• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.326-337
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• 2003

In order to evaluate the prevention effect of Sunkiwhajung-tang (SWT) which has been used as a traditional prescription for the treatment of digestive disease in Korea on the gastric ulcer induced by indomethacin in rats, the changes of number and size of ulcerative lesions, parietal, chief, Grimelius and Serotonin-positive cells in the peri-ulcerative tissues were detected with histological examinations of ulcerative and peri-ulcerative lesions after oral injections of SWT extracts (125, 250 and 500 mg/kg, respectively). SWT prevented to a great extent the expected indomethacin-induced elevation in hemorrhagic ulcerative lesions, the number and size of ulcerative lesions, and the number of parietal cell, chief cell, Grimelius-positive cells and Serotonin-positive cells in the peri-ulcerative lesions in a dose dependent manner. These results provide a story evidence that SWT produced an protective effect on gastric ulcer induced by indomethacin. Determination of the specific mechanisms involved in the protective effect of SWT on the gastric ulcer will require additional study.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.92-92
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• 1995

It has been suggested that oxygen-derived free radicals have an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothetized to exert its protective effect on NSAIDS-induced gastric injury by its antioxidant properties, Protect ive effect of taurine on indomethacin-induced gastric mucosal lesion and its protective mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats, Pretreatment with 0.25 g/kg of taurine for 3 days significantly reduced the gastric lesion formation and Inhibited the elevation of lipid peroxide level In gastric mucosa. Both resting and FMLP-induced luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment of indomethacin. 5-20mM of taurine inhibited chemiluminescence of neutrophils activated by indomethacin and/or FMLP. Human neutrophils (polymorphonuclear leukocytes) significantly adhered to confluent monolayer of human umbilical vein endothelial cells(HUVEC) after coincubation with aspirin or indomethacin. Also taurine prevented neutrophil adhesion induced by these drugs to HUVEC in dose-dependent manner. These results indicate that the protective effect of taurine against NSAIDS-induced gastric mucosal Injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.85-90
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• 1996

It has been suggested that oxygen-derived free radicals play an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothetized to exert its protective effect on NSAIDs-induced gastric injury by its antioxidant properties. Protective effect of taurine on indomethacin-induced gastric mucosal lesion and its protection mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats. Pretreatment with 0.25 or 0.5 g/kg of taurine one day before or for 3 days significantly reduced the gastric lesion formation and inhibited the elevation of lipid peroxide level in gastric mucosa. The luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment of FMLP or indomethacin. Taurine (5-20 mM) inhibited chemiluminescence of neutrophils activated by FMLP. Human neutrophils (polymorphonuclear leukocytes) significantly adhered to the confluent monolayer of human umbilical vein endothelial cells (HUVEC) after coincubation with indomethacin. This neutrophil adhesion induced by indomethacin to HUVEC was prevented by taurine in a dose-dependent manner. These results indicate that the protective effect of taurine against NSAIDs-induced gastric mucosal injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.

• The Journal of Internal Korean Medicine
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• v.22 no.4
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• pp.589-599
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• 2001

Objective: This study was carried out to investigate the effects of Hyangsayukgunja-tang extract on indomethacin-induced gastric mucosal lesions of mice. Methods: To evaluate the effects of Hyangsayukgunja-tang extract and Misoprostol, the morphology of gastric mucosa, and the distribution of mucose cells, PNA(Peanut Agglutinin), ICAM(intercellular adhesion molecule), and apoptotic cells were observed. Hyangsayukgunja-tang extract and Misoprostol were intragastric injected to the test groups at hour 72 before and just before indomethacin treatment(HYT-J, HYT-72, M-J, M-72), while the INDO group was injected only with indomethacin and the control group was subcutaneously injected only with saline. Results: The gastric mucosal lesions incresed in the fundus and body of INDO group, but softened in HYT group and M group, the effects were more excellent in the HYT-72, M-72 groups than the HYT-J, M-J groups and in the HYT group than M group. The disappearance of surface and neck mucose cells were shown in INDO group, but softened in HYT group and M group. The mucosal configuration of HYT-72 group was the same as control group. The numerical increase of PNA positive reaction in cytoplasm of perietal cells were appeared in INDO group. The PNA positive reaction in HYT group and Miso-group were shown in surface mucous cells and microvilli of apical surface in chief cells as control group, and were the same as control group in all mucosa of HYT-72 group. The distribution of ICAM positive cells, increased in INDO group, but decreased in M-72 group, and were the same as control group in HYT-72 group. The apoptotic cells, increased noticeably in gastric mucosa of INDO group, decreased in HYT group and M group, and decreased noticeably in HYT-72 group. Conclusions: Hyangsayukgunja-tang extract had excellent effects on indomethacin-induced gastric mucosal lesions.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.237-244
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• 1993

The effect of nicotine on the secretion of $[Met^{5}]-enkephalin$ (ME) in addition to proenkephalin A (proENK) mRNA levels and effects of indomethacin, nordihydroguaiaretic acid (NDGA), and captopril on nicotine-induced responses were studied in bovine adrenal medullary chromaffrin (BAMC) cells. Long-term exposure of BAMC cells to nicotine at a concentration of $10{\mu}M$ significantly increased proENK mRNA level and the secretion of ME into the medium. Treatment of BAMC cells with NDGA (a lipoxygenase inhibitor, $10{\mu}M$), indomethacin (a cycloooxygenase inhibitor) or captopril (an angiotensin converting enzyme inhibitor) alone did not affect ME secretion and proENK mRNA levels. The pretreatment of BAMC cells with NDGA inhibited the increased ME secretion and proENK mRNA level induced by nicotine. However, indomethacin and captopril did not affect nicotine-induced responses. Our results indicate that neuronal regulations of ME secretion and proENK mRNA level induced by nicotine in BAMC cells are in part mediated by a lipoxygenase-but not cyclooxygenase-and endogenous renin-angiotensin pathway.

• Clinical and Experimental Pediatrics
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• v.49 no.9
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• pp.959-965
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• 2006

Purpose : The purpose of this study was to investigate the effect of prophylactic indomethacin on reduction of patent ductus arteriosus(PDA) and intraventricular hemorrhage(IVH) in extremely low birth weight infants(ELBWI). Methods : Retrospective review of 84 ELBWI who were admitted to our neonatal intensive care unit from June 2004 to April 2006 was performed. Patients were divided into prophylactic group(n=28) and control group(n=56), where prophylactic indomethacin were given within 6 hours after birth. Clinical outcomes were compared between these groups. Results : There were no significant differences in gestational age, birth weight, incidence of hemodynamically significant PDA and severe IVH, and mortality between prophylactic group and control group. However, there were more frequent indications for therapeutic indomethacin, higher incidence of intestinal perforation, and longer time to achieve full enteral feeding in prophylactic group than control group. The incidence of other adverse events attributed to indomethacin prophylaxis did not differ between two groups. Conclusions : Prophylactic indomethacin may not prevent hemodynamically significant PDA and severe IVH in ELBWI. On the contrary, it may be associated with increased risk of adverse events. Further efforts should be investigated to decrease PDA and severe IVH in ELBWI.

• Food Science and Preservation
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• v.24 no.7
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• pp.1017-1024
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• 2017

The objective of this study was to investigate the inhibitory effects of Litsea japonica fruit flesh extract (LJF-HE) on gastritis in an indomethacin-induced SD rat model. Rats were randomly divided into six groups: G1 (normal group), G2 (control group, indomethacin-induced gastritis), G3 (positive group, indomethacin-induced gastritis and ranitidine 50 mg/kg), G4 (LJF-HE-L group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 30 mg/kg), G5 (LJF-HE-M group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 60 mg/kg), G6 (LJF-HE-H group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 120 mg/kg). In the group treated with LJF-HE (G4, G5, and G6), gastric mucosal damage, gastric juice secretion and pepsin activity were significantly decreased compared to the control group. Additionally, there were decreases in the expression of cholecystokinin 2 receptor (CCK-2r), histamine receptor H2 (H2r) and H+/K+ ATPase in the gastric lesions. The plasma levels of TNF-${\alpha}$ and IL-$1{\beta}$ significantly decreased in LJF-HE (G4, G5, and G6) treated groups compared with control. The plasma level of PGE2 was also significantly increased by LJF-HE (G5 and G6). These results suggest that LJF-HE (G4, G5, and G6) has the ability to inhibit on indomethacin-induced gastritis.

• Korean Chemical Engineering Research
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• v.55 no.2
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• pp.180-189
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• 2017

Pharmaceutical co-crystals primarily to improve the solubility as well as stability of insoluble drug are to be investigated more intensively for IMDs as US FDA has reclassified co-crystal as a special case of solvates in August this year. In this study, we proposed a mechanism of indomethacin-saccharin co-crystal formation and the creation of transient indomethacin meta-stable form using in-line monitoring tools with the addition rate of anti-solvent as a critical process parameter. Among various instruments, we combined PVM (particle vision measurement) and FBRM (focused beam reflectance measurement) for the in-line monitoring of anti-solvent co-crystallization process. The off-line characterization of resulting powders was carried out employing the PXRD (powder x-ray diffraction) and DSC (differential scanning calorimeter). It was observed that the pathway to the final IMC-SAC co-crystal was significantly dependent upon the anti-solvent addition rate. The process conditions to obtain high quality co-crystal powder effectively were established. Consequently, we concluded that in-line monitoring combing the PVM and FBRM should be useful for the in-line monitoring of pharmaceutical co-crystallization processes.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.36-44
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• 2006

Background: There is controversy regarding whether COX-2 specific inhibitors are associated with elevation of blood pressure. We compared the effects of aspirin, indomethacin, and celecoxib for vascular reactivity induced by phenylephrine. We also tested the effects of indomethacin and NO donor on COX-1 and COX-2 protein expression, as well as nitrite production in culture medium of vascular smooth muscle cells. Materials and Methods: In this experiment, we used the isometric tension study for vascular reactivity. After 45 minutes of pretreatment with aspirin, indomethacin, celecoxib, and phenylephrine induced contractions were tested. COX-1 and COX-2 protein expressions were analyzed by Western blot and nitrite production by the Griess reaction. Results: Although celecoxib pretreatment caused enhanced arterial contraction, aspirin pretreatment induced more potent arterial contraction than celecoxib in the isometric tension study of rabbit femoral artery. COX-1 protein expression was unchanged by indomethacin, SNP and NOR-3; COX-2 protein expression was increased by the addition of indomethacin, SNP, and NOR-3. Especially, NOR-3, a NO donor, significantly increased COX-2 protein expression with unstimulated conditions as well as LPS stimulation. Induction of nitrite production was higher with NOR-3 treatment than SNP treatment with LPS stimulation. Conclusion: These results suggest that aspirin caused more potent vascular contraction than celecoxib and indomethacin. COX-2 expression in VSMC depended on the types of NO donor and LPS stimulation.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.477-487
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• 2010

Objectives : This study was carried out to investigate the effects of sihogeji-tang on indomethacin-induced gastric mucosal lesions in rats. Methods : Experimental rats were classified into three groups. The normal group had no inflammation elicited. The control group was rats administered water after elicitation of gastro-inflammation. The sample group were administered sihogeji-tang after gastro-inflammation elicitation. Results : In the common morphology and histochemical change, the control group were observed to have various injuries by hemorrhagic erosion, while the sample group had noticeably fewer injuries than the control. In the immunohistochemical change, the distribution of HSP-70, PCNA treated with sihogeji-tang noticeably increased over the control group. The distribution of NF-kB, COX-2 treated with sihogeji-tang noticeably decreased compared to the control group. (p<0.05) Conclusions : Sihogeji-tang had significant effects on indomethacin-induced gastric mucosal lesions in rats.