and pain responses were evaluated in mice during the primary (acute) and secondary (inflammatory) phases of formalin test. The results highlighted that 10 mg/kg i.p. dose of AST showed the greatest antinociceptive effect. Besides, while L-NAME and glibenclamide reduced the antinociceptive effect of AST, it was significantly increased by l-arginine, SNAP and sildenafil during both the primary and secondary phases of formalin test. These data suggest that the antinociceptive activity of AST is passing through the l-arginine/NO/cGMP/KATP pathway.

Topics: Analgesics; Animals; Arginine; Cyclic GMP; Disease Models, Animal; Dose-Response Relationship, Drug; Glyburide; KATP Channels; Male; Mice; NG-Nitroarginine Methyl Ester; Nitric Oxide; Pain; Signal Transduction; Sildenafil Citrate; Xanthophylls

The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, β-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except β-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, β-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.

Topics: Animals; Antioxidants; Apigenin; beta Carotene; Biological Factors; Carotenoids; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Embryo, Nonmammalian; Embryonic Development; Flavanones; Lycopene; Oxidative Stress; Polyphenols; tert-Butylhydroperoxide; Xanthophylls; Zebrafish

Astaxanthin, originating from marine organisms, is a natural bioactive compound with powerful antioxidant activity. Here, we evaluated the antioxidant ability of astaxanthin on dendritic cells (DCs), a key target of immune regulation, for inflammatory control in a sepsis model. Our results showed that astaxanthin suppressed nitric oxide (NO) production, reactive oxygen species (ROS) production, and lipid peroxidation activities in LPS-induced DCs and LPS-challenged mice. Moreover, the reduced glutathione (GSH) levels and the GSH/GSSG ratio were increased, suggesting that astaxanthin elevated the level of cellular reductive status. Meanwhile, the activities of antioxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were significantly upregulated. Astaxanthin also inhibited the LPS-induced secretions of IL-1β, IL-17, and TGF-β cytokines. Finally, we found that the expressions of heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly upregulated by astaxanthin in LPS-induced DCs, suggesting that the HO-1/Nrf2 pathway plays a significant role in the suppression of oxidative stress. These results suggested that astaxanthin possesses strong antioxidant characteristics in DC-related inflammatory responses, which is expected to have potential as a method of sepsis treatment.

Topics: Animals; Antioxidants; Aquatic Organisms; Cytokines; Dendritic Cells; Disease Models, Animal; Inflammation; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Oxidative Stress; Random Allocation; Xanthophylls

Dietary change leads to a precipitous increase in non-alcoholic fatty liver disease (NAFLD) from simple steatosis to the advanced form of non-alcoholic steatohepatitis (NASH), affecting approximately 25% of the global population. Although significant efforts greatly advance progress in clarifying the pathogenesis of NAFLD and identifying therapeutic targets, no therapeutic agent has been approved. Astaxanthin (ASTN), a natural antioxidant product, exerts an anti-inflammation and anti-fibrotic effect in mice induced with carbon tetrachloride (CCl

Topics: Animals; Chemokine CCL2; Cytokines; Diet, High-Fat; Disease Models, Animal; Fibroblast Growth Factor 2; Hepatic Stellate Cells; Lipopolysaccharides; Liver; Liver Cirrhosis; Macrophages; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; RAW 264.7 Cells; Xanthophylls

Spinal cord injury (SCI) is a severely debilitating problem leading to substantial decrease in the quality of life. After spinal cord injury, inflammation and oxidative stress plays a key role in initiating the secondary injury cascades leading to progressive tissue degradation and extreme functional deficits. Given that the primary mechanical injuries to spinal cord are rarely repaired, the pharmacological interventions may improve the neurological outcomes caused by secondary injury. Astaxanthin (AST) is considered as a xanthophyll carotenoid with potent antioxidant and anti-inflammatory properties, which has various pharmacological activities. In the present study, we aimed to firstly assess the protective effect of AST, and then to define the AST mechanism of action on a rat model of SCI. Based on the results of von Frey test, AST treatment significantly alleviated the SCI-induced neuropathic pain compared with the control groups (P < 0.05). The expression analysis by western blot shows reduced expression levels of COX-2, TNF-α, IL-1β, and IL-6 following AST treatment (P < 0.05). The activity of antioxidant enzymes was evaluated using ELISA. Therefore, ELISA experiments showed a significant reduction in the level of oxidative stress in SCI rat following AST treatment (P < 0.05). Furthermore, histopathological evaluations revealed that myelinated white matter and motor neuron number were significantly preserved after treatment with AST (P < 0.05). In conclusion, our study shows that AST could improve SCI through anti-inflammatory and antioxidant effects which leads to decreased tissue damage and mechanical pain after SCI.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Disease Models, Animal; Quality of Life; Rats; Spinal Cord; Spinal Cord Injuries; Xanthophylls

This study investigates the inhibitory effect of astaxanthin (AST) on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Except for the sham operation, BPH model rats were randomly assigned to five groups: the BPH model control rats, AST-treated BPH model rats (20 mg/kg, 40 mg/kg, and 80 mg/kg), and epristeride (EPR)-treated BPH model rats. After treatment, as compared with the BPH model control rats, the prostate and ventral prostate weights of the AST-treated rats decreased, while there was a marked decline in the 80 mg/kg AST-treated rats. The same effect was also observed in the prostate index and ventral prostate index. The proliferation characteristics of epithelia observed in the BPH model control group were gradually alleviated in the AST-treated rats. As compared with the BPH model control rats, lower epithelial thicknesses of prostates and fewer secretory granules in epithelia were observed in the AST-treated rats. The superoxide dismutase (SOD) activity of prostates increased in all the AST-treated rats with a significant increase in the 40 mg/kg and 80 mg/kg AST-treated rats. The testosterone (T) and dihydrotestosterone (DHT) levels of prostates in the AST-treated groups were lower than those in the BPH model control group, and a significant decline was found in the T level of prostates in the 40 g/kg and 80 mg/kg AST-treated rats and the DHT level of prostates in the 40 mg/kg AST-treated rats. These results indicate that AST might have an inhibitory effect on T-induced BPH in rats, possibly due to SOD activity regulation and T and DHT levels.

Topics: Animals; Aquatic Organisms; Disease Models, Animal; Fishes; Male; Prostate; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms; Testosterone; Xanthophylls

Cisplatin-induced ototoxicity is related to oxidative stress. Astaxanthin is one of the most powerful antioxidants in nature.. To investigate the protective effect of astaxanthin on cisplatin-induced ototoxicity.. Thirty-five Sprague Dawley female rats were divided into 5 groups: control, cisplatin, and cisplatin with 10, 20, and 40 mg/kg astaxanthin groups. Cisplatin group received a single intraperitoneal injection of 14 mg/kg cisplatin. While saline was administered in the control group, in the other 3 groups, 10, 20, and 40 mg/kg daily doses of astaxanthin were administered through orogastric cannula before administration of cisplatin. Baseline and 10th day otoacoustic emission tests were administered. An intracardiac blood sample was taken to measure total antioxidant capacity (TAC), and the cochleas of the animals were investigated histopathologically.. Hearing level of astaxanthin 40 mg/kg + cisplatin group was higher at 24 kHz and 32 kHz frequencies compared to the cisplatin group. The TAC value of the cisplatin group was lower than both the control and astaxanthin + cisplatin groups (. Astaxanthin showed protective effect at high frequencies when it was administered at high dose. Thus, astaxanthin may have protective effect against cisplatin-induced ototoxicity.

Topics: Animals; Antioxidants; Cisplatin; Cochlea; Disease Models, Animal; Female; Otoacoustic Emissions, Spontaneous; Ototoxicity; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Xanthophylls

This study aimed to ascertain the effects of astaxanthin on the lungs of rat pups with bronchopulmonary dysplasia (BPD) induced by hyperoxia and lipopolysaccharide (LPS).. Forty-two newborn Wistar rats, born to spontaneous pregnant rats, were divided into three groups: Hyperoxia (95% O2) + lipopolysaccharide (LPS) group, hyperoxia + LPS + astaxhantin group, and control: no treatment group (21% O2). Pups in the hyperoxia + LPS + astaxanthin group were given 100 mg/kg/day oral astaxanthin from the first day to the fifth day. Histopathologic and biochemical evaluations, including glutathione (GSH), total anti-oxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), total thiol, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and caspase-3 activities, were performed.. Better survival rates and weight gain were demonstrated in the hyperoxia + LPS + astaxanthin group (p <0.001). In the histopathologic evaluation, the severity of lung damage was significantly reduced in the hyperoxia+LPS+astaxanthin group, as well as decreased apoptosis (ELİSA for caspase-3) (p <0.001). The biochemical analyses of lung tissues showed that TAS, GSH, and Total thiol levels were significantly higher in the astaxanthin treated group compared to the hyperoxia + LPS group (p <0.05) while TOS, AOPP, LPO, 8-OHdG, MPO levels were significantly lower (p <0.001). In addition, unlike the hyperoxia + LPS group, TNF-α and IL-1β levels in lung tissue were significantly lower in the astaxanthin-treated group (p <0.001).. Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its anti-inflammatory, anti-oxidant, anti-apoptotic properties, and to protect the lung from severe destruction.

Topics: Animals; Animals, Newborn; Disease Models, Animal; Female; Hyperoxia; Inflammation; Lung; Lung Injury; Pregnancy; Rats; Rats, Wistar; Xanthophylls

Astaxanthin (Ast) is an effective neuroprotective and antioxidant compound used to treat Alzheimer's disease (AD); however, the underlying in vivo molecular mechanisms remain unknown. In this study, we report that Ast can activate the mammalian target of rapamycin (mTOR) pathway in the 8-month-old APP/PS1 transgenic mouse model of AD. Our results suggest that Ast could ameliorate the cognitive defects in APP/PS1 mice by activating the mTOR pathway. Moreover, mTOR activation perturbed the mitochondrial dynamics, increased the synaptic plasticity after 21 days of treatment with Ast (10 mg/kg/day), and increased the expression of Aβ-degrading enzymes, mitochondrial fusion, and synapse-associated proteins and decreased the expression of mitochondrial fission proteins. Intraperitoneal injection of the mTOR inhibitor, rapamycin, abolished the effects of Ast. In conclusion, Ast activates the mTOR pathway, which is necessary for mitochondrial dynamics and synaptic plasticity, leading to improved learning and memory. Our results support the use of Ast for the treatment of cognitive deficits. Graphical abstract In summary, Ast ameliorates cognitive deficits via facilitating the mTOR-dependent mitochondrial dynamics and synaptic damage, and reducing Aβ accumulation. This model supports the use of Ast for the treatment of cognitive deficits.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Cognition; Disease Models, Animal; Mice; Mice, Transgenic; Presenilin-1; Sirolimus; TOR Serine-Threonine Kinases; Xanthophylls

Chronic excessive ethanol consumption is associated with a high incidence of mortality due to ethanol-induced dilated cardiomyopathy, known as alcoholic cardiomyopathy (ACM). Mechanistic studies have demonstrated that apoptosis is key to the pathogenesis of ACM, and endoplasmic reticulum (ER) stress-associated apoptosis contributes to various ethanol-related diseases. Astaxanthin (AST) is a natural carotenoid that exerts an anti-ER stress effect. Importantly, strong evidence has shown that AST induces beneficial effects in various cardiovascular diseases. The present study aimed to investigate whether AST induces beneficial effects on ACM by suppressing cardiac apoptosis mediated by ER stress. We showed that after 2 months of chronic excessive ethanol consumption, mice displayed obvious cardiac dysfunction and morphological changes associated with increased fibrosis, oxidative stress, ER stress and apoptosis. However, cardiac damage above was attenuated in response to AST treatment. The cardioprotective effect of AST against ethanol toxicity was also confirmed in both H9c2 cells and primary cardiomyocytes, indicating that AST-induced protection directly targets cardiomyocytes. Both in vivo and in vitro studies showed that AST inhibited all three ER stress signaling pathways activated by ethanol. Furthermore, administration of the ER stress inhibitor sodium 4-phenylbutyrate (4-PBA) strongly suppressed ethanol-induced cardiomyocyte damage. Interestingly, AST induced further anti-apoptotic effects once co-treated with 4-PBA, indicating that AST protects the heart from ACM partially by attenuating ER stress, but other mechanisms still exist. This study highlights that administration of AST ablated chronic excessive ethanol consumption-induced cardiomyopathy by suppressing cardiac ER stress and subsequent apoptosis.

Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Cardiomyopathy, Alcoholic; Cell Line; Disease Models, Animal; Endoplasmic Reticulum Stress; Ethanol; Fibrosis; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Oxidative Stress; Rats; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling; Xanthophylls

Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle-atrophy-mediated disturbance of mitochondria, which have a lipid bilayer. Tail suspension was used to establish a muscle-atrophied mouse model. AX diet fed to tail-suspension mice prevented loss of muscle weight, inhibited the decrease of myofiber size, and restrained the increase of hydrogen peroxide (H

Topics: Animals; Antioxidants; Apoptosis; Caspase 3; Disease Models, Animal; Down-Regulation; Hindlimb Suspension; Hydrogen Peroxide; Male; Mice; Mice, Inbred C57BL; Mitochondria; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Oxidative Stress; PPAR gamma; Reactive Oxygen Species; Up-Regulation; Xanthophylls

Oxidative stress, the renin-angiotensin system (RAS), and inflammation are some of the mechanisms involved in the pathogenesis of hypertension. The aim of this study is to examine the protective effect of the chronic administration of astaxanthin, which is extracted from the shell of crabs and shrimps, into hypothalamic paraventricular nucleus (PVN) in spontaneously hypertensive rats. Animals were randomly assigned to 2 groups and treated with bilateral PVN infusion of astaxanthin or vehicle (artificial cerebrospinal fluid) through osmotic minipumps (Alzet Osmotic Pumps, Model 2004, 0.25 μL/h) for 4 weeks. Spontaneously hypertensive rats had higher mean arterial pressure and plasma level of norepinephrine and proinflammatory cytokine; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1β, IL-6, ACE, and AT1-R; and lower PVN levels of IL-10 and Cu/Zn SOD, Mn SOD, ACE2, and Mas receptors than Wistar-Kyoto rats. Our data showed that chronic administration of astaxanthin into PVN attenuated the overexpression of reactive oxygen species, NOX2, NOX4, inflammatory cytokines, and components of RAS within the PVN and suppressed hypertension. The present results revealed that astaxanthin played a role in the brain. Our findings demonstrated that astaxanthin had protective effect on hypertension by improving the balance between inflammatory cytokines and components of RAS.

Topics: Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Arterial Pressure; Cytokines; Disease Models, Animal; Hypertension; Inflammation Mediators; Infusions, Parenteral; Male; Paraventricular Hypothalamic Nucleus; Rats, Inbred SHR; Rats, Inbred WKY; Renin-Angiotensin System; Time Factors; Xanthophylls

Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by memory loss and dementia, could be a consequence of the abnormalities of cortical milieu, such as oxidative stress, inflammation, and/or accompanied with the aggregation of β-amyloid. The majority of AD patients are sporadic, late-onset AD, which predominantly occurs over 65 years of age. Our results revealed that the ferrous amyloid buthionine (FAB)-infused sporadic AD-like model showed deficits in spatial learning and memory and with apparent loss of choline acetyltransferase (ChAT) expression in medial septal (MS) nucleus. In hippocampal CA1 region, the loss of pyramidal neurons was accompanied with cholinergic fiber loss and neuroinflammatory responses including glial reaction and enhanced expression of inducible nitric oxide synthase (iNOS). Surviving hippocampal CA1 pyramidal neurons showed the reduction of dendritic spines as well. Astaxanthin (ATX), a potent antioxidant, reported to improve the outcome of oxidative-stress-related diseases. The ATX treatment in FAB-infused rats decreased neuroinflammation and restored the ChAT + fibers in hippocampal CA1 region and the ChAT expression in MS nucleus. It also partly recovered the spine loss on hippocampal CA1 pyramidal neurons and ameliorated the behavioral deficits in AD-like rats. From these data, we believed that the ATX can be a potential option for slowing the progression of Alzheimer's disease.

Topics: Alzheimer Disease; Animals; CA1 Region, Hippocampal; Cholinergic Neurons; Dendritic Spines; Disease Models, Animal; Male; Maze Learning; Nitric Oxide Synthase Type II; Rats; Treatment Outcome; Xanthophylls

Astaxanthin, a xanthophyll belonging to the family of carotenoids, is a potent antioxidant. However, much less is known about its protective effects on the oxidative stress of ischemic optic nerve. We hypothesized that astaxanthin treatment could protect retinal ganglion cells (RGCs) from death via anti-oxidative and anti-apoptotic responses. Adult male Wistar rats were fed astaxanthin (100 mg/kg/day) by daily gavage for seven consecutive days, either before or after inducing oxidative stress in the retina by photodynamic treatment. The visual function, RGC apoptosis, macrophage infiltration in the optic nerve, expression of p-Akt, p-mTOR, SGK1, pS6K, Nrf2, p62, TNFα, Il1β in retinas were investigated. The visual function and the RGC densities were significantly higher in both pre- and post-treatment groups. The numbers of apoptotic RGCs and extrinsic macrophage infiltration in the optic nerve were significantly decreased in both astaxanthin-treated groups. Furthermore, pre- and post-treatment of astaxanthin showed a higher expression of p-Akt, p-mTOR, Nrf2 and superoxide dismutase activity, and a lower expression of cleaved caspase-3, suggesting anti-apoptotic and anti-oxidative roles. Our findings indicate that astaxanthin can preserve visual function and reduce RGC apoptosis after ischemic insults. Including astaxanthin in daily diet as a supplement may be beneficiary for ischemic optic neuropathy.

Topics: Animals; Chlorophyta; Disease Models, Animal; Male; Neuroprotective Agents; Optic Nerve; Optic Neuropathy, Ischemic; Rats; Retinal Ganglion Cells; Xanthophylls

Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect.. The aim of this study was to investigate the role of ASX on brain IRI.. A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated.. In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05).. Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

Topics: Animals; Brain; Disease Models, Animal; Hydrochloric Acid; Injections, Intraperitoneal; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Xanthophylls

Topics: Animals; Cells, Cultured; Combined Modality Therapy; Disease Models, Animal; Male; Mitochondria; Motor Disorders; Myelin Sheath; Neural Crest; Neural Stem Cells; Nuclear Respiratory Factor 1; Organelle Biogenesis; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Spinal Cord Injuries; Transcription Factors; Transplantation, Autologous; Up-Regulation; Xanthophylls

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. Since there is no cure for OA and no effective treatment to slow its progression, current pharmacologic treatments, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), only alleviate symptoms, such as pain and inflammation, but do not inhibit the disease process. Moreover, chronic intake of these drugs may result in severe adverse effects. For these reasons, patients have turned to the use of various complementary and alternative approaches, including diverse dietary supplements and nutraceuticals, in an effort to improve symptoms and manage or slow disease progression. The present study was conducted to evaluate the anti-osteoarthritic effects of FlexPro MD

Topics: Animals; Cartilage, Articular; Dietary Supplements; Disease Models, Animal; Euphausiacea; Hyaluronic Acid; Inflammation; Iodoacetates; Male; Osteoarthritis; Pain; Phytotherapy; Plant Oils; Rats, Sprague-Dawley; Treatment Outcome; Xanthophylls

The aim of this study is to probe a new function of astaxanthin (AST) from Haematococcus pluvialis on chemotherapeutic drug induced liver injury in mice. Doxorubicin-induced liver injury was treated with different doses of AST, and the body weight, food intake, urinalysis, liver function, and oxidative stress indexes were examined. The hepatocyte apoptosis level, pathological sections of liver tissue and the expression of antioxidant related genes were also determined. This study found that DOX could induce serious liver injury through cytotoxicity. AST treatment could decrease the level of liver function indexes (ALT, GOT, ALP and TBil), reduce the concentration of MDA and ROS, and increase the activities of SOD, CAT and GPX in the liver. AST could also repair the damaged hepatocyte in mice with liver injury and reduce the degree of the cellular apoptosis. In addition, AST could interfere with the expression of some related genes in the Keap1/Nrf2 signaling pathway by downregulating the expression of Keap1 and activating the transcription factor Nrf2 via enhancing the level of ERK, which upregulates downstream peroxiredoxins. The present research found and illustrated a new food function of AST, indicating that AST could be used in the therapy of chemotherapy induced side effects.

Topics: Animals; Antineoplastic Agents; Apoptosis; Chemical and Drug Induced Liver Injury; Chlorophyta; Disease Models, Animal; Dose-Response Relationship, Drug; Doxorubicin; Hepatocytes; Kelch-Like ECH-Associated Protein 1; Liver Cirrhosis; Male; Mice; Mice, Inbred ICR; NF-E2-Related Factor 2; Protective Agents; Xanthophylls

Hyperosmolarity is pro-inflammatory stress to the ocular surface epithelium associated with dry eye disease (DED). Astaxanthin (AST) is a kind of carotene, which exists in seafood and plays important roles in the amelioration of inflammatory diseases like arteriosclerosis, inflammatory bowel disease, sepsis, rheumatoid arthritis, gastric inflammation, brain inflammatory diseases. The aim of this study was to characterize the protective effect and potential mechanism of AST on DED in vitro and in vivo. Mouse models and human corneal epithelial cell (HCEC) cultures were exposed to hyperosmotic saline solution (HOSS) in in vitro and in vivo experiments, respectively. Experimental subjects were first pretreated with AST, and then the effect of the compound was assessed with clinical evaluation, real-time PCR (RT-PCR), western blot and immunofluorescent staining. We further investigated the possible mechanism of AST in DED by pre-treating with phosphoinositide 3-kinase inhibitor (LY294002). The addition of AST significantly reduced the expression of High-mobility group box 1 (HMGB1), as well as significantly inhibited the increases of TNF-α, IL-1β in a dose-dependent manner, but promoted the expression of phospho-Akt (p-Akt). BALB/c mice in DE group pretreated with AST showed significantly decreased corneal fluorescein staining scores. Moreover, pretreatment with LY294002 could eliminate the effects of AST preconditioning on the decrease of HMGB1. Our study provides evidence that AST could ameliorate DED which may be related to the inhibition of HMGB1, TNF-α, IL-1β, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of AST preconditioning.

Topics: Animals; Aqueous Humor; Blotting, Western; Cell Line; Cytokines; Disease Models, Animal; Dry Eye Syndromes; Epithelium, Corneal; Female; Fibrinolytic Agents; Humans; Mice; Mice, Inbred BALB C; Osmolar Concentration; Signal Transduction; Xanthophylls

Non-esterified astaxanthin (AST) has been reported to exhibit protective effects from Parkinson's disease (PD). Notably, DHA-acylated astaxanthin ester (DHA-AST) is widely distributed in the seafood. However, whether DHA-AST has an effect on PD, and the differences between DHA-AST, non-esterified AST and the combination of non-esterified AST (AST) with DHA (DHA + AST) is unclear. In the present study, mice with PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were employed to investigate the effects of DHA-AST, AST and DHA + AST on Parkinson's disease. The rotarod test results showed that DHA-AST significantly suppressed the PD development in MPTP-induced mice, and was better than the effects of AST and DHA + AST. Further mechanistic studies indicated that all three astaxanthin supplements could inhibit oxidative stress in the brain. It was noted that DHA-AST had the best ability to suppress the apoptosis of dopaminergic neurons via the mitochondria-mediated pathway and JNK and P38 MAPK pathway in the brain among the three treated groups. DHA-AST was superior to AST in preventing behavioral deficits coupled with apoptosis rather than oxidative stress, and might provide a valuable reference for the prevention and treatment of neurodegenerative diseases.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Apoptosis; Brain; Disease Models, Animal; Docosahexaenoic Acids; Dopaminergic Neurons; Esters; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Xanthophylls

Cardiac dysfunction is a significant manifestation of sepsis and it is associated with the prognosis of the disease. Astaxanthin (ATX) has been discovered to serve a variety of pharmacological effects, including anti‑inflammatory, antioxidant and antiapoptotic properties. The present study aimed to investigate the role and mechanisms of ATX in sepsis‑induced myocardial injury. Male C57BL/6 mice were divided into three groups (15 mice per group): Control group, lipopolysaccharide (LPS) group and LPS + ATX group. The cardiac dysfunction model was induced through an intraperitoneal injection of LPS (10 mg/kg) and ATX (40 mg/kg) was administered to the LPS + ATX group by intraperitoneal injection 30 min following the administration of LPS. All animals were sacrificed after 24 h. Inflammatory cytokine levels in the serum were detected using ELISAs, and cardiac B‑type natriuretic peptide (BNP) levels were analyzed using western blot analysis and reverse transcription‑quantitative PCR. Furthermore, the extent of myocardial injury was evaluated using pathological analysis, and cardiomyocyte apoptosis was analyzed using a TUNEL assay, in addition to determining the expression levels of Bcl‑2 and Bax. The expression levels of proteins involved in the mitogen activated protein kinase (MAPK) and PI3K/AKT signaling pathways were also analyzed using western blot analysis. ATX significantly suppressed the LPS‑induced increased production of TNF‑α and IL‑6 and suppressed the protein expression levels of BNP, Bax and Bcl‑2 to normal levels. ATX also prevented the histopathological changes to the myocardial tissue and reduced the extent of necrosis. Furthermore, the treatment with ATX suppressed the LPS‑activated MAPK and PI3K/AKT signaling. ATX additionally exerted a protective effect on cardiac dysfunction caused by sepsis by inhibiting MAPK and PI3K/AKT signaling.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Gene Expression Regulation; Glycogen Synthase Kinase 3 beta; Heart Diseases; Injections, Intraperitoneal; Lipopolysaccharides; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Sepsis; TOR Serine-Threonine Kinases; Treatment Outcome; Xanthophylls

The death of retinal ganglion cells (RGCs) during acute glaucoma causes progressive degeneration of the retinal nerve and irreversible blindness. Astaxanthin (AST) is a type of xanthophyll carotenoids and naturally synthesized by multiple halobios. It has been reported to protect the retina from acute glaucoma due to its anti-oxidative and anti-neuroinflammatory properties. However, the mechanism underlying this process remains unclear. We designed a mouse model with acute glaucoma and AST was administered by oral gavage. Hematoxylin and eosin staining was utilized to evaluate the condition of retina and the number of ganglion cells was counted. QRT-PCR was performed to evaluate the mRNA levels of Bax and Bcl2 while Western blot assay was used to determine the protein levels of Bax, Bcl2, Nrf2 and HO-1. AST protected the retinal integrity of mice with acute glaucoma. The apoptosis of RGCs induced by ischemia and reperfusion was repressed by AST. The protective functions of AST on the retinal and ganglion cells decreased with the knock-down of Nrf2. AST promoted the activation of Nrf2 and Ho-1 in the RGCs of the model mice. AST protected the RGCs from apoptosis during acute glaucoma and alleviated the severe retinopathy symptoms through the Nrf2/Ho-1 pathway.

Topics: Animals; Apoptosis; Disease Models, Animal; Glaucoma; Heme Oxygenase-1; Membrane Proteins; Mice; NF-E2-Related Factor 2; Oxidative Stress; Protective Agents; Retinal Ganglion Cells; Signal Transduction; Xanthophylls

Astaxanthin (ATX) is a naturally occurring carotenoid and a potent antioxidant. Various anti-inflammatory effects of ATX have been examined. We aimed to investigate the protective effect of ATX and its mechanism in a cerulein-induced acute pancreatitis rat model.. The rats were randomized into 2 main groups as control (C) and acute pancreatitis group (AP). AP group was subsequently divided into subgroups as AP+vehicle (AP), AP+ATX, and ATX+peroxisome proliferator-activated receptor-alpha antagonist GW6471 (ATX+GW) groups. To induce AP, the rats were administered cerulein (50 µg/kg, intraperitonally [ip]) at 1 hour intervals, whereas the C group received saline. The AP group was treated with vehicle olive oil, ATX 40 mg/kg/orally, or GW6471 and ATX (GW1 mg/kg/ip; ATX; 40 mg/kg/peroral). Treatments were administered after the 1st cerulein injection. At the 7th hour after the final injection, the rats were killed and the pancreatic tissue was used for the determination of malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) activities and luminol-lucigenin chemiluminescence levels. Serum amylase, lipase, and histopathological analyses were performed.. Elevated serum lipase and amylase levels in the vehicle-treated AP group (p<0.01) decreased in the ATX and ATX+GW groups (p<0.05). In the AP groups, GSH was reduced and MDA, MPO, luminol, and lucigenin levels were increased (p<0.05-0.001). ATX reversed these changes (p<0.05-0.001). The vehicle-treated group revealed significant severe cytoplasmic degeneration and vacuolization, whereas ATX ameliorated these destructions. GW6471 did not abolish the positive effects of ATX biochemically or histologically.. ATX has a potent protective effect on AP via its radical scavenging and antioxidant properties. Therefore, we believe that ATX may have therapeutic potential.

Topics: Acute Disease; Animals; Antioxidants; Ceruletide; Disease Models, Animal; Oxidative Stress; Pancreas; Pancreatitis; Rats; Xanthophylls

This study was designed to investigate the effects and underlying mechanisms of Astaxanthin (AST) on high-fructose-induced hyperuricemia (HUA) from the perspectives of the uric acid (UA) synthesis and excretion in rat models. Following six weeks of a 10% fructose diet, the level of serum UA effectively decreased in the AST groups as compared to the model group. The enzymatic activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly inhibited, and the mRNA expression levels of XOD and ADA significantly decreased after the AST administration. These results suggested that the AST reduced UA synthesis by inhibiting the mRNA expressions and enzyme activities of XOD and ADA, thereby contributing to HUA improvement. On the hand, the relative expressions of the mRNA and protein of kidney reabsorption transport proteins (GLUT9 and URAT1) were significantly down-regulated by AST, while that of the kidney secretion proteins (OAT1, OAT3 and ABCG2) were significantly up-regulated by AST. These results indicated that the AST promoted UA excretion by regulating the urate transport proteins, and thus alleviated HUA. This study suggested that the AST could serve as an effective alternative to traditional medicinal drugs for the prevention of fructose-induced HUA.

Topics: Adenosine Deaminase; Adenosine Deaminase Inhibitors; Animals; Biomarkers; Disease Models, Animal; Fructose; Hyperuricemia; Kidney; Liver; Male; Membrane Transport Proteins; Rats, Sprague-Dawley; Renal Reabsorption; Uric Acid; Xanthine Oxidase; Xanthophylls

Previously, we found that astaxanthin (AST) elicited an anti-inflammatory response in an experimental atopic dermatitis (AD) model. However, the use of AST was limited because of low bioavailability and solubility. We hypothesized that liposome formulation of AST could improve this. In this study, we compared the anti-inflammatory and anti-dermatotic effects of liposomal AST (L-AST) and free AST. We evaluated the effect of L-AST on a phthalic anhydride (PA)-induced animal model of AD by analyzing morphological and histopathological changes. We measured the mRNA levels of AD-related cytokines in skin tissue and immunoglobulin E concentrations in the serum. Oxidative stress and transcriptional activities of signal transducer and activator of transcription 3 (STAT3) and nuclear factor (NF)-κB were analyzed

Topics: Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Drug Delivery Systems; Liposomes; Male; Mice; Mice, Hairless; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; Phthalic Anhydrides; Signal Transduction; Skin; STAT3 Transcription Factor; Treatment Outcome; Xanthophylls

Topics: Administration, Oral; Alzheimer Disease; Amyloid beta-Peptides; Animal Shells; Animals; Cognitive Dysfunction; Disease Models, Animal; Lipid Peroxidation; Male; Maze Learning; Memory Disorders; Oxidative Stress; Penaeidae; Rats; Rats, Wistar; Vitamin E; Xanthophylls

Astaxanthin (AST) is a naturally occurring carotenoid with potent anti-oxidative and anti-inflammatory potency against chronic diseases. In this study, we suspended AST in different nonionic emulsifiers to produce nanodispersions. The basic physicochemical properties of the produced AST nanodispersions were verified to select the optimized nonionic emulsifier. Among the tested emulsifiers, Polysorbate 20 produced the AST nanoemulsions with smaller particle diameters, narrower size distributions, and higher AST contents among these emulsifiers. The

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Drug Carriers; Emulsifying Agents; Female; Male; Methylnitrosourea; Mice, Inbred C57BL; Nanoparticles; Photoreceptor Cells, Vertebrate; Retina; Retinal Degeneration; Xanthophylls

Inflammation plays a key role in the progression of subarachnoid hemorrhage (SAH). Here, we examined the effects of astaxanthin (ATX) on the inflammatory response and secondary damage after SAH and the underlying mechanisms of action. In vivo, a prechiasmatic cistern injection model was established in rats and mice. In addition, neuron-microglia cocultures were exposed to oxyhemoglobin to mimic SAH in vitro. Western blotting revealed that protein expression of TLR4 was markedly increased in microglia at 24 h after SAH, with consequent increases in the downstream molecules myeloid differentiation factor 88 and NF-кB. Treatment with ATX significantly inhibited the TLR4 activation, increased sirtuin 1 expression, and inhibited the subsequent inflammatory response both in vivo and in vitro. ATX also significantly decreased high-mobility group box 1 nuclear translocation and secretion in neurons, an effect that was reversed by the sirtuin 1-specific inhibitor sirtinol. ATX administered 4 h after SAH ameliorated cerebral inflammation, brain edema, and neuronal death and improved neurologic function. ATX reduced neuronal death but did not improve neurologic function in TLR4 knockout mice. These results suggest that ATX reduces the proinflammatory response and secondary brain injury after SAH, primarily by increasing sirtuin 1 levels and inhibiting the TLR4 signaling pathway.-Zhang, X., Lu, Y., Wu, Q., Dai, H., Li, W., Lv, S., Zhou, X., Zhang, X., Hang, C., Wang, J. Astaxanthin mitigates subarachnoid hemorrhage injury primarily by increasing sirtuin 1 and inhibiting the Toll-like receptor 4 signaling pathway.

Topics: Animals; Disease Models, Animal; Female; Inflammation; Male; Mice; Mice, Knockout; Neuroprotective Agents; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1; Subarachnoid Hemorrhage; Toll-Like Receptor 4; Xanthophylls

With the constant failure of the clinical trials continuous exploration of a therapeutic target against Alzheimer's disease (AD) is the utmost need. Numerous studies have supported the hypothesis that central insulin resistance plays a significant role in AD. Serine phosphorylation of Insulin Receptor Substarte-1 (IRS-1) has been found to be a contributing factor in neuronal insulin resistance. Astaxanthin (ASX) is xanthophyll carotenoid which has previously demonstrated significant antidiabetic and neuroprotective actions. In the present study, AD was induced by i.c.v administration of Amyloid-β (1-42) peptides in Wistar rats. After 7 days of recovery, rats were treated with 0.5 mg/kg and 1 mg/kg of ASX orally for 28 days. Behavioral analysis was done in the last week of our experimental study. On the 36th day, rats were sacrificed and their hippocampus were separated from the whole brain, then homogenized and stored for biochemical estimations. ASX significantly and dose-dependently reversed the cognitive and memory impairment, assessed by Morris water maze test and Novel object Recognition test, Aβ (1-42) peptides infused Wistar rats. ASX also significantly attenuated soluble Aβ (1-42) level, IRS-S307 activity, GSK-3β activity, TNF-α level, AChE level, nitrite level and oxidative stress in the hippocampus. Histopathological evaluation, done through H&E and Congo red staining, also demonstrated neuroprotective and anti-amyloidogenic effects of ASX in hippocampus. Our study concludes preventive action of Astaxanthin against hippocampal insulin resistance and Alzheimer's disease complications, supporting potential role of hippocampal insulin resistance targeting against AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hippocampus; Injections, Intraventricular; Insulin Resistance; Maze Learning; Neuroprotective Agents; Peptide Fragments; Random Allocation; Rats; Rats, Wistar; Xanthophylls

Alzheimer's disease is characterized by progressive disruption of cholinergic neurotransmission and impaired cognitive functions. In rodents, scopolamine has been used to induce cholinergic dysfunction resulting in cognitive impairments and an increment of oxidative stress in the brain. Here we tested whether oxidative stress can be attenuated via an antioxidant (astaxanthin) to rescue scopolamine-induced spatial memory. For this purpose, we administered either 0.9% saline (control), or scopolamine (SCP), or scopolamine plus astaxanthin (SCP + AST) to Swiss albino mice (ten weeks old; n = 20) for 28 consecutive days and subsequently examined animals' locomotor activity, spatial learning, and memory performance. The mice were then euthanized and prefrontal cortex (PFC), striatum (ST), hippocampus (HP), and liver tissues were assayed for antioxidant enzymes, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and nitric oxide (NO). The SCP group exhibited impaired spatial learning and significantly altered levels of antioxidant enzymes and NO in the PFC, ST, and HP. In contrast, SCP + AST treatment did not cause spatial learning deficits. Furthermore, this condition also showed unaltered levels of SOD and NO in the ST and HP. Taken together, our results show that scopolamine may interrupt the striatal-hippocampal cholinergic activity resulting in impaired spatial memory. At the same time, these impairments are extinguished with astaxanthin by preventing oxidative damage in the striatal-hippocampal cholinergic neurons. Therefore, we suggest astaxanthin as a potential treatment to slow the onset or progression of cognitive dysfunctions that are elicited by abnormal cholinergic neurotransmission in Alzheimer's disease.

Topics: Acetylcholine; Alzheimer Disease; Animals; Antioxidants; Brain; Catalase; Cognition; Cognitive Dysfunction; Disease Models, Animal; Glutathione; Hippocampus; Lipid Peroxidation; Male; Maze Learning; Memory Disorders; Mice; Oxidative Stress; Scopolamine; Spatial Memory; Superoxide Dismutase; Xanthophylls

The present study was carried out to evolve an effective treatment strategy for chronic obstructive pulmonary disease (COPD). Astaxanthin (AS) is abundantly present in red pigments of crustaceans, and has also been proven to have considerable biological activities. The anti-inflammatory effect of AS was evaluated in lipopolysaccharide (LPS)-exposed RAW264.7 macrophages. It was found that AS markedly inhibited elevation of NO and pro-inflammatory mediators. Moreover, it downregulated iNOS in LPS-stimulated RAW264.7 cells, suppressed the release of pro-inflammatory cytokines, and decreased ROS levels in mice exposed to cigarette smoke (CS) and LPS. These results imply that AS has therapeutic and prophylactic potential in the airway inflammatory response associated with COPD.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cell Death; Cell Survival; Cytokines; Disease Models, Animal; Enzyme Induction; Heme Oxygenase-1; Inflammation Mediators; Lipopolysaccharides; Lung; Macrophages; Male; Mice; Mice, Inbred C57BL; Neutrophils; Nitric Oxide; Nitric Oxide Synthase Type II; Pneumonia; RAW 264.7 Cells; Reactive Oxygen Species; RNA, Messenger; Smoking; Xanthophylls

Loss of peritubular capillaries is a notable feature of progressive renal interstitial fibrosis. Astaxanthin (ASX) is a natural carotenoid with various biological activities. The present study aimed to evaluate the effect of ASX on unilateral ureteral obstruction (UUO)‑induced renal fibrosis in mice. For that purpose, mice were randomly divided into five treatment groups: Sham, ASX 100 mg/kg, UUO, UUO + ASX 50 mg/kg and UUO + ASX 100 mg/kg. ASX was administered to the mice for 7 or 14 days following UUO. The results demonstrated that UUO‑induced histopathological changes in the kidney tissue were prevented by ASX. Renal function was improved by ASX treatment, as evidenced by decreased blood urea nitrogen and serum creatinine levels. Furthermore, the extent of renal fibrosis and collagen deposition induced by UUO was suppressed by ASX. The levels of collagen I, fibronectin and α‑smooth muscle actin were increased by UUO in mice or by transforming growth factor (TGF)‑β1 treatment in NRK‑52E cells, and were reduced by ASX administration. In addition, ASX inhibited the UUO‑induced decrease in peritubular capillary density by upregulating vascular endothelial growth factor and downregulating thrombospondin 1 levels. Inactivation of the TGF‑β1/Smad signaling pathway was involved in the anti‑fibrotic mechanism of ASX in UUO mice and TGF‑β1‑treated NRK‑52E cells. In conclusion, ASX attenuated renal interstitial fibrosis and peritubular capillary rarefaction via inactivation of the TGF‑β1/Smad signaling pathway.

Topics: Animals; Biomarkers; Biopsy; Cell Line; Disease Models, Animal; Fibrinolytic Agents; Fibrosis; Kidney Diseases; Male; Mice; Microvascular Rarefaction; Rats; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1; Ureteral Obstruction; Vascular Endothelial Growth Factor A; Xanthophylls

To evaluate the impact of intravitreal (IV) and intraperitoneal (IP) astaxanthin (AST) injections on neovascular development (ND), retinal morphology, and apoptotic activity in a C57BL/6J mouse model with hyperoxia-induced retinopathy (HIR).. C57BL/6J mouse model.. Two negative control groups (n = 6 each; one of which received IV sterile dimethyl sulfoxide [DMSO]) of C57BL/6J-type mice were exposed to room air. The HIR groups included 36 C57BL/6J-type mice exposed to 75% ± 2% oxygen from postnatal day (PD) 7 to PD 12. On PD 12, these mice were randomized into 6 groups (n = 6 each): 2 HIR control groups (one of which received IV-DMSO), 2 IV-AST groups (10 and 100 µg/mL), and 2 IP-AST groups (0.5 and 5 mg/kg). We measured ND by counting neovascular tufts in cross sections and examined histological, ultrastructural changes via light and electron microscopy. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated nick end-labeling.. No ND was detected in the negative control groups. ND levels were not significantly different between high- and low-dose AST for either means of administration. However, ND levels were significantly lower in the AST groups, regardless of delivery, compared to the control groups. The means of delivery (IP versus IV) also yielded significant differences in ND. The incidence of mitochondrial dysmorphology and apoptosis were lower in groups receiving AST.. AST seems to suppress ND and has anti-apoptotic activity in the HIR mouse model.

Topics: Animals; Animals, Newborn; Apoptosis; Cell Proliferation; Disease Models, Animal; Dose-Response Relationship, Drug; Fibrinolytic Agents; Hyperoxia; In Situ Nick-End Labeling; Intravitreal Injections; Mice; Mice, Inbred BALB C; Microscopy, Electron; Oxygen; Random Allocation; Retina; Retinal Diseases; Xanthophylls

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. It is a complex process, including a broad spectrum of hepatic lesions from fibrosis to cirrhosis. Our previous study suggested that astaxanthin (AST) could alleviate the hepatic inflammation and lipid dysmetabolism induced by ethanol administration. In this study, a total of 48 male C57BL/6J mice were divided into 4 groups: a Con group (fed with a Lieber⁻DeCarli liquid diet), an AST group (fed with a Lieber⁻DeCarli liquid diet and AST), an Et group (fed with an ethanol-containing Lieber⁻DeCarli liquid diet), and a EtAST group (fed with an ethanol-containing Lieber⁻DeCarli liquid diet and AST). Then, comparative hepatic transcriptome analysis among the groups was performed by Illumina RNA sequencing. Gene enrichment analysis was conducted to identify pathways affected by the differentially expressed genes. Changes of the top genes were verified by quantitative real-time PCR (qRT-PCR) and Western blot. A total of 514.95 ± 6.89, 546.02 ± 15.93, 576.06 ± 21.01, and 690.85 ± 54.14 million clean reads were obtained for the Con, AST, Et, and EtAST groups, respectively. Compared with the Et group, 1892 differentially expressed genes (DEGs) (including 351 upregulated and 1541 downregulated genes) were identified in the AST group, 1724 differentially expressed genes (including 233 upregulated and 1491 downregulated genes) were identified in the Con group, and 1718 DEGs (including 1380 upregulated and 338 downregulated genes) were identified in the EtAST group. The enrichment analyses revealed that the chemokine signaling, the antigen processing and presentation, the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, and the Toll-like receptor signaling pathways enriched the most differentially expressed genes. The findings of this study provide insights for the development of nutrition-related therapeutics for ALD.

Topics: Animals; Aquatic Organisms; Disease Models, Animal; Ethanol; Gene Expression Profiling; Gene Expression Regulation; Humans; Liver; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred C57BL; Protective Agents; Sequence Analysis, RNA; Signal Transduction; Transcriptome; Treatment Outcome; Xanthophylls

(1) Background: Reperfusion injury refers to the cell and tissue damage induced, when blood flow is restored after an ischemic period. While reperfusion reestablishes oxygen supply, it generates a high concentration of radicals, resulting in tissue dysfunction and damage. Here, we aimed to challenge and achieve the potential of a delivery system based on astaxanthin, a natural antioxidant, in attenuating the muscle damage in an animal model of femoral hind-limb ischemia and reperfusion. (2) Methods: The antioxidant capacity and non-toxicity of astaxanthin was validated before and after loading into a polysaccharide scaffold. The capacity of astaxanthin to compensate stress damages was also studied after ischemia induced by femoral artery clamping and followed by varied periods of reperfusion. (3) Results: Histological evaluation showed a positive labeling for CD68 and CD163 macrophage markers, indicating a remodeling process. In addition, higher levels of Nrf2 and NQO1 expression in the sham group compared to the antioxidant group could reflect a reduction of the oxidative damage after 15 days of reperfusion. Furthermore, non-significant differences were observed in non-heme iron deposition in both groups, reflecting a cell population susceptible to free radical damage. (4) Conclusions: Our results suggest that the in situ release of an antioxidant molecule could be effective in improving the antioxidant defenses of ischemia/reperfusion (I/R)-damaged muscles.

Topics: 3T3 Cells; Animals; Antioxidants; Cell Line; Disease Models, Animal; Macrophages; Male; Mice; Muscle, Skeletal; Oxidative Stress; Rats; Reperfusion Injury; Xanthophylls

To investigate the effect of astaxanthin on the neurological function of the middle cerebral artery occlusion (MCAO) mice and its possible mechanism.. The male C57BL/6 mice were selected to establish the model of MCAO via electrocoagulation, and they were randomly divided into 4 groups: the sham operation group (Sham group), the cerebral ischemia model group (MCAO group), the astaxanthin intervention group (gavage with 30 mg/kg astaxanthin for 28 days, twice a day; Ast group), and astaxanthin + H89 group (Ast + H89 group). At 3, 7, 14, and 28 d after the operation, the Rotarod test and the balance beam footstep error test were performed. The brain tissues were taken for immunofluorescence to observe the expression of the growth-associated protein 43 (GAP43) in the cortex around the infarction. The GAP43 protein and mRNA levels in the cortex around the infarction were detected via Western blotting, and the Reverse Transcription-Polymerase Chain Reaction (RT-PCR), the levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the bilateral cerebral cortex were detected via enzyme-linked immunosorbent assay (ELISA), and the PKAc and phosphorylated-cAMP-response element-binding protein (p-CREB) levels in the bilateral cerebral cortex were detected via Western blotting. Biotin dextran amine (BDA) was injected at 14 d after the operation, and the brain was taken at 28 d. The BDA-labeled neurons or axons were observed in the bilateral cortex via immunohistochemistry and immunofluorescence, and the colocalization of BDA and GAP43 in the cortex around the infarction was observed using double immunofluorescence staining.. Compared with those in the MCAO group, the mean residence time in the Rotarod test was significantly increased, and the times of the footstep error on the balance beam were significantly reduced in the Ast group. In the Ast group, the expression of GAP43 in the cortex around the infarction, the GAP43 protein, and the mRNA levels were all significantly elevated. Immunofluorescence showed that in the Ast group, the number of the labeled neurons and axons in the bilateral cortex was slightly larger than that in the other groups, and the number of labeled axonal fibers in the ischemic cortex was significantly increased. The colocalization area of BDA and GAP43 was observed, and it was found that the positive area in the Ast group was significantly larger than that in the MCAO group. The cAMP level was higher in the Ast group and Ast + H89 group at 7, 14, and 28 d after operation, while the PKA level was lower in the Ast + H89 group at 7 and 14 d after operation and higher in the Ast group at 7, 14, and 28 d after operation. The results of the Western blotting manifested that the PKAc and p-CREB levels were upregulated in the Ast group at 7, 14, and 28 d after the operation, and downregulated in the Ast + H89 group at 7, 14, and 28 d after the operation.. Astaxanthin activates the cAMP/PKA/CREB signaling pathway by increasing the cAMP concentration in brain tissues, ultimately promoting the axonal regeneration in the cerebral cortex and improving the motor function.

Topics: Animals; Axons; Cerebral Infarction; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Disease Models, Animal; Drug Administration Schedule; GAP-43 Protein; Gene Expression Regulation, Neoplastic; Male; Mice; Mice, Inbred C57BL; Nerve Regeneration; Random Allocation; Signal Transduction; Xanthophylls

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Cell Count; Cyclooxygenase 2; Dermatitis, Atopic; Disease Models, Animal; Immunoglobulin E; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Lymph Nodes; Mast Cells; Mice; NF-kappa B; Nitric Oxide Synthase; Organ Size; Phthalic Anhydrides; RAW 264.7 Cells; Severity of Illness Index; Signal Transduction; Tumor Necrosis Factor-alpha; Xanthophylls

Chemobrain refers to a common sequelae experienced by 15-80% of cancer patients exposed to chemotherapeutics. The antineoplastic agent doxorubicin (DOX) has been implicated in a strenuous neurotoxicity manifested as decline in cognitive functions, most probably via cytokine-induced oxidative and nitrosative damage to brain tissues. Astaxanthin (AST), a naturally occurring carotenoid, is reputable for its outstanding antioxidant, anti-inflammatory, and antiapoptotic activities. Therefore, the aim of the current study was to investigate the potential neuroprotective and memory-enhancing effects of AST against DOX-induced behavioral and neurobiological abnormalities. Briefly, AST treatment (25 mg/kg) significantly protected against DOX-induced memory impairment. Furthermore, AST restored hippocampal histopathological architecture, halted DOX-induced oxidative and inflammatory insults, mitigated the increase in acetylcholinesterase activity, and consistently downregulated the overactive apoptotic machineries. In conclusion, these findings suggest that AST offers neuroprotection against DOX-induced cognitive impairment which could be explained at least partly by its antioxidant, anti-inflammatory, and antiapoptotic effects.

Topics: Acetylcholinesterase; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Behavior, Animal; Biomarkers; Cognitive Dysfunction; Disease Models, Animal; Doxorubicin; Glial Fibrillary Acidic Protein; Hippocampus; Inflammation; Male; Models, Biological; Motor Activity; Nerve Degeneration; Neuroprotective Agents; Oxidative Stress; Rats; Xanthophylls

Astaxanthin is a keto-carotenoid that has a strong antioxidant effect. The purpose of this study was to evaluate the effects of astaxanthin on alveolar bone loss and histopathological changes in ligature-induced periodontitis in rats.. Wistar rats were divided into four experimental groups: non-ligated (C, n = 6); ligature only (L, n = 6); ligature and astaxanthin (1 mg/kg/day astaxanthin, AS1 group, n = 8); ligature and astaxanthin (5 mg/kg/day astaxanthin, AS5 group, n = 8). Silk ligatures were placed at the gingival margin of lower first molars of the mandibular quadrant. The study duration was 11 days and the animals were killed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were immunohistochemically examined, osteocalcin, bone morphogenic protein-2, inducible nitric oxide synthase, Bax and bcl-2 levels in alveolar bone and tartrate-resistant acid phosphatase-positive osteoclast cells, osteoblast and inflammatory cell counts were determined.. Alveolar bone loss was highest in the L group and the differences among the L, AS1 and AS5 groups were also significant (P < .05). Both doses of astaxanthin decreased tartrate-resistant acid phosphatase-positive+ osteoclast cell and increased osteoblast cell counts (P < .05). The inflammation in the L group was also higher than those of the C and AS1 groups were (P < .05) indicating the anti-inflammatory effect of astaxanthin. Although inducible nitric oxide synthase, osteocalcin, bone morphogenic protein-2 and bax staining percentages were all highest in the AS5 group and bcl-2 staining percentage was highest in the AS1 group, values were close to each other (P > .05).. Within the limits of this study, it can be suggested that astaxanthin administration may reduce alveolar bone loss by increasing osteoblastic activity and decrease osteoclastic activity in experimental periodontitis model.

Topics: Alveolar Bone Loss; Animals; Antioxidants; bcl-2-Associated X Protein; Bone Morphogenetic Protein 2; Cell Count; Disease Models, Animal; Nitric Oxide Synthase; Osteoblasts; Osteocalcin; Periodontitis; Rats, Wistar; Xanthophylls

The aim of the study was to investigate the effect of astaxanthin and its possible mechanisms on acute cerebral infarction (ACI) in rat model. Male Sprague Dawley rats were randomly divided into sham group, model group, and astaxanthin-treated groups (20, 40, and 80 mg/kg). Neurological examination, the ratio of cerebral edema, and histopathology changes were assessed. Moreover, some oxidative stress markers were obtained for biochemical analysis, and the expression of neurotrophic factors gene was detected by real-time polymerase chain reaction (RT-PCR) method. The results showed that treatment with astaxanthin notably reduced neurological deficit scores and the ratio of cerebral edema compared with the model group. Meanwhile, astaxanthin increased the activity of catalase, superoxide dismutase, and glutathioneperoxidase as well as decreased the content of malondialdehyde in brain tissue. RT-PCR results showed that the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNA were increased with astaxanthin treatment. The results indicated that astaxanthin could ameliorate ACI followed by suppressing oxidative stress and upregulating the expression of BDNF and NGF mRNA.

Topics: Acute Disease; Animals; Antioxidants; Brain; Brain Edema; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Infarction, Middle Cerebral Artery; Male; Motor Activity; Nerve Growth Factor; Neuroprotective Agents; Oxidative Stress; Rats, Sprague-Dawley; Signal Transduction; Up-Regulation; Xanthophylls

A various of pharmacological effects of astaxanthin has been confirmed. However, the mechanism underlying protective effect of astaxanthin on acute pancreatitis (AP) induced by cerulein still unclear. The present study is to investigate the mechanism underlying the effect of astaxanthin on autophagy and apoptosis via the JAK/STAT3 pathway.. Intraperitoneal injection of cerulein at hourly intervals followed by lipopolysaccharide injection were used in Balb/C mice. Vehicle or astaxanthin, which intraperitoneal injected in two doses (20 mg/kg and 40 mg/kg), were injected in mice 1 h before the first cerulein injection. At 3 h after the last injection, when the pathological changes were most severe, pancreatic tissue was analyzed by pathologically scored and hematoxylin and eosin (H&E) staining. The severity of AP was assessed by histological grading, proinflammatory cytokine levels, biochemistry, myeloperoxidase (MPO) activity, and analysis of JAK/STAT3 activity.. Astaxanthin administration markedly reduced serum digestive enzyme activities, pancreatic histological scores, proinflammatory cytokine levels (tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6)), MPO and JAK/STAT3 activity.. Collectively, these results indicate that astaxanthin inhibits pancreatic injury in AP by targeting JAK/STAT3-mediated apoptosis and autophagy.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Apoptosis; Autophagy; Ceruletide; Cytokines; Disease Models, Animal; Humans; Inflammation Mediators; Janus Kinases; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Pancreas; Pancreatitis; Peroxidase; STAT3 Transcription Factor; Xanthophylls

Excitotoxic damage caused by increased glutamate levels is involved in the pathogenesis of neurodegenerative diseases. Astaxanthin, a natural carotenoid with multiple health benefits, inhibits glutamate release from the brain tissue; however, whether it possesses the ability to affect glutamate-induced brain injury is unknown. The present study investigated the neuroprotective effects of astaxanthin on kainic acid (KA)-induced excitotoxicity in rats and the possible underlying intracellular signaling pathway. The rats were orally administrated with astaxanthin (50 or 100 mg/kg) for 7 days (once a day), and KA (15 mg/kg) was administered intraperitoneally at 1 h after the final administration. The results revealed that KA induced seizures, increased the hippocampal glutamate levels, caused considerable neuronal death and microglial activation in the hippocampal CA3 regions, and increased the production of proinflammatory cytokines. Astaxanthin pretreatment prevented these changes. Furthermore, astaxanthin pretreatment increased the expression of neuronal cell survival-related factors, including phosphorylated Akt, phosphorylated glycogen synthase kinase-3β, and Bcl-2 in the hippocampus of KA-injected rats. These results suggested that astaxanthin can attenuate seizures, mitigate inflammation, augment survival signals, and prevent hippocampal neuronal damage in the animal model of KA-induced excitotoxicity.

Topics: Animals; Cell Death; Disease Models, Animal; Excitatory Amino Acid Agonists; Glutamic Acid; Hippocampus; Kainic Acid; Neurons; Neuroprotective Agents; Rats, Sprague-Dawley; Seizures; Xanthophylls

The aim of the present study was to reveal the effect of therapeutic and prophylactic potential of astaxanthin in experimental autoimmune encephalomyelitis (EAE) as an acceptable model for the study of multiple sclerosis (MS).. Astaxanthin has powerful antioxidant activities as well as several essential biological functions while multiple sclerosis prevention is highly regarded by researchers.. The astaxanthin potential in prevention of multiple sclerosis was examined in the chronic model of experimental autoimmune encephalomyelitis (EAE) by using female C57BL/6 mice induced with oligodendrocyte glycoprotein (MOG). Splenocytes were assessed to measure the levels of proinflammatory and anti-inflammatory cytokines, proliferation rate and FoxP3+Treg cell frequency. Immunohistochemical examinations were performed on spinal cord and brain tissue.. Astaxanthin reduced splenocytes proliferation index and proinflammatory cytokine levels, and vice versa increased the anti-inflammatory cytokine levels. Immunohistochemical studies of the spinal cord and brain showed that the infiltration with inflammatory cells was highly confined in the central nervous system. Protective effects of astaxanthin were visible by assigning low score recording in clinical behavior and disease severity.. Astaxanthin is a powerful tool for intervention in EAE on a model of multiple sclerosis, so it can be studied further to prevent and treat MS (Tab. 2, Fig. 3, Ref. 41).

Topics: Animals; Antioxidants; Brain; Cell Proliferation; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Spinal Cord; Spleen; Xanthophylls

Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains limited. Astaxanthin, a marine natural drug, having potent anti-oxidant and anti-inflammatory activities is known to possess neuroprotective effects. However, effects of astaxanthin against nerve injury induce chronic pain remains unknown. Overactivity of glutamatergic NMDARs results in excitotoxicity which may participate in astrocytic and microglial activation during pathology which further contribute to the development of neuropathic pain. In this study, we investigate the effects of astaxanthin on oxido-inflammatory and NMDA receptor down-regulation pathway by using in-silico, in-vitro and in-vivo models of neuropathic pain. In-silico molecular docking study ascertained the binding affinity of astaxanthin to NMDA receptors and showed antagonistic effects. Data from in-vitro studies suggest that astaxanthin significantly reduces the oxidative stress induced by the lipopolysaccharides in C6 glial cells. In male Sprague dawley rats, a significant attenuation of neuropathic pain behavior was observed in Hargreaves test and von Frey hair test after astaxanthin treatment. Findings from the current study suggest that astaxanthin can be used as potential alternative in the treatment of chronic neuropathic pain. However, more detailed investigations are required to further probe the in-depth mechanism of action of astaxanthin.

Topics: Analgesics; Animals; Antioxidants; Behavior, Animal; Cell Survival; Cells, Cultured; Disease Models, Animal; Hyperalgesia; Inflammation; Lipopolysaccharides; Male; Molecular Docking Simulation; Neuralgia; Oxidative Stress; Pain Threshold; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Xanthophylls

The development and progression of alcoholic fatty liver disease (AFLD) is influenced by the intestinal microbiota. Astaxanthin, a type of oxygenated carotenoid with strong antioxidant and anti-inflammatory properties, has been proven to relieve liver injury. However, the relationship between the gut microbiota regulation effect of astaxanthin and AFLD improvement remains unclear. The effects of astaxanthin on the AFLD phenotype, overall structure, and composition of gut microbiota were assessed in ethanol-fed C57BL/6J mice. The results showed that astaxanthin treatment significantly relieves inflammation and decreases excessive lipid accumulation and serum markers of liver injury. Furthermore, astaxanthin was shown to significantly decrease species from the phyla Bacteroidetes and Proteobacteria and the genera

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Disease Models, Animal; Dysbiosis; Fatty Liver, Alcoholic; Gastrointestinal Microbiome; Gastrointestinal Tract; Inflammation Mediators; Lipid Metabolism; Liver; Male; Metagenome; Mice, Inbred C57BL; Xanthophylls

Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model. The hepatic steatosis and inflammation induced by ethanol administration were alleviated by AXT. Serum levels of aspartate transaminase and alanine transaminase were decreased in the livers of AXT administrated group. The ethanol-induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins, cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced in the livers of AXT administrated group. Moreover, ethanol-induced infiltration of neutrophils was decreased in the livers of AXT administrated group. Docking model and pull-down assay showed that AXT directly binds to the DNA binding site of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT administration group. Therefore, these results suggest that AXT could prevent ethanol-induced hepatic injury via inhibition of oxidant and inflammatory responses via blocking of STAT3 activity.

Topics: Animals; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cytokines; Disease Models, Animal; Ethanol; Inflammation; Liver; Male; Mice; Oxidative Stress; Phosphorylation; Reactive Oxygen Species; Signal Transduction; STAT3 Transcription Factor; Xanthophylls

Spinal cord injury (SCI) is a debilitating condition in which inflammatory responses in the secondary phase of injury leads to long lasting sensory-motor dysfunction. The medicinal therapy of SCI complications is still a clinical challenge. Understanding the molecular pathways underlying the progress of damage will help to find new therapeutic candidates. Astaxanthin (AST) is a ketocarotenoid which has shown anti-inflammatory effects in models of traumatic brain injury. In the present study, we examined its potential in the elimination of SCI damage through glutamatergic-phospo p38 mitogen-activated protein kinase (p-p38MAPK) signaling pathway. Inflammatory response, histopathological changes and sensory-motor function were also investigated in a severe compression model of SCI in male rats. The results of acetone drop and inclined plane tests indicated the promising role of AST in improving sensory and motor function of SCI rats. AST decreased the expression of n-methyl-d-aspartate receptor subunit 2B (NR2B) and p-p38MAPK as inflammatory signaling mediators as well as tumor necrosis factor-α (TNF-α) as an inflammatory cytokine, following compression SCI. The histopathological study culminated in preserved white mater and motor neurons beyond the injury level in rostral and caudal parts. The results show the potential of AST to inhibit glutamate-initiated signaling pathway and inflammatory reactions in the secondary phase of SCI, and suggest it as a promising candidate to enhance functional recovery after SCI.

Topics: Animals; Cytokines; Disease Models, Animal; Glutamic Acid; Inflammation; Male; Motor Disorders; Neuralgia; Neuroimmunomodulation; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Wistar; Recovery of Function; Signal Transduction; Spinal Cord; Spinal Cord Injuries; Xanthophylls

Spinal cord injury (SCI) often leads to constant neurological deficits and long-term unalterable disability. Apoptosis plays an important role in the initiation of the secondary injury cascades leading to progressive tissue damage and severely functional deficits after SCI. Although the primary mechanical destructive events cannot be reversed, a therapeutic intervention could be carried out in order to moderate the secondary injury damage several hours to weeks after injury. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agents with the potential to render anti-apoptotic and neuroprotective effects. In the current study, we examined the therapeutic potential of AST on adult rats after severe SCI contusion. Results of BBB scores showed that AST improved motor function after SCI compared to control groups. Western blot analysis showed reduced expression of Bax and Cleaved-caspase-3 proteins and increased expression of the Bcl-2 protein in response to AST treatment (p<0.05). The histology results also showed that AST considerably preserved myelinated white matter and the number of motor neurons. This study is the first to report that AST reduces neuronal apoptosis, diminishes pathological tissue damage and improves functional recovery after SCI. The observed prominent neuroprotective effects, introduces AST as a promising therapy for SCI.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Disease Models, Animal; Locomotion; Male; Neurons; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries; Time Factors; Xanthophylls

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Topics: Animals; Computational Biology; Diet; Disease Models, Animal; Liver; Mice; Non-alcoholic Fatty Liver Disease; Transcriptome; Vitamin E; Xanthophylls

Oxidative stress has been implicated in the pathogenesis of neurodegenerative disorders, such as vascular cognitive impairment (VCI). The present study was performed to investigate the potential neuroprotective effect of the antioxidant astaxanthin (ATX) in a mouse model of VCI. VCI was induced in male ICR mice by repeated occlusion of the bilateral common carotid artery, leading to repeated cerebral ischemia/reperfusion (IR) injury. After surgery, the mice received ATX or an equal volume of vehicle by daily intragastric administration for 28days. The results showed that ATX treatment ameliorated learning and memory deficits after repeated cerebral IR. ATX administration rescued the number of surviving pyramidal neurons in the CA1 and CA3 regions. The concentration of malondialdehyde was decreased, and the levels of reduced glutathione and superoxide dismutase in the hippocampus were increased. Electron microphotography revealed that damage to the ultrastructure of neurons was also reduced by ATX administration. In addition, the expression levels of Cytochrome C (Cyt C), cleaved Caspase-3 and Bax were lower and the expression of Bcl-2 was higher compared to control IR mice. Our findings demonstrate that ATX is able to suppresse learning and memory impairment caused by repeated cerebral IR and that this effect is associated with attenuation of oxidative stress.

Topics: Animals; Antioxidants; Apoptosis; Brain Ischemia; Cytochromes c; Dementia, Vascular; Disease Models, Animal; Glutathione; Hippocampus; Learning; Male; Malondialdehyde; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Neurons; Neuroprotective Agents; Oxidative Stress; Reperfusion; Reperfusion Injury; Superoxide Dismutase; Xanthophylls

β-Cryptoxanthin and astaxanthin are antioxidant carotenoid pigments that inhibit lipid peroxidation as potently as vitamin E. We hypothesized that acute treatment with β-cryptoxanthin and astaxanthin causes similar reductions in the sizes of cardiac infarcts caused by ischemia-reperfusion (I/R) injury by attenuating oxidative stress and cardiac mitochondrial dysfunction.. C57BL/6 mice (n = 36) were randomized to receive vehicle, β-cryptoxanthin, astaxanthin, or vitamin E at 50 mg/kg by gavage feeding prior to I/R injury. Cardiac I/R was induced by left anterior descending coronary artery ligation followed by reperfusion. All treatments significantly reduced infarct sizes by 36-57%, attenuated apoptosis and also attenuated cardiac mitochondrial dysfunction in the treated groups compared to the control group. Although astaxanthin and vitamin E exhibited similar efficacy with respect to cardioprotection, β-cryptoxanthin exhibited greater efficacy than its counterparts, as it reduced infarct sizes by 60%. β-Cryptoxanthin was more effective than astaxanthin and vitamin E because it reduced cardiac mitochondrial swelling, mitochondrial depolarization, the Bax/Bcl-2 ratio, and plasma and cardiac thiobarbituric acid reactive substances levels more significantly than its counterparts.. Acute β-cryptoxanthin treatment exhibits greater cardioprotective efficacy against I/R injury than astaxanthin and vitamin E by reducing infarct sizes and attenuating apoptosis, oxidative stress, and mitochondrial dysfunction.

Topics: Animals; Beta-Cryptoxanthin; Cardiotonic Agents; Disease Models, Animal; Heart; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Mitochondrial Diseases; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Vitamin E; Xanthophylls

During Trypanosoma cruzi infection, oxidative stress is considered a contributing factor for dilated cardiomyopathy development. In this study, the effects of astaxanthin (ASTX) were evaluated as an alternative drug treatment for Chagas disease in a mouse model during the acute infection phase, given its anti-inflammatory, immunomodulating, and anti-oxidative properties. ASTX was tested in vitro in parasites grown axenically and in co-culture with Vero cells. In vivo tests were performed in BALB/c mice (4-6 weeks old) infected with Trypanosoma cruzi and supplemented with ASTX (10 mg/kg/day) and/or nifurtimox (NFMX; 100 mg/kg/day). Results show that ASTX has some detrimental effects on axenically cultured parasites, but not when cultured with mammalian cell monolayers. In vivo, ASTX did not have any therapeutic value against acute Trypanosoma cruzi infection, used either alone or in combination with NFMX. Infected animals treated with NFMX or ASTX/NFMX survived the experimental period (60 days), while infected animals treated only with ASTX died before day 30 post-infection. ASTX did not show any effect on the control of parasitemia; however, it was associated with an increment in focal heart lymphoplasmacytic infiltration, a reduced number of amastigote nests in cardiac tissue, and less hyperplasic spleen follicles when compared to control groups. Unexpectedly, ASTX showed a negative effect in infected animals co-treated with NFMX. An increment in parasitemia duration was observed, possibly due to ASTX blocking of free radicals, an anti-parasitic mechanism of NFMX. In conclusion, astaxanthin is not recommended during the acute phase of Chagas disease, either alone or in combination with nifurtimox.

Topics: Animals; Chagas Disease; Chlorocebus aethiops; Disease Models, Animal; Drug Therapy, Combination; Female; Heart; Malondialdehyde; Mice; Mice, Inbred BALB C; Myocardium; Nifurtimox; Organ Size; Parasitemia; Spleen; Trypanocidal Agents; Trypanosoma cruzi; Vero Cells; Xanthophylls

Although astaxanthin has a variety of biological activities such as anti-oxidant effects, inhibitory effects on skin deterioration and anti-inflammatory effects, its effect on asthma has not been studied. In this paper, the inhibitory effect of astaxanthin on airway inflammation in a mouse model of ovalbumin (OVA)-induced asthma was investigated. We evaluated the number of total cells, Th1/2 mediated inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness as well as histological structure. The level of total IgE, IgG1, IgG2a, OVA-specific IgG1, and OVA-specific IgG2a were also examined. The oral administration of 50 mg/mL astaxanthin inhibited the respiratory system resistance, elastance, newtonian resistance, tissue damping, and tissue elastance. Also, astaxanthin suppressed the total cell number, IL-4, and IL-5, and increased the IFN-γ in the BALF. In the sera, total IgE, IgG1, and OVA-specific IgG1 were reduced by astaxanthin exposure and IgG2a and OVA-specific IgG2a were enhanced via oral administration of astaxanthin. Infiltration of inflammatory cells in the lung, production of mucus, lung fibrosis, and expression of caspase-1 or caspase-3 were suppressed in OVA-induced asthmatic animal treated with astaxanthin. These results suggest that astaxanthin may have therapeutic potential for treating asthma via inhibiting Th2-mediated cytokine and enhancing Th1-mediated cytokine.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Immunoglobulin E; Mice; Ovalbumin; Protective Agents; T-Lymphocytes, Helper-Inducer; Xanthophylls

Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear.. The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats.. Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively.. ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold).. ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats. These activities were closely correlated with ASTX, maintaining the balance of t-PA/PAI-1, NO/ROS and TXA2/PGI2 in vivo.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Biomarkers; Blood Coagulation; Diet, High-Fat; Disease Models, Animal; Dose-Response Relationship, Drug; Fibrinolysis; Fibrinolytic Agents; Hyperlipidemias; Lipid Peroxidation; Lipids; Male; Nitric Oxide; Nitric Oxide Synthase Type III; P-Selectin; Partial Thromboplastin Time; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prothrombin Time; Rats, Sprague-Dawley; Thromboxane B2; Time Factors; Tissue Plasminogen Activator; Xanthophylls

Traumatic brain injury (TBI) produces lasting neurological deficits that plague patients and physicians. To date, there is no effective method to combat the source of this problem. Here, we utilized a mild, closed head TBI model to determine the modulatory effects of a natural dietary compound, astaxanthin (AST). AST is centrally active following oral administration and is neuroprotective in experimental brain ischemia/stroke and subarachnoid hemorrhage (SAH) models. We examined the effects of oral AST on the long-term neurological functional recovery and histological outcomes following moderate TBI in a mice model.. Male adult ICR mice were divided into 3 groups: (1) Sham+olive oil vehicle treated, (2) TBI+olive oil vehicle treated, and (3) TBI+AST. The olive oil vehicle or AST were administered via oral gavage at scheduled time points. Closed head brain injury was applied using M.A. Flierl weight-drop method. NSS, Rotarod, ORT, and Y-maze were performed to test the behavioral or neurological outcome. The brain sections from the mice were stained with H&E and cresyl-violet to test the injured lesion volume and neuronal loss. Western blot analysis was performed to investigate the mechanisms of neuronal cell survival and neurological function improvement.. AST administration improved the sensorimotor performance on the Neurological Severity Score (NSS) and rotarod test and enhanced cognitive function recovery in the object recognition test (ORT) and Y-maze test. Moreover, AST treatment reduced the lesion size and neuronal loss in the cortex compared with the vehicle-treated TBI group. AST also restored the levels of brain-derived neurotropic factor (BDNF), growth-associated protein-43 (GAP-43), synapsin, and synaptophysin (SYP) in the cerebral cortex, which indicates the promotion of neuronal survival and plasticity.. To the best of our knowledge, this is the first study to demonstrate the protective role and the underlining mechanism of AST in TBI. Based on these neuroprotective actions and considering its longstanding clinical use, AST should be considered for the clinical treatment of TBI.

Topics: Animals; Brain Concussion; Cerebral Cortex; Cognition; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Male; Maze Learning; Mice, Inbred ICR; Neurons; Neuroprotective Agents; Nootropic Agents; Recognition, Psychology; Rotarod Performance Test; Severity of Illness Index; Spatial Memory; 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

Astaxanthin alleviates hepatic lipid accumulation and peroxidation, inflammation, and fibrosis in mice with high-cholesterol, high-cholate, and high-fat (CL) diet-induced nonalcoholic steatohepatitis (NASH) [...].

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Eukaryotic Initiation Factor-2; Gene Expression Profiling; Liver; Male; Mice; Mitochondria; Non-alcoholic Fatty Liver Disease; PPAR alpha; PPAR delta; Protein Interaction Mapping; Protein Interaction Maps; Retinoic Acid Receptor alpha; Signal Transduction; Transcriptome; Vitamin E; Xanthophylls

Astaxanthin exhibits various pharmacological activities, including anti-oxidative, anti-tumor, and anti-inflammatory effects, and is thought to exert a neuroprotective effect via these mechanisms. The purpose of this study was to investigate the protective effects of astaxanthin on neuronal cell death using a retinal ischemia/reperfusion model.. In vivo, retinal ischemia was induced by 5 h unilateral ligation of the pterygopalatine artery (PPA) and the external carotid artery (ECA) in ddY mice. Astaxanthin (100 mg/kg) was administered orally 1 h before induction of ischemia, immediately after reperfusion, at 6 or 12 h after reperfusion, and twice daily for the following 4 days. Histological analysis and an electroretinogram (ERG) were performed 5 days after ischemia/reperfusion. In vitro, cell death was induced in the RGC-5 (retinal precursor cells) by oxygen-glucose deprivation (OGD), and the rates of cell death and production of intracellular reactive oxygen species (ROS) were measured using nuclear staining and a ROS reactive reagent, CM-H. Histological studies revealed that astaxanthin significantly reduced retinal ischemic damage and ERG reduction. In in vitro studies, astaxanthin inhibited cell death and ROS production in a concentration-dependent manner.. Collectively, these results indicate that astaxanthin inhibits ischemia-induced retinal cell death via its antioxidant effect. Hence, astaxanthin might be effective in treating retinal ischemic pathologies.

Topics: Animals; Apoptosis; Cells, Cultured; Disease Models, Animal; Electroretinography; Fibrinolytic Agents; Ischemia; Male; Mice; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Xanthophylls

Astaxanthin is a carotenoid pigment that possesses potent antioxidative, anti-inflammatory, antitumor, and immunomodulatory activities. Previous studies have demonstrated that astaxanthin displays potential neuroprotective properties for the treatment of central nervous system diseases, such as ischemic brain injury and subarachnoid hemorrhage. This study explored whether astaxanthin is neuroprotective and ameliorates neurological deficits following traumatic brain injury (TBI).. Our results showed that, following CCI, treatment with astaxanthin compared to vehicle ameliorated neurologic dysfunctions after day 3 and alleviated cerebral edema and Evans blue extravasation at 24 h (p < 0.05). Astaxanthin treatment decreased AQP4 and NKCC1 mRNA levels in a dose-dependent manner at 24 h. AQP4 and NKCC1 protein expressions in the peri-contusional cortex were significantly reduced by astaxanthin at 24 h (p < 0.05). Furthermore, we also found that bumetanide (BU), an inhibitor of NKCC1, inhibited trauma-induced AQP4 upregulation (p < 0.05).. Our data suggest that astaxanthin reduces TBI-related injury in brain tissue by ameliorating AQP4/NKCC1-mediated cerebral edema and that NKCC1 contributes to the upregulation of AQP4 after TBI.

Topics: Animals; Aquaporin 4; Brain; Brain Edema; Brain Injuries, Traumatic; Bumetanide; Capillary Permeability; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Male; Mice, Inbred C57BL; Neuroprotective Agents; Random Allocation; RNA, Messenger; Sodium Potassium Chloride Symporter Inhibitors; Solute Carrier Family 12, Member 2; Xanthophylls

To examine whether astaxanthin (AST) prevent the cataract formation induced by glucocorticoid in chick embryo.. Hydrocortisone hemisuccinate sodium (HC) (0.5 μmol/egg) was administered directly into the air chamber in the egg shell of chick embryo day 15. The eggs were then kept in an incubator at same conditions and administered 100 μL of 50 (HC + AST50 group), 80 (HC + AST80 group), 100 (HC + AST100 group) mg/mL of AST solutions dissolved in dimethyl sulfoxide (DMSO) 3 h after administration of HC. In addition, non-HC treated group (treated with physiological saline without HC and 100 μL of DMSO), HC-alone group (treated with 0.5 μmol of HC and 100 μL of DMSO), and AST100 group (treated with physiological saline without HC and 100 μL of DMSO) were also incorporated. After 48 h of treatment, lenses were removed from embryo and classified into five stages according to developed opacity. The amounts of reduced glutathione in the lenses and the blood glucose levels were measured.. The average scores of lens opacitiy were 2.63 ± 1.02 nmol/lens (HC-alone), 2.78 ± 0.97 nmol/lens (HC + AST50), 2.22 ± 1.20 nmol/lens (HC + AST80) and 1.84 ± 0.83 nmol/lens (HC + AST100; p < 0.05), respectively. Administration of AST decreased the lens opacity dose-dependently. The amounts of reduced glutathione in lenses were 11.6 ± 2.8 nmol/lens (HC-alone), 11.3 ± 2.7 nmol/lens (HC + AST50), 13.4 ± 2.4 nmol/lens (HC + AST80) and 13.7 ± 3.1 nmol/lens (HC + AST100; p < 0.05), respectively. Higher levels of AST prevented loss of reduced glutathione from the lens.. These findings support that AST protects glucocorticoid-induced cataract in chick embryo.

Topics: Animals; Cataract; Chick Embryo; Disease Models, Animal; Fibrinolytic Agents; Glucocorticoids; Lens, Crystalline; Oxidative Stress; Xanthophylls

Prenatal exposure to valproic acid on gestational day 12.5 may lead to the impaired behavior in the offspring, which is similar to the human autistic symptoms. To the contrary, astaxanthin shows neuroprotective effect by its antioxidant mechanism. We aimed to (i) develop mice model of autism and (ii) investigate the effect of astaxanthin on such model animals. Valproic acid (600 mg/kg) was administered intraperitoneally to the pregnant mice on gestational day 12.5. Prenatal valproic acid-exposed mice were divided into 2 groups on postnatal day 25 and astaxanthin (2mg/kg) was given to the experimental group (VPA_AST, n=10) while saline was given to the control group (VPA, n=10) for 4 weeks. Behavioral test including social interaction, open field and hot-plate were conducted on postnatal day 25 and oxidative stress markers such as lipid peroxidation, advanced protein oxidation product, nitric oxide, glutathione, and activity of superoxide dismutase and catalase were estimated on postnatal day 26 to confirm mice model of autism and on postnatal day 56 to assess the effect of astaxanthin. On postnatal day 25, prenatal valproic acid-exposed mice exhibited (i) delayed eye opening (ii) longer latency to respond painful stimuli, (iii) poor sociability and social novelty and (iv) high level of anxiety. In addition, an increased level of oxidative stress was found by determining different oxidative stress markers. Treatment with astaxanthin significantly (p<0.05) improved the behavioral disorder and reduced the oxidative stress in brain and liver. In conclusion, prenatal exposure to valproic day in pregnant mice leads to the development of autism-like features. Astaxanthin improves the impaired behavior in animal model of autism presumably by its antioxidant activity.

Topics: Animals; Anxiety; Autistic Disorder; Brain; Catalase; Disease Models, Animal; Female; Glutathione; Liver; Male; Mice; Nitric Oxide; Oxidative Stress; Pain Perception; Pregnancy; Prenatal Exposure Delayed Effects; Psychotropic Drugs; Social Behavior; Superoxide Dismutase; Valproic Acid; Xanthophylls

Astaxanthin, a xanthophyll carotenoid, holds exceptional promise as an antioxidant, anti-inflammatory, and anticancer agent. No evidence has been published whether it has protective effects on sepsis. The study aimed to investigate the potential effects of astaxanthin on sepsis and multiple organ dysfunctions.. Sepsis was induced by cecal ligation and puncture (CLP) in Sprague-Dawley rats. Animals subjected to CLP and sham-operated control rats were given vehicle or astaxanthin 100 mg/kg/d by oral gavage for 7 d before the operation. The rats were killed at the indicated time points, and the specimen was collected. Cytokines and multiorgan injury-associated enzymatic and oxidative stress indicators were investigated. Multiorgan tissues were assessed histologically, the peritoneal bacterial load and the 72-h survival was observed too.. Sepsis resulted in a significant increase in serum tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels showing systemic inflammatory response; it also caused a remarkable decrease in the superoxide dismutase activity and a significant increase in the malondialdehyde content showing oxidative damage; sepsis caused a great increase in organ injury-associated indicators, including blood urea nitrogen, creatinine, lactate dehydrogenase, creatine kinase isoenzyme-MB isotype, alanine aminotransferase, and aspartate aminotransferase, which was confirmed by histologic examination. And there was a dramatical increase of colony-forming units in the peritoneal cavity in septic rats. Astaxanthin reversed these inflammatory and oxidant response, alleviated the organ injury, reduced the peritoneal bacterial load, and improved the survival of septic rats induced by CLP.. Astaxanthin exerts impressively protective effects on CLP-induced multiple organ injury. It might be used as a potential treatment for clinical sepsis.

Topics: Animals; Creatine Kinase, MB Form; Cytokines; Disease Models, Animal; Male; Multiple Organ Failure; Rats; Rats, Sprague-Dawley; Sepsis; Xanthophylls

To clarify the protective effect of astaxanthin (AST) against light-induced retinal damage in rats.. Albino rats were divided into three groups: a group treated orally with 1 mg/kg AST daily (group H), a group treated with 0.2 mg/kg AST (group L), and a control group (group C). Rats were administered AST in groups H and L and olive oil in group C followed by a 12-hour exposure to 3000-lux white light. After exposure for 7 days, the protective effect of AST was evaluated functionally by electroretinogram (ERG) and histologically by measuring outer nuclear layer (ONL) thickness and by counting rate of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stained cells.. After exposure to light, the b-wave amplitudes were significantly preserved in the AST groups compared to group C, Further the rate of the residual amplitude was higher in group H than in group L. The ONL thicknesses were significantly thicker in AST-treated rats compared to group C. The rates of TUNEL stained cells were significantly lower in the following order: group H, L and C.. AST may have a protective effect against light-induced retinal damage in albino rats.

Topics: Animals; Apoptosis; Disease Models, Animal; Female; Light; Olive Oil; Plant Oils; Rats, Sprague-Dawley; Retinal Degeneration; Xanthophylls

Hepatic ischemia reperfusion (IR) is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX), an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK) pathway.. Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT), aspartate aminotransferase (AST), inflammation factors, ROS, and key proteins in the MAPK family.. ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury.. Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

Topics: Animals; Antioxidants; Apoptosis; Autophagy; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Inflammation Mediators; Liver Diseases; Male; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Reactive Oxygen Species; Reperfusion Injury; Time Factors; Xanthophylls

Promotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin-related protein-1 (Drp1)-mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro-apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin-induced mitochondrial fission and apoptosis in myofibroblasts. Drp1-associated genes, such as Bcl-2-associated X protein, cytochrome c, tumour suppressor gene p53 and p53-up-regulated modulator of apoptosis, were highly up-regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1-dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Cell Count; Cell Line, Tumor; Disease Models, Animal; Dynamins; Gene Expression Regulation, Neoplastic; GTP Phosphohydrolases; Humans; Microtubule-Associated Proteins; Mitochondrial Dynamics; Mitochondrial Proteins; Myofibroblasts; Protein Transport; Proto-Oncogene Proteins; Pulmonary Fibrosis; Rats, Sprague-Dawley; Tumor Suppressor Protein p53; Xanthophylls

We have previously shown that astaxanthin (ATX) reduces the blood-brain barrier (BBB) disruption and neurovascular dysfunction following subarachnoid hemorrhage (SAH) insults. However, the underlying mechanisms remain unclear. It is known that the matrix metalloproteinases (MMPs), especially matrix metalloproteinase-9 (MMP-9) plays a crucial role in the pathogenesis of secondary brain injury after SAH. And ATX has the ability to regulate MMP-9 in other models. Herein, we investigated whether ATX could ameliorate MMP-9 activation and expression in a rat model of SAH. A total of 144 rats were randomly divided into the following groups: control group (n=36), SAH group (n=36), SAH+vehicle group (n=36), and SAH+ATX group (n=36). The SAH model was induced by injection of 0.3 ml autologous blood into the prechiasmatic cistern. ATX (20 μl of 0.1 mmol) or vehicle was administered intracerebroventricularly 30 min after SAH induction. Mortality, neurological function, brain edema and blood-brain barrier (BBB) permeability were measured at 24 and 72 h after SAH. Biochemical and zymographic methods were used to analyze MMP-9 expression and activity in brain samples. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were also evaluated at 24h. Our data indicated that ATX could significantly reduce the expression and activity of MMP-9, leading to the amelioration of brain edema, BBB impairment, neurological deficits and TUNEL-positive cells at 24h but not 72 h after SAH. The ATX-mediated down-regulation of MMP-9 was correlated with the decreased levels of IL-1β, TNF-α, oxidative stress, activated microglia and infiltrating neutrophils. These results suggest that the neurovascular protection of ATX in SAH is partly associated with the inhibition of MMP-9 expression and activity.

Topics: Analysis of Variance; Animals; Blood-Retinal Barrier; Brain; Brain Edema; Capillary Permeability; Disease Models, Animal; Gene Expression Regulation, Enzymologic; In Situ Nick-End Labeling; Male; Malondialdehyde; Matrix Metalloproteinase 9; Neurologic Examination; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Time Factors; Xanthophylls

Neurons in the hippocampal and cortical functional regions are more susceptible to damage induced by hyperglycemia, which can result in severe spatial learning and memory impairment. Neuroprotection ameliorates cognitive impairment induced by hyperglycemia in diabetic encephalopathy (DE). Astaxanthin has been widely studied in diabetes mellitus and diabetic complications due to its hypoglycemic, antioxidant and anti-apoptotic effects. However, whether astaxanthin can alleviate cognition deficits induced by DE and its precise mechanisms remain undetermined. In this study, DE was induced by streptozotocin (STZ, 150 mg/kg) in ICR mice. We observed the effect of astaxanthin on cognition and investigated its potential mechanisms in DE mice. Results showed that astaxanthin treatment significantly decreased the latency and enhanced the distance and time spent in the target quadrant in the Morris water maze test. Furthermore, neuronal survival was significantly increased in the hippocampal CA3 region and the frontal cortex following treatment with astaxanthin. Meanwhile, immunoblotting was used to observe the nuclear translocation of nuclear factor-kappaB (NF-κB) p65 and the expression of tumor necrosis factor-α (TNF-α) in the hippocampus and frontal cortex. The results indicated that astaxanthin could inhibit NF-κB nuclear translocation and downregulate TNF-α expression in the hippocampus and frontal cortex. Overall, the present study implied that astaxanthin could improve cognition by protecting neurons against inflammation injury potentially through inhibiting the nuclear translocation of NF-κB and down-regulating TNF-α.

Topics: Analysis of Variance; Animals; Blood Glucose; Cognition Disorders; Diabetes Mellitus, Experimental; Disease Models, Animal; Frontal Lobe; Hippocampus; Inflammation; Locomotion; Male; Maze Learning; Mice; Mice, Inbred ICR; NF-kappa B; Reaction Time; Tumor Necrosis Factor-alpha; Xanthophylls

Mangiferin has antioxidant, antiviral, apoptosis regulating, anti‑inflammatory, antitumor and antidiabetic effects, which can also inhibit osteoclast formation and bone resorption. However, whether mangiferin ameliorates the neurological pain of spinal cord injury (SCI) in ratS remains to be elucidated. The present study investigated the therapeutic effects of mangiferin on neurological function, the water content of spinal cord, oxidative stress, the expression of inflammatory cytokines and the protein expression of Bcl‑2/Bax in a SCI rat model. In the present study, the Basso, Beattie and Bresnahan scores, and the water content of the spinal cord were used to analyze the therapeutic effects of mangiferin on neurological pain in the SCI rat. The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and the serum levels of glutathione peroxidase (GSH‑PX), nuclear factor‑κB p65 unit, tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and caspase‑3/9 were detected using commercial kits. The expression levels of Bcl‑2 and Bax were measured using western blot analysis. The results demonstrated that administrating mangiferin began to ameliorate neurological function and the water content of the spinal cord in the SCI rat. The mangiferin‑treated group were found to have lower oxidative stress activity and lower expression levels of inflammatory cytokines, compared with the SCI rat. In addition, mangiferin significantly reduced the protein expression of Bax and promoted the protein expression of Bcl-2 in the SCI rat model. Finally, mangiferin markedly suppressed the expression of caspase‑3/9, indicating that the protective action of mangiferin may be associated with anti‑apoptosis activation. In conclusion, mangiferin attenuated contusive SCI in the rats through regulating oxidative stress, inflammation and the Bcl‑2 and Bax pathway.

Topics: Animals; Antioxidants; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Catalase; Cytokines; Disease Models, Animal; Glutathione Peroxidase; Inflammation; Male; Malondialdehyde; Neuroprotective Agents; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Superoxide Dismutase; Xanthones; Xanthophylls

Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese mice. In a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet, astaxanthin alleviated excessive hepatic lipid accumulation and peroxidation, increased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis. Moreover, astaxanthin caused an M2-dominant shift in macrophages/Kupffer cells and a subsequent reduction in CD4(+) and CD8(+) T cell recruitment in the liver, which contributed to improved insulin resistance and hepatic inflammation. Importantly, astaxanthin reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. Overall, astaxanthin was more effective at both preventing and treating NASH compared with vitamin E in mice. Furthermore, astaxanthin improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects. These results suggest that astaxanthin might be a novel and promising treatment for NASH.

Topics: Animals; Antioxidants; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Diet, High-Fat; Disease Models, Animal; Female; Glucose Metabolism Disorders; Humans; Insulin Resistance; Kupffer Cells; Lipid Peroxidation; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Sterol Regulatory Element Binding Protein 1; Vitamin E; Xanthophylls

To evaluate the effect of astaxanthin on renal angiotensin-I converting enzyme (ACE) levels, osteopontin (OPN) and transforming growth factor β1 (TGF-β1) expressions and the extent of crystal deposition in experimentally induced calcium oxalate kidney stone disease in a male Wistar rat model. To compare the efficacy of astaxanthin treatment with a currently used treatment strategy (citrate administration) for kidney stones.. The expression of OPN was assessed by immunohistochemistry. One step reverse transcriptase polymerase chain reaction followed by densitometry was used to assess renal OPN and TGF-β1 levels. Renal ACE levels were quantified by an enzyme-linked immunosorbent assay method. Crystal deposition in kidney was analysed by scanning electron microscopic (SEM)-energy-dispersive X-ray (EDX).. The renal ACE levels and the expression of OPN and TGF-β1 were upregulated in the nephrolithiasis-induced rats. Astaxanthin treatment reduced renal ACE levels and the expression OPN and TGF-β1. SEM-EDX analysis showed that crystal deposition was reduced in the astaxanthin-treated nephrolithiatic group. Astaxanthin treatment was more effective than citrate administration in the regulation of renal ACE levels, OPN and TGF-β1 expressions.. Astaxanthin administration reduced renal calcium oxalate crystal deposition possibly by modulating the renal renin-angiotensin system (RAS), which reduced the expression of OPN and TGF-β1 levels. Astaxanthin administration was more effective than citrate treatment in reducing crystal deposition and down-regulating the expression of OPN and TGF-β1.

Topics: Animals; Chelating Agents; Citric Acid; Disease Models, Animal; Down-Regulation; Immunohistochemistry; Kidney; Male; Nephrolithiasis; Osteopontin; Peptidyl-Dipeptidase A; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta1; Xanthophylls

OBJECT.: Aneurysmal subarachnoid hemorrhage (SAH) causes devastating rates of mortality and morbidity. Accumulating studies indicate that early brain injury (EBI) greatly contributes to poor outcomes after SAH and that oxidative stress plays an important role in the development of EBI following SAH. Astaxanthin (ATX), one of the most common carotenoids, has a powerful antioxidative property. However, the potential role of ATX in protecting against EBI after SAH remains obscure. The goal of this study was to assess whether ATX can attenuate SAH-induced brain edema, blood-brain barrier permeability, neural cell death, and neurological deficits, and to elucidate whether the mechanisms of ATX against EBI are related to its powerful antioxidant property.. Two experimental SAH models were established, including a prechiasmatic cistern SAH model in rats and a one-hemorrhage SAH model in rabbits. Both intracerebroventricular injection and oral administration of ATX were evaluated in this experiment. Posttreatment assessments included neurological scores, body weight loss, brain edema, Evans blue extravasation, Western blot analysis, histopathological study, and biochemical estimation.. It was observed that an ATX intracerebroventricular injection 30 minutes post-SAH could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell apoptosis, and neurological dysfunction) after SAH in rats. Meanwhile, delayed treatment with ATX 3 hours post-SAH by oral administration was also neuroprotective in both rats and rabbits. In addition, the authors found that ATX treatment could prevent oxidative damage and upregulate the endogenous antioxidant levels in the rat cerebral cortex following SAH.. These results suggest that ATX administration could alleviate EBI after SAH, potentially through its powerful antioxidant property. The authors conclude that ATX might be a promising therapeutic agent for EBI following SAH.

Topics: Animals; Blood-Brain Barrier; Brain; Disease Models, Animal; Fibrinolytic Agents; Male; Neuroprotective Agents; Oxidative Stress; Rabbits; Rats; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Xanthophylls

Reactive oxygen species (ROS) are associated with aging. Astaxanthin (AST) is a strong antioxidant and has been reported to prevent various ROS-induced diseases. In the current study, we investigated the effect of AST on age-associated histological and mRNA changes of vocal folds.. Prospective animal experiment with control.. Six-month-old Sprague-Dawley rats were fed on a normal powder diet with 0.01% (w/w) AST (aged AST-treated group) or without AST (aged sham-treated group). After 12 months of feeding, the larynges were harvested for histology, immunohistochemical detection of 4-hydroxy-2-nonenal (4-HNE), and quantitative real-time polymerase chain reaction for basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Thirteen-week-old rats were used as a young control group (young group).. The expression of 4-HNE, an oxidative stress marker, significantly increased in the two aged groups compared with the young group. Histological examination showed that the deposition of hyaluronic acid in the lamina propria (LP) was significantly reduced in the aged sham-treated group compared with the young group, but no significant difference was observed between the aged AST-treated group and the young group. There were no significant differences in the mRNA expression of bFGF and HGF between the aged AST-treated group and the young group, although the expression of these genes was significantly reduced in the aged sham-treated group as compared with the young group.. These results suggest that AST has the potential to attenuate age-associated changes of vocal folds.

Topics: Aging; Aldehydes; Animals; Antioxidants; Chromatography, High Pressure Liquid; Disease Models, Animal; Fibrinolytic Agents; Fibroblast Growth Factor 2; Follow-Up Studies; Gene Expression Regulation; Hepatocyte Growth Factor; Immunohistochemistry; Male; Oxidative Stress; Prospective Studies; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; RNA, Messenger; Vocal Cord Dysfunction; Vocal Cords; Xanthophylls

Astaxanthin is a strong antioxidant with the ability of reducing the markers of inflammation. To explore the protective effect of astaxanthin on maternal ethanol induced embryonic deficiency, and to investigate the underlying mechanisms, we detected the morphology, expression of neural marker genes, oxidative stress indexes, and inflammatory factors in mice model of fetal alcohol spectrum disorder with or without astaxanthin pretreatment. Our results showed that astaxanthin blocked maternal ethanol induced retardation of embryonic growth, and the down-regulation of neural marker genes, Otx1 and Sox2. Moreover, astaxanthin also reversed the increases of malondialdehyde (MDA), hydrogen peroxide (H2O2), and the decrease of glutathione peroxidase (GPx) in fetal alcohol spectrum disorder. In addition, maternal ethanol induced up-regulation of toll-like receptor 4 (TLR4), and the down-streaming myeloid differentiation factor 88 (MyD88), NF-κB, TNF-α, and IL-1β in embryos, and this was inhibited by astaxanthin pretreatment. These results demonstrated a protective effect of astaxanthin on fetal alcohol spectrum disorder, and suggested that oxidative stress and TLR4 signaling associated inflammatory reaction are involved in this process.

Topics: Animals; Central Nervous System Depressants; Disease Models, Animal; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Fetal Development; Glutathione Peroxidase; Hydrogen Peroxide; Interleukin-1beta; Malondialdehyde; Mice, Inbred C57BL; Myeloid Differentiation Factor 88; Neuroprotective Agents; NF-kappa B; Otx Transcription Factors; Oxidative Stress; Pregnancy; Random Allocation; SOXB1 Transcription Factors; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Xanthophylls

Neuroinflammation has been proven to play a crucial role in early brain injury pathogenesis and represents a target for treatment of subarachnoid hemorrhage (SAH). Astaxanthin (ATX), a dietary carotenoid, has been shown to have powerful anti-inflammation property in various models of tissue injury. However, the potential effects of ATX on neuroinflammation in SAH remain uninvestigated. The goal of this study was to investigate the protective effects of ATX on neuroinflammation in a rat prechiasmatic cistern SAH model.. Rats were randomly distributed into multiple groups undergoing the sham surgery or SAH procedures, and ATX (25 mg/kg or 75 mg/kg) or equal volume of vehicle was given by oral gavage at 30 min after SAH. All rats were sacrificed at 24 h after SAH. Neurologic scores, brain water content, blood-brain barrier permeability, and neuronal cell death were examined. Brain inflammation was evaluated by means of expression changes in myeloperoxidase, cytokines (interleukin-1β, tumor necrosis factor-α), adhesion molecules (intercellular adhesion molecule-1), and nuclear factor kappa B DNA-binding activity.. Our data indicated that post-SAH treatment with high dose of ATX could significantly downregulate the increased nuclear factor kappa B activity and the expression of inflammatory cytokines and intercellular adhesion molecule-1 in both messenger RNA transcription and protein synthesis. Moreover, these beneficial effects lead to the amelioration of the secondary brain injury cascades including cerebral edema, blood-brain barrier disruption, neurological dysfunction, and neuronal degeneration.. These results indicate that ATX treatment is neuroprotective against SAH, possibly through suppression of cerebral inflammation.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Cell Death; Disease Models, Animal; Interleukin-1beta; Male; Neuritis; Neuroprotective Agents; NF-kappa B; Optic Chiasm; Rats, Sprague-Dawley; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha; Xanthophylls

Apoptosis has been proven to play a crucial role in early brain injury pathogenesis and to represent a target for the treatment of subarachnoid hemorrhage (SAH). Previously, we demonstrated that astaxanthin (ATX) administration markedly reduced neuronal apoptosis in the early period after SAH. However, the underlying molecular mechanisms remain obscure. In the present study, we tried to investigate whether ATX administration is associated with the phosphatidylinositol 3-kinase-Akt (PI3K/Akt) pathway, which can play an important role in the signaling of apoptosis. Our results showed that post-SAH treatment with ATX could cause a significant increase of phosphorylated Akt and Bad levels, along with a significant decrease of cleaved caspase-3 levels in the cortex after SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also significantly reduce secondary brain injury characterized by neurological dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX in the early period after SAH by downregulating ATX-induced activation of Akt/Bad and upregulating cleaved caspase-3 levels. These results provided the evidence that ATX could attenuate apoptosis in a rat SAH model, potentially, in part, through modulating the Akt/Bad pathway.

Topics: Animals; Apoptosis; bcl-Associated Death Protein; Blood-Brain Barrier; Brain Injuries; Caspase 3; Cerebral Cortex; Disease Models, Animal; Down-Regulation; Male; Neurons; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; Subarachnoid Hemorrhage; Up-Regulation; Xanthophylls

Astaxanthin (ATX) has been proven to ameliorate early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH) by modulating cerebral oxidative stress. This study was performed to assess the effect of ATX on the Nrf2-ARE pathway and to explore the underlying molecular mechanisms of antioxidant properties of ATX in EBI after SAH. A total of 96 male SD rats were randomly divided into four groups. Autologous blood was injected into the prechiasmatic cistern of the rat to induce an experimental SAH model. Rats in each group were sacrificed at 24 h after SAH. Expressions of Nrf2 and heme oxygenase-1 (HO-1) were measured by Western blot and immunohistochemistry analysis. The mRNA levels of HO-1, NAD (P) H: quinone oxidoreductase 1 (NQO-1), and glutathione S-transferase-α1 (GST-α1) were determined by real-time polymerase chain reaction (PCR). It was observed that administration of ATX post-SAH could up-regulate the cortical expression of these agents, mediated in the Nrf2-ARE pathway at both pretranscriptional and posttranscriptional levels. Meanwhile, oxidative damage was reduced. Furthermore, ATX treatment significantly attenuated brain edema, blood-brain barrier (BBB) disruption, cellular apoptosis, and neurological dysfunction in SAH models. This study demonstrated that ATX treatment alleviated EBI in SAH model, possibly through activating the Nrf2-ARE pathway by inducing antioxidant and detoxifying enzymes.

Topics: Animals; Antioxidant Response Elements; Antioxidants; Apoptosis; Blood-Brain Barrier; Brain; Brain Injuries; Disease Models, Animal; Glutathione Transferase; Heme Oxygenase-1; Isoenzymes; Male; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction; Subarachnoid Hemorrhage; Xanthophylls

The effect of astaxanthin on N(Ω)-nitro-L-arginine methyl ester (L-NAME) induced preeclampsia disease rats was investigated. Thirty pregnant Sprague-Dawley rats were randomly divided into three groups (n = 10): blank group, L-NAME group and astaxanthin group. From day 5 to 20, astaxanthin group rats were treated with astaxanthin (25 mg x kg(-1) x d(-1) x bw(-1)) from pregnancy (day 5). To establish the preeclamptic rat model, L-NAME group and astaxanthin group rats were injected with L-NAME (125 mg x kg(-1) x d(-1) x bw(-1)) from days 10-20 of pregnancy. The blood pressure and urine protein were recorded. Serum of each group was collected and malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities were analyzed. Pathological changes were observed with HE stain. The expression of NF-κB (nuclear factor kappa B), ROCK II (Rho-associated protein kinase II), HO-1 (heme oxygenase-1) and Caspase 3 were analyzed with immunohistochemistry. L-NAME induced typical preeclampsia symptoms, such as the increased blood pressure, urinary protein, the content of MDA, etc. Astaxanthin significantly reduced the blood pressure (P < 0.01), the content of MDA (P < 0.05), and increased the activity of SOD (P < 0.05) of preeclampsia rats. The urinary protein, NO, and NOS were also decreased. HE stain revealed that after treated with astaxanthin, the thickness of basilal membrane was improved and the content of trophoblast cells and spiral arteries was reduced. Immunohistochemistry results revealed that the expressions of NF-κB, ROCK II and Caspase 3 in placenta tissue were effectively decreased, and HO-1 was increased. Results indicated that astaxanthin can improve the preeclampsia symptoms by effectively reducing the oxidative stress and inflammatory damages of preeclampsia. It revealed that astaxanthin may be benefit for prevention and treatment of preeclampsia disease.

Topics: Animals; Blood Pressure; Caspase 3; Disease Models, Animal; Female; Heme Oxygenase (Decyclizing); Malondialdehyde; NF-kappa B; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Rats; Rats, Sprague-Dawley; rho-Associated Kinases; Superoxide Dismutase; Xanthophylls

The oncogenic transcription factors NF-κB and β-catenin, constitutively activated by upstream serine/threonine kinases control several cellular processes implicated in malignant transformation including apoptosis evasion. The aim of this study was to investigate the chemopreventive effects of astaxanthin, an antioxidant carotenoid, in the hamster buccal pouch (HBP) carcinogenesis model based on its ability to modulate NF-κB and Wnt signaling pathways and induce apoptosis.. We determined the effect of dietary supplementation of astaxanthin on the oncogenic signaling pathways - NF-κB and Wnt/β-catenin, their upstream activator kinases - Erk/MAPK and PI-3K/Akt, and the downstream event - apoptosis evasion by real-time quantitative RT-PCR, western blot, and immunohistochemical analyses.. We found that astaxanthin inhibits NF-κB and Wnt signaling by downregulating the key regulatory enzymes IKKβ and GSK-3β. Analysis of gene expression and docking interactions revealed that inhibition of these pathways may be mediated via inactivation of the upstream signaling kinases Erk/Akt by astaxanthin. Astaxanthin also induced caspase-mediated mitochondrial apoptosis by downregulating the expression of antiapoptotic Bcl-2, p-Bad, and survivin and upregulating proapoptotic Bax and Bad, accompanied by efflux of Smac/Diablo and cytochrome-c into the cytosol, and induced cleavage of poly (ADP-ribose) polymerase (PARP).. The results provide compelling evidence that astaxanthin exerts chemopreventive effects by concurrently inhibiting phosphorylation of transcription factors and signaling kinases and inducing intrinsic apoptosis.. Astaxanthin targets key molecules in oncogenic signaling pathways and induces apoptosis and is a promising candidate agent for cancer prevention and therapy.

Topics: Animals; Apoptosis; beta Catenin; Cricetinae; Disease Models, Animal; Male; Mesocricetus; Mitogen-Activated Protein Kinases; Mouth Neoplasms; NF-kappa B; Real-Time Polymerase Chain Reaction; Signal Transduction; Wnt Proteins; Xanthophylls

Dietary carotenoids exhibit various biological activities, including antioxidative activity. In particular, astaxanthin, a type of carotenoid, is well known as a powerful antioxidant. We investigated whether astaxanthin would protect against light-induced retinal damage. In an in vivo study, ddY male mice were exposed to white light at 8,000 lux for 3 h to induce retinal damage. Five days after light exposure, retinal damage was evaluated by measuring electroretinogram (ERG) amplitude and outer nuclear layer (ONL) thickness. Furthermore, expression of apoptotic cells, 8-hydroxy-deoxyguanosine (8-OHdG), was measured. In an in vitro study, retinal damage was induced by white light exposure at 2,500 lux for 24 h, and propidium iodide (PI)-positive cells was measured and intracellular reactive oxygen species (ROS) activity was examined. Astaxanthin at 100 mg/kg inhibited the retinal dysfunction in terms of ERG and ONL loss and reduced the expression of apoptotic and 8-OHdG-positive cells induced by light exposure. Furthermore, astaxanthin protected against increases of PI-positive cells and intracellular reactive oxygen species (ROS) activity in 661W cells. These findings suggest that astaxanthin has protective effects against light-induced retinal damage via the mechanism of its antioxidative effect.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Ophthalmic; Animals; Antioxidants; Apoptosis; Cells, Cultured; Deoxyguanosine; Disease Models, Animal; Electroretinography; Light; Macular Degeneration; Male; Mice; Mice, Inbred Strains; Propidium; Reactive Oxygen Species; Retina; Retinal Cone Photoreceptor Cells; Retinitis Pigmentosa; Xanthophylls

The purpose of this study was to investigate the effect of astaxanthin extracted from Paracoccus carotinifaciens on gastric mucosal damage in murine gastric ulcer models. Mice were pretreated with astaxanthin for 1 h before ulcer induction. Gastric ulcers were induced in mice by oral administration of hydrochloride (HCl)/ethanol or acidified aspirin. The effect of astaxanthin on lipid peroxidation in murine stomach homogenates was also evaluated by measuring the level of thiobarbituric acid reactive substance (TBARS). The free radical scavenging activities of astaxanthin were also measured by electron spin resonance (ESR) measurements. Astaxanthin significantly decreased the extent of HCl/ethanol- and acidified aspirin-induced gastric ulcers. Astaxanthin also decreased the level of TBARS. The ESR measurement showed that astaxanthin had radical scavenging activities against the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide anion radical. These results suggest that astaxanthin has antioxidant properties and exerts a protective effect against ulcer formation in murine models.

Topics: Acids; Animals; Anti-Ulcer Agents; Aspirin; Biphenyl Compounds; Disease Models, Animal; Ethanol; Free Radical Scavengers; Gastric Mucosa; Lipid Peroxidation; Male; Mice; Paracoccus; Picrates; Stomach; Stomach Ulcer; Thiobarbituric Acid Reactive Substances; Xanthophylls

The aim of this study was to investigate the effects of astaxanthin-enriched diet on blood pressure, cardiac hypertrophy, both vascular structure and function and superoxide ((*)O(2-)) production in spontaneously hypertensive rats (SHR). Twelve-week-old SHR were treated for 8 weeks with an astaxanthin-enriched diet (75 or 200mg/kg body weight per day). Systolic blood pressure was monitorized periodically during the study by the tail cuff method. At the end of the study animals were sacrificed and heart, kidneys and aorta were removed. Left ventricular weight/body weight ratio was used as left ventricular hypertrophy index (LVH). Vascular function and structure were studied in conductance (aortic rings) and resistance (renal vascular bed) arteries. Also (*)O(2-) production was evaluated by lucigenin-enhanced chemiluminescence. Systolic blood pressure was lower in astaxanthin-treated groups than the control group from the first week of treatment, and LVH was significantly reduced. Astaxanthin improved endothelial function on resistance arteries, but had no effect on aorta. These effects were accompanied by a decrease in oxidative stress and improvements in NO bioavailability. Taken together, these results show that diet supplemented with astaxanthin has beneficial effects on hypertension, by decreasing blood pressure values, improving cardiovascular remodeling and oxidative stress.

Topics: Animals; Antihypertensive Agents; Aorta; Blood Pressure; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Hypertension; Hypertrophy, Left Ventricular; Male; NADPH Oxidases; Nitric Oxide; Oxidative Stress; Rats; Rats, Inbred SHR; Renal Artery; Superoxides; Time Factors; Vascular Resistance; Vasodilation; Vasodilator Agents; Xanthophylls

This study investigated the effect of astaxanthin (ASX; 3,3-dihydroxybeta, beta-carotene-4,4-dione), a water-dispersible synthetic carotenoid, on liver ischemia-reperfusion (IR) injury. Astaxanthin (5 mg/kg/day) or olive oil was administered to rats via intragastric intubation for 14 consecutive days before the induction of hepatic IR. On the 15th day, blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60 min, followed by 60 min reperfusion. At the end of the experimental period, blood samples were obtained from the right ventricule to determine plasma alanine aminotransferase (ALT) and xanthine oxidase (XO) activities and animals were sacrificed to obtain samples of nonischemic and postischemic liver tissue. The effects of ASX on IR injury were evaluated by assessing hepatic ultrastructure via transmission electron microscopy and by histopathological scoring. Hepatic conversion of xanthine dehygrogenase (XDH) to XO, total GSH and protein carbonyl levels were also measured as markers of oxidative stress. Expression of NOS2 was determined by immunohistochemistry and Western blot analysis while nitrate/nitrite levels were measured via spectral analysis. Total histopathological scoring of cellular damage was significantly decreased in hepatic IR injury following ASX treatment. Electron microscopy of postischemic tissue demonstrated parenchymal cell damage, swelling of mitochondria, disarrangement of rough endoplasmatic reticulum which was also partially reduced by ASX treatment. Astaxanthine treatment significantly decreased hepatic conversion of XDH to XO and tissue protein carbonyl levels following IR injury. The current results suggest that the mechanisms of action by which ASX reduces IR damage may include antioxidant protection against oxidative injury.

Topics: Alanine Transaminase; Animals; Antioxidants; Disease Models, Animal; Glutathione; Liver; Male; Nitrates; Nitric Oxide Synthase Type II; Nitrites; Protein Carbonylation; Rats; Rats, Wistar; Reperfusion Injury; Xanthine Dehydrogenase; Xanthine Oxidase; Xanthophylls

Retinol (ROH) and provitamin-A carotenoids are recommended to treat ROH deficiency. Xanthophyll carotenoids, being potent antioxidants, can modulate health disorders. We hypothesize that nonprovitamin-A carotenoids may yield ROH and suppress lipid peroxidation under ROH deficiency. This study aimed to (i) study the possible bioconversion of astaxanthin and lutein to ROH similar to β-carotene and (ii) determine the antioxidant potential of these carotenoids with reference to Na(+)/K(+)-ATPase, antioxidant molecules, and lipid peroxidation (Lpx) induced by ROH deficiency in rats. ROH deficiency was induced in rats (n = 5 per group) by feeding a diet devoid of ROH. Retinol-deficient (RD) rats were gavaged with astaxanthin, lutein, β-carotene, or peanut oil alone (RD group) for 7 days. Results show that the RD group had lowered plasma ROH levels (0.3 µmol/L), whereas ROH rose in astaxanthin and β-carotene groups (4.9 and 5.7 µmol/L, respectively), which was supported by enhanced (69% and 70%) intestinal β-carotene 15,15'-monooxygenase activity. Astaxanthin, lutein, and β-carotene lowered Lpx by 45%, 41%, and 40% (plasma), respectively, and 59%, 64%, and 60% (liver), respectively, compared with the RD group. Lowered Na(+)/K(+)-ATPase and enhanced superoxide dismutase, catalase, and glutathione-S-transferase activities support the lowered Lpx. To conclude, this report confirms that astaxanthin is converted into β-carotene and ROH in ROH-deficient rats, and the antioxidant potential of carotenoids was in the order astaxanthin > lutein > β-carotene.

Topics: Animals; Antioxidants; beta Carotene; Biotransformation; Chromatography, High Pressure Liquid; Disease Models, Animal; Fatty Acids; Lipid Peroxidation; Liver; Lutein; Male; Microsomes, Liver; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Vitamin A Deficiency; Xanthophylls

Colon cancer is one of the major causes of cancer mortality worldwide. Several carotenoids with antioxidant properties are reported for their chemopreventive nature. In this study, we have evaluated the chemopreventive efficacy of astaxanthin on lipid peroxidation, antioxidant status, total number of aberrant crypt foci (ACF), and cell proliferation in 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis using a rat model. DMH was induced subcutaneously at a dosage of 40 mg/kg body weight, twice a week for 2 weeks. Astaxanthin was administered before and after the DMH induction, orally at a concentration of 15 mg/kg body weight throughout the experimental period. At the end of 16 weeks, pre-treatment with astaxanthin markedly reduced the degree of histological lesions, ACF development and also lowered the number of argyrophilic nucleolar organizer regions. Our results also showed the decreased levels of colon enzymic and non-enzymic antioxidants and increased levels of lipid peroxidation marker levels in DMH-induced rats, which were significantly reversed on astaxanthin administration. In conclusion, the results of this study suggest that astaxanthin has an affirmative and beneficial effect against chemically induced colonic pre-neoplastic progression in rats induced by DMH.

Topics: 1,2-Dimethylhydrazine; Administration, Oral; Animals; Antigens, Nuclear; Antioxidants; Cell Proliferation; Colon; Colonic Neoplasms; Disease Models, Animal; Lipid Peroxidation; Male; Precancerous Conditions; Rats; Rats, Wistar; Xanthophylls

The consumption of alcoholic drinks is a frequent drug-abuse situation, which is associated to a wide variety of pathological disturbances affecting several organs, including the brain. We have previously shown in the developing rat brain that ethanol intake facilitates the propagation of cortical spreading depression (CSD), an excitability-related neural phenomenon present in several animal species. This electrophysiological effect was attenuated by a shrimp (Litopenaeus vannamei) carotenoids extract. Here we investigated the effects of pure astaxanthin, the main carotenoid found in shrimp, on CSD.. Adult Wistar rats were treated per gavage, during 18 days, with 2.5, 10 or 90 microg/kg/d astaxanthin dissolved in ethanol (3 g/kg) and CSD was recorded on the cortical surface 1 to 3 days thereafter. Four groups, treated respectively with ethanol, distilled water and soybean oil with- and without astaxanthin were also studied for comparison with the ethanol + astaxanthin groups.. Ethanol-treated rats displayed higher CSD-velocities (mean values, in mm/min, per hour of recording ranging from 4.08 +/- 0.09 to 4.12 +/- 0.16), compared to the distilled water-group (from 3.19 +/- 0.13 to 3.27 +/- 0.06). Addition of astaxanthin to ethanol lead to lower CSD-velocities in a dose-dependent manner, ranging from 3.68 +/- 0.09 to 3.97 +/- 0.22 for the 2.5 microg/kg/d-dose, from 3.29 +/- 0.09 to 3.32 +/- 0.07 for the 10 microg/kg/d-dose, and from 2.89 +/- 0.13 to 2.92 +/- 0.11 for the 90 microg/kg/d-dose. The velocities of the soybean oil groups (with and without astaxanthin) were not statistically different from the 10 microg/kg/d astaxanthin + ethanol and distilled water groups.. The results demonstrate the antagonistic effect of astaxanthin against the ethanol-induced facilitation of CSD propagation. Probably carotenoid antioxidant properties are involved in such effects.

Topics: Alcohol Drinking; Alcoholism; Animals; Central Nervous System Depressants; Cerebral Cortex; Cortical Spreading Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Male; Penaeidae; Rats; Rats, Wistar; Reactive Oxygen Species; Receptors, GABA; Xanthophylls

Astaxanthin (AST) is a carotenoid found in marine animals and vegetables. The purpose of the present study was to investigate the effect of AST on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms.. Laser photocoagulation was used to induce CNV in C57BL/6J mice. Mice were pretreated with intraperitoneal injections of AST daily for 3 days before photocoagulation, and treatments were continued daily until the end of the study. CNV response was analyzed by volumetric measurements 1 week after laser injury. Retinal pigment epithelium-choroid levels of IkappaB-alpha, intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2 were examined by Western blotting or ELISA. AST was applied to capillary endothelial (b-End3) cells, macrophages, and RPE cells to analyze the activation of NF-kappaB and the expression of inflammatory molecules.. The index of CNV volume was significantly suppressed by treatment with AST compared with that in vehicle-treated animals. AST treatment led to significant inhibition of macrophage infiltration into CNV and of the in vivo and in vitro expression of inflammation-related molecules, including VEGF, IL-6, ICAM-1, MCP-1, VEGFR-1, and VEGFR-2. Importantly, AST suppressed the activation of the NF-kappaB pathway, including IkappaB-alpha degradation and p65 nuclear translocation.. AST treatment, together with inflammatory processes including NF-kappaB activation, subsequent upregulation of inflammatory molecules, and macrophage infiltration, led to significant suppression of CNV development. The present study suggests the possibility of AST supplementation as a therapeutic strategy to suppress CNV associated with AMD.

Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Chemokine CCL2; Choroid; Choroidal Neovascularization; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; I-kappa B Proteins; Injections, Intraperitoneal; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Mice; Mice, Inbred C57BL; NF-kappa B; NF-KappaB Inhibitor alpha; Pigment Epithelium of Eye; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Xanthophylls

Frequently used for humans as non-steroidal anti-inflammatory drug, naproxen has been known to induce ulcerative gastric lesion. The present study investigated the in vivo protective effect of astaxanthin isolated from Xanthophyllomyces dendrorhous against naproxen-induced gastric antral ulceration in rats. The oral administration of astaxanthin (1, 5, and 25 mg/kg of body weight) showed a significant protection against naproxen (80 mg/kg of body weight)-induced gastric antral ulcer and inhibited elevation of the lipid peroxide level in gastric mucosa. In addition, pretreatment of astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly proved that the acute gastric mucosal lesion induced by naproxen nearly disappeared after the pretreatment of astaxanthin. These results suggest that astaxanthin removes the lipid peroxides and free radicals induced by naproxen, and it may offer potential remedy of gastric ulceration.

Topics: Adjuvants, Immunologic; Animals; beta Carotene; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione Peroxidase; Male; Malondialdehyde; Naproxen; Pyloric Antrum; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Superoxide Dismutase; Time Factors; Xanthophylls

The aim of this study was to evaluate the influence of -tocopherol and astaxanthin on low-density lipoprotein (LDL) oxidation lag time and atherosclerotic lesion formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one, 3-month-old WHHL rabbits were divided into three experimental groups. One group (n=10) was fed standard rabbit feed alone and served as a control, a second group (n=11) was supplied with the same feed containing 500 mg alpha-tocopherol/kg and a third group (n=10) was given a feed containing 100 mg astaxanthin/kg. Plasma lipids, lipoproteins and LDL oxidation lag time were followed for 24 weeks. At the end of the treatment period, the animals were killed and the thoracic aorta was used for evaluation of the degree of atherosclerosis. Colour photographs of the intimal surface of the vessel were taken for determination of the atherosclerotic area. Cross-sections of the thoracic aorta were used for histological examination and for determination of intimal thickening. Specimens of the vessel were used for determination of the tissue cholesterol content. Plasma cholesterol remained at a high level during the time of the experiment and there were no differences between the experimental groups. After 24 weeks, the LDL oxidation lag time was 53.7+/-1.7 min, 109+/-4 min (P<0.001) and 56.4+/-3.4 min (P=0.47) in the control, alpha-tocopherol and astaxanthin groups, respectively. In the thoracic aorta, the atherosclerotic area was 80.7+/-5.1%, 67.1+/-6.7% (P=0.13) and 75.2+/-5.7% (P=0.49) in the control, alpha-tocopherol and astaxanthin groups, respectively. The intimal thickening was 45.6+/-3.2%, 44.0+/-4.1% (P=0.89) and 40.0+/-4.5% (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. Finally, the cholesterol content was 107+/-9 mol/g, 95.7+/-11.5 mol/g (P=0.31) and 101+/-5 mol/g (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. It can be concluded that alpha-tocopherol but not astaxanthin prolonged the LDL oxidation lag time. The two antioxidative substances did not prevent atherogenesis in WHHL rabbits in this setting.

Topics: alpha-Tocopherol; Animals; Arteriosclerosis; beta Carotene; Biopsy, Needle; Disease Models, Animal; Female; Hyperlipoproteinemia Type II; Immunohistochemistry; Lipid Peroxidation; Lipoproteins, LDL; Male; Probability; Rabbits; Reference Values; Sensitivity and Specificity; Xanthophylls

Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. Astaxanthin, which is found as a common pigment in algae, fish, and birds, is a carotenoid with significant potential for antioxidative activity. In this study, we examined whether chronic administration of astaxanthin could prevent the progression of diabetic nephropathy induced by oxidative stress in mice. We used female db/db mice, a rodent model of type 2 diabetes, and their non-diabetic db/m littermates. The mice were divided into three groups as follows: non-diabetic db/m, diabetic db/db, and diabetic db/db treated with astaxanthin. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were performed for 12 weeks from the beginning of treatment. After 12 weeks of treatment, the astaxanthin-treated group showed a lower level of blood glucose compared with the non-treated db/db group; however, both groups had a significantly high level compared with the db/m mice. The relative mesangial area calculated by the mesangial area/total glomerular area ratio was significantly ameliorated in the astaxanthin-treated group compared with the non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with astaxanthin. The 8-OHdG immunoreactive cells in glomeruli of non-treated db/db mice were more numerous than in the astaxanthin-treated db/db mice. In this study, treatment with astaxanthin ameliorated the progression and acceleration of diabetic nephropathy in the rodent model of type 2 diabetes. The results suggested that the antioxidative activity of astaxanthin reduced the oxidative stress on the kidneys and prevented renal cell damage. In conclusion, administration of astaxanthin might be a novel approach for the prevention of diabetes nephropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Albuminuria; Animals; beta Carotene; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Female; Kidney; Mice; Mice, Mutant Strains; Reference Values; Regression Analysis; Tissue Distribution; Xanthophylls

Oxidative stress induced by hyperglycemia possibly causes the dysfunction of pancreatic beta-cells and various forms of tissue damage in patients with diabetes mellitus. Astaxanthin, a carotenoid of marine microalgae, is reported as a strong anti-oxidant inhibiting lipid peroxidation and scavenging reactive oxygen species. The aim of the present study was to examine whether astaxanthin can elicit beneficial effects on the progressive destruction of pancreatic beta-cells in db/db mice--a well-known obese model of type 2 diabetes. We used diabetic C57BL/KsJ-db/db mice and db/m for the control. Astaxanthin treatment was started at 6 weeks of age and its effects were evaluated at 10, 14, and 18 weeks of age by non-fasting blood glucose levels, intraperitoneal glucose tolerance test including insulin secretion, and beta-cell histology. The non-fasting blood glucose level in db/db mice was significantly higher than that of db/m mice, and the higher level of blood glucose in db/db mice was significantly decreased after treatment with astaxanthin. The ability of islet cells to secrete insulin, as determined by the intraperitoneal glucose tolerance test, was preserved in the astaxanthin-treated group. Histology of the pancreas revealed no significant differences in the beta-cell mass between astaxanthin-treated and -untreated db/db mice. In conclusion, these results indicate that astaxanthin can exert beneficial effects in diabetes, with preservation of beta-cell function. This finding suggests that anti-oxidants may be potentially useful for reducing glucose toxicity.

Topics: Adjuvants, Immunologic; Age Factors; Animals; Antioxidants; beta Carotene; Blood Glucose; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose; Islets of Langerhans; Mice; Mice, Inbred C57BL; Oxidative Stress; Reactive Oxygen Species; Time Factors; Xanthophylls

Helicobacter pylori infection in humans is associated with chronic type B gastritis, peptic ulcer disease, and gastric carcinoma. A high intake of carotenoids and vitamin C has been proposed to prevent development of gastric malignancies. The aim of this study was to explore if the microalga Haematococcus pluvialis rich in the carotenoid astaxanthin and vitamin C can inhibit experimental H. pylori infection in a BALB/cA mouse model. Six-week-old BALB/cA mice were infected with the mouse-passaged H. pylori strain 119/95. At 2 weeks postinoculation mice were treated orally once daily for 10 days (i) with different doses of algal meal rich in astaxanthin (0.4, 2, and 4 g/kg of body weight, with the astaxanthin content at 10, 50, and 100 mg/kg, respectively), (ii) with a control meal (algal meal without astaxanthin, 4 g/kg), or (iii) with vitamin C (400 mg/kg). Five mice from each group were sacrificed 1 day after the cessation of treatment, and the other five animals were sacrificed 10 days after the cessation of treatment. Culture of H. pylori and determination of the inflammation score of the gastric mucosae were used to determine the outcome of the treatment. Mice treated with astaxanthin-rich algal meal or vitamin C showed significantly lower colonization levels and lower inflammation scores than those of untreated or control-meal-treated animals at 1 day and 10 days after the cessation of treatment. Lipid peroxidation was significantly decreased in mice treated with the astaxanthin-rich algal meal and vitamin C compared with that of animals not treated or treated with the control meal. Both astaxanthin-rich algal meal and vitamin C showed an inhibitory effect on H. pylori growth in vitro. In conclusion, antioxidants may be a new strategy for treating H. pylori infection in humans.

Topics: Agar; Animals; Ascorbic Acid; beta Carotene; Carotenoids; Disease Models, Animal; Helicobacter Infections; Helicobacter pylori; Lipid Peroxidation; Mice; Mice, Inbred BALB C; Xanthophylls