Using a hypoxanthine-xanthine oxidase (HX-XOD) reaction system, the effect of vitamin E (VE) on oxidative membrane injury was studied by the impedance method. Both VE-sufficient and VE-deficient erythrocytes showed an elevation of low frequency permittivity in the early phase of reaction. In the later phase of reaction, VE-sufficient erythrocytes showed a sustained elevation in permittivity, while VE-deficient erythrocytes showed a decrease in permittivity with time. These changes consisted with the process of hemolysis in the HX-XOD system. The similarity of early phase change between VE-sufficient and VE-deficient erythrocytes indicates that the HX-XOD system exerted a similar effect on both erythrocytes in the early phase. The difference in changes of later phase between the two types of erythrocytes suggests that VE suppressed the reduction in permittivity. When the results were analyzed by the Pauly-Schwan's theory based on the assumption that erythrocytes are spherical, the product of VE-deficient or VE-sufficient erythrocyte size (R) and membrane capacity (Cm) showed a change similar to that in permittivity.
Metabolism of orally administered ergosterol (Erg) and 7-dehydrocholesterol (7-DHC) in rats and their vitamin D biological activity were investigated. Most of orally administered Erg and 7-DHC were excreted in feces and the remaining sterols were absorbed through intestine. The absorbed sterols were not transported in skin as the intact forms but metabolized into brassicasterol and cholesterol, respectively, within 25h. Neither increment of intestinal calcium absorption nor plasma calcium concentrations were observed by oral administration of Erg and 7-DHC to vitamin D-deficient rats. Therefore, we have concluded that orally administered Erg and 7-DHC have no vitamin D biological activity.
AO-128 is a potent and structurally novel inhibitor of the intestinal disaccharidases, such as maltase and sucrase. Genetically obese-diabetic mice, KKAy, were used to examine the acute or long-term effectiveness of this compound. AO-128 decreased a postprandial rise in blood glucose after sucrose solution loading dose-dependently; the ED50 to reduce a delta increment of blood glucose by 50% was 0.22mg/kg. The intestinal sucrase and maltase activities were suppressed to 7 and 48% of the control levels, respectively, at a dose of 0.21mg/kg. Four-week-old female KKAy mice were kept on a laboratory diet containing 10 or 50 ppm of AO-128 for 12 weeks. The high dose of AO-128 reduced food intake and body weight gain throughout the experimental period. On the other hand, the low dose reduced body weight gain for the first 4 weeks without any effect on food intake. Development of the hyperglycemia and hyperinsulinemia characteristic of KKAy mice was moderately prevented by the low dose, and completely by the high dose. Hypertriglyceridemia tended to be suppressed by the AO-128 treatment. The high dose decreased the hemoglobin A1 level and parametrial adipose tissue weight. Hepatomegaly and fatty liver were ameliorated by AO-128 dose-dependently. Nephropathy was ameliorated by the high dose. These findings indicate that AO-128 may be useful for treating human obesity and diabetes.
The activity of dihydropyrimidine dehydrogenase, which is the rate-limiting enzyme in the catabolism of pyrimidine, in livers of 5-day-old rats increased 48h after glucocorticoid injection. The increase in the activity of dihydropyrimidine dehydrogenase by glucocorticoid ad-ministration and by aging did not decrease the uridine, uracil and ΣUMP (the sum of acid-soluble uracil 5'-nucleotides) pool in liver. The increase of liver uracil by a uridine diet not increase dihydropyrimidine dehy-drogenase activity. The increase of liver uracil did not increase dihydro-pyrimidine dehydrogenase activity. However, dihydropyrimidine dehy-drogenase activity which increased after glucocorticoid treatment in-creased the pyrimidine-degradation rate in rat livers and hepatocytes. Pyrimidine catabolism pathway in liver may play an important role in degradation of dietary pyrimidines and pyrimidines which are adminis-tered in the form of medicines as 5-fluorouridine.
A feeding study was conducted to elucidate the role of two different fibers, cellulose and agar, and mixture of the two fibers on fecal mucinase activity in rats. Fiber-free basal control diet was mixed with either 15% cellulose, 15% agar or half cellulose (7.5%) and half agar (7.5%). These diets were fed for 5 weeks to groups of 6 male Sprague-Dawley rats. Mucinase activity was assayed in fresh rat feces. Body weight gain of rats fed different diet groups did not show significant difference (p>0.05). Specific and total mucinase activity was highest in rats fed fiber-free control diet and 15% agar diet, intermediate in rats fed the fiber mixture group and lowest in rats fed 15% cellulose diet. The differences among the three groups were significant (p<0.05).
Accelerated senescence prone mice and resistant mice (SAM-P/1 and SAM-R/1) were fed 10% casein diet or that supplemented with 2.5% methionine (Met) diet for 4 weeks. Erythrocytes withdrawn from animals of each group were separated by density gradient centrifugation into four fractions of different cell density, that is, different age of erythrocytes, and were analyzed for the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and the level ofoxidized protein. Excess Met decreased the specific activity of GSH-Px in each fraction and the whole population of erythrocytes in SAM-P/1 but not in SAM-R/1. The changes in SOD activities were least significant among the erythrocyte fractions of every dietary group. The oxidized protein level in cell lysate increased with the increase of cell density in both strains of animals. These results were interpreted as indicating that excess Met had a positive effect on the erythrocytes senescence, and suggested that the activity of GSH-Px may be a useful enzymatic marker for the age of erythrocytes.
The effects of bovine bile (50-400mg⋅kg-1 BW) on plasmaethanol levels in male rats (6-8 weeks old) were examined. Bovine bile decreased and delayed the peak of plasma ethanol concentration: a dose response to bovine bile was observed in the concentration and time to maximum concentration of ethanol but no change in disappearance rate. These phenomena were observed in two conditions: 1) oral administration of bovine bile before oral intubation of ethanol (1.0g⋅kg-1 BW) and 2) simultaneous oral administration of bovine bile and ethanol. Similar responses were obtained in taurocholic acid. No changes in hepatic alcohol and aldehyde (low Km and high Km) dehydrogenase activities were observed. The remaining rate of ethanol in stomach was significantly higher with administration of bovine bile. A negative correlation between the maximum ethanol concentration and the remaining rate of ethanol in stomach was found. The intestinal absorption rate of ethanol decreased significantly in the presence of bovine bile. These results suggest that the delay of the gastric emptying and/or the decrease of the intestinal absorption rate of ethanol are major mechanisms for the decreasing and delaying effects on plasma ethanol by bovine bile. The present paper also suggests that bile acids such as taurocholic acid may participate in the lowering and delaying actions on the peak of plasma ethanol concentration by bovine bile.
An experiment was conducted to clarify the combined effect of simultaneous administrations of insulin (Ins, 4 units/100g body weight/day) and testosterone propionate (TP, 2mg/100g body weight/day) and feeding a high-protein-high-fat (HPHF) diet (50% protein, 36% fat) on corticosterone (CTC, 10mg/100g body weight/day)-induced muscle proteolysis or growth retardation in young growing male rats. After 6 days prefeeding of the standard (STD) diet (25% protein, 9% fat) and the HPHF diet, hormones were injected subcutaneously for 4 days. Urine was collected every day for the 4-day experimental period to measure Nτ-methylhistidine excretions. The results were as follows. The growth was markedly inhibited and muscle proteolysis was accelerated by the CTC treatment. Feeding HPHF diet reduced CTC-induced muscle proteolysis and the growth retardation, and administrations of Ins and TP further reduced the proteolysis and the growth retardation. From these results, it is thought that administrations of Ins and TP and feeding HPHF diet minimize the muscle protein wasting by counteracting insulin resistance caused by CTC, and masking the CTC receptor.
Hypotaurine increased in some tissues, especially in muscle, and urine of rats fed methionine excess diet. The significant depression of the body weight and food intake of rats caused by excess methionine was remarkably alleviated as previous reports and hypotaurine content in muscle and urine increased further by supplement with glycine to the excess methionine diet.
The analysis of respiratory hydrogen and methane was estimated as a useful index of intestinal fermentation of undigestible carbohydrate. A simultaneous and precious analysis of these gases as well as carbon dioxide was studied. A gas-impermeable multi-laminated film bag metalized by aluminum vapor was fitted to use as a storage bag; its impermeability was verified by measuring the residual rate of hydrogen after 3 months' storage. Hydrogen, methane and carbon dioxide of the breath gas even at 1ppm could be determined simultaneously by using a gas-solid chromatography installed with a photoionization detector and active carbon column. To observe the genesis of hydrogen and methane after carbohydrate ingestion, pectin, a typical water-soluble dietary fiber, was fed to healthy volunteers. Increasing excretion of pulmonary hydrogen or methane showed the sign of intestinal fermentation as the results of carbohydrate malabsorption.