Taiki Miyazawa

Tocotrienol Distribution in Foods: Estimation of Daily Tocotrienol Intake of Japanese Population

Tocotrienol (T3) is an unsaturated form of natural vitamin E that has been focused on because of its potential health benefits (i.e., antioxidative, antihypercholesterolemic, and antiangiogenic effects). The presence of T3 in some plant sources (e.g., rice bran and palm oil) is known, but its distribution in other edible sources and its daily intake remain unclear. In this study, we aimed at clarifying the distribution of T3 in various food sources and estimating the daily T3 intake of Japanese population. T3 contents of 242 food items and 64 meal items were measured by using normal-phase HPLC with fluorescence detection. As for the results, T3 contents were nondetectable to 12 mg T3/kg wet wt of food items, and nondetectable to 1.3 mg T3/item of processed (cooked) meal. Accordingly, the daily intake of T3 was estimated as 1.9-2.1 mg T3/day/person. The estimated daily intake of T3 appears rather low compared with the intake of tocopherol (8-10 mg/day/person as reported in the Japanese National Nutrition Survey), and additional T3 is important for its therapeutic aspects.

Amyloid β-induced erythrocytic damage and its attenuation by carotenoids

The presence of amyloid β‐peptide (Aβ) in human blood has recently been established, and it has been hypothesized that Aβ readily contacts red blood cells (RBC) and oxidatively impairs RBC functions. In this study, we conducted in vitro and in vivo studies, which provide evidence that Aβ induces oxidative injury to RBC by binding to them, causing RBC phospholipid peroxidation and diminishing RBC endogenous carotenoids, especially xanthophylls. This type of damage is likely to injure the vasculature, potentially reducing oxygen delivery to the brain and facilitating Alzheimers disease (AD). As a preventive strategy, because the Aβ‐induced RBC damage could be attenuated by treatment of RBC with xanthophylls, we suggest that xanthophylls may contribute to the prevention of AD.

Plasma carotenoid concentrations before and after supplementation with astaxanthin in middle-aged and senior subjects.

A randomized, double-blind human trial was conducted to assess the effect on the plasma carotenoid concentration of 4- or 12-week astaxanthin supplementation (1 or 3 mg/d) of 20 Japanese middle-aged and senior subjects. The plasma carotenoid concentration was significantly higher after the astaxanthin supplementation than that before in both the 1 mg/d (10 subjects) and 3 mg/d (10 subjects) groups.

Amyloid β Induces Adhesion of Erythrocytes to Endothelial Cells and Affects Endothelial Viability and Functionality

It has been suggested that amyloid β-peptide (Aβ) might mediate the adhesion of erythrocytes to the endothelium which could disrupt the properties of endothelial cells. We provide evidence here that Aβ actually induced the binding of erythrocytes to endothelial cells and decreased endothelial viability, perhaps by the generation of oxidative and inflammatory stress. These changes are likely to contribute to the pathogenesis of Alzheimer’s disease.

The combination of maternal and offspring high-fat diets causes marked oxidative stress and development of metabolic syndrome in mouse offspring

Maternal overnutrition (e.g., high-fat (HF) diet) during pregnancy and lactation is believed to cause oxidative stress and increase the risk of metabolic syndrome in offspring. In the present study, we investigated the effects of both maternal and offspring HF diets on metabolic syndrome risk and oxidative stress profiles in mice. Dams of the C57BL/6J mouse strain were fed a HF or control (CO) diet during gestation and lactation. Offspring were weaned at 3weeks of age. The female offspring were sacrificed at weaning, while the males were maintained on the HF or CO diet until 11weeks of age. Tissue samples, including those from liver, were collected from offspring at 3 and 11weeks of age, and lipids, phosphatidylcholine hydroperoxide (PCOOH, an oxidative stress marker), and gene expression were evaluated. Accumulation of lipids, but not PCOOH, was found in the livers of 3-week-old offspring from dams fed the HF diet. When the offspring were maintained on a HF diet until 11weeks of age, marked accumulation of both liver lipids and PCOOH was observed. PCOOH manifestation was supported by the expression of genes such as Gpx4, encoding a PCOOH degrading enzyme. These results suggest that the combination of maternal and offspring overnutrition causes marked oxidative stress in offspring, which accelerates metabolic syndrome. The present findings in offspring from infancy to adulthood may be useful for better understanding the cause-and-effect relationships between oxidative stress and metabolic syndrome development.

Oxidative Stress during Development of Alcoholic Fatty Liver: Therapeutic Potential of Cacao Polyphenol

The lipid and antioxidative/oxidative profiles of livers from rats fed an ethanol liquid diet for 8 weeks provided evidence for an involvement of oxidative stress (e.g., phospholipid peroxidation) in the development of alcoholic fatty liver (AFL), possibly in an early stage. Cacao polyphenol supplementation produced an ameliorating effect, and may help in AFL prevention.

Carbon tetrachloride-induced hepatic and renal damages in rat: inhibitory effects of cacao polyphenol

Here, we investigated the protective effect of cacao polyphenol extract (CPE) on carbon tetrachloride (CCl4)-induced hepato-renal oxidative stress in rats. Rats were administered CPE for 7 days and then received intraperitoneal injection of CCl4. Two hours after injection, we found that CCl4 treatment significantly increased biochemical injury markers, lipid peroxides (phosphatidylcholine hydroperoxide (PCOOH) and malondialdehyde (MDA)) and decreased glutathione peroxidase activity in kidney rather than liver, suggesting that kidney is more vulnerable to oxidative stress under the present experimental conditions. CPE supplementation significantly reduced these changes, indicating that this compound has antioxidant properties against CCl4-induced oxidative stress. An inhibitory effect of CPE on CCl4-induced CYP2E1 mRNA degradation may provide an explanation for CPE antioxidant property. Together, these results provide quantitative evidence of the in vivo antioxidant properties of CPE, especially in terms of PCOOH and MDA levels in the kidneys of CCl4-treated rats. Graphical abstract Rats were supplemented with CPE prior to CCl4 treatment. CCl4 significantly increased PCOOH and MDA in kidney rather than liver, and CPE significantly ameliorated these damages.

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

Purpose Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Methods Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Results Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. Conclusion These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.

Distribution of β-carotene-encapsulated polysorbate 80-coated poly(D, L-lactide-co-glycolide) nanoparticles in rodent tissues following intravenous administration

Purpose Biodegradable nanoparticles (NPs) composed of poly(D, L-lactide-co-glycolide) (PLGA) have attracted considerable attention as delivery systems of drugs and antioxidative compounds, such as β-carotene (BC). Intravenous (IV) administration of BC-containing PLGA-NPs (BC-PLGA-NPs) coated with polysorbate 80 (PS80) has been shown to effectively deliver BC to the brain. However, the whole-body distribution profile of BC is still not clear. Therefore, we investigated the accumulation of BC in various organs, including the brain, following IV administration of PS80-coated BC-PLGA-NPs in rats. Methods PS80-coated and uncoated BC-PLGA-NPs were prepared by solvent evaporation, and administered intravenously to Sprague Dawley rats at a BC dose of 8.5 mg/rat. Accumulation of BC in various organs (brain, heart, liver, lungs, and spleen) and blood plasma was evaluated by high performance liquid chromatography with ultraviolet (UV) detection, 1 hour after administration. Results We prepared PS80-coated BC-PLGA-NPs with an entrapment efficiency of 14%, a particle size of 260 nm, and a zeta potential of −26 mV. Coating with PS80 was found to result in significant accumulation of BC in the lungs, rather than in the brain and other tissues. Further, plasma levels of BC in the PS80-coated BC-PLGA-NP group were much lower than those of the uncoated BC-PLGA-NP group. Conclusion Following IV administration, PS80-coated BC-PLGA-NPs are quickly transferred from plasma circulation to the lungs, rather than the brain. Significant accumulation of BC in the lungs may be useful for health-related applications.

Chapter 12:Liquid Chromatography-based Assay for Carotenoids in Human Blood

Membrane phospholipid peroxidation has received attention in relation to oxidative stress occurring during pathophysiological changes such as atherogenesis and aging (Kinoshita et al 2000; Miyazawa et al 1988; 1992a; Moriya et al 2001; Stocker et al 2004). We previously confirmed that significantly ...