Kiyoshi Ebihara

Lack of an Inducible Effect of Dietary Soy Isoflavones on the mRNA Abundance of Hepatic Cytochrome P-450 Isozymes in Rats

Modulation of the activity and content of cytochrome P-450 (CYP) in hepatic microsomes may be important to human health since these enzymes activate and inactivate a wide range of xenobiotics and food components. Regulation of the inducibility of most CYPs involves transcriptional regulation and post-transcriptional mRNA stabilization. We examined in the present study the effect of dietary soy isoflavone (0–300 mg of isoflavone/kg of diet) on the mRNA abundance of rat hepatic CYP1A1, CYP1A2, CYP2B1/2, CYP2C11, CYP2E1, CYP3A1, CYP3A2 and CYP4A1 by quantitative competitive RT-PCR and real-time monitored RT-PCR. A fermented soy extract containing 155 mg/g of genistein, 127 mg/g of daidzein, and other minor isoflavones was used as the isoflavone source. The dietary soy isoflavone had no affect on the hepatic mRNA abundance of these CYPs. The results by both methods were well matched and indicate that the dietary soy isoflavone did not cause the induction of CYPs by transcriptional step-up regulation or post-transcriptional mRNA stabilization.

Dietary Soy Isoflavone–Aglycone Lowers Food Intake in Female Rats With and Without Ovariectomy

Objective: Estrogens downregulate eating behavior, and soy isoflavones are known to be estrogenic agents. We aimed to examine whether the estrogenic property of soy isoflavones can affect food intake and body weight.

Increase of bile acids synthesis and excretion caused by taurine administration prevents the ovariectomy-induced increase in cholesterol concentrations in the serum low-density lipoprotein fraction of Wistar rats

We examined the effect of dietary taurine on the concentrations of serum cholesterol and apolipoprotein in lipoprotein fractions of Six-month-old ovariectomized, which were used as a model of hypercholesterolemia in postmenopausal woman, or sham operated rats. Taurine significantly reduced the serum total and low-density lipoprotein cholesterol concentrations only in the ovariectomized rats. In contrast, taurine significantly lowered the serum apolipoprotein B concentration and serum very low-density lipoprotein-apolipoprotein E concentration only in the sham operated rats. The serum total and high density lipoprotein-apolipoprotein E concentrations were significantly lower in the rats fed taurine than in those fed the control diet regardless of whether they had undergone ovariectomy. The esterified cholesterol level in the liver was significantly lower and the level of hepatic cholesterol 7 alpha-hydroxylase activity was significantly higher in the rats fed taurine than in those fed the control diet. The total bile acids concentration in the feces and intestinal contents of rats fed taurine were significantly higher than those in rats fed the control diet regardless of whether they had undergone ovariectomy. In the sham-rats, taurine accelerated bile acid synthesis and excretion, thereby increasing cholesterol consumption. The increased cholesterol consumption might be compensated by accelerating cholesterol synthesis and/or reducing the synthesis and release of very low-density lipoprotein from the liver. But in the ovariectomized rats, although taurine also accelerated bile acid synthesis and excretion, cholesterol demand might be compensated by excess cholesterol in the blood.

The mechanism of the cholesterol-lowering effect of water-insoluble fish protein in ovariectomised rats

The purpose of the present study was to investigate whether water-insoluble fish protein (IFP) from Alaska pollock (Theragra chalcogramma) prevents hypercholesterolaemia induced by ovarian hormone deficiency. Wistar female rats, aged 6 months, were subjected to sham-operation or ovariectomy, and fed a cholesterol-free diet containing casein or IPF as a protein source for 28 d. Body-weight gain and food intake increased in the ovariectomised rats as compared with the sham-operated rats. Plasma total cholesterol concentration was decreased and faecal bile acid excretion was increased by IFP in the ovariectomised rats, but not in the sham-operated rats. Plasma homocysteine concentration was decreased by IFP in the ovariectomised rats, but not in the sham-operated rats. Liver lipids and liver cholesterol concentrations were increased and cholesterol 7alpha-hydroxylase (CYP7A1) activity was decreased by ovariectomy, but not by diet. Bile acid content and the ratio of cholic acid groups to chenodeoxycholic acid groups in bile were increased by ovariectomy, but decreased by IFP. Bile acid content in the small intestine was increased by IFP in the ovariectomised rats, but not in the sham-operated rats. 3-Hydroxy-3-methylglutaryl-CoA reductase and microsomal TAG transfer protein mRNA levels were decreased by ovariectomy and IFP, whereas LDL-receptor mRNA level was decreased by ovariectomy but unaffected by diet. Thus, the preventive effect of IFP on the ovarian hormone deficiency-associated increase in plasma cholesterol concentration seems to be mediated by accelerated faecal excretion of bile acids, coupled with an increase in the intestinal pool of bile acids.

Comparative effect of water-soluble and -insoluble dietary fiber on bowel function in rats fed a liquid elemental diet

The effect of dietary fibers on the digestive tract mass, diamine oxidase (DAO) activities in the small intestine and plasma and pool of ammonia and organic acids such as acetic, propionic, butyric, lactic and succinic acid in the cecum in rats fed a liquid formula diet was compared. Rats were fed an elemental liquid diet (ED) or ED containing 3g/100 ml of dietary fiber either a mixture of crystal cellulose and carboxymethyl cellulose sodium salt (CC), sugar-beet pectin (BP) or hydrolyzed xyloglucan (HXG) for 14 days. The mass of colon plus rectum was higher in rats fed CC, but not in rats fed BP and HXG than in rats fed ED. Cecal tissue mass was higher in rats fed BP and HXG, but not in rats fed CC, than in rats fed ED. Cecal contents and cecal pH were higher and lower in rats fed CC, BP and HXG than in rats fed ED. DAO activities in the small intestine and plasma were higher in CC than in rats fed ED. Cecal ammonia were lower in rats fed CC, BP and HXG than in rats fed ED. Production of organic acids was similar between rats fed ED and CC except for acetic acid that was much lower in rats fed CC. Diarrhea and loose feces were also improved in rats fed CC. The results suggest that the addition of a combination of water -soluble and -insoluble dietary fiber to a liquid formula diet would have more beneficial effects on the bowel function than water-soluble dietary fiber alone.

Effect of the particle size of corn bran on the plasma cholesterol concentration, fecal output and cecal fermentation in rats

We studied the effect of the particle size of corn brain (CB) on the plasma cholesterol concentration, fecal output, and cecal fermentation. Rats were fed a fiber-free diet (FF) or FF containing CB (50 g/kg diet) of six different particle sizes (500, 350, 250, 177, 149, 105 μm in diameter) for 21 days. The fecal wet weight and wet weight of cecal content were significantly higher in the rats fed CB than in those fed FF. Liver total lipids, fecal moisture, fecal bile acids excretion and moisture of cecal content were significantly lower in the rats fed CB than in those fed FF. As the particle size decreased, the plasma cholesterol concentration, fecal wet weight, and fecal bulking effect decreased, while the liver cholesterol concentration, cecal wall weight, wet weight of cecal content, and total organic acids, acetic acid and n-butyric acid in the cecal content increased.

Comparison of ferrous and ferric iron bioavailability following rat cecal infusion

Abstract The comparison of ferrous and ferric iron bioavailability following cecal infusion was studied in ileally fistulated rats. Rats were divided into four groups of 10 rats after recovery from surgery. Group 1 (control) was given an iron-adequate diet (45 mg Fe/kg diet) and infused with NaCl solution (150 mM). Group 2 was given an iron-deficient diet (8 mg Fe/kg diet) and infused with NaCl solution. Group 3 and 4 were given an iron-deficient diet and infused with ferrous sulfate [Fe(II)] suspension or ferric sulfate [Fe(III)] solution (800 ppm as Fe, pH 6.8) to provide the same amount of iron as that consumed one day before by the control group. NaCl, Fe(II) and Fe(III) were infused through the fistula at two times (1000h and 1800h) for 28 days. The volume of NaCl infused was about equal to the volume of Fe(II) and Fe(III) suspension or solution infused. Compared with the control group, body mass gain and food intake for Group 3 and 4 did not decrease. However, the hematological indices and total iron contents in the liver and spleen for Group 3 and 4 showed 20 to 30% and 30 to 40% lower, respectively, compared with those of the control group. There was no significant difference between Group 3 and 4 on iron bioavailability. These results suggest that the lower part of the digestive tract plays an important role in iron absorption.

Lowering Effect of an Isoflavone-Rich Fermented Soybean Extract on the Serum Cholesterol Concentrations in Female Rats, with or without Ovariectomy, but Not in Male Rats

We examined the effect of administering an isoflavone-rich fermented soybean extract (FSBE) on the serum cholesterol concentrations in male rats and in intact and ovariectomized (OVX) female rats. Dietary FSBE decreased the serum cholesterol concentrations in intact female and OVX rats, but did not affect the concentrations in male rats. Dietary FSBE increased the hepatic total and esterified cholesterol contents in the intact female rats, but decreased them in the OVX rats. This hypocholesterolemic effect was not a simple estrogenic effect because it has appeared in some reports that estrogen administration decreased serum cholesterol both male and female rats. Dietary FSBE increased the hepatic low-density lipoprotein receptor (LDLR) gene expression in the intact female rats as has previously been reported from many studies, but did not affect that of the OVX rats. Further investigation is needed into the hypocholesterolemic mechanism of FSBE.

Effect of Dietary Soy Isoflavone Aglycones on the Urinary 16α-to-2-Hydroxyestrone Ratio in C3H/HeJ Mice

Estradiol is metabolized through two mutually exclusive pathways. 2-Hydroxyestrone (2-OHE1) is antiestrogenic, while 16α-hydroxyestrone (16α-OHE1) is a potent estrogen. It is suggested that a high urinary 16α-OHE1-to-2-OHE1 rato is a biomarker of increased mammary tumor risk. Mice were fed one of the test diets for 21 days. Indole-3-carbinol (2,500 mg/kg diet) increased the cytochrome P-450 content of hepatic microsomes and liver weight and reduced the urinary 16α-OHE1-to-2-OHE1 ratio in comparison with the respective value in the control mice. Fermented soy extract (100, 200, or 400 mg isoflavonoid/kg diet), genistein (200 mg/kg diet), and daidzein (200 mg/kg diet) each reduced the urinary 16α-OHE1-to-2-OHE1 ratio without increasing the cytochrome P-450 content of hepatic microsomes or liver weight. The combination of genistein and daidzein (100 mg and 100 mg/kg diet) did not have a synergistic effect on the reduction in urinary 16α-OHE1-to-2-OHE1 ratio. These data suggest that the soy isoflavonoid aglycones genistein and daidzein and indole-3-carbinol each exert a cancer-preventive effect by shifting metabolism away from the production of genotoxic metabolites toward the production of inactive metabolites.

Comparison of bioavailability and hemoglobin repletion of ferric and ferrous iron infused into the cecum in anemic rats

The bioavailability of ferrous and ferric iron following cecal infusion was compared by assessing the hemoglobin regeneration method in ileally fistulated anemic rats. Rats were fed an iron-deficient diet (8 mg Fe/kg diet) for 14 days after recovery from surgery. The anemic rats were then divided into three groups of 11 rats. Group 1 (control) was fed an iron-adequate diet (45 mg Fe/kg diet) and infused with NaCl solution (150 mM). Group 2 and 3 were fed an iron-deficient diet and infused with ferrous sulfate [Fe(II)] suspension or ferric sulfate [Fe(III)] solution (800 ppm as Fe, pH 6.8) to provide the same amount of iron as that consumed one day before by the control group. NaCl, Fe(II) and Fe(III) were infused through the fistula as two times (1000h and 1800h) for 14 days. The volume of NaCl infused was about equal to the volume of Fe(II) suspension and Fe(III) solution infused. Hemoglobin regeneration efficiency, hematocrit, plasma iron concentration, transferrin saturation, total iron-binding capacity, iron contents in organs (liver, spleen and kidney), body weight gain and food intake were almost the same among groups. These results suggest that inorganic iron is absorbed from the large intestine and is not influenced by forms of iron, ferrous iron or ferric iron.