Biomedical subjects

Yuji Naito

Publications and source records attributed to Yuji Naito.

At least 37 records · Page 2Linked to original sources

PubMed2006

Lansoprazole, a proton pump inhibitor, reduces the severity of indomethacin-induced rat enteritis.

The spread of capsule endoscopy has led to a focus on small intestinal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). However, it has been proposed that proton pump inhibitors (PPI), a strong anti-secretary agent, have anti-inflammatory action beyond acid suppression. Therefore, we evaluated the biological effects of lansoprazole, a PPI used in the clinical area, in the setting of experimental rat non-steroidal anti-inflammatory drug-induced enteritis. The animals were given indomethacin subcutaneously and the intestinal mucosa was examined 24 h later. Lansoprazole was given subcutaneously just after following indomethacin injection. Single administration of indomethacin at 10 mg/kg provoked severe hemorrhagic lesions in the small intestine, mostly the jejunum and ileum. The levels of thiobarbituric acid-reactive substances (TBARS), the myeloperoxidase (MPO) activity and the content of cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the intestinal mucosa significantly increased in indomethacin-treated groups compared with the sham-operated groups. The development of intestinal lesions in response to indomethacin was dose-dependently prevented by lansoprazole at a dose of 5 mg/kg together with significant suppression of the increased level of TBARS, MPO activities and CINC-1 in the small bowel. Furthermore, the increased CINC-1 mRNA expression after administration of indomethacin was also inhibited by treatment with lansoprazole. These results suggest that lansoprazole administered exogenously prevented the small intestine against indomethacin-induced damage, the action being dependent on its anti-inflammatory and anti-oxidative responses. This evidence supports the theory that PPI have an expanding role beyond acid suppression.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2006

Effect of a novel water-soluble vitamin E derivative as a cure for TNBS-induced colitis in rats.

Lipid peroxidation mediated by oxygen free radicals plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Vitamin E is a lipid-soluble antioxidant and is generally considered to protect against lipid peroxidation of the cell membrane and to scavenge singlet oxygen and superoxide anion radical. Therefore, vitamin E or its derivatives are expected to have particular application for patients suffering from IBD. The aim of this study was to investigate the antioxidative effects of the water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetra-methylchroman-6-ol(TMG), on the therapy of experimental colitis in rats. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS) dissolved in 50% ethanol; TMG dissolved in physiological saline was injected intra-peritoneally every day from 24 h after the enema of TNBS. The damage score, wet weight of the colon, and increase in body weight were estimated 1 week after the enema of TNBS. Thiobarbituric acid-reactive substances (TBA-RS), an index of lipid peroxidation, and tissue-associated myeloperoxidase (MPO) activity in the colonic mucosa were measured 1 week after the induction of colitis. As a result, increase in body weight was inhibited by the induction of colitis, although the inhibition was reduced in the group treated with TMG. The damage score, wet weight, TBA-RS and MPO activity were increased significantly in the colitis group; however, they were inhibited by the administration of TMG. These results suggest that TMG is effective for the treatment of colitis in rats induced by TNBS. In the future, TMG could be a new therapeutic agent for IBD.

Animals↗

PubMed2006

Rosuvastatin, a new HMG-CoA reductase inhibitor, reduces the colonic inflammatory response in dextran sulfate sodium-induced colitis in mice.

The aim of the present study was to elucidate the beneficial effects of rosuvastatin, a new HMG-CoA reductase inhibitor, on colonic mucosal damage and on the inflammatory response in a dextran sulfate sodium (DSS) colitis model. Acute colitis was induced using 8% DSS in female BALB/c mice. Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically. Mucosal protein contents and mRNA levels of tumor necrosis factor (TNF)-alpha were determined by immunoassay and real time-PCR. The mRNA levels of endothelial nitric oxide synthase (eNOS) were determined by real-time PCR. Disease activity scores in DSS-induced colitis model mice, as determined by weight loss, stool consistency, and blood in stool, were significantly lower in the rosuvastatin-treated mice than in control mice. Shortening of the colon was significantly reversed by rosuvastatin. Increases in tissue-associated myeloperoxidase activity and thiobarbituric acid-reactive substances after DSS administration were both significantly inhibited by treatment with rosuvastatin. Rosuvastatin also inhibited increases in intestinal TNF-alpha protein and mRNA expression after DSS administration, respectively. The mucosal mRNA levels of eNOS were decreased after DSS administration, but preserved in mice treated with rosuvastatin. These results suggest that rosuvastatin prevents the development of DSS-induced colitis in mice via the inhibition of mucosal inflammatory responses associated with the preservation of eNOS transcription.

Animals↗

PubMed2006

[A case of Henoch-Schönlein purpura with relapse of ileitis and duodenitis for a short period].

A 60-year old man admitted our hospital due to abdominal pain, melena and arthralgia. There was purpura on his legs. On admission, the abdominal CT showed segmental mural thickening of terminal ileum and ascites. On the 4th hospital day, the abdominal CT showed severe mural thickening of the third portion of duodenum. On the 8th hospital day, the abdominal CT showed severe mural thickening of terminal ileum. We reported a rare case of Henoch-Schönlein purpura with relapse of ileitis and duodenitis for a short period which could be examined on the abdominal CT.

Duodenitis↗

PubMed2006

[Prophylactic effect of magnesium infusion against postoperative atrial fibrillation].

BACKGROUND: Atrial fibrillation (AF) is a common complication of cardiac operation. For the development of postoperative AF, various risk factors have been identified over the years. In a recent study, it was detected that low serum magnesium levels was an independent predictor of AF after coronary artery bypass grafting (CABG). The purpose of this study was to assess the prophylactic effect of intravenous magnesium infusion on postoperative AF. METHODS: A total of 62 consecutive patients who had elective, first time cardiac operation on cardiopulmonary bypass were prospectively categorized to 2 group. In the treatment group, 30 patients received 8.3 mmol of magnesium sulfate in 100 ml of saline solution that was administered over 4 hours, preoperatively, just after admission in the ICU, and at the postoperative day 1, 2, 3, and 4. RESULTS: Postoperative AF occurred in 3/30 (10.0%) patients in the treatment group and in 14/32 (43.8%) patients in the control group (p<0.01). The arrhythmia developed on the 2.9 postoperative day on average. The postoperative length of hospital stay was significantly shortened in the treatment group (15.9 +/- 4.0 days) than that in the control group (20.5 +/- 7.0, p < 0.01). CONCLUSION: Our findings indicate that magnesium sulfate infusion is effective for the prophylaxis of post operative AF.

Atrial Fibrillation↗

PubMed2006

Microarray profiling of gene expression patterns in glomerular cells of astaxanthin-treated diabetic mice: a nutrigenomic approach.

We have demonstrated that astaxanthin reduces glomerular oxidative stress as well as inhibits the increase in urinary albumin in diabetic db/db mice. The aim of the present study was to determine the gene expression patterns in the glomerular cells of the diabetic mouse kidney, and to investigate the effects of astaxanthin on the expression of these genes using a high-density DNA microarray. The diet administered to the astaxanthin-supplementation group was prepared by mixing a control powder with astaxanthin at a concentration of 0.02%. Glomerular cells were obtained from the kidneys of mice by laser capture microdissection. Preparation of cRNA and target hybridization were performed according to the Affymetrix GeneChip eukaryotic small sample target labeling assay protocol. The gene expression profile was evaluated by the mouse expression set 430A GeneChip. Array data analysis was carried out using Affymetrix GeneChip operating and Ingenuity Pathway analysis software. Comparison between diabetic db/db and non-diabetic db/m mice revealed that 779 probes (3.1%) were significantly affected, i.e. 550 probes were up-regulated, and 229 probes were down-regulated, both at levels of >/=1.5-fold in the diabetic mice. Ingenuity signal analysis of 550 up-regulated probes revealed the mitochondrial oxidative phosphorylation pathway as the most significantly affected caronical pathway. The affected genes were associated with complexes I, III, and IV located on the mitochondrial inner membrane, and the expression levels of these genes were decreased in mice treated with astaxanthin as compared to the levels in the control mice. In addition, the expression of many genes associated with oxidative stress, collagen synthesis, and transforming growth factor-beta signaling was enhanced in the diabetic mice, and this enhancement was slightly inhibited in the astaxanthin-treated mice. In conclusion, this genome-wide nutrigenomics approach provided insight into genes and putative genetic pathways that are thought to be affected by stimulation by high-glucose concentrations. In addition, the present approach may help us gain a better understanding of the genes and pathways involved in the anti-diabetic mechanism of astaxanthin.

Animals↗

PubMed2006

Inflammatory response of esophageal epithelium in combined-type esophagitis in rats: a transcriptome analysis.

Recent studies have shown that esophageal mucosal inflammatory response is involved in the pathophysiology of gastro-esophageal reflux disease. The aim of the present study was to identify specific gene expression profiles of the esophageal mucosa in a rat model of combined-type chronic reflux esophagitis. Esophagogastroduodenal anastomosis was carried out in male Wistar rats by anastomosing the jejunum to the gastroesophageal junction under diethyl-ether inhalation anesthesia. Esophageal epithelial cells were obtained from esophagi of rats by laser capture microdissection. Preparation of cRNA and target hybridization were performed according to the Affymetrix GeneChip eukaryotic small sample target labeling assay protocol. The gene expression profile was evaluated by the rat toxicology U34 GeneChip. Array data analysis was carried out using Affymetrix GeneChip operating software, ingenuity pathway analysis software, and Gene Springs software. A comparison between esophagitis and sham-operated rats 2 weeks after the operation revealed that 368 probes (36%) were significantly affected, i.e. 185 probes were up-regulated, and 183 probes were down-regulated, both at levels of at least 1.5-fold in the esophagitis rats. Ingenuity signal analysis of 207 affected probes revealed the interleukin-6 signaling pathway as the most significantly affected caronical pathway. In addition, the expression of many genes associated with cytokine and transcription factor was enhanced in the esophagitis rats. This transcriptome approach provided insight into genes and putative genetic pathways thought to be affected by stimulation with gastroduodenal refluxates.

Animals↗

PubMed2005

Partially hydrolyzed guar gum down-regulates colonic inflammatory response in dextran sulfate sodium-induced colitis in mice.

Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by a controlled partial enzymatic hydrolysis of guar gum beans, has various physiological actions. The aim of the present study was to elucidate the beneficial effects of PHGG on colonic mucosal damage and on the inflammatory response in a dextran sulfate sodium (DSS) colitis model. After 2 weeks of prefeeding of PHGG, acute colitis was induced with 8% DSS in female BALB/c mice. Colonic mucosal inflammation was evaluated clinically, biochemically and histologically. Mucosal protein contents and mRNA levels of tumor necrosis factor-alpha (TNF-alpha) were determined by immunoassay and reverse transcription polymerase chain reaction. Disease activity scores determined by weight loss, stool consistency and blood in stool in DSS-treated mice were significantly lower in the PHGG-treated mice compared with the control mice. Shortening of the colon was significantly reversed by PHGG. Histological study also showed a reduced infiltration of inflammatory cells, especially neutrophils, and mucosal cell disruption in PHGG-treated mice compared with the control mice. The increases in tissue-associated myeloperoxidase activity and thiobarbituric acid-reactive substances after DSS administration were both significantly inhibited by pretreatment with PHGG. Partially hydrolyzed guar gum also inhibited increases in intestinal TNF-alpha protein and mRNA expression after DSS administration, respectively. These results suggest that chronic ingestion of PHGG prevents the development of DSS-induced colitis in mice via the inhibition of mucosal inflammatory response.

Animals↗

PubMed2005

Biomarkers in patients with gastric inflammation: a systematic review.

BACKGROUND: The importance of examining the status of gastric inflammation has been acknowledged; the new classification by the updated Sydney system (USS) allows us to evaluate the quantitative status of gastric inflammation. However, this system is based on the histological classification derived from biopsy specimens. Therefore, more convenient, objective and practical biomarkers are recommended. AIM: We undertook a systematic review to find out potential biomarkers by summarizing the relationship between biomarkers and grades of inflammation. METHODS: By a primary search via Medline up to December 2004, we extracted a total of 6,526 papers that described biomarkers for human gastric inflammation. All papers were screened by title and abstract. The authors then retrieved 435 citations for complete review; ultimately 231 were appropriate for inclusion criteria. These papers were subclassified into several categories and summarized by each author. RESULTS: In addition to standard markers such as pepsinogens, we confirmed the close relationship between the levels of several biomarkers including gastrin, interleukin-8, HLA class II molecules, reactive oxygen species, and the histological grades. CONCLUSIONS: This review provides valuable information describing the clinical implication of these biomarkers for evaluating the static conditions or dynamic alterations of human gastric inflammation.

Biomarkers↗

PubMed2005

The radical scavenger edaravone enhances the anti-tumor effects of CPT-11 in murine colon cancer by increasing apoptosis via inhibition of NF-kappaB.

The transcription factor NF-kappaB is reportedly activated by anti-cancer chemotherapeutic compounds in many cancer cell lines and NF-kappaB activation is one mechanism by which tumors become resistant to apoptosis. Antioxidants have been reported to serve as potent NF-kB inhibitors. In this study, we investigated the ability of edaravone to enhance apoptosis induced by CPT-11 through inhibition of NF-kB. In vitro, SN38, the active metabolite of CPT-11, induced activation of NF-kB, the production of intracellular reactive oxygen species, the activation of caspase-3, and apoptosis in colon26 cells. Pretreatment with edaravone scavenged the SN38-produced reactive oxygen species, and inhibited the SN38-induced activation of NF-kB. Moreover, edaravone enhanced the activation of caspase-3, and the level of apoptosis induced by SN38. In vivo, the combination of edaravone with CPT-11 reduced subcutaneous tumor growth and number of pulmonary metastases more effectively than CPT-11 alone. These results demonstrate that the combination of edaravone with CPT-11 may constitute a new strategy for treating primary and metastatic colon cancer.

Adenocarcinoma↗

PubMed2005

Synergic action of insulin and genistein on Na+/K+/2Cl- cotransporter in renal epithelium.

Transepithelial Cl(-) secretion in polarized renal A6 cells is composed of two steps: (1) Cl(-) entry step across the basolateral membrane mediated by Na(+)/K(+)/2Cl(-) cotransporter (NKCC) and (2) Cl(-) releasing step across the apical membrane via cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. We estimated CFTR Cl(-) channel activity and transcellular Cl(-) secretion by measuring 5-nitro 2-(3-phenylpropylamino)benzoate (NPPB, a blocker of CFTR Cl(-) channel)-sensitive transepithelial conductance (Gt) and short-circuit current (Isc), respectively. Pretreatment with 1 microM insulin for 24 h had no effects on NPPB-sensitive Gt or Isc. On the other hand, in A6 cells treated with carbobenzoxy-L-leucyl-leucyl-L-leucinal (MG132; 100 microM for 2 h) that inhibits endocytosis of proteins at the plasma membrane into the cytosolic space, insulin pretreatment increased the NPPB-sensitive Isc with no effects on NPPB-sensitive Gt. Genistein (100 microM) induced sustained increases in NPPB-sensitive Gt and Isc, which were diminished by brefeldin A (a blocker of protein translocation to Golgi apparatus from endoplasmic reticulum). Co-application of insulin and genistein synergically stimulated the NPPB-sensitive Isc without any effects on NPPB-sensitive Gt. These observations suggest that: (1) insertion and endocytosis of NKCC are stimulated by insulin, (2) the insulin-induced stimulation of NKCC insertion into the basolateral membrane is offset by the stimulatory action on NKCC endocytosis from the basolateral membrane, (3) genistein stimulates insertion of both CFTR Cl(-) channel into the apical membrane and NKCC into the basolateral membrane, and (4) insulin and genistein synergically stimulated NKCC insertion into the basolateral membrane.

Amiloride↗

PubMed2005

Interleukin-10 plasmid DNA inhibits subcutaneous tumor growth of Colon 26 adenocarcinoma in mice.

The transcription factor NF-kappa B is constitutively activated in many human cancers, and induces the expression of multiple proteins including antiapoptotic proteins. Recent papers indicate that NF-kappa B activation is inhibited by interleukin (IL)-10. In this study, we investigated the effect of IL-10 plasmid DNA on colon cancer in mice. In vitro study: Colon 26 murine colon adenocarcinoma cells were either treated or untreated with IL-10 for 60 min. The cells were subsequently stimulated with TNF-alpha. In vivo study: to induce a high level of IL-10 in plasma, we transferred the naked plasmid vectors encoding the mouse IL-10 gene into the liver via the intravenous route. To establish tumors, we injected Colon 26 cells into BALB/c mice subcutaneously. In vitro study: a 24-h incubation with TNF-alpha did not affect cell viabilities; however, pretreatment with IL-10 significantly enhanced the level of apoptosis induced by TNF-alpha. Pretreating Colon 26 cells with IL-10 significantly attenuated the TNF-alpha-induced NF-kappa B activation. In vivo study: IL-10 plasmid controlled the growth of subcutaneous tumors. In subcutaneous tumor, NF-kappa B was activated in response to tumor growth. IL-10 plasmid markedly inhibited this activation of NF-kappa B in subcutaneous tumor. IL-10 plasmid induced cancer cell apoptosis linked to the down-regulation of antiapoptotic proteins, and the activation of caspase-3. These results demonstrate that IL-10 plasmid may constitute a new strategy for treating cancer growth.

Adenocarcinoma↗

PubMed2005

Tocotrienols reduce 25-hydroxycholesterol-induced monocyte-endothelial cell interaction by inhibiting the surface expression of adhesion molecules.

The migration of circulating monocytes into the subendothelial space occurs through the expressing of some adhesion molecules on endothelial cells. In the present study, using human aortic endothelial cells (HAECs), we investigated whether a model compound for oxysterols, 25-hydroxycholesterol, can enhance the monocyte adherence to HAECs exposed to 25-hydroxycholesterol via increasing expression of vascular cell adhesion molecule-1 (VCAM-1). We also aimed to determine the in vitro effects of tocotrienols on the enhanced interaction between monocytes and endothelial cells. We found that 25-hydroxycholesterol enhances surface expression determined by ELISA, induces VCAM-1 mRNA expression by real time-PCR, and stimulates adhesiveness of HAECs to U937 monocytic cells in a dose-dependent fashion. The combination treatment with anti-VCAM-1 and anti-CD11b monoclonal antibodies significantly reduced the monocyte adherence to 25-hydroxycholesterol-stimulated HAECs. Compared to alpha-tocopherol, tocotrienols displayed a more profound inhibitory effect on adhesion molecule expression and monocytic cell adherence. We observed that delta-tocotrienol exerted a most profound inhibitory action on monocytic cell adherence when compared to alpha-tocopherol and alpha-, beta-, and gamma-tocotrienols. Tocotrienols accumulated in HAECs to levels approximately 25-95-fold greater than that of alpha-tocopherol. In conclusion, these results indicate that a model compound 25-hydroxycholesterol can enhance the interaction between monocytes and HAECs, and that tocotrienols had a profound inhibitory effect on monocytic cell adherence to HAECs relative to alpha-tocopherol via inhibiting the VCAM-1 expression. These superior inhibitory effects of tocotrienols may be dependent on their intracellular accumulation.

Antibodies, Monoclonal↗

PubMed2005

Reduction of diabetes-induced renal oxidative stress by a cantaloupe melon extract/gliadin biopolymers, oxykine, in mice.

Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. Oxykine is the cantaloupe melon extract rich in vegetal superoxide dismutase covered by polymeric films of wheat matrix gliadin. In this study, we examined whether chronic oral administration of oxykine could prevent the progression of diabetic nephropathy induced by oxidative stress using preclinical rodent model of type 2 diabetes. We used female db/db mice and their non-diabetic db/m littermates. The mice were divided into the following three groups: non-diabetic db/m; diabetic db/db, and diabetic db/db treated with oxykine. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were preformed on 12 weeks from the beginning of treatment. After 12 weeks of treatment, the levels of blood glucose and the body weight were not significantly different between the oxykine-treated group and the non-treated db/db group, however both groups kept significantly high levels rather than db/m mice. The relative mesangial area calculated by mesangial area/total glomerular area ratio was significantly ameliorated in the oxykine treated group compared with non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with oxykine. The 8-OHdG immunoreactive cells in the glomeruli of non-treated db/db mice were more numerous than that of oxykine-treated db/db mice. In this study, treatment of oxykine ameliorated the progression and acceleration of diabetic nephropathy for rodent model of type 2 diabetes. These results indicated that the oxykine reduced the diabetes-induced oxidative stress and renal mesangial cell injury. In conclusion, oxykine might be a novel approach for the prevention of diabetes nephropathy.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Global analysis of gene expression in gastric ischemia-reperfusion: a future therapeutic direction for mucosal protective drugs.

Gastric ischemia-reperfusion is a relatively common condition leading to mucosal injury and may affect mucosal repair via modulating the gene expression of growth factors. Therefore, precise understanding of the molecular mechanism of ischemia or ischemia-reperfusion may lead to the discovery of new mucosal protective drugs. DNA microarray analysis followed by powerful data analysis has the potential to uncover previously undescribed genes involved in gastric injury and lead to an increased understanding of gastric mucosal cytoprotection. We introduced the laser-assisted microdissection to obtain cell-specific RNA from gastric mucosa in vivo and obtained sufficient amounts of cRNA for GeneChip analysis. This comprehensive approach enabled the simultaneous analysis of many genes, including transcriptional factors, as well as the generation of novel hypothesis on the mechanism of action of gastro-protective agents.

Gastric Mucosa↗

PubMed2005

Prevention by rebamipide of acute reflux esophagitis in rats.

Proinflammatory factors, including neutrophil-derived oxygen free radicals and inflammatory cytokines, have recently been implicated in the pathogenesis of reflux esophagitis. Rebamipide has been widely used as an anti-ulcer agent. The aim of the present study was to assess the protective effect of rebamipide against acute reflux esophagitis in rats. Esophagitis was induced in rats by ligation at the limiting ridge and the lower portion of the duodenum. Vehicle or rebamipide were given as a single dose intraduodenally. Lesion index (LI), thiobarbituric acid-reactive substances (TBA-RS), myeloperoxidase (MPO) activity, mRNA and protein of tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant (CINC)-1 in the esophageal mucosa were markedly increased; pretreatment with rebamipide, however, significantly reduced both macroscopic and microscopic injuries and increases in inflammatory mediators. The results of this study indicate that rebamipide protects against the occurrence of esophagitis and has highly promising potential as a new therapeutic agent for reflux esophagitis.

Acute Disease↗

PubMed2005

Rebamipide, a gastro-protective drug, inhibits indomethacin-induced apoptosis in cultured rat gastric mucosal cells: association with the inhibition of growth arrest and DNA damage-induced 45 alpha expression.

Rebamipide, a gastromucosal protective drug, suppresses indomethacin-induced gastropathy in humans and rodents. Effects of rebamipide on gene expression in indomethacin-treated gastric mucosal cells (RGM1) were investigated using high-density oligonucleotide arrays. Indomethacin induced apoptosis in RGM1 cells in a dose-dependent manner. Rebamipide pretreatment significantly reduced indomethacin-induced apoptosis. We used gene expression profiling on high-density oligonucleotide probe arrays to characterize the transcriptional response of RGM1 cells to indomethacin treatment for 6 hr. Of the 8,799 probes examined, 717 (8.1%) were induced (400 probes) or repressed (317 probes) at least 1.5-fold. Among the 158 genes that were induced by indomethacin at least 2.0-fold, four genes that were down-regulated by rebamipide at least 2.0-fold are listed: growth arrest and DNA-damage-inducible 45 alpha (GADD 45 alpha), golgi SNAP receptor complex member 1, iodothyronine deiodinases, and transcription factor 8. Real time-PCR confirmed GADD 45 alpha expression and its inhibition by rebamipide. Inhibition of apoptosis-related genes is possibly important for the cytoprotective effect of rebamipide against indomethacin-induced gastric mucosal cell injury.

Alanine↗

PubMed2005

A comparative study on endoscopic ulcer healing of omeprazole versus rabeprazole with respect to CYP2C19 genotypic differences.

Omeprazole is mainly metabolized in the liver by CYP2C19, a genetically determined enzyme, while rabeprazole is mainly nonenzymatically degraded with a minor involvement by CYP2C19. We investigated the gastric ulcer healing effect of omeprazole versus rabeprazole evaluated endoscopically with reference to the different CYP2C19 genotypes. Eighty patients with active gastric ulcer were treated with a daily dose of 20 mg of omeprazole or 10 mg of rabeprazole. The endoscopic evaluation was performed at the baseline and 2- and 8-week posttreatment periods. The endoscopic improvement of gastric ulcer size and ulcer healing rates using a thin rubber disc with a diameter of 6 mm, were evaluated in relation to the CYP2C19 genotypic status. The mean 2-week posttreatment ulcer size value by rabeprazole did not significantly differ among the different CYP2C19 genotypes, whereas the mean value in the homozygous extensive metabolizer patients treated with omeprazole was significantly (P = 0.0057) greater than in those with rabeprazole. However, after the 8-week treatment, omeprazole and rabeprazole showed the similarly high healing rates of 87.8% (31/37) and 88.9% (32/36), respectively. Although both omeprazole and rabeprazole showed a high healing rate of gastric ulcer after the 8-week treatment period, the healing effect of rabeprazole appears to be relatively independent of the CYP2C19 status, resulting in an earlier repair of gastric mucosal damage evaluated endoscopically compared to that of omeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗