astaxanthine and Hyperglycemia

Astaxanthin has been reported to possess anti-inflammatory effect but the exact mechanism in protecting the retinal pigment epithelial (RPE) cells is not clear. Hence, we hypothesized that astaxanthin could protect RPE by inhibiting ROS-mediated inflammation. The purpose of this study is to understand the retinal protective mechanism of astaxanthin in modulating hyperglycemia (HG) induced inflammation in ARPE-19 cell and diabetic rat retina. ARPE-19 cells were treated with 30 mM glucose to induce hyperglycemia whereas diabetes was induced in rats with streptozotocin followed by astaxanthin treatment. The level of oxidative stress markers, antioxidant enzyme activity, inflammatory markers (NF-κB, TNF-α, ICAM-1), signaling mediators (PI3K, p-Akt) and nuclear translocation of NF-κB were analyzed in ARPE-19 cells and rat retina. HG-mediated ROS generation and lipid peroxidation were declined upon astaxanthin treatment in ARPE-19 cells. Similarly, astaxanthin treatment found to reduce the elevated levels of nitric oxide, protein carbonyl, and lipid peroxides in diabetic group. Astaxanthin restored the activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase in serum and retina of diabetic rats. NF-κB, TNF-α, and ICAM-1 levels were higher in HG-treated ARPE-19 cells and diabetic retina compared to control group, whereas astaxanthin treatment lowered their expression. PI3K and p-Akt were higher in high glucose treated ARPE-19 cells and diabetic retina. NAC, LY294002 and PDTC treatment resulted in reduced nuclear translocation of NF-κB and decreased expression of inflammatory markers in HG treated ARPE-19 cells. Thus, we conclude that astaxanthin protected the retinal cells from HG-induced inflammation by modulating NF-κB through ROS-PI3K/Akt signaling cascade.

Topics: Animals; Antioxidants; Diabetes Mellitus, Experimental; Glucose; Hyperglycemia; Inflammation; Intercellular Adhesion Molecule-1; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Reactive Oxygen Species; Retina; Tumor Necrosis Factor-alpha; Xanthophylls

Numerous studies highlight that astaxanthin (ASTX) ameliorates hyperglycemic condition and hyperglycemia-associated chronic complications. While periodontitis and periodontic tissue degradation are also triggered under chronic hyperglycemia, the roles of ASTX on diabetes-associated periodontal destruction and the related mechanisms therein are not yet fully understood. Here, we explored the impacts of supplemental ASTX on periodontal destruction and systemic complications in type I diabetic mice. To induce diabetes, C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg), and the hyperglycemic mice were orally administered with ASTX (12.5 mg/kg) (STZ+ASTX group) or vehicle only (STZ group) daily for 60 days. Supplemental ASTX did not improve hyperglycemic condition, but ameliorated excessive water and feed consumptions and lethality in STZ-induced diabetic mice. Compared with the non-diabetic and STZ+ASTX groups, the STZ group exhibited severe periodontal destruction. Oral gavage with ASTX inhibited osteoclastic formation and the expression of receptor activator of nuclear factor (NF)-κB ligand, 8-OHdG, γ-H2AX, cyclooxygenase 2, and interleukin-1β in the periodontium of STZ-injected mice. Supplemental ASTX not only increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and osteogenic transcription factors in the periodontium, but also recovered circulating lymphocytes and endogenous antioxidant enzyme activity in the blood of STZ-injected mice. Furthermore, the addition of ASTX blocked advanced glycation end products-induced oxidative stress and growth inhibition in human-derived periodontal ligament cells by upregulating the Nrf2 pathway. Together, our results suggest that ASTX does not directly improve hyperglycemia, but ameliorates hyperglycemia-triggered periodontal destruction and oxidative systemic complications in type I diabetes.

Topics: Adolescent; Alveolar Process; Animals; Antioxidants; Blood Glucose; Catalase; Cell Proliferation; Cytokines; Diabetes Mellitus, Experimental; Dietary Supplements; DNA Damage; Feeding Behavior; Glycation End Products, Advanced; Humans; Hyperglycemia; Inflammation Mediators; Injections; Lymphocytes; Male; Mice, Inbred C57BL; NF-E2-Related Factor 2; Osteoclasts; Oxidative Stress; Periodontal Ligament; Periodontitis; Reactive Oxygen Species; Streptozocin; Superoxide Dismutase; Up-Regulation; Xanthophylls; Young Adult

This study investigated the hypoglycemic and antioxidant effects of shrimp astaxanthin on the kidney of alloxan-induced diabetic rats.. Animals were distributed into four groups of six rats each: a control group (C), a diabetic group (D), a diabetic group supplemented with Astaxanthin (D+As) dissolved in olive oil and a diabetic group supplemented with olive oil (D+OO). In vitro antidiabetic effect was tested in plasma and kidney tissue.. The group D of rats showed significant (P < 0.05) increase of glycemia, creatinine, urea and uric acid levels compared to those of the control group (C). Moreover, plasma and kidney malondialdehyde (MDA) and protein carbonyl (PCO) levels for the rats of the group D were significantly increased compared to the control group. Contrariwise, antioxidant enzyme activities, such as catalase (EC 1.11.1.6), superoxide dismutase (EC 1.15.1.1) and non-enzymatic levels of reduced glutathione, were significantly (P < 0.05) decreased in the plasma and kidney of diabetic rats compared to the control ones. The astaxanthin supplementation in rats diet improved the antioxidant enzyme activities and significantly decreased the MDA and PCO levels compared to diabetic rats. Indeed, no significant (P ≥ 0.05) improvement was observed for the fourth group (D+OO) compared to the control group (C). Histological analysis of kidney showed glomerular hypertrophy and tubular dilatation for the diabetic rats. For D+As rats, these histopathological changes were less prominent.. Our results suggest that shrimp astaxanthin may play an important role in reduction of oxidative damage and could prevent pathological changes in diabetic rats suggesting promising application of shrimp astaxanthin in diabet treatment.

Topics: Animal Shells; Animals; Antioxidants; Decapoda; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Dietary Supplements; Food-Processing Industry; Glutathione; Hyperglycemia; Hypoglycemic Agents; Kidney; Lipid Peroxidation; Male; Oxidative Stress; Oxidoreductases; Rats, Wistar; Renal Insufficiency; Waste Products; Xanthophylls

This study was conducted to compare the protective effects of astaxanthin (ASX) with Corni Fructus (CF) against diabetes-induced pathologies such as oxidative stress-induced inflammation and advanced glycation end product (AGE) formation in the liver of type 1 diabetic rats. ASX (50 mg/kg body weight/day) or CF (200 mg/kg body weight/day) was orally administered every day for 18 days to streptozotocin (STZ)-induced diabetic rats, and their effects were compared with nondiabetic and diabetic control rats. The administration of CF, but not ASX, decreased both the elevated serum and hepatic glucose concentration in diabetic rats. In diabetic rats, increased levels of AGE, reactive oxygen species, and lipid peroxidation were significantly decreased by treatment with both ASX and CF in the liver of diabetic rats. STZ treatment markedly augmented the protein expressions of AGE, and both ASX and CF efficiently attenuated these increases in hepatic protein expressions. In addition, oxidative stress and proinflammatory protein expressions were upregulated in the diabetic rats. On the contrary, these upregulations of protein expressions were decreased by the administration of ASX or CF. These results suggest that the inhibitory effect of ASX on diabetes-induced hepatic dysfunction could be derived from the blocking of AGE formation and further anti-inflammation and that CF exhibited beneficial effects through the attenuation of hyperglycemia, and thus the inhibition of AGE formation and the inflammatory responses. Therefore, ASX as well as CF may help prevent ongoing diabetes-induced hepatic injury.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cornus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Fruit; Glycation End Products, Advanced; Hyperglycemia; Inflammation; Lipid Peroxidation; Liver; Male; Oxidative Stress; Phytotherapy; Plant Extracts; Rats, Wistar; Xanthophylls

Astaxanthin (ASX), a xanthophyll carotenoid from the marine algae Hematococcus pluvialis, has anti-obesity and insulin-sensitivity effects. The specific molecular mechanisms of its actions are not yet established. The present study was designed to investigate the mechanisms underlying the insulin sensitivity effects of ASX in a non-genetic insulin resistant animal model. A group of male Swiss albino mice was divided into two and fed either a starch-based control diet or a high fat-high fructose diet (HFFD). Fifteen days later, mice in each dietary group were divided into two and were treated with either ASX (6 mg kg(-1) per day) in olive oil or olive oil alone. At the end of 60 days, glucose, insulin and pro-inflammatory cytokines in plasma, lipids and oxidative stress markers in skeletal muscle and adipose tissue were assessed. Further, post-receptor insulin signaling events in skeletal muscle were analyzed. Increased body weight, hyperglycemia, hyperinsulinemia and increased plasma levels of tumor necrosis factor-α and interleukin-6 observed in HFFD-fed mice were significantly improved by ASX addition. ASX treatment also reduced lipid levels and oxidative stress in skeletal muscle and adipose tissue. ASX improved insulin signaling by enhancing the autophosphorylation of insulin receptor-β (IR-β), IRS-1 associated PI3-kinase step, phospho-Akt/Akt ratio and GLUT-4 translocation in skeletal muscle. This study demonstrates for the first time that chronic ASX administration improves insulin sensitivity by activating the post-receptor insulin signaling and by reducing oxidative stress, lipid accumulation and proinflammatory cytokines in obese mice.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Blood Glucose; Cytokines; Diet; Diet, High-Fat; Fructose; Glucose Transporter Type 4; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Interleukin-6; Lipid Metabolism; Lipids; Male; Mice; Mice, Obese; Muscle, Skeletal; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phosphorylation; Receptor, Insulin; Signal Transduction; Tumor Necrosis Factor-alpha; Volvocida; Xanthophylls

This study investigates the effects of astaxanthin (ASX) on insulin signaling and glucose metabolism in the liver of mice fed a high fat and high fructose diet (HFFD). Adult male Mus musculus mice of body mass 25-30 g were fed either normal chow or the HFFD. After 15 days, mice in each group were subdivided among 2 smaller groups and treated with ASX (2 mg·(kg body mass)⁻¹) in olive oil for 45 days. At the end of 60 days, HFFD-fed mice displayed insulin resistance while ASX-treated HFFD animals showed marked improvement in insulin sensitivity parameters. ASX treatment normalized the activities of hexokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, and increased glycogen reserves in the liver. Liver tissue from ASX-treated HFFD-fed animals showed increased tyrosine phosphorylation and decreased serine phosphorylation of insulin receptor substrates (IRS)-1 and -2. ASX increased IRS 1/2 and phosphatidylinositol 3-kinase (PI3K) association and serine phosphorylation of Akt. In addition, ASX decreased HFFD-induced serine kinases (c-jun N-terminal kinase-1 and extracellular signal-regulated kinase-1). The results suggest that ASX treatment promotes the IRS-PI3K-Akt pathway of insulin signaling by decreasing serine phosphorylation of IRS proteins, and improves glucose metabolism by modulating metabolic enzymes.

Topics: Animals; Antioxidants; Dietary Supplements; Hyperglycemia; Hypoglycemic Agents; Insulin Receptor Substrate Proteins; Insulin Resistance; Liver; Liver Glycogen; Male; Mice; Phosphatidylinositol 3-Kinase; Phosphorylation; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt; Random Allocation; Serine; Signal Transduction; Tyrosine; Xanthophylls

Astaxanthin (ASX) is a carotenoid that has potent protective effects on diabetic nephropathy in mice model of type 2 diabetes. In this study, we investigated the protective mechanism of ASX on the progression of diabetic nephropathy using an in vitro model of hyperglycemia, focusing on mesangial cells. Normal human mesangial cells (NHMCs) were cultured in the medium containing normal (5 mM) or high (25 mM) concentrations of D-glucose. Reactive oxygen species (ROS) production, the activation of nuclear transcription factors such as nuclear factor kappa B (NFkappaB) and activator protein-1 (AP-1), and the expression/production of transforming growth factor-beta 1 (TGFbeta(1)) and monocyte chemoattractant protein-1 (MCP-1) were evaluated in the presence or absence of ASX. High glucose (HG) exposure induced significant ROS production in mitochondria of NHMCs, which resulted in the activation of transcription factors, and subsequent expression/production of cytokines that plays an important role in the mesangial expansion, an important event in the pathogenesis of diabetic nephropathy. ASX significantly suppressed HG-induced ROS production, the activation of transcription factors, and cytokine expression/production by NHMCs. In addition, ASX accumulated in the mitochondria of NHMCs and reduced the production of ROS-modified proteins in mitochondria. ASX may prevent the progression of diabetic nephropathy mainly through ROS scavenging effect in mitochondria of mesangial cells and thus is expected to be very useful for the prevention of diabetic nephropathy.

Topics: Cell Line; Chemokine CCL2; Diabetic Neuropathies; Humans; Hyperglycemia; Mesangial Cells; Mitochondria; Mitogen-Activated Protein Kinases; NF-kappa B; Oxidation-Reduction; Reactive Oxygen Species; Signal Transduction; Transcription Factor AP-1; Transforming Growth Factor beta1; Xanthophylls