Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 73 records · Page 4Linked to original sources

PubMed2001

Active Crohn disease with maternal vitamin K deficiency and fetal subdural hematoma.

BACKGROUND: Fetal subdural hematoma is a rare condition not considered a complication of Crohn disease in pregnancy. CASE: A young woman with a diagnosis of Crohn disease presented at 22 weeks' gestation with diarrhea and melena for 3 weeks. Dietary and medicinal therapies were begun. At 28 weeks' gestation, fetal ultrasonography showed an intracranial mass, which was seen to expand on serial ultrasound and magnetic resonance imaging studies. A hematoma was suspected, and, although the mother had no overt hemorrhagic manifestations, maternal vitamin K deficiency was diagnosed by enzyme immunoassay and corrected. After cesarean delivery at 36 weeks' gestation, the newborn was normal, but magnetic resonance imaging showed a chronic subdural hematoma. CONCLUSION: Maternal vitamin K deficiency in active Crohn disease might cause fetal hemorrhage. Monitoring of vitamin K status during pregnancy with Crohn disease seems warranted.

Adult↗

PubMed2001

Different binding sites for the neuropeptide Y Y1 antagonists 1229U91 and J-104870 on human Y1 receptors.

The peptidic Y1 antagonist 1229U91 and the non-peptidic antagonist J-104870 have high binding affinities for the human Y1 receptor. These Y1 antagonists show anorexigenic effects on NPY-induced feeding in rats, although they have completely different structures and molecular sizes. To identify the binding sites of these ligands, we substituted amino acid residues of the human Y1 receptor with alanine and examined the abilities of the mutant receptors to bind the radio-labeled ligands. Alanine substitutions, F98A, D104A, T125A, D200A, D205A, L215A, Q219A, L279A, F282A, F286A, W288A and H298A, in the human Y1 receptor lost their affinity for the peptide agonist PYY, but not for 1229U91 and J-104870, while L303A and F173A lost affinity for 1229U91 and J-104870, respectively. N283A retained its affinity for 1229U91, but not for PYY and J-104870. Y47A and N299A retained their affinity for J-104870, but not for PYY and 1229U91. W163A and D287A showed no affinity for any of the three ligands. Taken together, these data indicate that the binding sites of 1229U91 are widely located in the shallow region of the transmembrane (TM) domain of the receptor, especially TM1, TM6 and TM7. In contrast, J-104870 recognized the pocket formed by TM4, TM5 and TM6, based on the molecular modeling of the Y1 receptor and J-104870 complex. In conclusion, 1229U91 and J-104870 have high affinities for Y1 receptors using basically different binding sites. D287 of the common binding site in the TM6 domain could be crucial for the binding of Y1 antagonists.

Alanine↗

PubMed2001

Oral toxicity of a tocotrienol preparation in rats.

Tocotrienols are added as antioxidants to food. As there have been no reports of toxicological evaluation, a 13-week oral toxicity study was performed in Fischer 344 rats of both sexes at dose levels of 0 (group 1), 0.19 (group 2), 0.75 (group 3) and 3% (group 4) of a preparation in powdered diet. Suppression of body weight gain was observed in group 4 males. On hematological examination, significant decrease in mean corpuscular volume (MCV) was observed in all treated males. Platelets were significantly reduced in group 3 and 4 males. Hemoglobin concentration, MCV, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were significantly decreased in group 3 and 4 females and hematocrit in group 4 females. On serum biochemical examination, increase in the albumin/globulin ratio (A/G) and alkaline phosphatase in all treated males, elevated alanine transaminase in group 4 of both sexes and increases in asparagine transaminase and gamma-glutamyl transaminase in group 4 females were observed. With regard to relative organ weights, liver weights in group 4 of both sexes and adrenal weights in all treated males demonstrated an increase, and ovary and uterus weights in group 4 females were reduced. Histopathologically, slight hepatocellular hypertrophy in group 3 and 4 males, and reduction of cytoplasmic vacuolation in the adrenal cortical region in group 4 males were observed. Because of pathological changes in male liver and hematological changes in females, the no-observed-adverse-effect level (NOAEL) was concluded to be 0.19% in the diet (120 mg/kg body weight/day for male rats and 130 mg/kg body weight/day for female rats). As a decrease in MCV, an increase in the A/G, elevation of alkaline phosphatase and increase in adrenal weight were observed in all treated males, a no-observed-effect level (NOEL) could not be determined in this examination.

Administration, Oral↗

PubMed2001

Subchronic toxicity study of gallic acid by oral administration in F344 rats.

Subchronic toxicity of gallic acid (GA) was investigated in F344 rats by feeding diet containing 0, 0.2, 0.6, 1.7 and 5% GA for 13 weeks. Each group consisted of 10 rats of each sex. Toxicological parameters included clinical signs, body weight, food consumption, hematology, blood biochemistry, organ weights and histopathological assessment. Body weight gain in the 5% GA-treated animals of both sexes from week 1 to the end of the experiment was significantly lower than that of the untreated controls. Toxic effects following administration of 0.6% or more in males and 5% in females included reduction of hemoglobin concentration, hematocrit and red blood cell counts and increase in reticulocytes. Histopathologically, extramedullary hematopoiesis, hemosiderin deposition and congestion appeared in the spleens of 5% GA-treated animals, suggesting development of hemolytic anemia. In addition, centrilobular liver cell hypertrophy, reflected in increase in liver weight, was observed in animals of both sexes from 1.7%. In the kidney, Berlin blue-negative brown pigment deposition in the proximal tubular epithelium was observed at 5% GA. However, the severity of these pathological changes was weak. Based on the present toxicology data, 0.2% was determined to be a no-observed-adverse-effect level (NOAEL) in rats. This level was translated into 119 and 128 mg/kg/day, respectively for male and female rats.

Animals↗

PubMed2001

Mechanism of tonic spasms in West syndrome viewed from ictal SPECT findings.

To clarify the pathophysiology of tonic spasms, 21 patients with West syndrome were analyzed using ictal and interictal single photon emission computed tomography (SPECT). We focused on whether ictal perfusion changes were observed in the focal cortical region. Eight of the patients studied showed definite focal cortical ictal hyperperfusion, indicating that there is a unique subset of West syndrome that can be classified as infantile localization-related epilepsy. Of those eight patients, only two showed asymmetric spasms, suggesting that seizure symptomatology in infants gives only limited information on the localization-related nature of epilepsy. Furthermore, the activation of subcortical structures by focal cortical regions might be attributable to the symmetric seizure phenomena. Thirteen patients showed a diffuse pattern in their ictal SPECTs; this probably included patients with diffuse hyperperfusion and those with no changes. The following have yet to be determined: (1) whether West syndrome is divided into subgroups based on the origin of spasms, in that some patients have the origin in the cortical hemisphere and some have the origin in structures other than the cortical hemisphere, such as the brain stem; (2) whether differences in ictal SPECT patterns reflect a unique nature of tonic spasms in West syndrome, where tonic spasms appear in clusters and the interval of each spasm is different among each patient.

Brain↗

PubMed2001

Preoperative blood pressure and intraoperative hypothermia during lower abdominal surgery.

BACKGROUND: Preoperative factors including age and body habitus affect intraoperative hypothermia during general anesthesia. We hypothesized that preoperative blood pressure also plays a contributory role in the induction of intraoperative hypothermia. METHODS: We evaluated the effect of preoperative systolic blood pressure (SBP) on core temperature during lower abdominal surgery under general anesthesia. In 36 female patients under 65 years of age, patients with a preoperative SBP of 140 mmHg or greater upon arrival in the operating theater were assigned to the high SBP group (n=18), while those with SBP below 140 mmHg were assigned to the normal SBP group (n=18). Anesthesia was maintained with isoflurane and nitrous oxide combined with epidural buprenorphine, and routine thermal care was provided intraoperatively. RESULTS: There were no significant differences in age, height or weight between the two groups. Tympanic membrane temperature in the normal SBP group started to decrease significantly from 15 min after induction of anesthesia compared to that in the high SBP group, and continued to decrease further at two hours after induction. Vasoconstriction threshold, determined to be tympanic membrane temperature at the time when a forearm minus finger skin surface gradient exceeded 0 degrees C, was significantly higher in the high SBP group than in the normal SBP group. CONCLUSION: These results suggest that preoperative SBP has some preventive effect on the decrease in intraoperative core temperature during lower abdominal surgery under general anesthesia.

Adult↗

PubMed2001

Mechanism for pituitary adenylate cyclase-activating polypeptide-induced atrial fibrillation.

INTRODUCTION: Pituitary adenylate cyclase-activating polypeptide (PACAP), which activates intracardiac postganglionic parasympathetic nerves, has a greater profibrillatory effect than vagal stimulation. However, the mechanism responsible for this is unclear. METHODS AND RESULTS: We examined the effective refractory period (ERP), conduction time, and incidence of atrial fibrillation (AF) induced by a single premature extrastimulus at four atrial sites as well as the AF cycle length at 65 atrial sites in 12 autonomically decentralized, open chest, anesthetized dogs. These parameters were measured in the control condition, during cervical vagal stimulation, and after PACAP administration. PACAP shortened the ERP to a similar extent at all four sites. Vagal stimulation shortened the ERP primarily at the high right atrium, but not at the other three sites. Global dispersion of ERP and variation in the AF cycle length (P < 0.01) were less after PACAP than during vagal stimulation. A premature extrastimulus induced AF more frequently after PACAP than during vagal stimulation (P < 0.001). The ERP at the pacing site was shorter when AF was induced than when it was not induced regardless of the intervention and the pacing site. Conduction time following premature beats that induced AF was shorter after PACAP than during vagal stimulation (P < 0.01). CONCLUSION: Global ERP shortening contributes to the greater profibrillatory effect of PACAP. In addition, the decreased conduction time following premature beats may be associated with AF induction in this model.

Animals↗

PubMed2001

Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals.

Lines of evidence suggested a possible link between leptin and hepatic fibrosis; however, whether leptin modulates the fibrogenesis in the liver remains unclear. The purpose of this study, therefore, was to evaluate the effect of leptin on inflammatory and profibrogenic responses in the liver caused by hepatotoxic chemicals. Male C57Bl/6 mice were given carbon tetrachloride (CCl(4)) (0.1 microL/g body weight [BW], intraperitoneally [IP]) and/or recombinant murine leptin (1 microg/g BW, IP) simultaneously, and sacrificed up to 72 hours later. Further, some mice were given thioacetamide (TAA; 200 microg/g BW, IP) and leptin 3 times per week for 4 weeks to evaluate the effect of leptin on chronic fibrogenic responses. A simultaneous injection of leptin enhanced acute CCl(4)-induced necroinflammatory and subsequent fibrotic changes in the hepatic lobules. The steady-state messenger RNA (mRNA) levels of alpha1(I) procollagen and heat shock protein 47 (HSP47) in the liver were potentiated when leptin was injected together with CCl(4). Expression of alpha smooth muscle actin (alpha-SMA) in the liver after CCl(4) treatment was also augmented markedly in combination with leptin. Further, leptin increased transforming growth factor beta1 (TGF-beta1) mRNA in the liver 24 hours after acute CCl(4) about 4-fold higher than CCl(4) alone. Moreover, leptin enhanced hepatic fibrosis and induction of alpha1(I) procollagen mRNA caused by chronic TAA administration. Collectively, these findings indicated that leptin augments both inflammatory and profibrogenic responses in the liver caused by hepatotoxic chemicals. It is postulated that the increase in systemic leptin levels enhances up-regulation of TGF-beta1, leading to activation of stellate cells, thereby augmenting the fibrogenic response in the liver.

Actins↗

PubMed2001

Long-term denervation impairs insulin receptor substrate-1-mediated insulin signaling in skeletal muscle.

Long-term denervation is associated with insulin resistance. To investigate the molecular bases of insulin resistance, the downstream signaling molecules of insulin receptor including insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI 3-K) were examined in skeletal muscle of rats after 7 days of denervation. Long-term denervation attenuated insulin-stimulated activation of the initial steps of the intracellular signaling pathway. Insulin-stimulated tyrosine phosphorylation of insulin receptor was reduced to 36% (P < .005), as was the phosphorylation of IRS-1 to 34% (P < .0001) of control. While insulin receptor protein level was unchanged, the protein expression of IRS-1 was significantly decreased in denervated muscles. Insulin-stimulated percent tyrosine phosphorylation of IRS-1, normalized to the IRS-1 protein expression, was also reduced to 55% (P < .01) of control in denervated muscle. Denervation caused a decline in the insulin-induced binding of p85 regulatory subunit of PI 3-K to IRS-1 to 61% (P < .001) and IRS-1-associated PI 3-K activity to 57% (P < .01). These results provide evidence that long-term denervation results in insulin resistance because of derangements at multiple points, including tyrosine phosphorylation of insulin receptor and its downstream signaling molecule, IRS-1, protein expression of IRS-1, and activation of PI 3-K.

Animals↗

PubMed2001

E-cadherin is essential for gastric epithelial restitution in vitro: a study using the normal rat gastric mucosal cell line RGM1.

The proliferation and migration of epithelial cells appear to have important roles in intercellular adhesion and the regeneration of gastric mucosal lesions. However, the role of E-cadherin, an important intercellular adhesion molecule, in restitution after gastric mucosal damage is unknown. This study was designed to investigate the possible role of E-cadherin in the regeneration of gastric mucosal lesions. Artificial small wounds were made in an RGM1 confluent monolayer sheet, and the healing process was monitored with or without the presence of different concentrations of anti-E-cadherin antibodies. E-cadherin mRNA and protein expression were determined by Northern blot analysis and immunostaining, respectively. Epithelial restitution in anti-E-cadherin antibody-treated monolayers was inhibited as compared with that in the controls without antibody. E-cadherin mRNA and protein expression were up-regulated transiently during the healing process. E-cadherin plays an important role during wound healing of gastric epithelial lesions and is crucial for sheet migration.

Animals↗

PubMed2001

Promoting effects of xylazine on development of thyroid tumors in rats initiated with N-bis(2-hydroxypropyl)nitrosamine and the mechanism of action.

To cast light on whether xylazine hydrochloride (XZ), a veterinary medicine commonly used as a sedative agent for food-producing animals, has any promoting potential for thyroid carcinogenesis, the following studies were performed. In Experiment I, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ for 52 weeks with or without initiation with 2400 mg/kg N:-bis(2-hydroxypropyl)nitrosamine (DHPN). Focal follicular cell hyperplasias, adenomas and/or carcinomas were induced in the DHPN alone, XZ alone and DHPN+XZ groups, and the incidences and multiplicities of these lesions in the DHPN+XZ group were significantly increased as compared with the DHPN alone case. In Experiment II, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ and were examined for serum levels of triiodothyronine (T(3)), thyroxine (T(4)) and thyroid-stimulating hormone (TSH) at weeks 1, 2 and 4. In the XZ group, significant increase in thyroid weight and decrease in serum T(4) levels were observed at all time points. Serum T(3) and TSH levels were significantly decreased and increased, respectively, at week 1, but returned to within the control range thereafter. In Experiment III, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ, they were examined for thyroid iodine uptake and organification of XZ after 1 and 2 weeks. The thyroidal iodine uptake per milligram of thyroid and the amount of iodine bound to 1 mg protein showed a tendency for decrease at week 1 and significant decrease at week 2. These results indicate that XZ has tumor-promoting effects on thyroid follicular cells, and suggest an involvement of alterations in thyroid-related hormone levels due to inhibition of thyroid iodine uptake and organification, resulting, provably, in serum TSH stimulation depending on continuous reduction of serum T(4) level through the feedback system in the pituitary-thyroid axis.

Adenoma↗

PubMed2001

CD44 binds a chondroitin sulfate proteoglycan, aggrecan.

Here we report that CD44 binds a chondroitin sulfate (CS) proteoglycan, aggrecan, a major component of cartilage. Soluble CD44-IgG and CD44(+) cells bound to aggrecan from rat chondrosarcoma and bovine cartilage, immobilized on microtiter plates. In both cases, binding was blocked by a neutralizing anti-CD44 mAb or by the pretreatment of aggrecan with chondroitinase, but not hyaluronidase or keratanase, indicating that CD44 binds aggrecan in a manner dependent on CS side chains of aggrecan and that hyaluronic acid is not involved in the binding. Structural analysis showed that glycosaminoglycans of aggrecan from rat chondrosarcoma and bovine articular cartilage consist of mainly CS A and a mixture of CS A and C respectively. When immobilized on microtiter plates, both CS A and C bound CD44-IgG, and the reaction was specifically inhibited by an anti-CD44 mAb. In addition, aggrecan augmented apoptosis in cells expressing CD44-Fas chimeric molecules in synergy with a non-blocking anti-CD44 mAb IRAWB14.4, suggesting that CD44-aggrecan interaction can induce oligomerization of the chimeric molecules. These results suggest that aggrecan interacts with CD44 to mediate cell adhesion and to trigger oligomerization of CD44 molecules, which may lead to intracellular signaling.

Aggrecans↗

PubMed2001

How is the liver primed or sensitized for alcoholic liver disease?

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-alpha gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFalpha gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.

Animals↗

PubMed2001

Neuroreceptors and ion channels as targets of alcohol.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Kinya Kuriyama. The presentations were (1) Modulation of neuroreceptors and ion channels by alcohol, by T. Narahashi; (2) Inhibition by ethanol of NMDA and AMPA receptor-channels, by P. Illes, K. Wirkner, W. Fischer, K. Mühlberg, P. Scheibler, and C. Allgaier; (3) Effects of ethanol on metabotropic glutamate receptors, by K. Minami; (4) Acute alcohol actions on the 5-HT3 ligand-gated ion channel, by D. Lovinger; (5) Inhibition of NMDA receptors by MK801 attenuates ethanol-induced taurine release from the hippocampus, by F. Lallemand, R.J. Ward, and P. DeWitte; and (6) Effect of ethanol on voltage-operated Ca2+ channels in hepatic stellate cells, by T. Itatsu, Y. Takei, H. Oide, M. Hirose, X. E. Wang, S. Watanabe, M. Tateyama, R. Ochi, and N. Sato.

Animals↗

PubMed2001

Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin.

BACKGROUND: Studies with gut sterilization and Kupffer cell inactivation support the hypothesis that endotoxin and Kupffer cells are involved in mechanisms of alcohol-induced liver injury. Recently, we found that Kupffer cells isolated from rats treated only once with ethanol were sensitized to endotoxin 24 hr later. Moreover, we established a new, simple animal model of ethanol hepatotoxicity based on Kupffer cell sensitization. The purpose of this study was to determine the mechanisms by which alcohol sensitizes Kupffer cells to lipopolysaccharide (LPS). METHODS: Female Wistar rats were given ethanol (5 g/kg body weight) once every 24 hr intragastrically, and ethanol concentration, ethanol elimination, and portal vein endotoxin were measured. Gut permeability was measured in isolated segments of ileum by translocation of horseradish peroxidase. Kupffer cells were isolated 24 hr after ethanol administration in vivo and were cultured in RPMI 1640 with 10% fetal bovine serum. After the addition of LPS, intracellular Ca2+ was measured by using a microspectrofluorometer with the fluorescent indicator fura-2, and tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay. CD14 was evaluated by Western analysis. RESULTS: Ethanol levels exhibited a cyclic pattern in ethanol-treated rats. Similar results were obtained in groups given ethanol and antibiotics for 4 weeks. Rates of alcohol elimination were around 3.5 mmol/kg/hr in control rats. After 4 weeks of ethanol treatment with or without antibiotics, elimination rates were not changed. Translocation of horseradish peroxidase was increased about 3-fold in gut segments by treatment with ethanol. This increase was not altered by treatment with antibiotics. Moreover, portal vein endotoxin levels were increased from nearly undetectable levels to 80 pg/ml in plasma of rats treated with ethanol. As expected, this increase was prevented (<20 pg/ml) by antibiotics. In isolated Kupffer cells from rats treated with ethanol for 4 weeks, CD14, LPS-induced intracellular Ca2+, and TNF-alpha all were increased. These phenomena were blocked by antibiotics. CONCLUSIONS: Kupffer cells isolated from rats treated with ethanol for 4 weeks exhibit sensitization to LPS. It is likely that increased permeability of the gut is a prominent event that leads to alcoholic liver injury.

Animals↗

PubMed2001

Involvement of lipid peroxidation in spontaneous pancreatitis in WBN/Kob rats.

To cast light on the mechanisms underlying development of spontaneous pancreatitis lesions, tissues from WBN/Kob rats at various ages were histopathologically and immunohistochemically investigated with special reference to the existence of the lipid peroxidation products 4-hydroxy-2-nonenal (HNE), 4-hydroxy-2-hexenal (HHE), and malondialdehyde (MDA). Male 4-20-week-old WBN/Kob rats were killed to allow sampling of pancreatic tissues, which were fixed in cold acetone and 10% neutral-buffered formalin. and then processed for routine histopathology as well as immunohistochemistry for proteins modified by HNE, HHE, and MDA. Although no remarkable histologic changes were noted in younger animals, edema, hemorrhage, inflammatory cell infiltration, fibrosis, vacuolation of acinar cells, and ductular proliferation were observed in exocrine pancreatic tissue from animals at 10-15 weeks of age. In animals aged 20 weeks, the lesions had progressed remarkably and deposits of hemosiderin were apparent with fibrosis. Immunohistochemical examination for lipid peroxidation product-modified proteins showed HNE and MDA to be negative in all pancreatic tissues, but HHE was positive in the areas involving atrophy of acinar cells and fibrosis in the islets. The results of the present study thus provide support for the conclusion that lipid peroxidation during spontaneous pancreatitis in WBN/Kob rats may possibly be involved in the development of diabetes in this model.

Aging↗

PubMed2001

Lack of effect of soy isoflavone on thyroid hyperplasia in rats receiving an iodine-deficient diet.

We have reported a dramatic synergism between soy intake and iodine deficiency regarding induction of thyroid hyperplasia in rats. Because isoflavones are active constituents of soybeans, in the present study, their possible contribution was examined. Female F344 rats were divided into 8 groups, exposed to diet containing a 0.2% soy isoflavone mixture (SI), 0.2% SI + iodine deficiency (ID), 0.04% SI, 0.04% SI + ID, 20% defatted soybean (DS) alone, 20% DS + ID, ID alone or basal diet alone for 5 weeks. Thyroid weight was not influenced by SI, but was increased by the ID and DS diets with a further significant increment in the DS + ID group (P < 0.01). Compared to the control value, serum T(4) was significantly (P < 0.01) increased by 20% DS alone and decreased in all groups given the ID treatment (P < 0.001). Serum thyroid stimulating hormone (TSH) level was increased by ID, and further enhanced by DS (P < 0.01) but not SI. Histopathologically, diffuse hypertrophy and / or hyperplasia of thyroid follicles were observed in the ID-treated groups, the severity being enhanced by DS but not SI. Proliferating cell nuclear antigen labeling indices (%) were elevated in the ID diet groups and again enhanced by DS, but not SI. These results thus suggest that isoflavones may not be involved in the mechanisms underlying the synergistic goitrogenic effect of soybean with iodine deficiency.

Animals↗

PubMed2001

Synergistic effects of high-dose soybean intake with iodine deficiency, but not sulfadimethoxine or phenobarbital, on rat thyroid proliferation.

The specificity and dose dependence of the synergistic effects of soybean intake with iodine deficiency on the induction of thyroid proliferation were investigated in female F344 rats. In the first experiment, rats were divided into 6 groups, each consisting of 5 animals, and fed a basal diet containing 20% gluten, an iodine-deficient basal diet alone or an iodine-deficient diet containing 0.2%, 1.0%, 5.0% or 25% defatted soybean for 5 weeks. Soybean feeding synergistically induced thyroid hyperplasias with iodine deficiency only at the 25% dose. In the second experiment, rats were also divided into 6 groups, each consisting of 5 animals, and fed a basal diet, a diet containing 20% defatted soybean, 0.025% sulfadimethoxine (SDM), 20% defatted soybean + 0.025% SDM, 0.05% phenobarbital (PB) or 20% defatted soybean + 0.05% PB for 5 weeks. The SDM treatments significantly (P < 0.05 - 0.01) increased the thyroid weights, but this increase rate was less prominent in the SDM + soybean group than in the SDM alone group. The PB treatment was also associated with a tendency for increase in thyroid weight, but again this was smaller in the PB + soybean group than in the PB alone group. Although the SDM or PB treatments reduced the serum triiodothyronine and thyroxine levels and consequently increased the serum thyroid-stimulating hormone (TSH) levels, the soybean feeding did not affect or rather attenuated these changes. Our results clearly indicate that soybean feeding does not synergistically enhance the effects of SDM or PB on the rat thyroid. Thus it can be concluded that soybean intake specifically interacts with iodine deficiency in induction of thyroid proliferative lesions in rats, only at high doses.

Animals↗