Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

Severe Hypercalcemia due to Drowning in an Onsen (Hot Spring).

Hypercalcemia is generally caused by primary hyperparathyroidism, malignancies, and drugs. Herein, we report a case of severe hypercalcemia due to drowning in hot springs. A 55-year-old woman was found floating in a public bath at a hotel and was admitted to a nearby hospital. The patient was intubated because of hypoxia and shock, and noradrenaline was titrated. Computed tomography revealed bilateral aspiration pneumonia. Blood tests revealed hypercalcemia (serum total calcium [Ca]: 18.7 mg/dL). Hyperparathyroidism, malignancy, and drug-related factors were ruled out as the causes of hypercalcemia. In addition, the public bath in which the patient drowned contained high concentrations of Ca. We concluded that the reason for hypercalcemia was accidental ingestion of the hot spring water containing a high concentration of Ca through the gastrointestinal tract. In the case of drowning and hypercalcemia, the cause may be clarified by examining the components that were accidentally swallowed.

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial.

BACKGROUND: Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. METHODS: A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80-85 mmHg (high-target) and 65-70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients' condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 µg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. DISCUSSION: The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

A fatal case of traumatic brain injury with severe coagulopathy due to Rhabdophis tigrinus (yamakagashi) bites: a case report.

BACKGROUND: Yamakagashi venom is a prothrombin activator, leading to disseminated intravascular coagulation. We report a fatal case of severe coagulopathy from head trauma assumed to be caused by a yamakagashi bite. CASE PRESENTATION: An 80-year-old man fell and developed systemic tonic-clonic convulsions. Head computed tomography revealed brain contusion and acute subdural hematoma. Physical examination revealed two bite marks with persistent bleeding on the right lower leg. The patient stated that he had been bitten by some creature 3 days prior, but the bite was left untreated. Laboratory tests showed fibrinogen levels below the detection limit. Although eighteen units of fresh frozen plasma were administered for coagulopathy, fibrinogen levels did not improve. He died about 18 h after a head injury. CONCLUSION: In this case of a yamakagashi bite with active bleeding due to trauma, early administration of yamakagashi antivenom should be considered to control coagulopathy.

The Beneficial Effects of Astaxanthin on Glucose Metabolism and Modified Low-Density Lipoprotein in Healthy Volunteers and Subjects with Prediabetes.

Astaxanthin (ASTX) is an antioxidant agent. Recently, its use has been focused on the prevention of diabetes and atherosclerosis. We examined the effects of astaxanthin supplementation for 12 weeks on glucose metabolism, glycemic control, insulin sensitivity, lipid profiles and anthropometric indices in healthy volunteers including subjects with prediabetes with a randomized, placebo-controlled trial. METHODS: We enrolled 53 subjects who met our inclusion criteria and administered them with 12 mg astaxanthin or a placebo once daily for 12 weeks. Subsequently, their HbA1c levels, lipid profiles and biochemical parameters were determined. The participants also underwent a 75 g oral glucose tolerance test (OGTT), vascular endothelial function test and measurement of the visceral fat area. RESULTS: After astaxanthin supplementation for 12 weeks, glucose levels after 120 min in a 75 g OGTT significantly decreased compared to those before supplementation. Furthermore, the levels of HbA1c (5.64 ± 0.33 vs. 5.57 ± 0.39%, p < 0.05), apo E (4.43 ± 1.29 vs. 4.13 ± 1.24 mg/dL, p < 0.05) and malondialdehyde-modified low-density lipoprotein (87.3 ± 28.6 vs. 76.3 ± 24.6 U/L, p < 0.05) were also reduced, whereas total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-C (HDL-C) levels were unaltered. The Matuda index, which is one of the parameters of insulin resistance, was improved in the ASTX group compared to that before supplementation. CONCLUSIONS: our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.

The effect of aging on the antioxidative activity of astaxanthin in human aqueous humor.

We previously evaluated the antioxidative effects of astaxanthin intake in the aqueous humor by measuring reactive oxygen species-related parameters, including O2 •- scavenging activity, H2O2 level, and total hydroperoxides level. In this study, we analyzed the antioxidative effects of astaxanthin in relation to age in 16 males and 19 females (average age 71.3 and 70.6, respectively) who underwent bilateral cataract surgery on one side before and the other side after astaxanthin intake (6 mg/day for 2 weeks). None of the parameters correlated with age before astaxanthin intake, but only total hydroperoxides level was significantly correlated after the astaxanthin intake (r = 0.4, p<0.05). Total hydroperoxides levels were similar in younger and older patients (<70 vs ≥70 years) before astaxanthin, but decreased significantly more in younger patients (-0.21 ± 0.18 vs -0.05 ± 0.31, p<0.05) after the intake, resulting in significantly different levels (p<0.05). The previously observed decrease in mean total hydroperoxides levels following astaxanthin intake was therefore considered likely to be attributable to a greater response in younger subjects. Given that total hydroperoxides levels reflect general antioxidative status, astaxanthin intake may exert a greater antioxidative effect in younger patients. Further comparative studies involving younger subjects and different astaxanthin doses are needed.

Effect of Astaxanthin on the Expression and Activity of Aquaporin-3 in Skin in an In-Vitro Study.

Astaxanthin (3,3'-dihydroxy-ß,ß-carotene-4,4'-dione) is a red lipophilic pigment with strong antioxidant action. Oral or topical administration of astaxanthin has been reported to improve skin function, including increasing skin moisture. In this study, we examined the mechanism by which astaxanthin improves skin function by focusing on the water channel aquaporin-3 (AQP3), which plays important roles in maintaining skin moisture and function. When astaxanthin was added to PHK16-0b or HaCaT cells, the mRNA expression level of AQP3 increased significantly in a concentration-dependent manner in both cell lines. The AQP3 protein expression level was also confirmed to increase when astaxanthin was added to HaCaT cells. Similarly, when astaxanthin was added to 3D human epidermis model EpiSkin, AQP3 expression increased. Furthermore, when glycerol and astaxanthin were simultaneously added to EpiSkin, glycerol permeability increased significantly compared with that observed for the addition of glycerol alone. We demonstrated that astaxanthin increases AQP3 expression in the skin and enhances AQP3 activity. This result suggests that the increased AQP3 expression in the skin is associated with the increase in skin moisture by astaxanthin. Thus, we consider astaxanthin useful for treating dry skin caused by decreased AQP3 due to factors such as diabetes mellitus and aging.

Effects of astaxanthin on VEGF level and antioxidation in human aqueous humor: difference by sex.

In our previous report, we showed the effect of astaxanthin intake on VEGF level in the aqueous humor and the relationship between VEGF level and reactive oxygen species-related parameters and other relevant factors. VEGF level is associated with total hydroperoxide level, and a multivariate analysis identified sex as a secondary factor affecting these relationships. Here, we analyzed the effects of astaxanthin on the relationship between VEGF level and reactive oxygen species-related parameters by sex. Patients (16 males and 19 females, aged 71.3 and 70.6, respectively) underwent bilateral cataract surgery on one side before and the other side after astaxanthin treatment (6 mg/day for 2 weeks). Levels of VEGF, hydrogen peroxide, and total hydroperoxide, and O2 •- scavenging activity, were measured in the aqueous humor. In females only, VEGF level was negatively correlated with O2 •- scavenging activity before the astaxanthin intake (r = -0.6, p<0.01) and positively correlated with total hydroperoxide level before and after the astaxanthin intake (r = 0.7 and 0.8, respectively, p<0.01). In conclusion, astaxanthin appears to affect O2 •- scavenging activity in the aqueous humor in females, and is likely to be involved in the control of VEGF levels in the anterior eye.

The effect of astaxanthin on vascular endothelial growth factor (VEGF) levels and peroxidation reactions in the aqueous humor.

We explored the effect of astaxanthin on vascular endothelial growth factor in the aqueous humor, by measuring vascular endothelial growth factor levels and oxidation-related parameters, including O2 (•-) scavenging activity, H2O2 level, and total hydroperoxide level in the aqueous humor, obtained from 35 patients before and after astaxanthin administration. We evaluated the relationship between vascular endothelial growth factor and the oxidation-related parameters as well as the patient's diabetic status, age, and sex. Vascular endothelial growth factor levels did not change significantly but O2 (•-) scavenging activity and total hydroperoxide level significantly (p<0.05) increased and decreased, respectively. Both pre- and post- astaxanthin intake, vascular endothelial growth factor and total hydroperoxide levels were positively correlated (Pearson: r = 0.42, p<0.05; r = 0.55, p<0.01, respectively). Analysis of vascular endothelial growth factor levels and O2 (•-) scavenging activities gave a negative correlation but only pre-astaxanthin intake (r = -0.37, p<0.05). Differences in levels pre- and post-astaxanthin only showed association between vascular endothelial growth factor and total hydroperoxide (r = 0.49, p<0.01) analyzed by multiple linear regression. Using multivariate analysis, pre-astaxanthin vascular endothelial growth factor level was associated with two factors of total hydroperoxide and O2 (•-) scavenging activity (r = 0.49, p<0.05), and post-astaxanthin vascular endothelial growth factor level with two factors of total hydroperoxide and sex (r = 0.60, p<0.01). Astaxanthin intake may have affected vascular endothelial growth factor level through its antioxidant effects by increasing O2 (•-) scavenging activity and suppressing peroxide production.

Effects of astaxanthin on antioxidation in human aqueous humor.

We evaluated the antioxidative effects of astaxanthin through the changes in superoxide scavenging activity, levels of hydrogen peroxide and total hydroperoxides in human aqueous humor. The study subjects were 35 patients who underwent bilateral cataract surgery on one side before and the other side after intake of astaxanthin (6 mg/day for 2 weeks). Their aqueous humor was taken during the surgery and subjected to measurements of the three parameters. After astaxanthin intake, the superoxide scavenging activity was significantly (p<0.05) elevated, while the level of total hydroperoxides was significantly (p<0.05) lowered. There was a significant negative correlation between the superoxide scavenging activity and the level of total hydroperoxides (r = -0.485, p<0.01), but no correlations between the hydrogen peroxide level and the other two parameters. Astaxanthin intake clearly enhanced the superoxide scavenging activity and suppressed the total hydroperoxides production in human aqueous humor, indicating the possibility that astaxanthin has suppressive effects on various oxidative stress-related diseases.

Astaxanthin functions differently as a selective peroxisome proliferator-activated receptor γ modulator in adipocytes and macrophages.

Astaxanthin (ASX), an oxygenated carotenoid (xanthophyll), has previously been shown to exert ameliorative effects on obesity and insulin resistance, but the underlying mechanisms were not clearly elucidated. In the present study, we investigated whether ASX serves as a novel selective peroxisome proliferator-activated receptor (PPAR) γ modulator. Analyses of PPARγ binding by CoA-BAP assays revealed that ASX bound to PPARγ in a dose-dependent manner. However, ASX was unable to activate transcription in PPARγ reporter assays, although it antagonized transcriptional activation by the PPARγ agonist rosiglitazone (RGZ). When the molecular interactions between PPARγ and three coactivators were examined, ASX increased the interactions of PPARγ with transcriptional intermediary factor 2 (TIF2) and steroid receptor coactivator-1 (SRC-1), but not cAMP responsive element-binding protein (CREB)-binding protein (CBP). In addition, ASX effectively blocked the increase in CBP recruitment to PPARγ mediated by RGZ. ASX alone did not stimulate 3T3-L1 cell differentiation, although it antagonized 3T3-L1 cell differentiation and lipid accumulation induced by RGZ, similar to the PPARγ antagonist GW9662. When the effects of cotreatment of 3T3-L1 cells with ASX and RGZ were determined based on the mRNA levels of PPARγ target genes, ASX effectively reduced the mRNA levels of aP2 and lipoprotein lipase, but not CD36. Intriguingly, ASX was capable of inducing PPARγ target genes such as liver X receptor, CD36 and ABCA1 in thioglycollate-elicited peritoneal macrophages. Collectively, the present findings indicate that ASX is a novel selective PPARγ modulator that acts as an antagonist or agonist depending on the cell context.

Effects of astaxanthin on human blood rheology.

Effects of astaxanthin (AX) derived from H. pluvialis on human blood rheology were investigated in 20 adult men with a single-blind method. The experimental group was 57.5 +/- 9.8 years of age and the placebo group was 50.8 +/- 13.1 years of age. A blood rheology test that measures whole blood transit time was conducted using heparinized blood of the volunteers by a MC-FAN apparatus (microchannel array flow analyzer). After administration of AX 6 mg/day for 10 days, the values of the experimental group were decreased from 52.8 +/- 4.9 s to 47.6 +/- 4.2 s (p<0.01) and a comparison of the values between the experimental (47.6 +/- 4.2 s) and the placebo (54.2 +/- 6.7 s) groups showed a significant difference (p<0.05). There were no adverse effects resulting from the administration of AX 6 mg/day for 10 days. Informed consent was obtained from each subject.

Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats.

The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.

Inhibitory effect of astraxanthin combined with Flavangenol on oxidative stress biomarkers in streptozotocin-induced diabetic rats.

In this study, the effect of dietary antioxidants, such as astaxanthin and Flavangenol, and a combination of both, in counteracting oxidative stress in streptozotocin-induced diabetes was investigated. Streptozotocin-induced diabetic rats were divided into four groups: control, astaxanthin, Flavangenol, and combined astaxanthin and Flavangenol (mix group). Each group other than the control group was fed with an astaxanthin diet (0.1 g/kg), Flavangenol diet (2.0 g/kg), or an astaxanthin (0.1 g/kg)-Flavangenol (2.0 g/kg) mixture diet, respectively. After 12 weeks of feeding, the results showed that the lipid peroxide levels of plasma and lens and the plasma triglyceride (TG) level in the mix group were significantly decreased by 44%, 20%, and 20%, respectively, compared with the control group. In the mix group, lipid peroxidation was also significantly reduced by 70% in the liver and 20% in the kidney compared with the control group. Furthermore, the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the mix group was significantly lower, 36%, than the control group. The alpha-tocopherol concentrations in the plasma, liver, and kidney in the astaxanthin and mix groups were significantly higher, 3-9 times, than in the control group. The degree of cataract formation in the Flavangenol and mix groups tended to be lower than the control group. These results indicate that the combination of astaxanthin with Flvangenol has an improved protective effect on oxidative stress associated with streptozotocin-induced diabetes than either agent used alone. Thus, this combination may be beneficial in preventing the progression of diabetic complications.

Effects of astaxanthin in obese mice fed a high-fat diet.

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

Effects of astaxanthin supplementation on exercise-induced fatigue in mice.

The present study was designed to determine the effect of astaxanthin on endurance capacity in male mice aged 4 weeks. Mice were given orally either vehicle or astaxanthin (1.2, 6, or 30 mg/kg body weight) by stomach intubation for 5 weeks. The astaxanthin group showed a significant increase in swimming time to exhaustion as compared to the control group. Blood lactate concentration in the astaxanthin groups was significantly lower than in the control group. In the control group, plasma non-esterfied fatty acid (NEFA) and plasma glucose were decreased by swimming exercise, but in the astaxanthin group, NEFA and plasma glucose were significantly higher than in the control group. Astaxanthin treatment also significantly decreased fat accumulation. These results suggest that improvement in swimming endurance by the administration of astaxanthin is caused by an increase in utilization of fatty acids as an energy source.

Microarray profiling of gene expression patterns in glomerular cells of astaxanthin-treated diabetic mice: a nutrigenomic approach.

We have demonstrated that astaxanthin reduces glomerular oxidative stress as well as inhibits the increase in urinary albumin in diabetic db/db mice. The aim of the present study was to determine the gene expression patterns in the glomerular cells of the diabetic mouse kidney, and to investigate the effects of astaxanthin on the expression of these genes using a high-density DNA microarray. The diet administered to the astaxanthin-supplementation group was prepared by mixing a control powder with astaxanthin at a concentration of 0.02%. Glomerular cells were obtained from the kidneys of mice by laser capture microdissection. Preparation of cRNA and target hybridization were performed according to the Affymetrix GeneChip eukaryotic small sample target labeling assay protocol. The gene expression profile was evaluated by the mouse expression set 430A GeneChip. Array data analysis was carried out using Affymetrix GeneChip operating and Ingenuity Pathway analysis software. Comparison between diabetic db/db and non-diabetic db/m mice revealed that 779 probes (3.1%) were significantly affected, i.e. 550 probes were up-regulated, and 229 probes were down-regulated, both at levels of >/=1.5-fold in the diabetic mice. Ingenuity signal analysis of 550 up-regulated probes revealed the mitochondrial oxidative phosphorylation pathway as the most significantly affected caronical pathway. The affected genes were associated with complexes I, III, and IV located on the mitochondrial inner membrane, and the expression levels of these genes were decreased in mice treated with astaxanthin as compared to the levels in the control mice. In addition, the expression of many genes associated with oxidative stress, collagen synthesis, and transforming growth factor-beta signaling was enhanced in the diabetic mice, and this enhancement was slightly inhibited in the astaxanthin-treated mice. In conclusion, this genome-wide nutrigenomics approach provided insight into genes and putative genetic pathways that are thought to be affected by stimulation by high-glucose concentrations. In addition, the present approach may help us gain a better understanding of the genes and pathways involved in the anti-diabetic mechanism of astaxanthin.

Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice.

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.

Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice.

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.