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Featured researches published by Yoko Idota.


Biological & Pharmaceutical Bulletin | 2016

Cholesterol-Lowering Effect of Calcium Alginate in Rats

Yoko Idota; Yumi Kogure; Takako Kato; Mana Ogawa; Shoko Kobayashi; Chihaya Kakinuma; Kentaro Yano; Hiroshi Arakawa; Chihiro Miyajima; Fumiyoshi Kasahara; Takuo Ogihara

We examined whether calcium alginate (Ca-Alg) reduces blood cholesterol levels in rats fed a high-cholesterol diet. First, we examined taurocholate adsorption in vitro by various types of sodium alginate (Na-Alg). High molecular-weight, guluronic acid-rich Na-Alg showed the greatest adsorption of taurocholate, and therefore the corresponding Ca-Alg was chosen for the in vivo study. Rats were fed a high-cholesterol diet or a Ca-Alg-containing diet for 2 weeks. Body weight and diet intake were measured, and the general condition of the animals was monitored during this period. After 14 d, the plasma concentration of cholesterol, portal plasma concentration of bile acid, and bile acid in feces were measured. The plasma concentration of cholesterol was significantly reduced in rats fed a 2% Ca-Alg-containing diet. Furthermore, the portal concentration of bile acid was significantly lowered in the 2% Ca-Alg group. A tendency for a Ca-Alg concentration-dependent increase in fecal excretion of bile acid was also seen, although it was not statistically significant. While several changes in biochemical parameters and histopathological findings were observed, all the values remained within the physiological range. These results indicate that Ca-Alg is effective in reducing plasma cholesterol. A possible mechanism would be enhanced fecal excretion of bile acid due to reduced intestinal reabsorption, which in turn might stimulate bile acid synthesis from cholesterol in the liver, leading to a decrease in plasma cholesterol.


Biological & Pharmaceutical Bulletin | 2017

Preliminary Evaluation of Three-Dimensional Primary Human Hepatocyte Culture System for Assay of Drug-Metabolizing Enzyme-Inducing Potential

Hiroshi Arakawa; Hiroki Kamioka; Tomoko Jomura; Satoshi Koyama; Yoko Idota; Kentaro Yano; Hajime Kojima; Takuo Ogihara

Drug-induced liver injury (DILI) is a common reason for withdrawal of candidate drugs from clinical trials, or of approved drugs from the market. DILI may be induced not only by intact parental drugs, but also by metabolites or intermediates, and therefore should be evaluated in the enzyme-induced state. Here, we present a protocol for assay of drug-metabolizing enzyme-inducing potential using three-dimensional (3D) primary cultures of human hepatocytes (hepatocyte spheroids). Hepatocyte spheroids could be used up to 21 d after seeding (pre-culture for 7 d and exposure to inducer for up to 14 d), based on preliminary evaluation of basal activities of CYP subtypes and mRNA expression of the corresponding transcription factor and xenobiotic receptors (aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR) and pregnane X receptor (PXR)). After 2 d exposure of hepatocyte spheroids to omeprazole, phenobarbital and rifampicin (typical inducers of CYP1A2, 2B6 and 3A4, respectively), CYP1A2, 2B6 and 3A4 mRNA expression levels were significantly increased. The mRNA induction of CYP2B6 remained reasonably stable between days 2 and 14 of exposure to inducers, while induction of both CYP1A2 and 3A4 continued to increase up to day 14. These enzyme activities were all significantly increased compared with the control until day 14. Our findings indicate that our 3D hepatocyte spheroids system would be especially suitable for long-term testing of enzyme activity induction by drugs, either to predict or to verify clinical events.


Biological & Pharmaceutical Bulletin | 2018

Mechanism of Suppression of Blood Glucose Level by Calcium Alginate in Rats

Yoko Idota; Takako Kato; Kazuyo Shiragami; Mariko Koike; Akari Yokoyama; Hitoe Takahashi; Kentaro Yano; Takuo Ogihara

Calcium alginate (Ca-Alg) is known to suppress the postprandial increase of blood glucose, and therefore may be helpful for preventing lifestyle-related diseases such as diabetes. In this work, we examined the mechanism of this effect. As α-amylase activity and α-glucosidase activity are involved in the digestion of starch, we examined the in vitro inhibitory effect of Ca-Alg on these enzymes. Ca-Alg showed little inhibition of α-amylase, but markedly inhibited α-glucosidase activity. The direct binding affinity of glucose for Ca-Alg was low. Also, Ca-Alg had essentially no effect on the membrane permeability of glucose. Therefore, we considered that the suppression of blood glucose by Ca-Alg is predominantly due to a decrease in the efficiency of starch digestion as a result of inhibition of α-glucosidase, possibly due to increased viscosity of the gastrointestinal contents. Next, we investigated the optimum amount in the diet and the optimum particle size of Ca-Alg for suppressing postprandial blood glucose level in rats orally administered a diet containing starch with various amounts and particle sizes of Ca-Alg. We found that 5% by weight of 270-mesh-pass Ca-Alg was most effective.


Journal of Toxicological Sciences | 2017

Utility of human hepatocyte spheroids without feeder cells for evaluation of hepatotoxicity

Takuo Ogihara; Hiroshi Arakawa; Tomoko Jomura; Yoko Idota; Satoshi Koyama; Kentaro Yano; Hajime Kojima

We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured. The cumulative AST, LDH or γ-GTP leakages from Sph(f-) were similar to or greater than those from Sph(f+) for all drugs tested, although ALT leakages showed no consistent difference between Sph(f+) and Sph(f-). In the case of Sph(f-), significant correlations among all the toxicity markers except for γ-GTP were observed. As regards the drug concentrations causing 1.2-fold elevation of enzyme leakage (F1.2), no consistent difference between Sph(f+) and Sph(f-) was found, although several F1.2 values were undetermined, especially in Sph(f+). The IC50 of albumin secretion and F1.2 of AST leakage from Sph(f-) were equal to or lower than those of Sph(f+) for all the tested drugs. These results indicate that feeder cells might contribute to resistance to hepatotoxicity, suggesting DILI could be evaluated more accurately by using Sph(f-). We suggest that long-term exposure of Sph(f-) to drugs might be a versatile method to predict and reproduce clinical chronic toxicity, especially in response to repeated drug administration.


Biological & Pharmaceutical Bulletin | 2018

Randomized, Double-Blind, Crossover Clinical Trial of the Effect of Calcium Alginate in Noodles on Postprandial Blood Glucose Level

Takako Kato; Yoko Idota; Kazuyo Shiragami; Mariko Koike; Fumiya Nishibori; Miho Tomokane; Takahiro Seki; Keiko Itabashi; Keiko Hakoda; Hitoe Takahashi; Kentaro Yano; Tsutomu Kobayashi; Nobuyuki Obara; Takuo Ogihara

We conducted a prospective, randomized, double-blind, 3-group, 3-phase crossover study to evaluate the effect of calcium alginate (Ca-Alg) on the postprandial increase of blood glucose in 15 healthy adult subjects who were given udon noodles containing or not containing Ca-Alg (5 or 8%). The value of ΔCmax (difference between the maximum (Cmax) and pre-feeding (C0) blood glucose levels) was significantly reduced in both Ca-Alg groups, and the area under the blood glucose level-time curve over 120 min (ΔAUC, with C0 as the baseline) was also significantly reduced. Thus, supplementation of noodles with Ca-Alg significantly suppressed both the peak postprandial blood glucose level and the total amount of glucose absorption. Blood calcium (Ca) concentration was significantly increased at 120 min after ingestion, but there was no marked change of other parameter values. A questionnaire indicated that addition of Ca-Alg did not affect the acceptability of the noodles. These results indicate that Ca-Alg might a useful food additive for helping to prevent lifestyle-related diseases without adversely affecting individual eating habits.


Journal of Pharmaceutical Sciences | 2016

Interaction of Peptide Transporter 1 With d-Glucose and l-Glutamic Acid; Possible Involvement of Taste Receptors

Hiroshi Arakawa; Taichi Ohmachi; Kiko Ichiba; Hiroki Kamioka; Takumi Tomono; Masahiko Kanagawa; Yoko Idota; Yasuko Hatano; Kentaro Yano; Kaori Morimoto; Takuo Ogihara

We investigated the influence of sweet and umami (savory) tastants on the intestinal absorption of cephalexin (CEX), a substrate of peptide transporter 1 (PEPT1, SLC15A1) in rats. After oral administration of glucose or mannitol to rats, CEX was administered together with a second dose of glucose or mannitol. Western blot analysis indicated that expression of PEPT1 in rat jejunum membrane was decreased by glucose, compared to mannitol. Furthermore, the maximum plasma concentration (Cmax) of orally administered CEX was reduced by glucose compared to mannitol. The effect of glucose was diminished by nifedipine, a L-type Ca(2+) channel blocker. We also found that Cmax of orally administered CEX was reduced by treatment with L-glutamic acid, compared to D-glutamic acid. Thus, excessive intake of glucose and L-glutamic acid may impair oral absorption of PEPT1 substrates.


Biopharmaceutics & Drug Disposition | 2016

Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide‐mimetic drugs

Hiroshi Arakawa; Hiroki Kamioka; Masahiko Kanagawa; Yasuko Hatano; Yoko Idota; Kentaro Yano; Kaori Morimoto; Takuo Ogihara

The study investigated whether quinolone antibiotics inhibit the PEPT1‐mediated uptake of its substrates. Among the quinolones examined, lomefloxacin, moxifloxacin (MFLX) and purlifloxacin significantly inhibited the uptake of PEPT1 substrate phenylalanine‐Ψ(CN‐S)‐alanine (Phe‐Ψ‐Ala) in HeLa/PEPT1 cells to 31.6 ± 1.3%, 27.6 ± 2.9%, 36.8 ± 2.2% and 32.6 ± 1.4%, respectively. Further examination showed that MFLX was an uncompetitive inhibitor, with an IC50 value of 4.29 ± 1.29 mm. In addition, MFLX significantly decreased the cephalexin and valacyclovir uptake in HeLa/PEPT1 cells. In an in vivo study in rats, the maximum plasma concentration (Cmax) of orally administered Phe‐Ψ‐Ala was significantly decreased in the presence of MFLX (171 ± 1 ng/ml) compared with that in its absence (244 ± 9 ng/ml). The area under the concentration–time curve (AUC) of orally administered Phe‐Ψ‐Ala in the presence of MFLX (338 ± 50 ng/ml · h) tended to decrease compared with that in its absence (399 ± 75 ng/ml · h). The oral bioavailability of Phe‐Ψ‐Ala in the presence and absence of MFLX was 41.7 ± 6.2% and 49.2 ± 9.2%, respectively. The results indicate that administration of quinolone antibiotics concomitantly with PEPT1 substrate drugs may potentially result in drug–drug interaction. Copyright


Drug Metabolism and Pharmacokinetics | 2013

The Role of Inter-segmental Differences in P-glycoprotein Expression and Activity along the Rat Small Intestine in Causing the Double-peak Phenomenon of Substrate Plasma Concentration

Sho Wada; Takashi Kano; Suzune Mita; Yoko Idota; Kaori Morimoto; Fumiyoshi Yamashita; Takuo Ogihara


Drug Metabolism and Pharmacokinetics | 2014

Role of P-Glycoprotein in Regulating Cilnidipine Distribution to Intact and Ischemic Brain

Kentaro Yano; Shinobu Takimoto; Toshimitsu Motegi; Takumi Tomono; Mihoko Hagiwara; Yoko Idota; Kaori Morimoto; Akira Takahara; Takuo Ogihara


Biological & Pharmaceutical Bulletin | 2013

Alginate Enhances Excretion and Reduces Absorption of Strontium and Cesium in Rats

Yoko Idota; Hitomi Harada; Takumi Tomono; Kaori Morimoto; Shoko Kobayashi; Chihaya Kakinuma; Chihiro Miyajima; Fumiyoshi Kasahara; Takuo Ogihara

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Takuo Ogihara

Takasaki University of Health and Welfare

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Kentaro Yano

Takasaki University of Health and Welfare

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Hiroshi Arakawa

Takasaki University of Health and Welfare

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Kaori Morimoto

Takasaki University of Health and Welfare

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Hiroki Kamioka

Takasaki University of Health and Welfare

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Takako Kato

Takasaki University of Health and Welfare

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Takumi Tomono

Takasaki University of Health and Welfare

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Chihiro Miyajima

Mochida Pharmaceutical Co.

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Masahiko Kanagawa

Takasaki University of Health and Welfare

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