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Masaru Odashima

Publications and source records attributed to Masaru Odashima.

At least 19 recordsLinked to original sources
PubMed2007

Protective effect of a novel rice extract against ethanol-induced gastric mucosal injury in rat.

The aim of this study was to investigate the protective action of rice extract on ethanol-induced mucosal damage in vivo and wound healing of epithelial cells in vitro. Also, the effect of rice extract on gastric mucosal prostaglandin E(2) level, HSP72 expression, gastric acid secretion, and contribution of vanilloid receptor-mediated action was studied. In addition, using cultured gastric mucosal cells (RGM-1), the effect of rice extract on cytoprotection and wound healing of epithelial cells was evaluated. Rice extract significantly reduced gastric mucosal damage produced by ethanol in vivo, and heat treatment (80 degrees C, 3 min) of this agent did not alter its protective effect. Rice extract also protected RGM-1 from ethanol-induced damage in a dose-dependent manner. Rice extract accelerated wound healing of gastric epithelial cells. Our results demonstrate that rice extract could be an alternative ulcer treatment that provides cytoprotection and enhancement of wound healing not dependent on acid secretion, prostaglandin E(2) level, HSP72 expression, or vanilloid receptors.

Animals↗
PubMed2006

The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by Geranylgeranylacetone (HSP-inducer).

To elucidate the induction mechanism of HSP70 by geranylgeranylacetone (GGA), we investigated GGA specific binding proteins using a GGA-affinity column. Alteration of chaperone activity of HSP70 and binding affinity of HSP70 to heat shock factor-1 (HSF-1) was evaluated in the presence or absence of GGA. The binding domain of HSP70 to GGA was also analyzed. A 70-kDa protein eluted by 10 mM GGA from the GGA-affinity column was identical to constitutively expressed HSP70 on immunoblotting. GGA-binding domain of HSP70 was C-terminal of the protein as peptide-binding domain (HSP70C). The chaperone activity of HSP70 and recombinant HSP70C was suppressed by GGA. Furthermore, dissociation of the HSP70 from HSF-1 was observed in the presence of GGA. GGA preferentially binds to the C-terminal of HSP70 which binds to HSF-1. After dissociation of HSP70, free HSF-1 could acquire the ability to bind to HSE (the promoter region of HSP70) gene.

Animals↗
PubMed2006

Gene expression profiling following constitutive activation of MEK1 and transformation of rat intestinal epithelial cells.

BACKGROUND: Constitutive activation of MEK1 (caMEK) can induce the oncogenic transformation of normal intestinal epithelial cells. To define the genetic changes that occur during this process, we used oligonucleotide microarrays to determine which genes are regulated following the constitutive activation of MEK in normal intestinal epithelial cells. RESULTS: Microarray analysis was performed using Affymetrix GeneChip and total RNA from doxycycline inducible RIEtiCAMEK cells in the presence or absence of doxycycline. MEK-activation induced at least a three-fold difference in 115 gene transcripts (75 transcripts were up-regulated, and 40 transcripts were down-regulated). To verify whether these mRNAs are indeed regulated by the constitutive activation of MEK, RT-PCR analysis was performed using the samples from caMEK expressing RIE cells (RIEcCAMEK cells) as well as RIEtiCAMEK cells. The altered expression level of 69 gene transcripts was confirmed. Sixty-one of the differentially expressed genes have previously been implicated in cellular transformation or tumorogenesis. For the remaining 8 genes (or their human homolog), RT-PCR analysis was performed on RNA from human colon cancer cell lines and matched normal and tumor colon cancer tissues from human patients, revealing three novel targets (rat brain serine protease2, AMP deaminase 3, and cartilage link protein 1). CONCLUSION: Following MEK-activation, many tumor-associated genes were found to have significantly altered expression levels. However, we identified three genes that were differentially expressed in caMEK cells and human colorectal cancers, which have not been previously linked to cellular transformation or tumorogenesis.

Animals↗
PubMed2006

Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats-correlation of HSP72 expression with mucosal protection.

BACKGROUND AND AIM: The real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. MATERIALS AND METHODS: Expression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6 N HCl was compared between control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc L-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. RESULTS: HSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. CONCLUSION: Our results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist.

Animals↗
PubMed2006

Zinc L-carnosine protects colonic mucosal injury through induction of heat shock protein 72 and suppression of NF-kappaB activation.

In this study, we investigated the effects of zinc L-carnosine, an anti-ulcer drug, on acetic acid-induced colonic mucosal injury and the correlation of these effects with expression of 72-kDa heat shock proteins (HSP72) and nuclear factor kappa B (NF-kappaB) activation in rat colonic mucosa in vivo. After intrarectal administration of zinc L-carnosine, the rats received intrarectal infusion of 5% acetic acid (1 ml). The colonic mucosal damage was evaluated by macroscopic assessments 24 h after the intrarectal infusion of acetic acid. Expression of HSP72 in rat colonic mucosa was evaluated by Western blot analysis before and after zinc L-carnosine administration. NF-kappaB activation was evaluated by electrophoretic mobility shift assays (EMSA). Zinc L-carnosine inhibited visible damage in rat colonic mucosa by acetic acid. Expression of HSP72 was significantly increased at 6 h after zinc L-carnosine administration. Furthermore, NF-kappaB activation in colonic mucosa was suppressed 6 h after zinc L-carnosine treatment. These results suggested that zinc L-carnosine protects the colonic mucosa against acetic acid by induction of HSP72 and suppression of NF-kappaB activation and zinc L-carnosine may be a novel therapeutic agent for the therapy of inflammatory bowel disease.

Acetic Acid↗
PubMed2006

A selective adenosine A2A receptor agonist, ATL-146e, prevents concanavalin A-induced acute liver injury in mice.

BACKGROUND AND AIMS: Concanavalin A (Con A) activates T lymphocytes and induces CD4+ T cell-mediated hepatic injury in mice. Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6), are critical mediators in this experimental model. Activation of adenosine A2A receptors reduces the production of various pro-inflammatory cytokines and suppresses T cell activation. A selective adenosine A2A receptor agonist (ATL-146e) has been shown to be a potent inhibitor of inflammation by increasing intracellular cyclic AMP (cAMP) in leukocytes. The aim of the present study was to determine whether ATL-146e could ameliorate Con A-induced hepatic injury, reduction of pro-inflammatory cytokine production. METHODS: Balb/c mice were injected with 25mg/kg Con A with or without a single injection of ATL-146e (0.5-50 microg/kg), 5 min prior to Con A administration. Liver enzymes, histology, and serum levels of tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 were examined. We also assessed the effects of ATL-146e on pro-inflammatory cytokine production with CD4+ T cell. RESULTS: Pretreatment with ATL-146e significantly reduced serum levels of liver enzymes (P<0.001). The serum pro-inflammatory cytokines were all increased after Con A administration and reduced to near normal levels by ATL-146e. ATL-146e also inhibited CD4+ T cell pro-inflammatory cytokine production. CONCLUSION: A selective adenosine A2A receptor agonist, ATL-146e, can prevent concanavalin A-induced hepatic injury that is presumably mediated by its anti-inflammatory properties.

Adenosine A2 Receptor Agonists↗
PubMed2006

Role of heat shock proteins (molecular chaperones) in intestinal mucosal protection.

Most studies into the pathogenesis of inflammatory bowel diseases (IBD) have primarily focused on the cytotoxic agents and processes involved in producing mucosal injury, including the immune system. However, less consideration has been given to the inherent mechanisms of cytoprotection and cellular repair in the intestinal mucosa. This review will focus on intestinal mucosal protection against cytotoxic agents and cellular stress mainly from the viewpoint of expression and function of heat shock proteins, in their role of "molecular chaperones," as internal cytoprotectants. Elucidation of such stress-responses in the intestinal mucosa may provide a better understanding of the mechanisms of cytoprotection and cellular repair, and present new strategies for IBD therapy.

Animals↗
PubMed2006

Is Mongolian gerbil really adequate host animal for study of Helicobacter pylori infection-induced gastritis and cancer?

BACKGROUND: Many researches have been published to understand the pathogenesis and mechanism of Helicobacter pylori (Hp)-associated diseases, including gastritis followed by gastric cancer, using Mongolian gerbil (MG) model because Hp could be hardly inoculated in other animal species. The aim of this study was to evaluate the induction ability of heat shock protein (HSP70) and protective ability in the gastric mucosa of MG comparing with those of Sprague-Dawley (SD) rats, since HSP70 is a key molecule known to be involved in important biological activities such as apoptosis, carcinogenesis, and cytoprotection from cytotoxic damage. MATERIALS AND METHODS: Basal expression level and induction ability of gastric mucosal HSP70 were evaluated by immunoblotting and densitometric analysis in MG and SD rats before and after HSP-induction by zinc l-carnosine, gastric HSP70 inducer, administration. Mucosal protective ability against water-immersion stress-induced mucosal lesion was also compared. RESULTS: Basal expression level of HSP70 was not significantly different between MG and SD rats. However, HSP70-induction by zinc derivatives was not observed in MG. Mucosal lesion induced by water-immersion stress was significantly severe in MG compared with SD rats. CONCLUSIONS: MG might be special (not ordinary) animal, in which HSP70-induction was absent and has extremely poor mucosal protective ability in view of HSP-dependent cytoprotection in the gastric mucosa. Our results may suggest that MG is not an adequate animal to evaluate the effect of Hp-infection-associated gastric inflammation followed by development of gastric cancer.

Animals↗
PubMed2006

Specific type IV phosphodiesterase inhibitor ameliorates cerulein-induced pancreatitis in rats.

BACKGROUND AND AIMS: Type IV phosphodiesterase is a key enzyme to metabolize intracellular adenosine 3',5'-cyclic monophosphate (cAMP) expressed in inflammatory cells. The specific type IV phosphodiesterase inhibitor that increases intracellular cAMP is known to be potent suppressor of proinflammatory cytokines. However, the effect of phosphodiesterase inhibitors on the development of pancreatitis has not been well understood. In the present study, we examined the effect of a specific type IV phosphodiesterase inhibitor on experimentally induced pancreatitis. METHODS: Severity of cerulein-induced pancreatitis and pancreatic proinflammatory cytokine levels were studied with or without pretreatment with a specific type IV phosphodiesterase inhibitor (rolipram) in Sprague-Dawley rats. RESULTS: Administration of rolipram clearly ameliorated severity of pancreatitis evaluated by edema, serum amylase (P<0.05), and lipase levels (P<0.05) in rats. Also, the level of pancreatic proinflammatory cytokine (interleukin-1beta (IL-1beta)) was significantly reduced when rats were treated with rolipram prior cerulein injection (P<0.05). CONCLUSIONS: Our results demonstrated that intracellular cAMP and pancreatic proinflammatory cytokine level, which are regulated by type IV phosphodiesterase, might play an important role in the pathogenesis of acute pancreatitis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Over-expression of 70-kDa heat shock protein confers protection against monochloramine-induced gastric mucosal cell injury.

The major heat shock protein, HSP70, is known to be involved in cytoprotection against environmental stresses mediated by their function as a "molecular chaperone". Monochloramine (NH(2)Cl) is a potent cytotoxic oxidant generated by neutrophil-derived hypochlorous acid and Helicobacter pylori urease-induced ammonia. In this study, to evaluate the cytoprotective effect of HSP70 against NH(2)Cl-induced gastric mucosal cell injury, rat gastric mucosal cells (RGM-1) were stably transfected with pBK-CMV containing the human HSP70 gene (7018-RGM-1) or pBK-CMV alone (pBK-CMV-12) as control cells. These cells were treated with various concentrations of NH(2)Cl. Cell Viability was determined by MTT assay and the direct plasma membrane damage was analyzed by lactate dehydrogenase (LDH) release assay. Apoptosis was determined by DNA fragmentation analysis. NH(2)Cl caused injury to pBK-CMV-12 cells in a concentration-dependent manner. NH(2)Cl-induced gastric cell injury was significantly diminished in HSP70 over-expressing cell line (7018-RGM-1) both necrosis and apoptosis compared to the control cell line (pBK-CMV-12) transfected with CMV vector alone. These result suggest that overexpression of HSP70 plays an important role in protecting gastric cells against NH(2)Cl-induced injury.

Animals↗
PubMed2006

Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats.

AIM: To determine whether a specific adenosine A(2A) receptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines. METHODS: Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCl (0.15 mol/L, 8.0 mL/kg). 4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester (ATL-146e, 2.5-5 mug/kg, IP) was injected 30 min before the administration of aspirin. Tissue myeloperoxidase (MPO) concentration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined by ELISA. Also, we examined the effect of ATL-146e on tissue prostaglandin E2 (PGE2) production and gastric secretion. RESULTS: Intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. The total length of gastric erosions (ulcer index) in control rats was 29.8+/-7.75 mm and was reduced to 3.8+/-1.42 mm after pretreatment with 5.0 g/kg ATL-146e (P<0.01). The gastric contents of MPO and pro-inflammatory cytokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e. Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of ATL-146e. CONCLUSION: The specific adenosine A(2A) receptor agonist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties.

Animals↗
PubMed2006

Effect of cilostazol, a selective type-III phosphodiesterase inhibitor, on water-immersion stress-induced gastric mucosal injury in rats.

BACKGROUND: Cilostazol, a specific type-III phosphodiesterase inhibitor, is widely used for the treatment of ischemic symptoms of peripheral vascular disease. Recent studies have reported that the mechanism of cilostazol is related to the suppression of pro-inflammatory cytokine production and improvement of local microcirculation disturbances. The pathogenesis of stress-induced gastric mucosal lesions is characterized by the activation of inflammatory cells and the production of inflammatory cytokines. The effects of cilostazol on the development of gastric mucosal lesions have not been reported. In the present study, we examined the effect of a cilostazol on water-immersion stress-induced gastric mucosal lesions. METHODS: Rats were subjected to water-immersion stress with or without pretreatment with a single intraperitoneal injection of the selective type-III phosphodiesterase inhibitor, cilostazol. We measured the gastric mucosal lesion and the concentrations of myeloperoxidase (MPO), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1), as an index of neutrophil accumulation and pro-inflammatory cytokine production. RESULTS: Cilostazol ameliorated the gastric mucosal injury induced by water-immersion stress (P<0.001). The gastric contents of MPO, TNF-alpha, IL-1beta, and CRO/CINC-1 were all increased after water-immersion stress and were reduced to almost normal levels by cilostazol. CONCLUSIONS: In this study, we demonstrated that a selective type-III phosphodiesterase inhibitor, cilostazol, inhibited stress-induced gastric inflammation and damage via suppressing the production of pro-inflammatory cytokines. Cilostazol may be useful for preventing gastric mucosal lesions.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Systemic stress increases serum leptin level.

BACKGROUND AND AIM: Leptin, the product of the obese (ob) gene, is a circulating peptide mainly synthesized by adipocytes. Leptin inhibits food intake and decreases body weight. A recent report has suggested that the gastric mucosa is also the source of leptin, and that the stomach leptin also contributes to the regulation of the serum leptin level. The aim of the present study was to investigate the effect of water-immersion stress on serum, stomach and adipose tissue leptin levels to understand the relationship between stress and eating behavior. METHODS: Male Sprague-Dawley rats were used in this experiment. The leptin level in the serum, gastric mucosa and adipose tissue was measured using ELISA system before and after the initiation of water-immersion stress. RESULTS: The serum leptin level was significantly increased by water-immersion stress. The peak was observed 9 h after the initiation of the stress (P < 0.01). However, the gastric leptin level significantly decreased 6 and 9 h after the stress. The adipose tissue leptin level significantly increased 3 h after the stress. CONCLUSIONS: The results suggest that changes in serum leptin levels could be associated with stimulation of leptin secretion from the gastric mucosa and leptin production in the adipose tissue by systemic stress and that leptin might be regulated by stress-related events.

Adipocytes↗
PubMed2006

Zinc L-carnosine protects against mucosal injury in portal hypertensive gastropathy through induction of heat shock protein 72.

BACKGROUND AND AIMS: Increased susceptibility to gastric mucosal injury is observed in portal hypertensive gastropathy (PHG). In this study, the effects of zinc L-carnosine, an anti-ulcer drug, were evaluated on expression of heat shock protein (hsp) 72 and cytoprotection in gastric mucosa in a rat model of PHG. METHODS: Portal hypertensive gastropathy with liver cirrhosis was induced by bile duct ligation for 4 weeks in male Sprague-Dawley rats. Expression of gastric mucosal hsp72 was evaluated by Western blotting at 6 h after intragastric administration of L-carnosine, zinc sulfate, or zinc L-carnosine. Blood was also collected for determination of serum zinc level. Mucosal protective abilities against hydrochloric acid (HCl) (0.6N) followed by pretreatment with L-carnosine, zinc sulfate or zinc L-carnosine were also studied. RESULTS: L-carnosine, zinc sulfate, and zinc L-carnosine induced hsp72 in gastric mucosa of rats with bile duct ligation. Zinc sulfate and zinc L-carnosine suppressed HCl-induced mucosal injury. However, L-carnosine could not suppress HCl-induced mucosal injury. Serum zinc levels were significantly elevated after zinc L-carnosine administration. Furthermore, pretreatment with zinc L-carnosine (30-300 mg/kg) increased the expression of hsp72 in gastric mucosa and prevented HCl-induced mucosal injury in rats with bile duct ligation in a dose-dependent manner. CONCLUSIONS: Zinc derivatives, especially zinc L-carnosine, protected portal hypertensive gastric mucosa with increased hsp72 expression in cirrhotic rats. It is postulated that zinc L-carnosine may be beneficial to the mucosal protection in PHG as a 'chaperone inducer'.

Animals↗
PubMed2005

Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice.

BACKGROUND: D-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role. We examined the effects of a highly selective adenosine A2A receptor agonist (ATL-146e) on GalN/LPS-induced fulminant hepatic failure. METHODS: Mice were given an intraperitoneal dose of GalN (800 mg/g body weight)/LPS (100 ng/g body weight) with and without ATL-146e (0.01 microg/kg) treatment. Liver injury was assessed biochemically and histologically. Also, TNF-alpha levels in the serum were determined. RESULTS: The serum liver enzyme (ALT) level in vehicle-treated mice was 20 960 +/- 2800 IU/ml and was reduced by 63% to 7800 +/- 1670 IU/ml by treatment with 0.01 microg/kg per minute ATL146e, P < 0.05. Treatment with ATL-146e significantly reduced serum TNF-alpha and greatly reduced inflammation assessed by histopathologic examination compared with control mice treated with GalN/LPS. ATL-146e also reduced lethality at 12 h from 65% to 13%. CONCLUSION: The present findings suggest that the highly selective adenosine A2A receptor agonist (ATL-146e) prevents endotoxin-induced lethal liver injury by suppression of TNF-alpha secretion.

Adenosine A2 Receptor Agonists↗
PubMed2005

Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates aspirin-induced gastric mucosal injury in rats.

Inhibition of type IV phosphodiesterase (PDE IV) activity reduces the production of various proinflammatory cytokine and suppresses neutrophil activation. Nonsteroidal anti-inflammatory drugs such as aspirin induce gastric mucosal lesions. In the pathogenesis of aspirin-induced gastric mucosal lesion, the contributions, of activated inflammatory cells and proinflammatory cytokine production are critical. The specific PDE IV inhibitor rolipram is known to be a potent inhibitor of inflammation by increasing intracellular cyclic AMP in leukocytes. The aim of the present study was to determine whether rolipram can ameliorate aspirin-induced gastric mucosal lesions in rats and whether the agent can inhibit the inrease in neutrophil accumulation and the production of proinflammatory cytokines. Gastric lesions were produced by administration of aspirin (200 mg/kg) and HCI (0.15 N; 8.0 ml/kg). Rolipram was injected 30 min before aspirin administration. The tissue myeloperoxidase concentration in gastric mucosa was measured as an indicat or of neutrophil infiltration. The gastric mucosal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined by ELISA. The intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. Gastric mucosal lesions induced by aspirin were significantly inhibited by treatment with rolipram. The mucosal myeloperoxidase concentration was also suppressed by rolipram. Increases in the gastric content of TNF-alpha and IL-1beta after aspirin administration were inhibited by pretreatment with rolipram. We demonstrated that the specific type IV PDE inhibitor, rolipram, could have a potent antiulcer effect, presumably mediated by its anti-inflammatory properties.

Animals↗