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Serum ceruloplasmin (CP), a marker relevant to copper metabolism, is one of famous inflammation markers with a reduction in Wilson’s disease, whereas serum ferritin is a marker relevant to iron metabolism. Recently, ferritin is pointed out to be related with oxidative stress. However, there is still no population research which showed the relation of CP and ferritin. Therefore, we investigated the relationship between CP and ferritin including oxidative stress biomarkers among healthy Japanese (n = 389). We measured serum CP, ferritin, Fe, high-sensitivity C-reactive protein (hs-CRP), and urinary oxidative stress biomarkers [H2O2, 8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-isoprostane] and so on. Subjects showed that age; 41.7 ± 10.0 (year), CP; 31.9 ± 6.8 (mg/dl), ferritin; 123.5 ± 121.0 (ng/ml), hs-CRP; 0.89 ± 2.53 (mg/l), 8-OHdG; 10.2 ± 4.4 [ng/mg creatinine (Cre)] and H2O2; 6.5 ± 10.9 (µM/g Cre), (All data mentioned above were expressed as mean ± SD). CP was significantly and positively correlated with hs-CRP and inversely correlated with ferritin, Fe and 8-OHdG. By a multiple logistic regression analysis, odds ratio of CP according to quartiles of hs-CRP was 4.86, and according to quartiles of 8-OHdG was 0.39 after adjusting for age and other confounding factors. In conclusion, our findings suggest that CP was an antioxidative biomarker which controls oxidative stress, whereas ferritin was a marker which may participate in the generation of oxidative stress.

Although cigarette smoking is known to be an important risk factor for renal disease, the mechanism by which smoking induces progressive renal disease in a healthy population has not been established. We hypothesized that oxidative stress (measured as 8-iso-prostaglandin F(2α), 8-iso-PGF2a), inflammation (highly sensitive C-reactive protein (CRP), hs-CRP) and nitric oxide may be associated with an alteration in the estimated glomerular filtration rate (eGFR) and proteinuria in otherwise healthy smokers. A total of 649 eligible subjects were classified according to their smoking status. Plasma NOx was measured using ozone-based chemiluminescence, urinary 8-iso-PGF2a was measured using enzyme immunoassay and serum hs-CRP was measured using a latex aggregation nephelometry method. The levels of 8-iso-PGF2a and hs-CRP increased in current smokers (P=0.001 and P=0.029, respectively), although there was not an increase in the NOx level. The prevalence of a high eGFR increased in light smokers (odds ratio (OR) 1.15 (95% confidence interval (CI), 0.61-2.17)) and heavy smokers (OR 2.33 (95% CI, 1.06-5.10)) when compared with non- and past smokers (P for trend=0.024). The multivariable-adjusted mean values of the eGFR in current smokers, reported from the lowest to the highest quintiles of hs-CRP levels, were 82.1, 85.1, 86.4 and 88.5 ml per min per 1.73 m² (P for trend=0.027). The mean values of proteinuria were 28.6, 34.6, 37.2 and 39.5 mg g⁻¹ creatinine (P for trend=0.003). The correlation coefficient between hs-CRP and eGFR was increased significantly (P=0.03) across non- (r=0.03), past (r=-0.17), light (r=0.13) and heavy smokers (r=0.31). In conclusion, cigarette smoking is a risk factor for renal function alteration in healthy smokers and is characterized by a high eGFR and a high urinary protein associated with an increase in the hs-CRP. This finding suggests that hs-CRP may help mediate the alteration of renal function in smokers.

The urinary concentrations of 8-isoprostane and 8-hydroxy-2’-deoxyguanosine (8-OHdG), which are biomarkers of oxidative stress, were measured in 677 Japanese people without any diseases, and their correlations with lifestyle facotrs, lifestyle-related blood biochemical parameters, and dietary intake of antioxidative vitamins were investigated. The mean urinary concentration of 8-isoprostane and 8-OHdG was 0.58 ng/mg creatinine and 8.43 ng/mg creatinine, respectively. Mean urinary 8-isoprostane was significantly different in terms of age, gender, smoking and alcohol consumption but not different in terms of body mass index (BMI) and exercise. By multiple regression analysis, urinary 8-isoprostane was significantly influenced by smoking and age. On the other hand, mean urinary 8-OHdG showed differences only by age group. Multiple regression analysis revealed that urinary 8-OHdG was significantly influenced by age, smoking, body weight, levels of high-sensitivity C-reactive protein (Hs-CRP) and low density lipoprotein-cholesterol in females, although it was significantly influenced by body weight in males. The present study shows that urinary 8-isoprostane is associated with lipid peroxidation related-lifestyles such as smoking, and urinary 8-OHdG is associated with arteriosclerosis related-factors such as Hs-CRP. Our findings suggest that 8-isoprostane and 8-OHdG appear to be prospective biomarkers for early prediction of lifestyle related-disease risk at the population level.

To examine the relation between lifestyle factors and oxidative stress biomarkers, this study analysed plasma 3-nitrotyrosine (3-NT), urinary 8-isoprostane and 8-hydroxy-2'- deoxyguanosine (8-OHdG) of 323 healthy Japanese without any disease. Plasma 3-NT was significantly increased by excessive exercise (p=0.010), but it was not significantly different in terms of sex, age (40,==40), BMI (18.5, 18.5-24.9,==25.0), smoking (non-smokers, smokers) and alcohol drinking per week (non-drinkers,10 units,==10 units). Urinary 8-isoprostane was significantly associated with alcohol drinking (p0.01) and sex (p0.01), although it had no significant relevance to age and exercise. Moreover, urinary 8-OHdG was positively associated with age (p0.05) and negatively associated with BMI (p0.05) and fasting insulin (p0.001). However, it was not related with sex, smoking, alcohol drinking and exercise. In conclusion, the present results suggest that 3-NT, 8-isoprostane and 8-OHdG seem to be useful biomarkers for early prediction of lifestyle-related disease risk at the population level.

Retinol, α-tocopherol, and γ-tocopherol are fat-soluble vitamins acting as antioxidants via the prevention of lipid oxidation. Little is known about circulatory levels in healthy individuals. The present cross-sectional study aimed at elucidating the relationship between these antioxidants and clinical biomarkers in 206 male (median age 41 years, range 23–67) employees from companies located in the Okayama Prefecture, Japan. Subjects younger than 40 years (n = 94) showed a positive association of the frequency of alcohol consumption with the circulating retinol (β = 0.344, p = 0.001) and γ-tocopherol levels (β = 0.219, p = 0.041), and an inverse association of fast insulin with serum retinol (β = −0.301, p = 0.009). In participants older than 40 years (n = 112) we found that an inverse association of HOMA-R with serum retinol (β = −0.262, p = 0.021), α-tocopherol (β = −0.236, p = 0.035), and γ-tocopherol levels (β = −0.224, p = 0.052), and cigarette smoking was inversely associated with the levels of serum α-tocopherol (β = −0.286, p = 0.008) and γ-tocopherol (β = −0.229, p = 0.040). We further found negative relationships between serum ferritin and the retinol (β = −0.211, p = 0.032) and α-tocopherol levels (β = −0.223, p = 0.022) in men over 40 years of age. The present study suggests that the circulatory levels of antioxidant vitamins may modulate the action of insulin and that higher levels of iron might decrease the levels of antioxidant vitamins in the blood.

Herein the structures and peel contents of anthocyanins from 26 kinds of 11 species of edible legumes are reported. In the scarlet bean (Phaseolus coccineus) delphinidin 3-glucoside was found, and in the sultanipya bean (Phaseolus lunatus) peonidin 3-glucoside and peonidin 3-rutinoside. In the black turtle bean (Phaseolus vulgaris) delphinidin 3-glucoside, petunin, petunidin 3-glucoside, malvin, and malvidin 3-glucoside were assayed. We also succeeded in the isolation and structural analysis of an anthocyanin from the adzuki bean (Vigna angularis) as a cyanin for the first time. The anthocyanin contents of black colored seed coats were very high at around 0.2% for peel, and these beans may therefore be expected to find applications as food colorants. In individual Vigna species from different districts, consistency in the variety of anthocyanins was observed.

The usefulness of urinary hydrogen peroxide (H(2)O(2)) as an oxidative stress biomarker was evaluated in 766 healthy Japanese. The mean level of urinary concentrations of H(2)O(2) was 5.66 ± 8.27 μmol/g creatinine, and was significantly higher in females than in males. Significant correlations of H(2)O(2) were observed with age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), insulin, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and exercise habit in females. In both sexes, H(2)O(2) showed a significant correlation with 8-OHdG. By a multiple logistic regression analysis, urinary H(2)O(2) was positively associated with urinary 8-OHdG and TC and was inversely associated with insulin. By stratification of sex and age, the association of urinary H(2)O(2) with TC was positive in both sexes under 50 years old and was inverse in males over 50 years old, and that with insulin was inverse in males over 50 years old and in females under 50 years old. Moreover, by stratification of sex and age, a positive association of H(2)O(2) with exercise and an inverse association of H(2)O(2) with alcohol consumption became clear in males under 50 years old, although there were no significant odds for H(2)O(2) after adjustment for covariates. In conclusion, the present results suggest that urinary H(2)O(2) is a useful biomarker for oxidative stress, showing an association with 8-OHdG, TC, and insulin independently.

Several acyclic analogues of guanosine, 2′-deoxy-2′, 3′-secoguanosine(3), 3′-deoxy-2′, 3′-secoguanosine (4), and 2′-, 3′-dideoxy-2′-, 3′-secoguanosine were synthesized from guanosine. In addition, the 3′-, 5′-cyclic phosphate (21) and 3′-, 5′-cyclic methylphosphonates (22a, b) of 3 were also prepared. At concentrations up to 300 μM none of these compounds had significant antiherpetic activity in antiviral assays in vitro.

The effects of the simultaneous administration of selenium and mercurials on mercury distribution, and the binding properties of mercurials with the components in the soluble fraction of tissues in 140 male Wister rats were studied.The concentrations of mercury, in both liver and kidney, 120 hours after the simultaneous administration of methylmercuric chloride and sodium selenite were significantly higher than those for groups administered only with methylmercuric chloride. Furthermore, the amount of mercury in the kidney was higher than that in the liver.The concentrations of selenium in the livers and kidneys of the group administered with sodium selenite alone, decreased rapidly in comparison with the group administered with sodium selenite and mercury compounds simultaneously.The soluble portion were fractionated by the gel filtration method on Sephadex G-75. Mercury, both in the liver and kidney of rats administered only with mercuric chloride, was found in the low molecular weight fraction 17-18 and the high molecular weight fraction 32-33, although the fraction 32-33 might correspond to metallothionein. In addition, the amount of mercury bound to the low molecular weight fraction in the kidney showed a tendency to increase gradually with time. On the other hand, the gel filtration patterns of the liver and kidney for the groups administered with methylmercuric chloride and sodium selenite was obviously different from that for mercuric chloride. The groups administered with methylmercuric chloride and sodium selenite were mainly bound to the low molecular weight fraction 17-18 and the high molecular weight fraction 55, although the group administered with mercuric chloride was confined within the high molecular weight fraction 32-33.No obvious discrepancy was seen in the amount of methylmercury between the group administered simultaneously with methylmercury and sodium selenite and that administered with methylmercuric chloride alone.The results indicate that the administration of selenium is identified as the compound responsible for the selective binding and accumulation of mercury in the kidney and liver of rats.