The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Toshihiko Hirano - One of the best experts on this subject based on the ideXlab platform.
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Sofalcone upregulates the nuclear factor erythroid derived 2 like 2 heme oxygenase 1 pathway reduces soluble fms like tyrosine kinase 1 and quenches endothelial dysfunction potential therapeutic for preeclampsia
Hypertension, 2015Co-Authors: Kenji Onda, Toshihiko Hirano, Stephen Tong, Anzu Nakahara, Mei Kondo, Hideaki Monchusho, Tuuhevaha J Kaituulino, Sally Beard, Natalie Binder, Laura TuoheyAbstract:Preeclampsia is a severe complication of pregnancy, characterized by hypertension, oxidative stress, and severe endothelial dysfunction. Antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, play key pathophysiological roles in preeclampsia. Heme oxygenase-1 (HO-1) is a cytoprotective, antioxidant enzyme reported to be downregulated in preeclampsia. Studies propose that inducing HO-1 may also decrease sFlt-1 production. Sofalcone, a gastric antiulcer agent in clinical use, is known to induce HO-1 in gastric epithelium. We aimed to investigate whether Sofalcone induces HO-1 and reduces sFlt-1 release from primary human placental and endothelial cells and blocks endothelial dysfunction in vitro. We isolated human trophoblasts and endothelial cells (human umbilical vein endothelial cells) and also used uterine microvascular cells. We investigated the effects of Sofalcone on (1) HO-1 production, (2) activation of the nuclear factor (erythroid-derived 2)-like 2 pathway, (3) sFlt-1 and soluble endoglin release, (4) tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule upregulation, and (5) endothelial tubule formation. Sofalcone potently increased HO-1 mRNA and protein in both primary trophoblasts and human umbilical vein endothelial cells. Furthermore, Sofalcone treatment caused nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 and transactivation of other nuclear factor (erythroid-derived 2)-like 2 responsive genes (NQO1, TXN, and GCLC). Importantly, Sofalcone significantly decreased the secretion of sFlt-1 from primary human trophoblasts. Sofalcone potently suppressed endothelial dysfunction in 2 in vitro models, blocking tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule 1 expression in human umbilical vein endothelial cells. These results indicate that in primary human tissues, Sofalcone can potently activate antioxidant nuclear factor (erythroid-derived 2)-like 2/HO-1 pathway, decrease sFlt-1 production, and ameliorate endothelial dysfunction. We propose that Sofalcone is a novel therapeutic candidate for preeclampsia.
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Sofalcone a gastric mucosa protective agent increases vascular endothelial growth factor via the nrf2 heme oxygenase 1 dependent pathway in gastric epithelial cells
Biochemical and Biophysical Research Communications, 2010Co-Authors: Akiko Shibuya, Kenji Onda, Hirofumi Kawahara, Yuka Uchiyama, Hiroko Nakayama, Takamasa Omi, Masayoshi Nagaoka, Hirofumi Matsui, Toshihiko HiranoAbstract:Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that Sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of Sofalcone on HO-1 induction in gastrointestinal tissues is not clear. In the current study, we investigated the effects of Sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that Sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that Sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited Sofalcone-induced VEGF production, suggesting that the effect of Sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of Sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.
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Sofalcone an anti ulcer chalcone derivative suppresses inflammatory crosstalk between macrophages and adipocytes and adipocyte differentiation implication of heme oxygenase 1 induction
Biochemical and Biophysical Research Communications, 2009Co-Authors: Hideaki Tanaka, Kenji Onda, Seito Nakamura, Tomoya Tazaki, Toshihiko HiranoAbstract:Abstract Sofalcone, 2′-carboxymethoxy-4,4′-bis(3-methyl-2-butenyloxy)chalcone, has been used as an anti-ulcer agent, although its precise molecular mechanism has not been completely understood. In the current study, we tested the effects of Sofalcone on the inflammatory crosstalk between macrophages and adipocytes and on the differentiation of pre-adipocytes. We found that Sofalcone has a strong suppressive effect on the production of nitric oxide (NO), tumor necrosis factor (TNF)α, and monocyte chemoattractant protein (MCP)-1 in the culture medium of a coculture system containing RAW264.7 macrophages and 3T3-F442A adipocytes stimulated with lipopolysaccharide (LPS). The suppressive effect of Sofalcone on NO production was attenuated by treatment with tin-protoporphyrin (SnPP), a heme-oxygenase (HO)-1 inhibitor. Western blotting analysis showed that Sofalcone increased HO-1 expression in both 3T3-F442A mature adipocytes and undifferentiated fibroblasts. Sofalcone also inhibited the differentiation of 3T3-F442A pre-adipocytes into adipocytes, which was restored by SnPP treatment. These results suggest that Sofalcone has preferable properties for obesity or metabolic syndrome.
Kenji Onda - One of the best experts on this subject based on the ideXlab platform.
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Sofalcone upregulates the nuclear factor erythroid derived 2 like 2 heme oxygenase 1 pathway reduces soluble fms like tyrosine kinase 1 and quenches endothelial dysfunction potential therapeutic for preeclampsia
Hypertension, 2015Co-Authors: Kenji Onda, Toshihiko Hirano, Stephen Tong, Anzu Nakahara, Mei Kondo, Hideaki Monchusho, Tuuhevaha J Kaituulino, Sally Beard, Natalie Binder, Laura TuoheyAbstract:Preeclampsia is a severe complication of pregnancy, characterized by hypertension, oxidative stress, and severe endothelial dysfunction. Antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, play key pathophysiological roles in preeclampsia. Heme oxygenase-1 (HO-1) is a cytoprotective, antioxidant enzyme reported to be downregulated in preeclampsia. Studies propose that inducing HO-1 may also decrease sFlt-1 production. Sofalcone, a gastric antiulcer agent in clinical use, is known to induce HO-1 in gastric epithelium. We aimed to investigate whether Sofalcone induces HO-1 and reduces sFlt-1 release from primary human placental and endothelial cells and blocks endothelial dysfunction in vitro. We isolated human trophoblasts and endothelial cells (human umbilical vein endothelial cells) and also used uterine microvascular cells. We investigated the effects of Sofalcone on (1) HO-1 production, (2) activation of the nuclear factor (erythroid-derived 2)-like 2 pathway, (3) sFlt-1 and soluble endoglin release, (4) tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule upregulation, and (5) endothelial tubule formation. Sofalcone potently increased HO-1 mRNA and protein in both primary trophoblasts and human umbilical vein endothelial cells. Furthermore, Sofalcone treatment caused nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 and transactivation of other nuclear factor (erythroid-derived 2)-like 2 responsive genes (NQO1, TXN, and GCLC). Importantly, Sofalcone significantly decreased the secretion of sFlt-1 from primary human trophoblasts. Sofalcone potently suppressed endothelial dysfunction in 2 in vitro models, blocking tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule 1 expression in human umbilical vein endothelial cells. These results indicate that in primary human tissues, Sofalcone can potently activate antioxidant nuclear factor (erythroid-derived 2)-like 2/HO-1 pathway, decrease sFlt-1 production, and ameliorate endothelial dysfunction. We propose that Sofalcone is a novel therapeutic candidate for preeclampsia.
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Sofalcone a gastric mucosa protective agent increases vascular endothelial growth factor via the nrf2 heme oxygenase 1 dependent pathway in gastric epithelial cells
Biochemical and Biophysical Research Communications, 2010Co-Authors: Akiko Shibuya, Kenji Onda, Hirofumi Kawahara, Yuka Uchiyama, Hiroko Nakayama, Takamasa Omi, Masayoshi Nagaoka, Hirofumi Matsui, Toshihiko HiranoAbstract:Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that Sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of Sofalcone on HO-1 induction in gastrointestinal tissues is not clear. In the current study, we investigated the effects of Sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that Sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that Sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited Sofalcone-induced VEGF production, suggesting that the effect of Sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of Sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.
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Sofalcone an anti ulcer chalcone derivative suppresses inflammatory crosstalk between macrophages and adipocytes and adipocyte differentiation implication of heme oxygenase 1 induction
Biochemical and Biophysical Research Communications, 2009Co-Authors: Hideaki Tanaka, Kenji Onda, Seito Nakamura, Tomoya Tazaki, Toshihiko HiranoAbstract:Abstract Sofalcone, 2′-carboxymethoxy-4,4′-bis(3-methyl-2-butenyloxy)chalcone, has been used as an anti-ulcer agent, although its precise molecular mechanism has not been completely understood. In the current study, we tested the effects of Sofalcone on the inflammatory crosstalk between macrophages and adipocytes and on the differentiation of pre-adipocytes. We found that Sofalcone has a strong suppressive effect on the production of nitric oxide (NO), tumor necrosis factor (TNF)α, and monocyte chemoattractant protein (MCP)-1 in the culture medium of a coculture system containing RAW264.7 macrophages and 3T3-F442A adipocytes stimulated with lipopolysaccharide (LPS). The suppressive effect of Sofalcone on NO production was attenuated by treatment with tin-protoporphyrin (SnPP), a heme-oxygenase (HO)-1 inhibitor. Western blotting analysis showed that Sofalcone increased HO-1 expression in both 3T3-F442A mature adipocytes and undifferentiated fibroblasts. Sofalcone also inhibited the differentiation of 3T3-F442A pre-adipocytes into adipocytes, which was restored by SnPP treatment. These results suggest that Sofalcone has preferable properties for obesity or metabolic syndrome.
Hiromasa Ishii - One of the best experts on this subject based on the ideXlab platform.
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autonomic nervous regeneration in acetic acid induced ulcer from the viewpoint of synapse formation effect of basic fibroblast growth factor and Sofalcone in the rat
Alimentary Pharmacology & Therapeutics, 2000Co-Authors: Masahiko Nakamura, Hiromasa Ishii, H Kishikawa, N Kumagai, K TsuchimotoAbstract:Summary Background: Monoclonal antibodies against GAP43 and synaptophysin, markers of regenerated nerves, have recently become available. Aim: To investigate the regeneration of the autonomic nerves after acetic acid treatment, as well as the effect of recombinant basic fibroblast growth factor (bFGF-CS23) and Sofalcone on reinnervation. Methods: Ulcers were induced by the direct application of 100% acetic acid to the serosal surface of the rat fundic stomach. Some rats were treated with bFGF-CS23 or Sofalcone every 12 h after the acetic acid treatment. The immunohistochemical location of GAP43 and synaptophysin was observed by confocal laser microscopy, and the uptake sites of 14C-Sofalcone were observed by autoradiography. Results: Both GAP43 and synaptophysin immuno-reactivities surrounding microvessels were weak in the control group, whereas in the acetic acid-treated group, these immunoreactivities were increased. Treatment with bFGF-CS23 and Sofalcone increased these immunoreactivities. The binding sites of Sofalcone coincided with the location of regenerated nerves and surface mucous cells. The progenitors of the autonomic nerves were more abundant than expected. Conclusion: Both bFGF and Sofalcone seem to stimulate nerve regeneration.
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effect of combined administration of lansoprazole and Sofalcone on microvascular and connective tissue regeneration after ethanol induced gastric mucosal damage
Journal of Clinical Gastroenterology, 1998Co-Authors: Masahiko Nakamura, Yasutada Akiba, Masaya Oda, Hiroshi Kishikawa, Hiromasa IshiiAbstract:We undertook the present study to clarify the alteration of localization of basic fibroblast growth factor (bFGF), endothelial cells, and myofibroblasts in the healing of ethanol-induced gastric mucosal damage by the combined administration of lansoprazole and Sofalcone. Wistar strain male rats were used. Ethanol 50% was given through orogastric intubation. Thirty minutes later, an aqueous solution of lansoprazole, Sofalcone, a combination of lansoprazole and Sofalcone, or physiologic saline was given orally. The stomach was removed and the localization of bFGF, myofibroblast, and endothelial cells was examined using monoclonal antibodies. Some rats were pretreated with indomethacin to rule out the effect of endogenous prostaglandin. The combined administration of lansoprazole and Sofalcone brought about increased concentrations and immunoreactive areas of bFGF and a greater number of endothelial cells, compared with the ethanol-alone treatment. The number of myofibroblasts increased more significantly in the group treated with a combination of agents than in that treated with ethanol alone, ethanol plus Sofalcone, or ethanol plus lansoprazole. Indomethacin pretreatment partly abolished the effects of single and combined administration of these agents. In conclusion, the mixed administration of lansoprazole and Sofalcone accelerated the microvascular and connective tissue regeneration during the healing of ethanol-induced gastric mucosal damage.
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gastric urease activity is inversely associated with the success of treatment for helicobacter pylori effect of Sofalcone
Journal of Clinical Gastroenterology, 1998Co-Authors: Masayuki Suzuki, Tetsuo Kitahora, Shouichi Nagahashi, Hidekazu Suzuki, Mikiji Mori, Toshifumi Hibi, Hiromasa IshiiAbstract:Eradication therapy for Helicobacter pylori (H. pylori) has been established. However, the physiological factors influencing the success of treatment remain unclear. The aim of this study was to analyze these factors and to evaluate the efficacy of Sofalcone on H. pylori eradication therapy. Forty-four H. pylori-infected and peptic ulcer patients were enrolled in this study. Twenty-seven patients were treated with lansoprazole (LPZ, 30 mg o.d. for 1-8 weeks) and amoxicillin (AMPC, 500 mg q.i.d. 1-2 weeks), followed by 8 weeks of treatment with famotidine (FAM, 20 mg o.d.). Moreover, Sofalcone (SOF, 100 mg t.i.d) was administered to 17 patients throughout the therapeutic period. Endoscopic and serologic evaluations and the urea breath test (UBT) were performed before therapy. At the endoscopic examination, mucosal samples were biopsied and then tissue myeloperoxidase (MPO) content, an index of neutrophil infiltration was measured. Cure of H. pylori infection was determined 8 weeks after the cessation of LPZ. This eradication regimen afforded an overall cure rate of 63.0% (17/27) without SOF and 76.5% (13/17) with SOF. In the control group, treatment success was inversely associated with pre-UBT value (gastric urease activity), whereas this association was not observed in the SOF group. Furthermore, in the patients exhibiting a high pre-UBT value (>40%), a twofold higher eradication rate was obtained by the administration of SOF. In patients who were successfully eradicated, mucosal MPO level was slightly higher than those of unsuccessful cases, whereas there was no significant association with serum pepsinogen (PG I, PG II) concentration and its ratio (PG I/PG II). These results suggest that a low UBT value is a factor predicting treatment success. SOF administration may improve the eradication rate, especially in the high-UBT subgroup.
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alteration of basic fibroblast growth factor concentration and immunoreactivity in healing of ethanol induced gastric mucosal damage effect of Sofalcone
Journal of Clinical Gastroenterology, 1997Co-Authors: Masahiko Nakamura, Yasutada Akiba, Masaya Oda, Hiromasa IshiiAbstract:To clarify the interaction of endothelial cells, myofibroblasts, and basic fibroblast growth factor (bFGF) in healing of gastric mucosal damage, histochemical and biochemical observations were undertaken. In addition, the effect of Sofalcone on ulcer healing and especially on angiogenesis was studied. Male Wistar rats were used. Ethanol (50%) was administered through an orogastric tube. Thirty minutes after ethanol administration, an aqueous solution of Sofalcone (100 mg/100 g b.w.) or the same amount of physiologic saline was administered in the same way. At 1, 3, and 12 h after Sofalcone treatment, the localization of endothelial cells and myofibroblasts was studied. The bFGF concentration was decreased at 3 and 12 h in rats treated with ethanol alone, but addition of Sofalcone did not alter the content of bFGF 3.5 and 12.5 h after Sofalcone administration. Sofalcone had a strong influence on healing of ethanol-induced gastric mucosal damage, possibly through an indomethacin-sensitive, prostanoid-related increase in bFGF concentration.
Tetsuo Arakawa - One of the best experts on this subject based on the ideXlab platform.
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Sofalcone a gastroprotective drug promotes gastric ulcer healing following eradication therapy for helicobacter pylori a randomized controlled comparative trial with cimetidine an h2 receptor antagonist
Journal of Gastroenterology and Hepatology, 2010Co-Authors: Kazuhide Higuchi, Toshio Watanabe, Tetsuya Tanigawa, Kazunari Tominaga, Yasuhiro Fujiwara, Tetsuo ArakawaAbstract:Background and Aims: According to reports in Japanese patients, 1 week of Helicobacter pylori eradication therapy alone is not adequate for healing of gastric ulcers; 7–8 weeks of anti-ulcer therapy are subsequently required. We compared a gastroprotective drug, Sofalcone, and an H2-receptor antagonist, cimetidine, in terms of promoting ulcer healing after 7 weeks of administration following 1 week of eradication therapy. Methods: Eradication therapy was administered to 64 patients with H. pylori-positive active gastric ulcer at least 10 mm in diameter, after which 32 patients each received 7 weeks of ulcer treatment with Sofalcone (300 mg/day) or cimetidine (800 mg/day). Results: The H. pylori eradication rate was 81.3% (intention-to-treat: ITT) and 81.3% (per protocol: PP) in the Sofalcone group, and 62.5% (ITT) and 64.5% (PP) in the cimetidine group. The ulcer healing rate after 8 weeks was 71.9% (ITT) and 71.9% (PP) in the Sofalcone group, and 71.9% (ITT) and 71.0% (PP) in the cimetidine group. The rate of a flat pattern of scarred mucosa was 43.5% (ITT) and 43.5% (PP) in the Sofalcone group, and 47.8% (ITT) and 50.0% (PP) in the cimetidine group. No significant differences were seen between the two groups in terms of H. pylori eradication rate, ulcer healing rate and flat pattern rate. Conclusion: Sofalcone promoted gastric ulcer healing during 7 weeks of treatment following 1 week of eradication therapy, and the healing rate was equivalent to that of cimetidine. Symptom disappearance rates were significantly better in the Sofalcone group than in the cimetidine group. This may be a useful way of using a gastroprotective drug in the H. pylori era.
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effect of Sofalcone on localization of 15 hydroxyprostaglandin dehydrogenase an enzyme that metabolizes prostaglandin e an immunohistochemical study2 an immunohistochemical study in rat gastric mucosa an immunohistochemical study
Journal of Clinical Gastroenterology, 1992Co-Authors: Kenzo Kobayashi, Kazuhide Higuchi, Tetsuo Arakawa, Takayuki Matsumoto, Hiroshi NaguraAbstract:We identified the cells containing 15-hydroxyprostaglandin dehydrogenase (15-HPGD) in rat gastric mucosa and examined the effects of Sofalcone on the localization of the enzyme by use of an immunohistochemical technique. Also, we investigated the effects of Sofalcone on the localization of prostaglandin E2 (PGE2). Specific stainings for 15-HPGD and PGE2 were similarly observed in a granular pattern mainly in the cytoplasm of parietal and surface epithelial cells. The number of the stained cells for 15-HPGD, especially surface epithelial cells, decreased when rats were given Sofalcone, with a concomitant increase in PGE2 staining. These results suggest that parietal and surface epithelial cells are responsible for the degeneration of PGE2 in the rat gastric mucosa, and that Sofalcone increased the PGE2 level in the mucosa through inactivation of 15-HPGD in these cells, especially surface epithelial cells.
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effect of Sofalcone on localization of 15 hydroxyprostaglandin dehydrogenase an enzyme that metabolizes prostaglandin e2 in rat gastric mucosa an immunohistochemical study
Journal of Clinical Gastroenterology, 1992Co-Authors: Kenzo Kobayashi, Kazuhide Higuchi, Tetsuo Arakawa, Takayuki Matsumoto, Hiroshi NaguraAbstract:We identified the cells containing 15-hydroxyprostaglandin dehydrogenase (15-HPGD) in rat gastric mucosa and examined the effects of Sofalcone on the localization of the enzyme by use of an immunohistochemical technique. Also, we investigated the effects of Sofalcone on the localization of prostaglandin E2 (PGE2). Specific stainings for 15-HPGD and PGE2 were similarly observed in a granular pattern mainly in the cytoplasm of parietal and surface epithelial cells. The number of the stained cells for 15-HPGD, especially surface epithelial cells, decreased when rats were given Sofalcone, with a concomitant increase in PGE2 staining. These results suggest that parietal and surface epithelial cells are responsible for the degeneration of PGE2 in the rat gastric mucosa, and that Sofalcone increased the PGE2 level in the mucosa through inactivation of 15-HPGD in these cells, especially surface epithelial cells.
Masahiko Nakamura - One of the best experts on this subject based on the ideXlab platform.
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autonomic nervous regeneration in acetic acid induced ulcer from the viewpoint of synapse formation effect of basic fibroblast growth factor and Sofalcone in the rat
Alimentary Pharmacology & Therapeutics, 2000Co-Authors: Masahiko Nakamura, Hiromasa Ishii, H Kishikawa, N Kumagai, K TsuchimotoAbstract:Summary Background: Monoclonal antibodies against GAP43 and synaptophysin, markers of regenerated nerves, have recently become available. Aim: To investigate the regeneration of the autonomic nerves after acetic acid treatment, as well as the effect of recombinant basic fibroblast growth factor (bFGF-CS23) and Sofalcone on reinnervation. Methods: Ulcers were induced by the direct application of 100% acetic acid to the serosal surface of the rat fundic stomach. Some rats were treated with bFGF-CS23 or Sofalcone every 12 h after the acetic acid treatment. The immunohistochemical location of GAP43 and synaptophysin was observed by confocal laser microscopy, and the uptake sites of 14C-Sofalcone were observed by autoradiography. Results: Both GAP43 and synaptophysin immuno-reactivities surrounding microvessels were weak in the control group, whereas in the acetic acid-treated group, these immunoreactivities were increased. Treatment with bFGF-CS23 and Sofalcone increased these immunoreactivities. The binding sites of Sofalcone coincided with the location of regenerated nerves and surface mucous cells. The progenitors of the autonomic nerves were more abundant than expected. Conclusion: Both bFGF and Sofalcone seem to stimulate nerve regeneration.
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effect of combined administration of lansoprazole and Sofalcone on microvascular and connective tissue regeneration after ethanol induced gastric mucosal damage
Journal of Clinical Gastroenterology, 1998Co-Authors: Masahiko Nakamura, Yasutada Akiba, Masaya Oda, Hiroshi Kishikawa, Hiromasa IshiiAbstract:We undertook the present study to clarify the alteration of localization of basic fibroblast growth factor (bFGF), endothelial cells, and myofibroblasts in the healing of ethanol-induced gastric mucosal damage by the combined administration of lansoprazole and Sofalcone. Wistar strain male rats were used. Ethanol 50% was given through orogastric intubation. Thirty minutes later, an aqueous solution of lansoprazole, Sofalcone, a combination of lansoprazole and Sofalcone, or physiologic saline was given orally. The stomach was removed and the localization of bFGF, myofibroblast, and endothelial cells was examined using monoclonal antibodies. Some rats were pretreated with indomethacin to rule out the effect of endogenous prostaglandin. The combined administration of lansoprazole and Sofalcone brought about increased concentrations and immunoreactive areas of bFGF and a greater number of endothelial cells, compared with the ethanol-alone treatment. The number of myofibroblasts increased more significantly in the group treated with a combination of agents than in that treated with ethanol alone, ethanol plus Sofalcone, or ethanol plus lansoprazole. Indomethacin pretreatment partly abolished the effects of single and combined administration of these agents. In conclusion, the mixed administration of lansoprazole and Sofalcone accelerated the microvascular and connective tissue regeneration during the healing of ethanol-induced gastric mucosal damage.
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alteration of basic fibroblast growth factor concentration and immunoreactivity in healing of ethanol induced gastric mucosal damage effect of Sofalcone
Journal of Clinical Gastroenterology, 1997Co-Authors: Masahiko Nakamura, Yasutada Akiba, Masaya Oda, Hiromasa IshiiAbstract:To clarify the interaction of endothelial cells, myofibroblasts, and basic fibroblast growth factor (bFGF) in healing of gastric mucosal damage, histochemical and biochemical observations were undertaken. In addition, the effect of Sofalcone on ulcer healing and especially on angiogenesis was studied. Male Wistar rats were used. Ethanol (50%) was administered through an orogastric tube. Thirty minutes after ethanol administration, an aqueous solution of Sofalcone (100 mg/100 g b.w.) or the same amount of physiologic saline was administered in the same way. At 1, 3, and 12 h after Sofalcone treatment, the localization of endothelial cells and myofibroblasts was studied. The bFGF concentration was decreased at 3 and 12 h in rats treated with ethanol alone, but addition of Sofalcone did not alter the content of bFGF 3.5 and 12.5 h after Sofalcone administration. Sofalcone had a strong influence on healing of ethanol-induced gastric mucosal damage, possibly through an indomethacin-sensitive, prostanoid-related increase in bFGF concentration.