The dynamics of initiation and inhibition of lipid peroxidation by α-tocopherol (α-Toc) in membranes were investigated under biological conditions using phosphatidylcholine liposomes. First, I examined how superoxide generated in the bulk water phase is able to induce lipid peroxidation in the inner hydrophobic region of the membrane. Second, I studied the localization of the antioxidant OH group of α-Toc in membranes and its lipid radical-trapping dynamics. Third, I investigated how α-Toc that is oxidized during radical trapping in membranes is recycled by ascorbic acid (AsA) in the bulk water phase. Finally, I studied the deactivation by α-Toc of singlet oxygen (¹O₂), which was generated by photoirradiation at the membrane surface, in the hydrophobic membrane inner region, and in bulk water, and measured the ¹O₂ deactivating rate constant of α-Toc in membranes considering: the concentration and mobility of α-Toc molecule in membranes, especially those of its active OH moiety located at the membrane domains, such as the membrane surface polar zone, inner hydrogen belt, and hydrophobic core, and the dielectric constant reflecting the reactivity of the OH moiety and ¹O₂ in the membrane domains where they interact.

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Background: CoQ10 has come to be widely used as a dietary supplement, and daily intake of it has increased in recent years. CoQ10 is produced in all living organisms and is an essential coenzyme for energy synthesis in the mitochondria and an important scavenger of reactive oxygen species. Objective: This is a randomized, double-blind, placebo-controlled experiment to examine the acute effects of a single dose of CoQ10 on the autonomic nervous system (ANS) by using power spectral analysis of HRV and energy metabolism at rest and during low intensity exercise in healthy subjects. Eleven nonsmoking healthy male students (age: 26±1 y) volunteered to participate in this experiment. CM5 lead ECG and gas exchange parameters were recorded 5 min before, and 30 min and 60 min after the oral administration of CoQ10 or a placebo. Following this, the subjects exercised using a stationary cycle ergometer for 10 min at 60 rpm with an intensity of 30% of heart rate reserve. During the exercise, the ECG and gas exchange parameters were recorded continuously. Results: There were no significant differences in heart rate between the CoQ10 and placebo trials at rest or during exercise. With regard to the integrated values of the spectrum, there were no significant differences in the HF power representing parasympathetic activity or LF power representing both sympathetic and parasympathetic nervous activities between the trials at any timepoint. However, during the exercise, HF power and LF power in the CoQ10 trial showed a tendency to increase compared with the placebo trial (p<0.1). Total power representing the over-all ANS activity was significantly increased in the CoQ10 trial during exercise, which implied that autonomic nervous activity was augmented by CoQ10 (p<0.05). CoQ10 also induced enhanced lipid oxidation as shown by the significantly lower respiratory gas exchange ratio (R) and increased fat oxidation during exercise. The results shed some light upon the relationship between the autonomic nervous activity and energy metabolism. Conclusion: These results suggested that CoQ10 may increase fat oxidation with augmented autonomic nervous activity during low intensity exercise.

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This study assessed folate intake, folate concentrations in plasma and erythrocytes, plasma total homocysteine (tHcy) concentrations, and urinary excretion of folate metabolites in Korean women of childbearing age. A total of 36 women voluntarily participated in this study. Precise dietary intake for 3 consecutive days was determined by weighing all foods consumed, and folate intake was calculated with a computer-aided dietary analysis system. Folate concentrations in plasma and erythrocytes were determined via microbiological methods and in plasma by HPLC. Urine excreted over the same period of time was collected and assayed for folate catabolites, para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (ApABG) by reverse-phase HPLC after affinity chromatography. The mean folate intake was 206.9±90.8 μg DFE/d, and the mean concentrations in plasma and erythrocytes were 10.5±3.7 and 249.9±77.8 ng/mL, respectively. Erythrocyte folate concentration was low in 2.8% of the subjects (<140 ng/mL) and was marginal in 5.5% (140-156 ng/mL). The mean plasma tHcy concentration was 12.7±0.2 nmol/mL, and 11% of the subjects evidenced hyperhomocysteinemia (≥15 nmol/mL). The mean urinary excretion levels of pABG and ApABG were 10.7±3.8 and 89.1±19.5 nmol/d, respectively. The means of folate reserve and folate turnover rate were 26.2±11.6 and 10.5±3.9, respectively. We noted positive relationships between folate intake and the folate concentrations in plasma and erythrocytes, as well as the urinary excretions of ApABG and total folate catabolites. In addition, the erythrocytic folate concentrations were positively associated with the urinary excretions of ApABG and total folate catabolites. In conclusion, the folate status of Korean women of childbearing age was marginally deficient with inadequate concentrations of erythrocyte folate and elevated plasma tHcy, largely due to insufficient folate intake. The marginally deficient folate status was confirmed by the low excretion of folate catabolites in urine.

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It is reported that arachidonic acid strongly induces the conformational change in vitro and transactivity of PPARα in colorectal cancer cell line Caco-2. In this study, we demonstrated that the induction of conformational change and transactivity of PPARδ by arachidonic acid, as well as other polyunsaturated fatty acids, was considerably lower than that of PPARα. Mammalian two-hybrid assay showed that arachidonic acid enhanced binding of one of the coactivators, p300, to PPARα but not to PPARδ. Additionally, arachidonic acid induced in vitro binding of both PPARα-RXRα and PPARδ-RXRα heterodimers to several PPREs on CRBPII, L-FABP and ACO genes. Our results suggest that the lower transactivity of PPARδ for arachidonic acid in Caco-2 cells, compared with PPARα, is associated with the binding activity of p300 to the receptor.

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Chromium (Cr) is an essential trace element and is important for normal carbohydrate metabolism, and its deficiency in animals can cause a diabetic-like state. Human and experimental animal studies suggest that urinary Cr excretion is increased in diabetic populations. To investigate whether hyperglycemia-induced elevation of urinary Cr excretion reduces tissue Cr storage conditions, we assessed total Cr balance and Cr distribution in streptozotocin (STZ)-induced diabetic mice. Male C57BL mice were randomly assigned to STZ or control groups and their urine was collected 7, 14, 21 and 28 d after STZ injection. An inductively coupled plasma mass spectrometry instrument equipped with a dynamic reaction cell was used for determination of Cr in urine, plasma and tissues samples. The urinary excretions of Cr were 15.4±3.0 and 356±62 ng/d, and the renal Cr concentrations were 0.85±0.12 and 0.17±0.03 ng/mg for the control and diabetes groups, respectively (p<0.01), after 28 d. The Cr balance in STZ-treated mice was distinctly negative due to the increase in urinary Cr loss (p<0.01). These results suggest that in mice, STZ induces a reduction in renal Cr concentration and total negative Cr balance caused by an increase in urinary Cr output.

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Using a single-group time-series design, we determined that osmotic diarrhea caused by maltitol ingestion was suppressed by the addition of not only soluble but also insoluble dietary fiber in healthy humans. We then clarified that cellulose delayed gastric emptying in rats. Twenty-seven healthy volunteers ingested maltitol step-wise at doses of 15, 20, 25, 30, 35, 40 and 45 g from small to large amounts. Within that range of ingested amounts, 22 out of 27 subjects experienced osmotic diarrhea from maltitol ingestion, and the minimal dose level of maltitol that induced osmotic diarrhea (MMD) was established for each subject. When 5 g of cellulose was added to the MMD, osmotic diarrhea was suppressed in 13 out of 19 subjects (68.4%), while partially hydrolyzed alginate-Na (PHA-Na), a soluble dietary fiber, suppressed osmotic diarrhea in 10 out of 20 subjects (50.0%). When a mixed solution of cellulose and maltitol was administered to rats, the gastric emptying of maltitol was significantly delayed at 30 and 60 min after administration (p=0.019, p=0.013), respectively. PHA-Na also significantly delayed gastric emptying at 30 min (p=0.013). In conclusion, cellulose can suppress the osmotic diarrhea caused by maltitol ingestion in humans and delay the gastric emptying of maltitol in rats. A new physiological property of cellulose was clarified in this study.

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We performed oral loading of AsA or DAsA (1 mmol) in subjects who had consumed a diet low in vitamin C (C) (C≤5 mg/d) for 3 d before loading, and measured urinary and blood vitamin C. Since the crossover method was used, the same experiment was repeated after an interval of about 1 mo in each subject. The results of the experiment including a total of 17 subjects for 2005 and 2006, were as follows. (1) There were marked individual differences in urinary C excretion. (2) The C level in 24-h urine after C loading did not differ between the two orally administered C forms (AsA and DAsA). (3) C excretion between 0 and 3 h after C loading was significantly higher (p<0.05) for the DAsA group, while those between 3 and 6, 6 and 9, 9 and 12, and 12 and 24 h after C loading were significantly higher (p<0.05 or p<0.01) for the AsA group. (4) The blood C concentration and the increase in C 1 h after C loading were significantly higher (p<0.05 and p<0.01, respectively) in the DAsA than in the AsA group. (5) Evaluation of the association between C metabolism and the single nucleotide polymorphisms of glutathione S-transferase P (GSTP) 1-1 showed a lower urinary C excretion and a significantly lower C level in 24-h urine (p<0.05) after AsA loading, and a significantly lower urinary C excretion between 0 and 3 h after DAsA loading (p<0.05) for the GA heterozygotes than for the AA homozygotes. Considering the activity of C as DAsA in humans, based on urinary and blood C levels after a single loading of C, the utilization of DAsA is equivalent to that of AsA, although the metabolic turnover time is different. The involvement of polymorphisms in the xenobiotic metabolizing enzyme, GSTP1-1, in C metabolism, particularly urinary C excretion, was also clarified. This demonstrates the necessity of considering gene polymorphisms in determining individual C requirements. An abstract of this paper was reported by the Vitamin C Research Committee (Ochanomizu University) in 2007.

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Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The aim of this study was to clarify whether grape seed proanthocyanidins extracts (GSPE) are therapeutic agents against DPN. In this study, we used streptozocin (STZ) to induce diabetic rats. GSPEs (250 mg/kg body weight/d) were administrated to diabetic rats for 24 wk. Motor nerve conductive velocity (MNCV) and mechanical hyperalgesia were determined in the rats. Serum glucose, glycated hemoglobin, advanced glycation end products (AGEs), and tissue malondialdehyde (MDA) and superoxide dismutase (SOD) were determined. Light and electron microscopy were used to observe the changes of nerval ultrastructure.GSPE significantly increased the MNCV, mechanical hyperalgesia and SOD of diabetic rats (p<0.05) and reduced the AGEs and MDA of diabetic rats (p<0.05). After being treated by GSPE, the severe segmental demyelination was decreased and Schwann cells were improved. In conclusion, GSPE plays an important role against DPN. With the decreasing of AGEs and MDA, it can ameliorate oxidation-associated nerval damage. This study may provide a new recognition of natural medicine for the treatment of DPN.

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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, α-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), α-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 α-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the α-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 α-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 α-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.

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The induction of Parkinson's disease (PD) in senescence-accelerated mice (SAMP8) by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the effects of dimethylsulfoniopropionate (DMSP) on induced PD model mice of SAMP8 were investigated for 5 wk. After many trials, the tail suspension test determining the PD symptoms indicated that an appropriate amount of MPTP clearly raises the SAMP8 mice to the PD-model mice. Moreover, DMSP administration to the PD-SAM model mice proved to completely reduce the PD symptoms in the mice and to accumulate large amounts of norepinephrine, dopamine and dioxyphenylacetate in the mouse brains without cerebellums. These results suggest that catecholamines accumulated in large quantities by the supplementation of DMSP to the double-diseased mice, PD-SAMP8 model mice, completely ameliorated the PD symptoms in these model mice.

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