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Biomedical subjects

K Shimoi

Publications and source records attributed to K Shimoi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Suppressing effects of S-methyl methanethiosulfonate and diphenyl disulfide on mitomycin C-induced somatic mutation and recombination in Drosophila melanogaster and micronuclei in mice.

S-Methyl methanethiosulfonate (MMTS) and diphenyl disulfide (DPDS) are temporary enzyme-sulfhydryl blocking agents. They are naturally occurring phytoalexin-like and synthetic substances known to be very potent bio-antimutagens in Escherichia coli B/r WP2. In the present paper, the suppressing effects of MMTS on mitomycin C (MMC)-induced mutant wing spots in the somatic mutation and recombination test (SMART) of Drosophila melanogaster, and of MMTS and DPDS on MMC-induced micronucleated peripheral reticulocytes are described. MMTS consistently reduced the numbers of MMC-induced small single, large single and twin spots per wing at a dose of 10-1000 micrograms/vial, in a dose-dependent manner. MMTS reduced the number of twin spots per wing on the spontaneous mutation at the dose of 1000 micrograms/vial. MMTS and DPDS dose-dependently reduced the frequencies of MMC-induced micronucleated peripheral reticulocytes at a dose of 10-40, and 3-100 micrograms/kg, respectively. Our results confirmed that enzyme-sulfhydryl blocking agents, such as MMTS and DPDS, are effective antimutagens in vivo too.

Animals↗
PubMed1997

Gastrointestinal autonomic nerve tumor with giant abscess. A case report and literature review.

We report a gastrointestinal autonomic nerve tumor of the stomach with a giant abscess. The patient had fever and pain and was found to have anemia and an abdominal mass. X-ray and endoscopic examination showed a gastric submucosal tumor with a fistula to the gastric lumen. Partial gastrectomy was performed and no metastasis was found. On gross examination, the excised tumor was seen to be a submucosal solid tumor with a giant abscess. Alpha streptococci and anaerobic gram-negative rods were cultured from the pus of the abscess. The tumor resembled a gastric myogenic tumor composed of spindle cells, partly showing storiform and epithelioids. Tumor cells showed positive staining for vimentin and neuron-specific enolase but were negative for desmin, alpha-smooth muscle actin, and S-100 protein. Ultrastructural examination showed remarkable interdigitation of cytoplasmic processes with neurosecretory granules between the tumor cells. This lesion was similar to previously described gastrointestinal autonomic nerve tumors. Gastrointestinal autonomic nerve tumors are a rare, distinct subtype of gastrointestinal stromal tumors; although several cases of focally necrotic tumors have been reported, there has been only one report of the tumor with an abscess, as in our case.

Abscess↗
PubMed1997

Changes in serum pepsinogen, gastrin, and immunoglobulin G antibody titers in helicobacter pylori-positive gastric ulcer after eradication of infection.

There are no studies of changes in immunoglobulin G (IgG) titers to Helicobacter pylori, serum pepsinogen, and gastrin in patients with H. pylori-positive gastric ulcers. We investigated the effect of therapy for H. pylori-positive gastric ulcer on IgG titers to H. pylori, serum pepsinogen I and II, and gastrin. Thirty-six patients with H. pylori-positive gastric ulcer were treated with lansorazole and antibiotics for 2 weeks. Serum pepsinogen I and II concentrations, serum gastrin, and IgG titers to H. pylori were measured before treatment and then at 4 and 12 weeks after stopping the treatment. The presence or eradication of H. pylori was determined using the rapid urease test and by histologic H. pylori staining. For 19 patients in whom H. pylori had been successfully eradicated, the pepsinogen I/II ratio increased, pepsinogen II levels decreased, and the anti-H. pylori IgG decreased compared with the results from before therapy and with those from 4 and 12 weeks after therapy. Gastrin levels decreased compared with pretreatment results and those from 4 weeks after the end of treatment. In 17 patients in whom the therapy failed to eradicate H. pylori infection, there were no sequential significant changes in the pepsinogen I/II ratio or in the levels of pepsinogen I, pepsinogen II, anti-H. pylori IgG, and gastrin. A decrease in the serum levels of the IgG antibody to H. pylori and gastrin and also an increase in the pepsinogen I/II ratio could be used as predictors for the eradication of H. pylori infection in gastric ulcer.

Aged↗
PubMed1997

Protection by alpha G-rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate.

The protective effect of alpha G-Rutin against ferric nitrilotriacetate (Fe-NTA)-induced renal damage was studied in male ICR mice. Fe-NTA induces renal lipid peroxidation, leading to a high incidence of renal cell carcinoma in rodents. Administration of alpha G-Rutin (50 mumol as rutin/kg) by gastric intubation 30 min after i.p. injection of Fe-NTA (7 mg Fe/kg) most effectively suppressed renal lipid peroxidation. Repeated i.p. injection of Fe-NTA (2 mg Fe/kg/day for the first 3 days and 3 mg Fe /kg/day for 12 days, 5 days a week) causes subacute nephrotoxicity as revealed by induction of karyomegalic cells in renal proximal tubules. A protective effect was observed in mice given alpha G-Rutin 30 min after each Fe-NTA treatment. To elucidate the mechanism of protection by alpha G-Rutin, the pharmacokinetics and hydroxyl radical-scavenging effect of alpha G-Rutin were investigated by HPLC analysis and by electron spin resonance (ESR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), respectively. When mice were given alpha G-Rutin (50 mumol as rutin/kg) by gastric intubation, rapid absorption into the circulation was observed. The plasma concentration of alpha G-Rutin reached the highest level 30 min after oral administration and then decreased to the control level within 60 min, alpha G-Rutin inhibited the formation of DMPO-OH in a concentration-dependent manner. Further, chelating activity of alpha G-Rutin to ferric ions was shown by spectrophotometric analysis. These results suggest that absorbed alpha G-Rutin works as an antioxidant in vivo either by scavenging reactive oxygen species or by chelating ferric ions and this serves to prevent oxidative renal damage in mice treated with Fe-NTA.

Animals↗
PubMed1996

Radioprotective effects of antioxidative plant flavonoids in mice.

Radioprotective effects of tea infusions and plant flavonoids were investigated by using the micronucleus test for anticlastogenic activity and the thiobarbituric acid assay for antioxidative activity. A single gastric intubation of rooibos tea (Aspalathus linearis) infusion at 1 ml per mouse 2 h prior to gama-ray irradiation (1.5 Gy) reduced the frequency of micronucleated reticulocytes (MNRETs). After the fractionation of rooibos tea infusion, the flavonoid fraction was found to be most anticlastogenic and antioxidative. From this fraction, luteolin was isolated as an effective component. Then, anticlastogenic effects of 12 flavonoids containing luteolin and their antioxidative activities against lipid peroxidation by Fenton's reagent were examined. A good correlation (r=0.717) was observed between both activities. Luteolin showed the most effective potency. A gastric intubation of luteolin (10 micromoles/kg) 2 h prior to gamma-ray irradiation (6 Gy) suppressed lipid peroxidation in mouse bone marrow and spleen and a trend of protective effect of luteolin against the decrease of endogenous ascorbic acid in mouse bone marrow after gamma-ray irradiation (3 Gy) was observed. These results suggest that plant flavonoids, which show antioxidative potency in vitro, work as antioxidants in vivo and their radioprotective effects may be attributed to their scavenging potency towards free radicals such as hydroxyl radicals. Therefore, the flavonoids contained in tea, vegetables and fruits seem to be important as antioxidants in the human diet.

Animals↗
PubMed1996

Effects of beta- and gamma-carboline derivatives of DNA topoisomerase activities.

beta-Carbolines, harman (1-methyl-9H-pyrido[3,4-b]indole) and norharman (9H-pyrido[3,4-b]indole) and gamma-carbolines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-4-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), are present in cooked foods and cigarette smoke. We studied the effects of these heterocyclic amines on the activity of DNA topoisomerases. Trp-P-1 and Trp-P-2 inhibited topoisomerase I (topo I) activity with ED50 values of 1.48 and 1.55 micrograms/ml, respectively, in a relaxation assay. Harman and norharman inhibited topo I activity but with much higher ED50 values, 23.8 and 34.4 micrograms/ml, respectively. Trp-P-1 and Trp-P-2 also inhibited topoisomerase II (topo II) activity at about 50 micrograms/ml, in a decatenation assay. Harman and norharman showed a much lower inhibitory effect on topo II activity. None of these compounds stabilized the cleavable complex mediated by topo II. Trp-P-1 and Trp-P-2 intercalated into DNA at concentrations inhibitory to topoisomerases. We considered that the intercalation with DNA and the inhibition of DNA topoisomerases by heterocyclic amines might be partly related to their inhibition of DNA excision repair and their enhancing effect on UV- or chemically induced mutagenic activity.

Breast Neoplasms↗
PubMed1996

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) inhibits the binding activity of T4 endonuclease V to UV-damaged DNA.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is a mutagen/carcinogen derived from cooked foods which enhances the induction of mutations and chromosome aberrations by UV without microsomal activation. These co-mutagenic effects are considered to arise from inhibition of DNA excision repair at the incision step. However, the inhibition mechanism has not been clarified. In this study we show, using agarose gel electrophoresis, that Trp-P-1 inhibits incision by T4 endonuclease V, which cleaves DNA at the site of cyclobutane dimers. Trp-P-1 also inhibits the binding of this enzyme to UV-damaged DNA in a gel shift assay. In addition, the results of DNA unwinding assay with topoisomerase I suggest that Trp-P-1 intercalates into DNA molecules. The known intercalators ethidium bromide and acriflavine demonstrate similar effects in these experiments. However, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which showed no co-mutagenic effects in our previous study, does not demonstrate such effects. These results suggest that Trp-P-1 changes DNA conformation by intercalation, causing inhibition of binding of repair enzymes to UV-damaged DNA, and this in turn leads to inhibition of DNA excision repair and to co-mutagenic effects.

Carbolines↗
PubMed1996

S-methyl methanethiosulfonate, bio-antimutagen in homogenates of Cruciferae and Liliaceae vegetables.

The isolation of a new type of bio-antimutagen, S-methyl methanethiosulfonate (MMTS), from cauliflower (Brassica oleracea var. botrytis) and the distribution and formation of MMTS in Cruciferae and Liliaceae vegetables are described. For the separation and purification, cauliflower curds were homogenized, extracted with acetone, and then purified by organic solvent extraction and by various processes of chromatographic separation. The chemical structure of an active principle was identified as MMTS by GC-MS and 1H-NMR analyses. MMTS was widely found in vegetable homogenates of the Cruciferae and Liliaceae species, and is found from its precursor S-methyl-L-cysteinesulfoxide (SMCS), by wounding the vegetable tissues. Wounding may induce C-S lyase, which converts SMCS to MMTS. The amount of MMTS formed was affected by the pH value for C- lyase, but not by the SMCS content in a tissue homogenate.

Antimutagenic Agents↗
PubMed1995

Effect of tea (Camellia sinensis L.) on lipid peroxidation in rat liver and kidney: a comparison of green and black tea feeding.

The antioxidant effects in the liver and kidney obtained from rat fed diets containing 3% green or black tea leaf powder, which were prepared from the same lot tea leaves, were studied using the tissue slice-antioxidant evaluation method with two lipid peroxidation inducers. After 50 d on the diets, liver slices prepared from green and black tea-supplemented rats showed significant inhibitory effects against tert-butyl hydroperoxide-induced lipid peroxidation. These effects, however, were not proportional to the amounts of (-)-epicatechins and antioxidant vitamins in the tea leaves. In the kidney, the antioxidant effect was observed only in the green tea-fed group. A similar antioxidant effect on the kidney was observed after oral administration of a major tea polyphenol, (-)-epigallocatechin gallate (50 mg/kg body weight for 7 d). Liver slices from black tea-fed rats also inhibited bromotrichloromethane-induced lipid peroxidation. These results demonstrated that dietary green and black tea had antioxidant effects on tissue lipid peroxidation ex vivo.

Animals↗
PubMed1994

Radioprotective effect of antioxidative flavonoids in gamma-ray irradiated mice.

The anticlastogenic effect of 12 structurally different flavonoids was investigated in whole body gamma-ray irradiated mice. Each flavonoid was administered to ICR male mice by a single gastric intubation (5 mumol/kg) 6 h before gamma-ray irradiation (1.5 Gy) and the frequency of micronucleated reticulocytes (MNRETs) in peripheral blood was determined. In order to elucidate the mechanism of the anticlastogenic effect of these flavonoids, their antioxidative activities were examined by the thiobarbituric acid method using methyl linoleate and Fenton's reagent (Fe2+/H2O2). Of the 12 flavonoids, luteolin had the most marked effect on reducing the frequencies of MNRETs and also inhibiting lipid peroxidation. However, quercetin tetramethylether, which has methoxy groups instead of hydroxyl groups at the 3,7,3',4'-positions, and phloretin with an open C-ring showed the least anticlastogenic and antioxidative activity. A good correlation (r = 0.717, P < 0.01) was observed between the anticlastogenic activity and the antioxidative activity of the 12 flavonoids. These results suggest that the radioprotective effect of flavonoids in mice may be attributed to the hydroxyl radical scavenging potency in a direct or an endogenous enzyme mediated manner.

Animals↗
PubMed1993

The clastogen-suppressing effects of green tea, Po-lei tea and Rooibos tea in CHO cells and mice.

The suppressing effects of crude extracts of three kinds of tea-green tea (GT) from Japan, Po-lei tea (PT) from China, and Rooibos tea (RT) from South Africa-on the induction of chromosome aberrations in cultured CHO cells and mice were studied. When CHO cells were exposed to each tea extract in the presence of rat liver microsomal enzymes (S9 mix) together with benzo[a]pyrene (B(a)P) or mitomycin C (MMC), a decrease in the frequency of chromosome aberrations was observed. PT and RT, but not GT, also suppressed the induction of chromosome aberrations by MMC in the absence of S9 mix. When cells were treated with tea extract after B(a)P or MMC treatment, RT suppressed the induction of chromosome aberrations in the presence and absence of S9 mix whereas GT and PT showed suppressing effects only in the presence of S9 mix. These data suggest that catechines, well-known antimutagens in tea samples, might account for the inhibitory effect in the case of GT and PT. Since RT contains few catechines, several unknown antimutagenic components could be responsible for its effect. The antimutagenic effects of tea extracts at concentration levels consumed by humans were examined in mice using micronucleus induction with B(a)P or MMC. When mice received oral gavage of 0.2% GT, 0.1% PT, and 0.1% RT at 1.0 ml/mouse 6 h before intraperitoneal injection of MMC, a decrease in the frequency of micronuclei was observed. The induction of micronuclei by B(a)P was suppressed by oral dosage of GT, PT and RT at 1.0 ml/mouse/day for 28 days. This was not due to a delay in the maturation of micronucleated reticulocytes. In conclusion, intake of tea might suppress the mutagenic activity of certain potent mutagens in human beings.

Animals↗
PubMed1993

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) inhibits the removal of both cyclobutane dimers and (6-4) photoproducts from the DNA of ultraviolet-irradiated E. coli.

Heterocyclic amines have been isolated from cooked foods and found to be mutagens and carcinogens. Among them, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) were also found to enhance UV-induced mutation frequencies in Escherichia coli at the concentrations where they were neither toxic nor mutagenic by themselves. Using an immunological method recently developed to detect UV-induced DNA damage, we investigated the inhibitory effect of Trp-P-1 on the removal of both cyclobutane dimers and (6-4)photoproducts from the DNA of UV-irradiated E.coli. Cells repaired 60% of the initial cyclobutane dimers within 30 min and 75% at 120 min after UV-irradiation. Furthermore, the same cells repaired 90% of the initial (6-4)photoproducts within 30 min. On the other hand, Trp-P-1 clearly showed inhibition of repair of both photolesions in a concentration-dependent manner. The levels of repair inhibition by Trp-P-1 were almost the same between cyclobutane dimers and (6-4)photoproducts. These results suggested that the enhancing effect of Trp-P-1 on UV-induced mutagenesis in E.coli stemmed from the inhibition of the removal of photolesions from the DNA.

Carbolines↗
PubMed1993

S-methyl methane thiosulfonate, a new antimutagenic compound isolated from Brassica oleracea L. var. botrytis.

Though various antimutagens with desmutagenic activities have been found in our daily foods of plant origin, the numbers of antimutagens with bio-antimutagenic activities found so far are limited. In the present study, a compound with potential bio-antimutagenic activity to Escherichia coli B/r WP2 was newly isolated from cauliflower, Brassica oleracea L. var. botrytis, and its chemical structure was identified to be S-methyl methane thiosulfonate by NMR and MS analysis.

Antimutagenic Agents↗
PubMed1992

Enhancing effects of heterocyclic amines and beta-carbolines on the induction of chromosome aberrations in cultured mammalian cells.

The effects of post-treatment with heterocyclic amines and beta-carbolines on the induction of chromosome aberrations were studied in Chinese hamster CHO K-1 cells and SV40-transformed excision repair-deficient human XP2OSSV cells. The number of chromosome aberrations induced by UV and MMC were increased by post-treatment with Trp-P-1 and Trp-P-2, in both the presence and the absence of S9 mix. A alpha C, MeA alpha C, Glu-P-1, Glu-P-2, IQ, MeIQ, harman and harmine increased chromosome aberrations only in the presence of S9 mix. Glu-P-2, IQ, MeIQ, harman, and harmine did not induce chromosome aberrations by themselves at the concentrations used in this study. Trp-P-1, Trp-P-2, A alpha C, MeA alpha C and Glu-P-1 were weak clastogens by themselves, but at much higher concentrations than those at which they increased the induction of chromosome aberrations in cells pretreated with UV or MMC. Therefore, the increases in chromosome aberrations were not considered to be additive.

Amines↗
PubMed1992

Bio-antimutagenic activities of vitamin B6 in E. coli and mouse peripheral blood cells.

Pyridoxal (PL) and pyridoxal 5'-phosphate (PLP) showed a marked bio-antimutagenic effect on UV-induced mutagenesis in E. coli B/r WP2, but not in the DNA excision repair-deficient strain WP2suvrA under the condition where no cellular toxicity was observed. No delay in the first cell division was seen on post-treatment with PL after UV irradiation. PL reduced not only UV- but 4-nitroquinoline-1-oxide-induced mutation, while it was ineffective in N-methyl-N'-nitro-N-nitrosoguanidine- or gamma-ray-treated cells. These results suggest that PL promotes DNA excision repair directly or indirectly and the decrease in the amount of unrepaired DNA damage might cause the reduction of UV-induced mutations in E. coli B/r WP2. In addition to the above observation, PLP reduced the frequency of mitomycin C- (2 mg/kg, i.p.) induced micronuclei in mouse peripheral blood cells. Simultaneous or subsequent oral administration of PLP (25 mg/kg) decreased the frequency of micronucleated peripheral reticulocytes.

Animals↗